THE APhA COMPLETE REVIEW FOR PHARMACY, 7th Ed

Table 1-1. Metric System Prefixes

 

Prefix

Meaning

 

mega-

one million times the base unit (106)

 

kilo-

one thousand times the base unit (103)

 

deci-

one-tenth the base unit (10-1)

 

centi-

one-hundredth the base unit (10-2)

 

milli-

one-thousandth the base unit (10-3)

 

micro-

one-millionth the base unit (10-6)

 

nano-

one-billionth the base unit (10-9)

 

pico-

one-trillionth the base unit (10-12)

 

Table 1-2. Apothecaries' System of Measure

Weight

Volume

20 grains = 1 scruple

60 minims = 1 fluidram

3 scruples = 1 dram

8 fluidrams = 1 fluid ounce

8 drams = 1 ounce

16 fluid ounces = 1 pint

12 ounces = 1 pound

2 pints = 1 quart

 

4 quarts = 1 gallon

       

000137
Figure 3-1. Concentration Gradient of Diffusant across a Diaphragm of a Diffusion Cell

000051
Figure 3-2. Plots of Rate of Shear as a Function of Shearing Stress for (A) Newtonian, (B) Plastic, (C) Pseudoplastic, (D) Dilatant, and (E) Thixotropic flow

Table 3-1. Typical Pharmaceutical Ingredients

Ingredient type

Definition

Examples

Antifungal preservative

Used in liquid and semisolid formulations to prevent growth of fungi

Benzoic acid, butylparaben, ethylparaben, sodium benzoate, sodium propionate

Antimicrobial preservative

Used in liquid and semisolid formulations to prevent growth of microorganisms

Benzalkonium chloride, benzyl alcohol, cetylpyridinium chloride, phenyl ethyl alcohol

Antioxidant

Used to prevent oxidation

Ascorbic acid, ascorbyl palmitate, sodium ascorbate, sodium bisulfate, sodium metabisulfite

Binder

Used to cause adhesion of powder particles in tablet granulations

Acacia, alginic acid, ethylcellulose, starch, povidone

Diluent

Used as fillers to create desired bulk, flow properties, and compression characteristics in tablet and capsule preparations

Kaolin, lactose, mannitol, cellulose, sorbitol, starch

Disintegrant

Used to promote disruption of solid mass into small particles

Microcrystalline cellulose, carboxymethylcellulose calcium, sodium alginate, sodium starch glycolate, alginic acid

Emulsifying agent

Used to promote and maintain dispersion of finely divided droplets of a liquid in a vehicle in which it is immiscible

Acacia, cetyl alcohol, glyceryl monostearate, sorbitan monostearate

Glidant

Used to improve flow properties of powder mixture

Colloidal silica, cornstarch, talc

Humectant

Used for prevention of dryness of ointments and creams

Glycerin, propylene glycol, sorbitol

Lubricant

Used to reduce friction during tablet compression and to facilitate ejection of tablets from the die cavity

Calcium stearate, magnesium stearate, mineral oil, stearic acid, zinc stearate

Plasticizer

Used to enhance coat spread over tablets, beads, and granules

Glycerin, diethyl palmitate

Surfactant

Used to reduce surface or interfacial tension

Polysorbate 80, sodium lauryl sulfate, sorbitan monopalmitate

Suspending agent

Used to reduce sedimentation rate of drug particles dispersed throughout a vehicle in which they are not soluble

Carbopol, hydroxymethylcellulose, hydroxypropyl cellulose, methylcellulose, tragacanth

Table 3-2. Examples of Sustained-Release Drug Delivery Products

Dosage forms

Manufacturer

Active ingredients

Indications

Controlled-release tablets

Theo-Dur

ALZA Corp.

Theophylline

Asthma

Abacavir (Ziagen)

GlaxoSmithKline

Nucleoside reverse transcriptase inhibitor

HIV-1 infection

Sinemet

Bristol-Myers Squibb

Carbidopa + levodopa

Parkinson's disease

Volmax

ALZA Corp.

Albuterol

Bronchospasm

Voltaren

Novartis

Diclofenac sodium

Osteoarthritis and rheumatoid arthritis

Efidac 24

ALZA Corp.

Chlorpheniramine

Allergy symptoms and nasal congestion

DynaCirc CR

Novartis

Isradipine

Hypertension

Capsules

Dexedrine Spansules

GlaxoSmithKline

Dextroamphetamine

Narcolepsy

Adderall XL

Shire Pharmaceuticals

Amphetamine + dextroamphetamine

Attention-deficit/hyperactivity disorder (ADHD)

Ritalin LA

Novartis

Methylphenidate hydrochloride

ADHD

Videx EC

Bristol-Myers Squibb

Didanosine

HIV-1 infection

Aerosols

Ventolin HFA

GlaxoSmithKline

Albuterol sulfate

Bronchodilator

Azmacort

Kos

Triamcinolone acetonide

Asthma

Serevent

GlaxoSmithKline

Salmeterol

Bronchodilator

Osmotic systems

Oros System

ALZA Corp.

Oral delivery of different drugs

 

Ditropan XL

ALZA Corp.

Oxybutynin chloride

Overreacting bladder

Covera-HS

Pfizer

Verapamil

Antihypertensive

Concerta

ALZA Corp.

Methylphenidate HCl

ADHD

DUROS implant systems

Viadur

ALZA Corp.

Leuprolide

Prostate cancer

Inserts

Pilocarpine Ocusert

ALZA Corp.

Pilocarpine

Glaucoma

Lacrisert

ALZA Corp.

Hydroxypropyl cellulose

Ophthalmic moisturizer

Progestasert

CollaGenex

Progesterone

Contraceptive

Atridox

ALZA Corp.

Doxycycline

Periodontal disease

Transdermal patches

Alora

Watson Pharma

Estradiol

Menopausal symptoms

CombiPatch

Novartis

Estradiol/norethindrone acetate

Vasomotor symptoms associated with menopause

Androderm

Watson Pharmaceuticals

Testosterone

Testosterone deficiency

Nicotine transdermal system

Watson Pharmaceuticals

Nicotine

Smoking cessation

PEGylated proteins

PEGIntron

Schering Corp.

PEGylated interferon

Hepatitis C

PEGASYS

Roche

PEGylated interferon + ribavirin

Hepatitis B, hepatitis C

Liposomes

Doxil

Ortho Biotech

Doxorubicin HCl

Kaposi's sarcoma

DaunoXome

NeXstar Pharmaceuticals

Daunorubicin

Kaposi's sarcoma

Poly(lactic-co-glycolic acid)/polylactic acid microspheres

Lupron Depot

TAP Pharmaceuticals

Luteinizing hormone-releasing hormone agonist

Prostate cancer, endometriosis

Zoladex Depot

AstraZeneca

Goserelin acetate

Prostate cancer, endometriosis

Nutropin Depot

Genentech

Recombinant human growth hormone

Growth deficiencies

           

000266
Figure 3-3. Different Types of Ophthalmic inserts

000045
Figure 3-4. Essential Components of Drug Delivery

Table 4-1. Levigating Agents by Type and Ointment Base Classification

Type of agent

Ointment base classification

Aqueous

 

Glycerin

Oil-in-water emulsion

Propylene glycol

Water soluble

Polyethylene glycol 400

Water washable

Oily

 

Mineral oil

Oleaginous or hydrocarbon

Castor oil

Absorption

Cottonseed oil

Water-in-oil emulsion

Note: Other agents may be useful for certain preparations, such as Tween 80 for incorporating coal tar. Castor oil is useful for incorporating ichthammol and peru balsam.

000222
Figure 5-1. Horizontal Laminar Flow Workbench Illustration courtesy of the University of Tennessee Parenteral Medications Lab.

000135
Figure 5-2. Vertical Laminar Flow Workbench Illustration courtesy of the University of Tennessee Parenteral Medications Lab.

000026
Figure 5-3. Types of Syringes Illustration courtesy of the University of Tennessee Parenteral Medications Lab.

000209
Figure 5-4. Needle Illustration courtesy of the University of Tennessee Parenteral Medications Lab.

Table 6-1. IV Bolus Multiple Dose Regimen

Dose number

Equation

Maximum or peak concentration

Minimum or trough concentration at the end of the dosing interval

1

000215

000055

000050

n

000034

000252

000041

Steady state

000247

000268

000270

000205
Figure 6-1. The Three Concentration-Dependent Phases

Table 7-1. Milestones in Biotechnology

 

Event

Year

 

Identification of DNA as a genetic material

1940

 

Discovery of DNA double helix by James Watson and Francis Crick

1953

 

Elucidation of the genetic code (64 nucleic acid triplets, or codons, encode 20 amino acids)

1961

 

Cloning of DNA and the production of the first recombinant DNA-derived protein

1973

 

Introduction of monoclonal antibodies

1975

 

Production of the first human protein (somatostatin) from recombinant DNA technology

1977

 

Cloning of the human insulin gene

1978

 

Licensing in the United States of technology to derive human insulin from recombinant DNA

1982

 

Conception of the polymerase chain reaction for amplification of DNA

1983

 

Initiation of the Human Genome Project

1990

 

Sequencing of the human genome

2001

 

Table 7-2. Approved Biological Products

Generic name

Brand name (manufacturer)

Indications

Blood factors

   

Factor VII

NovoSeven (Novo Nordisk)

Hemophilia

Factor VIII

Bioclate, Recombinate, Advate (Baxter); Kogenate, Helixate (Bayer); ReFacto (Genetics Institute); Xyntha (Wyeth Pharmaceuticals)

Hemophilia A

Factor IX

BeneFIX (Genetics Institute)

Hemophilia B

Cytokines

   

Aldesleukin (IL-2)

Proleukin (Chiron)

Metastatic renal cell carcinoma and melanoma

Denileukin diftitox

Ontak (Ligand)

Cutaneous T-cell lymphoma

Interferon alfacon-1

Infergen (InterMune)

Hepatitis C

Interferon alfa-n1

Wellferon (GlaxoSK)

Chronic hepatitis C

Interferon alfa-2a

Roferon-A (Roche)

Hairy cell leukemia; AIDS-related Kaposi's sarcoma; chronic myelogenous leukemia

Interferon alfa-2b

Intron-A (Schering)

Hairy cell leukemia; AIDS-related Kaposi's sarcoma; chronic hepatitis B and C; condylomata acuminata; malignant melanoma

Interferon alfa-n3

Alferon-N (InterMune)

Condylomata acuminata

Interferon beta-1b

Betaseron (Berlex)

Acute relapsing-remitting multiple sclerosis

Interferon beta-1a

Avonex (Biogen); Rebif (Serono)

Acute relapsing-remitting multiple sclerosis

Interferon gamma-1b

Actimmune (InterMune)

Chronic granulomatous disease; osteoporosis

Oprelvekin (IL-11)

Neumega (Genetics Institute)

Thrombocytopenia from chemotherapy

Peginterferon alfa-2a

Pegasys (Roche)

Hepatitis C

Peginterferon alfa-2b

PegIntron (Schering)

Hepatitis C

Enzymes

   

Agalsidase beta

Fabrazyme (Genzyme)

Fabry disease

Alglucosidase alfa

Myozyme (Genzyme)

Lysosomal alpha-1,4-glucosidase deficiency

Alpha-1-proteinase inhibitor

Zemaira (Aventis)

Alpha-1-proteinase inhibitor deficiency

Alteplase

Activase (Genentech)

Acute myocardial infarction; pulmonary embolism; stroke

Bivalirudin

Angiomax (Medicines Co.)

Coronary angioplasty (PTCA); unstable angina

Dornase alfa

Pulmozyme (Genentech)

Respiratory complication from cystic fibrosis

Eptifibatide

Integrelin (Millennium)

Acute coronary syndromes; angioplasties

Galsulfase

Naglazyme (Biomarin Pharmaceutical Inc.)

Mucopolysaccharidosis

Idursulfase

Elaprase (Shire Human Genetic Therapies)

Mucopolysaccharidosis

Imiglucerase

Cerezyme (Genzyme)

Type 1 Gaucher's disease

Laronidase

Aldurazyme (Biomarin)

Mucopolysaccharidosis

Lepirudin

Refludan (Berlex)

Heparin-induced thrombocytopenia

Rasburicase

Elitek (Sanofi-Synthelabo)

Elevated plasma uric acid in pediatric malignancy

Reteplase

Retavase (Centocor/J&J)

Acute myocardial infarction

Tenecteplase

TNKase (Genentech)

Acute myocardial infarction

Tirobifan

Aggrastat (Merck)

Acute coronary syndromes

Growth factors

   

Becaplermin (PDGF)

Regranex (Ortho-McNeil)

Diabetic foot ulcer

Darbepoetin alfa

Aranesp (Amgen)

Anemia associated with end-stage renal disease and chronic renal insufficiency

Epoetin alfa

EPOGEN (Amgen); Procrit (Ortho Biotech)

Anemia attributable to chronic renal disease; zidovudine-induced anemia; anemia due to chemotherapy; surgery patients

Filgrastim

Neupogen (Amgen)

Neutropenia attributable to myelosuppressive chemotherapy; myeloid reconstitution after bone marrow transplant; severe chronic neutropenia; peripheral blood progenitor cell transplant; induction and consolidation therapy in acute myelogenous leukemia

Methoxy polyethylene glycol-epoetin beta

Mircera (Roche)

Anemia attributable to chronic renal failure

Palifermin

Kepivance (Biovitrum)

Oral mucositis; mucositis following chemotherapy

Pegfilgrastim

Neulasta (Amgen)

Febrile neutropenia attributable to myelosuppressive chemotherapy

Sargramostim

Leukine (Berlex)

Myeloid reconstitution after bone marrow transplant; bone marrow transplant failure; adjunct to chemotherapy in acute myelogenous leukemia; peripheral blood progenitor cell transplant

Hormones

   

Choriogonadotropin alfa

Ovidrel (Serono)

Fertility

Follitropin alfa

Gonal-F (Serono)

Ovulatory failure

Follitropin beta

Follistim (Organon)

Ovulatory failure

Human growth hormone

Protopin, Nutropin (Genentech)

Growth hormone deficiency in pediatric patients

 

Humatrope (Eli Lilly)

Growth retardation in chronic renal disease

 

Saizen, Serostim (Serono)

AIDS wasting

 

Norditropin (Novo Nordisk)

Turner's syndrome

 

Genotropin (Pharmacia); Biotropin (Sol Source Technologies)

Growth hormone deficiency in adults

Human insulin

Humulin; Humalog (Eli Lilly); Novolin (Novo Nordisk); Lantus (Aventis)

Insulin-dependent diabetes mellitus

Ganirelix

Antagon (Organon)

Luteinizing hormone surge during fertility therapy

Glucagon

GlucaGen (Novo Nordisk)

Hypoglycemia

Growth hormone-releasing hormone

Geref (Serono)

Growth hormone deficiency in pediatric patients

Thyrotropin

Thyrogen (Genzyme)

Thyroid cancer

Monoclonal antibodies

   

Abciximab

ReoPro (Centocor)

Prevention of blood clots following percutaneous coronary intervention; unstable angina prior to percutaneous coronary intervention

Adalimumab

Humira (Abbott)

Acute rheumatoid arthritis

Alemtuzumab

Campath (Berlex)

Chronic lymphocytic leukemia

Basiliximab

Simulect (Novartis)

Acute organ transplant rejection

Bevacizumab

Avastin (Genentech)

Colorectal cancer

Certolizumab pegol

Cimzia (UCB)

Crohn's disease

Cetuximab

Erbitux (ImClone Systems)

Colorectal cancer

Daclizumab

Zenapax (Roche)

Kidney transplant; acute rejection

Eculizumab

Soliris (Alexion)

Paroxysmal nocturnal hemoglobinuria

Efalizumab

Raptiva (Genentech)

Psoriasis

Gemtuzumab (ozogamicin)

Mylotarg (Wyeth/PDL)

Acute myeloid leukemia (CD33+)

Ibritumomab (tiuxetan)

Zevalin (IDEC)

B-cell non-Hodgkin's lymphoma

Infliximab

Remicade (Centocor)

Crohn's disease; rheumatoid arthritis

Natalizumab

Tysabri (Amgen)

Crohn's disease; multiple sclerosis

Omalizumab

Xolair (Genentech)

Asthma

Palivizumab

Synagis (MedImmune)

Prevention of respiratory syncytial virus and fatal pneumonia in pediatrics

Panitumumab

Vectibix (Amgen)

Metastatic colorectal cancer

Ranibizumab

Lucentis (Genentech)

Exudative age-related macular degeneration

Rituximab

Rituxan (IDEC/Genentech)

Low-grade non-Hodgkin's lymphoma

Tositumomab

Bexxar (Corixa)

CD20+ non-Hodgkin's lymphoma

Trastuzumab

Herceptin (Genentech/PDL)

Metastatic breast cancer (Her 2 Neu+)

Vaccines

   

Haemophilus b/hepatitis B

Comvax (Merck)

Prevention of Haemophilus influenzae and hepatitis B

Hepatitis B vaccine

Engerix-B (GlaxoSK); Recombivax HB (Merck)

Prevention of hepatitis B

Others

   

Abatacept

Orencia (BMS)

Rheumatoid arthritis

Anakinra

Kineret (Amgen)

Rheumatoid arthritis

BCNU polymer

Gliadel (Guilford)

Recurrent glioblastoma multiforme

Daunorubicin-liposomal

DaunoXome (Gilead)

Kaposi's sarcoma

Doxorubicin-liposomal

DOXIL (Alza)

Kaposi's sarcoma; ovarian cancer

Drotrecogin alfa

Xigris (Eli Lilly)

Sepsis

Etanercept

Enbrel (Amgen)

Rheumatoid arthritis; psoriatic arthritis

Fomivirsen

Vitravene (Isis)

Cytomegalovirus retinitis

Glatiramer

Copaxone (Teva)

Relapsing multiple sclerosis

Lipid-based amphotericin B

Abelcet (Elan); Amphotec (Sequus); AmBisome (Fujisawa/Gilead)

Aspergillosis; cryptococcal meningitis in HIV; systemic fungal infections

Nesiritide

Natrecor (Scios/Innovex)

Congestive heart failure

Rilonacept

Arcalyst (Regeneron)

Cryopyrin-associated periodic syndromes

Romiplostim

Nplate (Amgen)

Idiopathic thrombocytopenic purpura

AIDS, acquired immunodeficiency syndrome; BCNU, bis-chlorethylnitrosourea; HIV, human immunodeficiency virus; IL, interleukin; PDGF, platelet-derived growth factor; PCI, percutaneous coronary intervention; PTCA, percutaneous transluminal coronary angioplasty.

         

000015
Figure 7-1. Gene Expression: The Synthesis of Proteins Reproduced from Sindelar, 2002.

000240
Figure 7-2. Summary of Typical rDNA Production of a Protein from Either Genomic DNA or cDNA Reprinted by permission of Sindelar, 2002.

000020
Figure 7-3. Production of Monoclonal Antibodies Reproduced from Sindelar, 2002.

Table 7-3. Genetic Polymorphisms in Drug Target Genes That Can Influence Drug Responsea

Gene or gene product

Medication

Drug effect associated with polymorphism

Angiotensin-converting enzyme (ACE)

ACE inhibitors (e.g., enalapril)

Renoprotective effects; blood pressure reduction; reduction in left ventricular mass; endothelial function

 

Fluvastatin

Lipid changes (reductions in low-density lipoprotein cholesterol and apolipoprotein B); progression or regression in coronary atherosclerosis

Arachidonate 5-lipoxygenase

Leukotriene inhibitors

Improvement of FEV1

β2-adrenergic receptor

β2-agonists

Bronchodilatation; susceptibility to agonist-induced desensitization; cardiovascular effects

Bradykinin B2 receptor

ACE inhibitors

ACE inhibitor-induced cough

Dopamine receptors (D2, D3, D4)

Antipsychotics (e.g., haloperidol and clozapine)

Antipsychotic response (D2, D3, D4); antipsychotic-induced tardive dyskinesia (D3); antipsychotic-induced acute akathisia (D3)

Estrogen receptor-α

Conjugated estrogens

Increase in bone mineral density

 

Hormone replacement therapy

Increase in high-density lipoprotein cholesterol

Glycoprotein IIIa subunit of glycoprotein IIb/IIIa

Aspirin or glycoprotein IIb/IIIa inhibitors

Antiplatelet effect

Serotonin (5-hydroxytryptamine transporter)

Antidepressants (e.g., clomipramine, fluoxetine, and paroxetine)

Serotonin neurotransmission; antidepressant response

FEV1, forced expiratory volume in 1 second.

a. The examples shown are illustrative and are not representative of all published studies. Reprinted by permission from Evans, McLeod, 2003.

Table 7-4. Genetic Polymorphisms in Disease-Modifying or Treatment-Modifying Genes That Can Influence Drug Responsea

Gene or gene product

Disease or response association

Medication

Influence of polymorphism on drug effect or toxicity

Adducin

Hypertension

Diuretics

Myocardial infarction or strokes

Apolipoprotein E

Progression of atherosclerosis; ischemic cardiovascular events

Statins (e.g., simvastatin)

Enhanced survival

 

Alzheimer's disease

Tacrine

Clinical improvement

Human leukocyte antigen

Toxicity

Abacavir

Hypersensitivity reaction

Cholesterol ester transfer protein

Progression of atherosclerosis

Statins (e.g., pravastatin)

Slowing of progression of atherosclerosis

Ion channels (HERG, KvLQT1, Mink, and MiRP1)

Congenital long-QT syndrome

Erythromycin; terfenadine; cisapride; clarithromycin; and quinidine

Increased risk of drug-induced torsade de pointes

Methylguanine methyltransferase

Glioma

Carmustine

Response of glioma to carmustine

Parkin

Parkinson's disease

Levodopa

Clinical improvement and levodopa-induced dyskinesias

Prothrombin and factor V

Deep-vein thrombosis; cerebral-vein thrombosis

Oral contraceptives

Increased risk of deep-vein thrombosis and cerebral-vein thrombosis with oral contraceptives

Stromelysin-1

Atherosclerosis progression

Statins (e.g., pravastatin)

Reduction in cardiovascular events by pravastatin (death, myocardial infarction, stroke, angina, and others); reduction in risk of repeated angioplasty

a. The examples shown are illustrative and are not representative of all published studies. Reproduced with permission from Evans, McLeod, 2003.

           

Table 7-5. Pharmacogenomics of Phase I Drug Metabolisma

Drug-metabolizing enzyme

Frequency of variant poor-metabolism phenotype

Representative drugs metabolized

Effect of polymorphism

Butyrylcholinesterase (pseudocholinesterase)

Approximately 1 in 3,500 Europeans

Succinylcholine

Enhanced drug effect

Cytochrome P-450 2D6 (CYP2D6)

6.8% of Swedes

Debrisoquin

Enhanced drug effect

 

1% of Chinese

Sparteine

Enhanced drug effect

   

Nortriptyline

Enhanced drug effect

   

Codeine

Decreased drug effect

Cytochrome P-450 2C9 (CYP2C9)

Approximately 3% of English (those homozygous for the *2 and *3 alleles)

Warfarin

Phenytoin

Enhanced drug effect

Enhanced drug effect

Cytochrome P-450 2C19 (CYP2C19)

2.7% of white Americans; 3.3% of Swedes; 14.6% of Chinese; 18% of Japanese

Omeprazole

Enhanced drug effect

Dihydropyrimidine dehydrogenase

Approximately 1% of population is heterozygous

Fluorouracil

Enhanced drug effect

a. Examples of genetically polymorphic phase I enzymes that catalyze drug metabolism are listed, including selected examples of drugs that have clinically relevant variations in their effect.

Reproduced with permission from Weinshilboum, 2003.

Table 7-6. Pharmacogenomics of Phase II Drug Metabolisma

Drug-metabolizing enzyme

Frequency of variant poor-metabolism phenotype

Representative drugs metabolized

Effect of polymorphism

N-acetyltransferase 2

52% of white Americans

Isoniazid

Enhanced drug effect

 

17% of Japanese

Hydralazine

Enhanced drug effect

Uridine diphosphate-glucuronosyltransferase 1A1 (TATA box polymorphism)

10.9% of whites

Procainamide

Enhanced drug effect

 

4% of Chinese

Irinotecan

Enhanced drug effect

 

1% of Japanese

Bilirubin

Gilbert's syndrome

Thiopurine S-methyltransferase

Approximately 1 in 300 whites

Mercaptopurine

Enhanced drug effect (toxicity)

 

Approximately 1 in 2,500 Asians

Azathioprine

Enhanced drug effect (toxicity)

Catechol O-methyltransferase

Approximately 25% of whites

Levodopa

Enhanced drug effect

a. Examples of genetically polymorphic phase II (conjugating) enzymes that catalyze drug metabolism are listed, including selected examples of drugs that have clinically relevant variations in their effects.

Reproduced with permission from Weinshilboum, 2003.

             

Table 8-1. Trends in Awareness, Treatment, and Control of High Blood Pressure in Adults Ages 18-74

 

National Health and Nutrition Examination Survey

 

Aspect

II, 1976-80 (%)

III, phase 1, 1988-91 (%)

III, phase 2 1991-94 (%)

1999-2000 (%)

2005-06 (%)

Awareness

51

73

68

70

78

Treatment

31

55

54

59

68

Controla

10

29

27

34

64

Unpublished data for 1999-2000 computed by M. Woltz, National Heart, Lung, and Blood Institute; adapted from JNC-7 Express, National Heart, Lung, and Blood Institute. Information for 2005-06 comes from the most recent Nhanes data available.

High blood pressure is systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg, or it is evidenced by the taking of antihypertensive medication.

a. Those adults surveyed have systolic blood pressure < 140 mm Hg and diastolic blood pressure < 90 mm Hg.

Table 8-2. Prevalence of Hypertension by Ethnic Group for Adults Ages 20-74 (percent)

 

Ethnic group

Male

Female

 

Caucasians

24

19

 

African Americans

35

34

 

Mexican Americans

25

22

 

Asian Americans

13

13

 
             

Table 8-3. Classification and Management of Blood Pressure for Adults

     

Initial drug therapy

 

Blood pressure classification

SBPa(mm Hg)

DBP (mm Hg)

Lifestyle modification

Without compelling indication

With compelling indicationsb

Normal

< 120

and < 80

Encouraged

   

Prehypertension

120-139

or 80-89

Yes

No antihypertensive drug indicated

Drug(s) for compelling indications.c

Stage 1 hypertension

140-159

or 90-99

Yes

Thiazide-type diuretics for most; may consider ACEI, ARB, BB, CCB, or combination

Drug(s) for compelling indications;c other antihypertensive drugs (diuretics, ACEI, ARB, BB, or CCB) as needed

Stage 2 hypertension

≥ 160

or ≥ 100

Yes

Two-drug combination for mostd(usually thiazide-type diuretic and ACEI or ARB or BB or CCB)

 

Adapted from JNC-7 Express, National Heart, Lung, and Blood Institute.

ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BB, β-blocker; CCB, calcium channel blocker; DBP, diastolic blood pressure; SBP, systolic blood pressure

a. Treatment is determined by highest blood pressure category.

b. See

Table 8-12.

c. Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension.

d. Treat patients with chronic kidney disease or diabetes to blood pressure goal of < 130/80 mm Hg.

000250
Figure 8-1. Sympathetic Nervous System Activation Source: Carter, BL, Saseen, JL, 2002.

Table 8-4. Recommendations for Follow-Up Based on Initial BP Measurements for Adults

Initial BP (mm Hg)a

 

Systolic

Diastolic

Recommended follow-upb

< 130

< 85

Recheck in 2 years.

130-139

85-89

Recheck in 1 year.c

140-159

90-99

Confirm within 2 months.c

160-179

100-109

Evaluate or refer to source of care within 1 month.

~180

~110

Evaluate or refer to source of care immediately or within 1 week depending on clinical situation.

Adapted from JNC-7 Express, National Heart, Lung, and Blood Institute.

a. If systolic and diastolic readings are different, follow recommendations for shorter time to follow-up (e.g., a person with a reading of 160/86 mm Hg should be evaluated or referred to source of care within 1 month).

b. Modify the scheduling of follow-up according to reliable information about past BP measurements, other cardiovascular risk factors, or target organ disease.

c. Provide advice about lifestyle modifications.

000246
Figure 8-2. Algorithm for the Treatment of Hypertension Adapted from JNC-7 Express, National Heart, Lung, and Blood Institute.

Table 8-5. Identifiable Causes, Diagnostic Tests, and Clinical Findings for Secondary Hypertension

Cause or diagnosis

Diagnostic test (clinical finding)

Chronic kidney disease

Estimated GFR (abdominal or flank mass for polycystic kidney disease)

Coarctation of the aorta

CT angiography (delayed or absent femoral pulse)

Cushing's syndrome and other glucocorticoid excess states, including chronic steroid therapy

History; dexamethasone suppression test (truncal obesity, moon facies, buffalo hump, abdominal striae, and hirsutism)

Drug-induced or drug-related condition

History; drug screening

Pheochromocytoma

24-hour urinary metanephrine and normetanephrine (headache, palpitations, and sweating)

Primary aldosteronism and other mineralocorticoid excess states

24-hour urinary aldosterone level or specific measurements of other mineralocorticoids (hypokalemia)

Renovascular hypertension

Doppler flow study; magnetic resonance angiography (abdominal bruit)

Sleep apnea

Sleep study with oxygen saturation (obesity, snoring, and tired during wake time)

Thyroid or parathyroid disease

Thyroid-stimulating hormone; serum parathyroid hormone (goiter; hypercalcemia)

CT, computed tomography; GFR, glomerular filtration rate.

Table 8-6. Clinical Trial and Guideline Basis for Compelling Indications for Individual Drug Classes

 

RECOMMENDED DRUGS000042

 

COMPELLING INDICATION*

DIURETIC

BB

ACEI

ARB

CCB

ALDO ANT

CLINICAL TRIAL BASIS000153

Heart failure

 

ACC/AHA Heart Failure Guideline, MERIT-HF, COPERNICUS, CIBIS, SOLVD, AIRE, TRACE, ValHEFT, RALES

Postmyocardial infarction

 

   

ACC/AHA Post-MI Guideline, BHAT, SAVE, Capricorn, EPHESUS

High coronary disease risk

 

 

ALLHAT, HOPE, ANBP2, LIFE, CONVINCE

Diabetes

 

NKF-ADA Guideline, UKPDS, ALLHAT

Chronic kidney disease

   

   

NKF Guideline, Captopril Trial, RENAAL, IDNT, REIN, AASK

Recurrent stroke prevention

 

     

PROGRESS

* Compelling indications for antihypertensive drugs are based on benefits from outcome studies or existing clinical guidelines; the compelling indication is managed in parallel with the BP.

000042 Drug abbreviations: ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; Aldo ANT, aldosterone antagonist; BB, beta-blocker; CCB, calcium channel blocker.

000153 Conditions for which clinical trials demonstrate benefit of specific classes of antihypertensive drugs.

Adapted from JNC-7 Express, National Heart, Lung, and Blood Institute.

Table 8-7. Lifestyle Modifications to Manage Hypertension

MODIFICATION

RECOMMENDATION

APPROXIMATE SBP REDUCTION (RANGE)

Weight reduction

Maintain normal body weight (body mass index 18.5-24.9 kg/m2).

5-20 mmHg/10 kg weight loss

Adopt DASH eating plan

Consume a diet rich in fruits, vegetables, and lowfat dairy products with a reduced content of saturated and total fat.

8-14 mmHg

Dietary sodium reduction

Reduce dietary sodium intake to no more than 100 mmol per day (2.4 g sodium or 6 g sodium chloride).

2-8 mmHg

Physical activity

Engage in regular aerobic physical activity such as brisk walking (at least 30 min per day, most days of the week).

4-9 mmHg

Moderation of alcohol consumption

Limit consumption to no more than 2 drinks (1 oz or 30 mL ethanol; e.g., 24 oz beer, 10 oz wine, or 3 oz 80-proof whiskey) per day in most men and to no more than 1 drink per day in women and lighter weight persons.

2-4 mmHg30

Adapted from JNC-7 Express, National Heart, Lung, and Blood Institute.

DASH, Dietary Approaches to Stop Hypertension. For overall cardiovascular risk reduction, stop smoking. The effects of implementing these modifications are dose and time dependent, and could be greater for some individuals.

Table 8-8. Dietary Suggestions for Hypertensive Patients

Food group

Daily servings

Serving sizes

Examples and notes

Significance of each food group to the DASH diet pattern

Grains and grain products

7-8

1 slice bread; 1/2 c dry cereal; 1/2 c cooked rice, pasta, or cereal

Whole wheat bread, english muffins, pita bread, bagel, cereals, grits, and oatmeal

Major sources of energy and fiber

Vegetables

4-5

1 c raw leafy vegetable; 1/2 c cooked vegetable; 6 oz vegetable juice

Tomatoes, potatoes, carrots, peas, squash, broccoli, turnip greens, collards, kale, spinach, artichokes, beans, and sweet potatoes

Rich sources of potassium, magnesium, and fiber

Fruits

4-5

6 oz fruit juice; 1 medium fruit; 1/4 c dried fruit; 1/4 c fresh, frozen or canned fruit

Apricots, bananas, dates, grapes, oranges, orange juice, grapefruit, grapefruit juice, mangoes, melons, peaches, pineapple, prunes, raisins, strawberries, and tangerines

Important sources of potassium, magnesium, and fiber

Low-fat or nonfat dairy foods

2-3

8 oz milk; 1 c yogurt; 1.5 oz cheese

Skim or 1% milk, skim or low-fat buttermilk, nonfat or low-fat yogurt, part-skim mozzarella cheese, and nonfat cheese

Major sources of calcium and protein

Meats, poultry, and fish

2 or fewer

3 oz cooked meats, poultry, or fish

Select only lean cuts; trim away visible fats; broil, roast, or boil, instead of frying; and remove skin from poultry

Rich sources of protein and magnesium

Nuts, seeds, and legumes

4-5 per week

1.5 oz or 1/3 c nuts; 1/2 oz or 2 T seeds; 1/2 c cooked legumes

Almonds, filberts, mixed nuts, peanuts, walnuts, sunflower seeds, kidney beans, and lentils

Rich sources of energy, magnesium, potassium, protein, and fiber

Adapted from JNC-7 Express, National Heart, Lung, and Blood Institute.

DASH, Dietary Approaches to Stop Hypertension.

             

Table 8-9. The DASH Diet Sample Menu Based on 2000 Calories per Day

Food

Amount

Servings provided

Breakfast

   

Orange juice

6 oz

1 fruit

1% lowfat milk

8 oz (1 c)

1 dairy

Cornflakes (with 1 tsp sugar)

1 c

2 grains

Banana

1 medium

1 fruit

Whole wheat bread (with 1 T jelly)

1 slice

1 grain

Soft margarine

1 t

1 fat

Lunch

   

Chicken salad

3/4 c

1 poultry

Pita bread

1/2 large

1 grain

Raw vegetable medley

   
 

Carrot and celery sticks

3-4 sticks each

1 vegetable

 

Radishes

2

1 vegetable

Loose-leaf lettuce

2 leaves

1 vegetable

Part-skim mozzarella cheese

1.5 slices (1.5 oz)

1 dairy

1% lowfat milk

8 oz (1 c)

1 dairy

Fruit cocktail in light syrup

1/2 c

1 fruit

Dinner

   

Herbed baked cod

3 oz

1 fish

Scallion rice

1 c

2 grains

Steamed broccoli

1/2 c

1 vegetable

Stewed tomatoes

1/2 c

1 vegetable

Spinach salad:

   
 

Raw spinach

1/2 c

1 vegetable

 

Cherry tomatoes

2

1 vegetable

 

Cucumber

2 slices

1 vegetable

Light Italian salad dressing

1 T

1/2 fat

Whole wheat dinner roll

1 small

1 grain

Soft margarine

1 t

1 fat

Melon balls

1/2 c

1 fruit

Snacks

   

Dried apricots

1 oz (1/4 c)

1 fruit

Minipretzels

1 oz (3/4 c)

1 grain

Mixed nuts

1.5 oz (1/3 c)

1 nuts

Diet ginger ale

12 oz

0

Total number of servings in 2000-calorie per day menu

Food group

Servings

   

Grains

8

   

Vegetables

4

   

Fruits

5

   

Dairy foods

3

   

Meats, poultry, and fish

2

   

Nuts, seeds, and legumes

1

   

Fats and oils

2.5

   

Tips on eating the DASH way

    • Start small. Make gradual changes in your eating habits.

    • Center your meal around carbohydrates, such as pasta, rice, beans, or vegetables.

    • Treat meat as one part of the whole meal, instead of the focus.

    • Use fruits or low-fat, low-calorie foods such as sugar-free gelatin for desserts and snacks.

Remember: If you use the DASH diet to help prevent or control high blood pressure, make it part of a lifestyle that includes choosing foods lower in salt and sodium; keeping a healthy weight; being physically active; and if you drink alcohol, doing so in moderation.

Adapted from JNC-7 Express, National Heart, Lung, and Blood Institute.

DASH, Dietary Approaches to Stop Hypertension.

Table 8-10. Considerations for Individualizing Antihypertensive Drug Therapy

Indication

Drug therapy

Compelling indications unless contraindicated

 

Diabetes mellitus (type 1) with proteinuria

ACEI

Heart failure

ACEI, diuretics

Isolated systolic hypertension (older patients)

Diuretics (preferred), calcium antagonists (long-acting dihydropyridine)

Myocardial infarction

β-blockers (nonintrinsic sympathomimetic activity), ACEI (with systolic dysfunction)

Possible favorable effects on comorbid conditionsb

 

Angina

β-blockers, calcium antagonists

Atrial tachycardia and fibrillation

β-blockers, calcium antagonists (nondihydropyridine)

Cyclosporine-induced hypertension (use caution with the dose of cyclosporine)

Calcium antagonists

Diabetes mellitus (types 1 and 2) with proteinuria

ACEI (preferred), calcium antagonists

Diabetes mellitus (type 2)

Low-dose diuretics

Dyslipidemia

α-blockers

Essential tremor

β-blockers (noncardioselective)

Heart failure

Carvedilol, losartan potassium

Hyperthyroidism

β-blockers

Migraine

β-blockers (noncardioselective), calcium antagonists (nondihydropyridine)

Myocardial infarction

Diltiazem hydrochloride, verapamil hydrochloride

Osteoporosis

Thiazides

Preoperative hypertension

β-blockers

Prostatism (benign prostatic hyperplasia)

α-blockers

Renal insufficiency (use caution in renovascular hypertension and if creatinine ≥ 265.2 micromole/L [3 mg/dL])

ACEI

Possible unfavorable effects on comorbid conditionsa

 

Bronchospastic disease

β-blockersb

Depression

β-blockers, central α-agonist, reserpineb

Diabetes mellitus (types 1 and 2)

β-blockers, high-dose diuretics

Dyslipidemia

β-blockers (nonintrinsic sympathomimetic activity), diuretics (high-dose)

Gout

Diuretics

Heart block (second- or third-degree)

β-blockers,b calcium antagonists (nondihydropyridine)b

Heart failure

β-blockers (except carvedilol), calcium antagonists (except amlodipine besylate and felodipine)

Liver disease

Labetalol hydrochloride, methyldopab

Peripheral vascular disease

β-Blockers

Pregnancy

ACEI,b angiotensin II receptor blockersb

Renal insufficiency

Potassium-sparing agents

Renovascular disease

ACEI, angiotensin II receptor blockers

Adapted from JNC-7 Express, National Heart, Lung, and Blood Institute.

ACEI, angiotensin-converting enzyme inhibitors.

For initial drug therapy recommendations, see

Tables 8-11 through

8-19.

a. These drugs may be used with special monitoring unless contraindicated.

b. Contraindicated.

         

Table 8-11. Thiazide Diuretics, Thiazide-Like Diuretics, Loop Diuretics, Potassium-Sparing Agents, and Aldosterone-Receptor Blocker

Drug

Trade name

Usual dose range, total mg/d (frequency per day)

Adverse events and commentsa

Thiazide diuretics

Bendroflumethiazide

Naturetin

2.5-5 (1)

Short-term: increased cholesterol and glucose

Benzthiazide

Aquatag, Exna

12.5-50 (1)

Biochemical: decreased potassium, sodium, and magnesium; increased uric acid and calcium

Chlorothiazide

Diuril

125-500 (1)

 

Chlorthalidone

Hygroton, Hylidone

12.5-25 (1)

Rare: blood dyscrasias, photosensitivity, pancreatitis, hyponatremia, and sulfonamide-type immune reactions

Hydrochlorothiazide

HydroDIURIL, Microzide

12.5-50 (1)

Other: impotence, fatigue, headache, rash, and vertigo

Hydroflumethiazide

Saluron, Diucardin

25-50 (1)

 

Methyclothiazide

Renese

2.5-5 (1)

 

Polythiazide

Metahydrin, Naqua

2-4 (1)

 

Trichlormethiazide

 

2-4 (1)

 

Thiazide-like diuretics

Metolazone

Mykrox

2.5-10 (1)

(Less or no hypercholesterolemia compared to other thiazides; decreased microalbuminuria in diabetes)

Metolazone

Zaroxolyn

2.5-5 (1)

(Less or no hypercholesterolemia compared to other thiazides; decreased microalbuminuria in diabetes)

Indapamide

Lozol

2.5-5 (1)

 

Loop diuretics

     

Bumetanide

Bumex

0.5-2 (2)

Ototoxicity at high doses

Furosemide

Lasix

20-80 (2)

(Short duration and no hypercalcemia)

Torsemide

Demadex

2.5-10 (1)

(Short duration and no hypercalcemia)

Potassium-sparing agentsb

Amiloride

Midamor

5-10 (1-2)

Hyperkalemia

Triamterene

Dyrenium

50-100 (1-2)

(Avoid with history of kidney stones or hepatic disease)

Aldosterone-receptor blocker

Spironolactone

Aldactone

25-50 (1-2)

 

Adapted from JNC-7 Express, National Heart, Lung, and Blood Institute.

a. Adverse events, or side effects, listed are for the class of drugs, except where noted for individual drugs (in parentheses).

b. See

Table 8-12 for combination products.

Table 8-12. Combination Drugs for Hypertension

 

Fixed-dose combination (mg)a

Trade name

 

ACEIs and CCBs

   

Amlodipine/benazepril hydrochloride (2.5/10, 5/10, 5/20, 10/20)

Lotrel

 

Enalapril maleate/felodipine (5/5)

Lexxel

 

Trandolapril/verapamil (2/180, 1/240, 2/240, 4/240)

Tarka

 

ACEIs and diuretics

   

Benazepril/hydrochlorothiazide (5/6.25, 10/12.5, 20/12.5, 20/25)

Lotensin HCT

 

Captopril/hydrochlorothiazide (25/15, 25/25, 50/15, 50/25)

Capozide

 

Enalapril maleate/hydrochlorothiazide (5/12.5, 10/25)

Vaseretic

 

Lisinopril/hydrochlorothiazide (10/12.5, 20/12.5, 20/25)

Prinzide

 

Moexipril HCL/hydrochlorothiazide (7.5/12.5, 15/25)

Uniretic

 

Quinapril HCL/hydrochlorothiazide (10/12.5, 20/12.5, 20/25)

Accuretic

 

ARBs and CCBs

   

Amlodipine/valsartan (5/160, 5/320, 10/160, 10/320)

Exforge

 

Amlodipine/olmesartan (5/20, 5/40, 10/20, 10/40)

Azor

 

ARBs and diuretics

   

Candesartan cilexetil/hydrochlorothiazide (16/12.5, 32/12.5)

Atacand HCT

 

Eprosartan mesylate/hydrochlorothiazide (600/12.5, 600/25)

Teveten/HCT

 

Irbesartan/hydrochlorothiazide (150/12.5, 300/12.5)

Avalide

 

Losartan potassium/hydrochlorothiazide (50/12.5, 100/25)

Hyzaar

 

Telmisartan/hydrochlorothiazide (40/12.5, 80/12.5)

Micardis/HCT

 

Valsartan/hydrochlorothiazide (80/12.5, 160/12.5)

Diovan/HCT

 

BBs and diuretics

   

Atenolol/chlorothalidone (50/25, 100/25)

Tenoretic

 

Bisoprolol fumarate/hydrochlorothiazide (2.5/6.25, 5/6.25, 10/6.25)

Ziac

 

Propranolol LA/hydrochlorothiazide (50/25, 80/25)

Inderide

 

Metoprolol tartrate/hydrochlorothiazide (50/25, 100/25)

Lopressor HCT

 

Nadolol/bendrofluthiazide (40/5, 80/5)

Corzide

 

Timolol maleate/hydrochlorothiazide (10/25)

Timolide

 

Centrally acting drug and diuretics

   

Methyldopa/hydrochlorothiazide (250/15, 250/25, 500/30, 500/50)

Aldoril

 

Reserpine/chlorothiazide (0.125/250, 0.25/500)

Diupres

 

Reserpine/hydrochlorothiazide (0.125/25,0.25/50)

Hydropres

 

RIs and diuretics

   

Aliskiren/hydrochlorothiazide (150/12.5, 150/25, 300/12.5, 300/25)

Tekturna HCT

 

Other combinations

   

Amiloride HCL/hydrochlorothiazide (5/50)

Moduretic

 

Spironolactone/hydrochlorothiazide (25/25, 50/50)

Aldactazide

 

Triamterene/hydrochlorothiazide (37.5/25, 50/25, 75/50)

Dyazide, Maxzide

 

Adapted from JNC-7 Express, National Heart, Lung, and Blood Institute.

Abbreviations: BB, β-blocker; RI, renin inhibitor.

 

a. Some drug combinations are available in multiple fixed doses. Each drug dose is reported in milligrams.

 

Table 8-13. Postganglionic Adrenergic Neuron Blockers

Drug

Trade name

Usual dose range, total mg/d (frequency per day)

Adverse events and comments

Guanadrel

Hylorel

10-75 (2)

Postural hypotension and diarrhea

Guanethidine monosulfate

Ismelin

10-150 (1)

Postural hypotension and diarrhea

Reserpinea

Serpasil

0.05-0.25 (1)

Nasal congestion, sedation, depression, activation of peptic ulcer, dizziness, lethargy, memory impairment, sleep disturbances, and weight gain

Adapted from JNC-7 Express, National Heart, Lung, and Blood Institute.

a. Reserpine also acts centrally.

Table 8-14. Centrally Active α2-Agonists

Drug

Trade name

Usual dose range, total mg/d (frequency per day)

Adverse events and commentsa

Clonidine HClb

Catapres

0.1-0.8 (2)

Sedation, dry mouth, bradycardia, withdrawal hypertension, orthostatic hypotension, depression, impotence, and sleep disturbances

Guanabenz acetate

Wytensin

8-32 (2)

(More withdrawal)

Guanfacine HCl

Tenex

1-3 (1)

(Less withdrawal)

Methyldopa

Aldomet

250-1,000 (2)

(Hepatic and "autoimmune" disorders)

Adapted from JNC-7 Express, National Heart, Lung, and Blood Institute.

a. Adverse events, or side effects, listed are for the class of drugs, except where noted for individual drugs (in parentheses).

b. Clonidine HCl is also available as a once-weekly transdermal patch.

         

Table 8-15. Peripherally Acting α1-Adrenergic Blockers

Drug

Trade name

Usual dose range, total mg/d (frequency per day)

Adverse events and comments

Doxazosin mesylate

Prazosin HCl

Terazosin HCl

Cardura

Minipress

Hytrin

1-16 (1)

2-20 (2-3)

1-20 (1-2)

Postural hypotension, syncopal episode with first dose, postural hypotension, diarrhea, weight gain, peripheral edema, dry mouth, urinary urgency, constipation, priapism, nausea, dizziness, headache, palpitations, and sweating; no effects on glucose or cholesterol

Reprinted with permission from JNC-VII.

Table 8-16. β-Blockers and Combination α- and β-Blockers

Drug

Trade name

Lipid solubility/primary (secondary) routes of elimination

Usual dose range, total mg/d (frequency per day)

Adverse events and commentsa

β-blockers

Acebutololb,c

Atenololb

Betaxololb

Bisoprolol fumarateb

Carteolol HClc

Sectral

Tenormin

Kerlone

Zebeta

Cartrol

Low/H (R)

Low/R (H)

Low/H (R)

Low/R (H)

Low/R

200-800 (1)

25-100 (1)

5-20 (1)

2.5-10 (1)

2.5-10 (1)

Bronchospasm, bradycardia, and heart failure; may mask insulin-induced hypoglycemia; less serious: impaired peripheral circulation, insomnia, fatigue, decreased exercise tolerance, and hypertriglyceridemia, except agents with intrinsic sympathomimetic activity

Metoprolol tartrateb

Lopressor

Moderate/H (R)

50-100 (2)

 

Metoprolol succinateb

Toprol-XL

Moderate/H (R)

50-100 (1)

 

Nadolol

Corgard

Low/R

40-120 (1)

 

Penbutolol sulfatec

Levatol

High/H (R)

10-20 (1)

 

Pindololc

Visken

Moderate/H (R)

10-60 (2)

 

Propranolol HCl

Inderal

High/H

40-160 (2)

 
 

Inderal LA

High/H

60-180 (1)

 

Timolol maleate

Blocadren

Low-moderate/H (R)

20-40 (2)

 

Combined α- and β-blockers

Carvedilol

Coreg

Moderate/bile into feces

12.5-50 (2)

Postural hypotension, bronchospasm

Labetalol

Normodyne, Trandate

Moderate/R (H)

200-800 (2)

 

Reprinted with permission from JNC-VII.

H, hepatic; R, renal.

a. Adverse events, or side effects, listed are for the class of drugs.

b. Cardioselective.

c. Intrinsic sympathomimetic activity.

Table 8-17. Direct Vasodilators

Drug

Trade name

Usual dose range, total mg/d (frequency per day)

Adverse events and commentsa

     

Headaches, fluid retention, tachycardia, peripheral neuropathy, and postural hypotension

Hydralazine HCl

Apresoline

25-100 (2)

(Lupus syndrome)

Minoxidil

Loniten

2.5-80 (1-2)

(Hirsutism)

Adapted from JNC-7 Express, National Heart, Lung, and Blood Institute.

a. Adverse events, or side effects, listed are for the class of drugs, except where noted for individual drugs (in parentheses).

Table 8-18. Calcium Antagonists

Drug

Trade name

Usual dose range, total mg/d (frequency per day)

Adverse events and commentsa

Nondihydropyridines

Diltiazem HCl

Cardizem SR, Cardizem CD, Dilacor XR, Tiazac

180-420 (1) 120-360 (1)

Conduction defects, worsening of systolic dysfunction, and gingival hyperplasia

Verapamil immediate-release

Calan, Isoptin

80-320 (2)

(Nausea and headache)

Verapamil long-acting

Calan SR, Isoptin SR

120-360 (1-2)

(Constipation)

Verapamil COER

Covera HS, Verelan PM

120-360 (1)

 

Dihydropyridines

Amlodipine besylate

Norvasc

2.5-10 (1)

Edema of the ankle, flushing, headache, and gingival hyperplasia

Felodipine

Plendil

2.5-20 (1)

 

Isradipine

DynaCirc

2.5-10 (2)

 
 

DynaCirc CR

5-20 (1)

 

Nicardipine

Cardene SR

60-120 (1)

 

Nifedipine

Procardia XL, Adalat CC

30-60 (1)

 

Nisoldipine

Sular

10-40 (1)

 

Adapted from JNC-7 Express, National Heart, Lung, and Blood Institute.

a. Adverse events, or side effects, listed are for the class of drugs, except where noted for individual drugs (in parentheses).

           

Table 8-19. Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers

Drug

Trade name

Usual dose range, total mg/d (frequency per day)

Adverse events and commentsa

ACEIs

Benazepril HCl

Lotensin

10-40 (1-2)

Common: cough

Captopril

Capoten

25-100 (2-3)

Rare: angioedema, hyperkalemia, rash, loss of taste, and leucopenia

Enalapril maleate

Fosinopril

Lisinopril

Vasote

Monopril

Prinivil, Zestril

2.5-40 (1-2)

10-40 (1-2)

10-40 (1)

Other: vertigo; headache; fatigue; first-dose hypotension; minor GI disturbances; acute renal insufficiency in patients with predisposing factors such as renal stenosis and coadministration with thiazide diuretics; and proteinuria (especially in patients with history of renal disease)

Moexipril

Univasc

7.5-30 (1)

 

Perindopril

Aceon

4-8 (1-2)

 

Quinapril HCl

Accupril

10-40 (1-2)

 

Ramipril

Altace

1.25-20 (1)

 

Trandolapril

Mavik

1-4 (1)

 

ARBs

     

Candesartan

Atacand

8-32 (1)

Angioedema and hyperkalemia

Eprosartan

Teveten

400-800 (1-2)

 

Irbesartan

Avapro

150-300 (1)

 

Losartan

Cozaar

25-100 (1-2)

 

Olmesartan

Benicar

20 (1)

 

Telmisartan

Micardis

40-80 (1)

 

Valsartan

Diovan

80-320 (1)

 

Reprinted with permission from JNC-VII.

Table 8-20. Direct Renin Inhibitors

Drug

Trade name

Usual dose range, total mg/d (frequency per day)

Adverse events and comments

Aliskiren

Tekturna

150-300 mg (1)

Common: diarrhea

Rare: elevated uric acid, gout, renal stone, angioedema, and rash

Other: headache, nasopharyngitis, dizziness, fatigue, upper respiratory tract infection, back pain, and cough

Drug product package insert.

             

Table 8-21. Parenteral Drugs for Treatment of Hypertensive Emergencies

Drug

Dose

Onset of action

Duration of action

Adverse effectsa

Special indications

Vasodilators

Sodium nitroprusside

0.25-10 mcg/kg/min IV infusionb (maximal dose for 10 min only)

Immediate

1-2 min

Nausea, vomiting, muscle twitching, sweating, and thiocyanate and cyanide intoxication

Most hypertensive emergencies; caution with high intracranial pressure or azotemia

Nicardipine hydrochloride

5-15 mg/h IV

5-10 min

1-4 h

Tachycardia, headache, flushing, and local phlebitis

Most hypertensive emergencies, except acute heart failure; caution with coronary ischemia

Fenoldopam mesylate

0.1-0.3 mcg/kg/min IV infusion

< 5 min

30 min

Tachycardia, headache, nausea, and flushing

 

Nitroglycerin

5-100 mcg/min IV infusionc

2-5 min

3-5 min

Headache, vomiting, methemoglobinemia, and tolerance with prolonged use

Coronary ischemia

Enalaprilat

1.25-5 mg every 6 h IV

15-30 min

6 h

Precipitous fall in pressure in high-renin states; response variable

Acute left ventricular failure; avoid in acute myocardial infarction

Hydralazine hydrochloride

10-20 mg IV; 10-50 mg IM

10-20 min; 20-30 min

3-8 h

Tachycardia, flushing, headache, vomiting, and aggravation of angina

Eclampsia

Diazoxide

50-100 mg IV bolus repeated, or 15-30 mg/min IV infusion

2-4 min

6-12 h

Nausea, flushing, tachycardia, and chest pain

Now obsolete; when no intensive monitoring available

Adrenergic inhibitors

Labetalol hydrochloride

20-80 mg IV bolus every 10 min;

0.5-2.0 mg/min IV infusion

5-10 min

3-6 h

Vomiting, scalp tingling, burning in throat, dizziness, nausea, heart block, and orthostatic hypotension

Most hypertensive emergencies, except acute heart failure

Esmolol hydrochloride

250-500 mcg/kg/min for 1 min, then 50-100 mcg/kg/min for 4 min; may repeat sequence

1-2 min

10-20 min

Hypotension and nausea

Aortic dissection, perioperative

Phentolamine

5-15 mg IV

1-2 min

3-10 min

Tachycardia, flushing, and headache

Catecholamine excess

Reprinted with permission from JNC-VII.

a. Hypotension may occur with all agents.

b. Requires special delivery system.

Table 8-22. Selected Agents for Specific Hypertensive Emergencies

Emergency

Recommended therapy

Comments

Encephalopathy

Labetalol, nicardipine, and nitroprusside

Avoid methyldopa (sedation), diazoxide (reduces cerebral blood flow), reserpine (sedation), and hydralazine (increases intracranial pressure).

Myocardial infarction or unstable angina

Nitroglycerin and esmolol

Reduce BP until pain is relieved, and use in conjunction with conventional therapy for MI/angina.

Avoid diazoxide and hydralazine (increases oxygen demand), dihydropyridines (may worsen angina), and nitroprusside (coronary steal).

Congestive heart failure

Nitroprusside, nitroglycerin, and enalaprilat

Avoid labetalol, esmolol, and other β-blockers (reduces cardiac output).

Subarachnoid hemorrhage, intracerebral hemorrhage, and stroke

Nitroprusside

BP reduction is controversial because it may cause hypoperfusion; generally recommended for severe hypertension (systolic blood pressure > 220 or diastolic blood pressure > 120 mm Hg).

Dissecting aortic aneurysm

Trimethaphan, esmolol, and nitroprusside

Avoid diazoxide and hydralazine (increase shear force).

Pheochromocytoma and cocaine overdose

Phentolamine and labetalol

Anecdotal reports suggest increased BP with labetalol; unopposed β blockade may worsen crisis.

Renal insufficiency

Nitroprusside, calcium channel blocker, and labetalol

Monitor cyanide and thiocyanate levels.

Postoperative hypertension

Nitroprusside, nicardipine, and labetalol

Blood pressure levels of >180/110 should be controlled before surgery. Contributing factors to postoperative hypertension may include pain and increased intravascular volume, which may require parenteral loop diuretics.

             

Table 8-23. Agents Used to Treat Hypertensive Urgencies

Drug

Dose

Onset

Duration

Adverse effects

Captopril

25 mg, repeat in 1-2 hours as needed

5-15 min

4-6 h

Hypotension, acute renal failure, and angioedema

Clonidine

0.1-0.2 mg, repeat in 1-2 hours as needed (up to 0.6 mg)

5-15 min

6-12 h

Hypotension, drowsiness, sedation, and dry mouth

Labetalol

100-400 mg, repeat in 2-3 hours as needed

15-30 min

4-6 h

Hypotension, heart block, and bronchoconstriction

000106
Figure 9-1. American College of Cardiology-American Heart Association Stages of Heart Failure and Recommended Therapy by Stage Hunt et al., 2005.

000038
Figure 9-2. Acute Decompensated Heart Failure SBP, systolic blood pressure; D/C, discontinue.

Parker et al., 2008.

Table 9-1. Loop Diuretics

Generic name

Trade name

Dosage form

Dosage range and frequency

Furosemide

Lasix

Oral tablet

20.0-160.0 mg qd bid

Bumetanide

Bumex

Oral tablet

0.5-5.0 mg qd bid

Torsemide

Demadex

Oral tablet

10.0-100.0 mg qd bid

Table 9-2. Angiotensin-Converting Enzyme Inhibitors

Generic name

Trade name

Dosage form

Dosage range and frequency

Captopril

Capoten

Oral tablet

6.25-50.0 mg tid

Enalapril

Vasotec

Oral tablet

2.5-20.0 mg bid

Fosinopril

Monopril

Oral tablet

5.0-40.0 mg qd

Lisinopril

Zestril, Prinivil

Oral tablet

2.5-40.0 mg qd

Quinapril

Accupril

Oral tablet

10.0-40.0 mg bid

Ramipril

Altace

Oral capsule

2.5-5.0 mg bid

Perindopril

Aceon

Oral tablet

2.0-16.0 mg qd

Trandolapril

Mavik

Oral tablet

0.5-4.0 mg qd

           

Table 9-3. Angiotensin Receptor Blockers

Generic name

Trade name

Dosage form

Dosage range and frequency

Candesartan

Atacand

Oral tablet

4-32 mg qd

Valsartan

Diovan

Oral tablet

20-160 mg bid

Table 9-4. β-Blockers

 

Generic name

Trade name

Dosage form

Dosage range and frequency

 

Bisoprolol

Zebeta

Oral tablet

1.25-10.0 mg qd bid

 

Carvedilol

Coreg

Oral tablet

3.125-50.0 mg bid

 

Carvedilol

Coreg CR

Oral capsule

10.0-80.0 mg qd

 

Metoprolol succinate extended-release

Toprol-XL

Oral tablet

12.5-200.0 mg qd

 
               

Table 9-5. Aldosterone Antagonists

Generic name

Trade name

Dosage form

Dosage range and frequency

Spironolactone

Aldactone

Oral tablet

12.5-50.0 mg qd or qod

Eplerenone

Inspra

Oral tablet

25.0-50.0 mg qd

Table 9-6. Digoxin

Generic name

Trade name

Dosage form

Dosage range and frequency

Digoxin

Lanoxin

Oral tablet, IV, elixir

0.125-0.25 mg qd

Digoxin

Lanoxicaps

Oral capsule

0.1-0.2 mg qd

             

Table 9-7. Digoxin Pharmacokinetics

 

Oral bioavailability

   

Tablets

0.50-0.90 (average 0.65)

 

Elixir

0.75-0.85 (average 0.80)

 

Capsules

0.90-1.00 (average 0.95)

 

Elimination half-life

   

Normal renal function

36 hours

 

Anuric patients

5 days

 

Volume of distribution

7 L/kg

 

Fraction excreted unchanged in urine

0.65-0.70

 

Table 9-8. Vasodilators

Generic name

Trade name

Mechanism of action

Dosea

Adverse effects and comments

Nitroprusside

Nipride

Arterial and venous dilator

Initial dose 0.1-0.25 mcg/kg/min and titrate to response

Hypotension, headache, tachycardia, cyanide and thiocyanate toxicity, myocardial ischemia

Nitroglycerin

Nitro-Bid, Nitrostat

Venous dilator but also an arterial dilator at higher doses

Initial dose 5-10 mcg/min and titrate to response

Hypotension, headache, tachycardia, tolerance to hemodynamic effects

Nesiritide

Natrecor

B-type natriuretic peptide that increases diuresis and is an arterial and venous dilator

Initially 2 mcg/kg bolus followed by 0.01 mcg/kg/min infusion; can increase to 0.03 mcg/kg/min

Hypotension, headache when used in combination with diuretics

a. All are given by continuous IV infusion.

           

Table 9-9. Inotropes

Generic name

Trade name

Mechanism of action

Dosea

Adverse effects and comments

Dopamine

Intropin

Dose-dependent agonist of dopamine, β-, and α1--receptors

0-3 mcg/kg/min: stimulates dopamine receptors; may improve urine output

3-10 mcg/kg/min: stimulates β1- and β2-receptors to increase cardiac output

> 10 mcg/kg/min: stimulates α1-receptors to increase blood pressure

Increases heart rate, contractility, myocardial oxygen demand, myocardial ischemia, arrhythmias, and systemic vascular resistance; should be used only in patients with marked systemic hypotension or cardiogenic shock

Dobutamine

Dobutrex

β1- and β2-receptor agonist and weak α1 agonist; increases cardiac output and vasodilates

2.5-20.0 mcg/kg/min

Increases heart rate, contractility, myocardial oxygen demand, myocardial ischemia, arrhythmias; not useful to increase blood pressure in hypotensive patients

Milrinone

Primacor

Inhibits phosphodiesterase III, resulting in positive inotropic and vasodilating effects

50 mcg/kg loading dose over 10 min, followed by 0.375 mcg/kg/min; can titrate to 0.75 mcg/kg/min on basis of response

Arrhythmias, hypotension, and headache; is an alternative to patients not responding to dobutamine or dopamine; may be useful for patients receiving β-blockers because its positive inotropic effects are not mediated by β-receptors; adjust dose in patients with renal insufficiency; preferred over inamrinone because of decreased risk of thrombocytopenia

a. All are given by continuous IV infusion.

000145
Figure 10-1. Action Potential for Atrial and Ventricular Tissue

Table 10-1. Phases of Atrial and Ventricular Tissue Action Potential

Phase

Process

Ion flow

Corresponding ECG

0

Depolarization

Na+ fast channel opens; Na+ enters cell.

Atrial: P wave; ventricular: QRS

1

Initial repolarization

Na+ channel closes; passive Cl- influx.

 

2

Prolongs depolarized state

Predominantly Ca2+ enters cell.

ST segment

3

Repolarization

Rapid efflux of K+ out of cell.

T wave, QT interval

4

Repolarization

Na+ leaks into cell; K+ pumped out of cell.

 

000166
Figure 10-2. Treatment Algorithm for Atrial Fibrillation Note: Selection of the most appropriate antithrombotic therapy is based on the presence of risk factors for stroke, regardless of whether the rhythm or rate control approach is selected. AADs = antiarrhythmic drugs; AF = atrial fibrillation; BB = β-blocker; CCB = nondihydropyridine calcium channel blocker; DCC = direct-current cardioversion; TEE = transesophageal echocardiography.

Reproduced with permission from Sanoski CA, Schoen MD, Bauman JL, 2008.

Table 10-2. Management of Elevated International Normalized Ratio

INR

Significant bleeding

Recommendations

< 5.0 but above therapeutic range

No

Lower dose or omit single dose and restart at lower dose when INR is therapeutic.

≥ 5.0 and < 9.0

No

Omit 1-2 doses and resume at lower dose when INR is therapeutic; if more rapid reversal desired, omit dose and give ≤ 5 mg vitamin K orally; restart warfarin at lower dose when INR is therapeutic or clinically appropriate.

> 9.0

No

Hold warfarin and give 2.5-5.0 mg vitamin K orally; use additional vitamin K if necessary; resume warfarin at lower dose when INR is therapeutic.

Serious bleeding at any elevation of INR

Yes

Hold warfarin; give 10 mg vitamin K IV via slow infusion (over at least 10 minutes); supplement with fresh-frozen plasma, rVIIa, or prothrombin complex concentrate if necessary; repeat vitamin K 10 mg IV q12h if necessary.

Life-threatening bleeding at any elevation of INR

Yes, life threatening

Hold warfarin; give fresh-frozen plasma, prothrombin complex concentrate, or rVIIa with vitamin K 10 mg via IV slow infusion; repeat as necessary

000261
Figure 10-3. Treatment Algorithm for Paroxysmal Supraventricular Tachycardia Reproduced with permission from Sanoski CA, Schoen MD, Bauman JL, 2008.

Table 10-3. Effects of Antiarrhythmic Drugs on Cardiac Electrophysiology

Drug class

Ion block

Conduction

Refractory period

Automaticity

Ia

Sodium

¯

­

¯

Ib

Sodium

0/¯

¯

¯

Ic

Sodium

¯¯

­

¯

II

Calcium (Indirect effect)

¯

­

¯

III1

Potassium

0

­­

0

IV

Calcium

¯

­

¯

¯ Decreases

­ Increases

1Sotalol also possesses β-blocking activity. Amiodarone also possesses sodium and calcium channel blockade.

Table 10-4. Antiarrhythmic Drug Availability and Standard Dosing Regimens

Generic name

Trade name

Dosage forms

Loading dose

Maintenance dose

Class Ia

Quinidine gluconate

Quinaglute Dura-Tabs, Duraquin, Quinalan, Quinatime

324, 330 mg tablets 80 mg/mL injection

IV: not recommended

328-648 mg PO tid

Quinidine sulfate

Quinidex Extentabs, Cin-Quin, Quinora

100, 200, 300 mg tablets

PO: 200 mg q 2-3 h for 5-8 doses (sulfate salt only)

200-400 mg PO qid

Quinidine polygalacturonate

Cardioquin

275 mg tablets

 

275 mg PO bid or tid

Procainamide

Pronestyl

100, 500 mg/mL injection Oral procainamide no longer available

IV: 15-18 mg/kg at 20-50 mg/min

IV: 1-6 mg/min

Disopyramide

Norpace, Norpace CR

100, 150 mg capsules 100, 150 mg capsules

 

150-300 mg q6h 300-600 mg q12h

Moricizine

Ethmozine

200, 250, 300 mg tablets

 

200-300 mg q8h

Class Ib

Lidocaine

 

10 mg/mL (5 mL and 10 mL)

20 mg/mL (5 mL)

IV: 100 mg repeat up to 2 times

IV: 1-4 mg/min

   

IV infusion: 2 (500 mL), 4 (250, 500, 1,000 mL), 8 (250, 500 mL) mg/mL in D5W

   

Tocainide

Tonocard

400, 600 mg tablets

 

400-600 mg q8h

Mexiletine

Mexitil

150, 200, 250 mg capsules

 

100-300 mg q8h

Class Ic

Flecainide

Tambocor

50, 100, 150, 200 mg tablets

600 mg PO for conversion of atrial fibrillation to sinus rhythm

50-200 mg q12h

Propafenone

Rythmol, Rythmol-SR

150, 225, 300 mg tablets 225, 325, 425 mg capsules

 

150-300 mg q8h 225-425 mg q12h

Class II: β-blockers

Metoprolol

Lopressor, Toprol XL

25, 50, 100 mg tablets 25, 50, 100, 200 mg tablets; 1 mg/mL injection

IV: 2.5-5 mg up to 3 doses

25-450 mg PO daily

Propranolol

Inderal, Inderal LA

10, 20, 40, 60, 80 mg tablets

60, 80, 120, 160 mg capsules

20, 40 mg/mL oral solution 1 mg/mL (5 mL) injection

IV: 0.15 mg/kg IV: 0.5 mg/kg

PO: 80-240 mg daily

Esmolol

Brevibloc

10 and 250 mg/mL injection

0.5 mg/kg/min × 1 min

IV: 0.05-0.2 mg/kg/min

Class III

Amiodarone

Cordarone, Pacerone

100, 200, 400 mg tablets

800-1,600 mg/d in divided doses × 2-4 weeks

PO: 100-400 mg qd

   

5, 50 mg/mL IV solution

IV (VT/VF): 150 mg/10 min or 900 mg in 500 mL D5W at 1 mg/min × 6 h IV (cardiac arrest): 300 mg

IV: 0.5 mg/min

Sotalol

Betapace, Betapace AF

80, 120, 160, 240 mg tablets

 

80-160 mg q12h

Ibutilide

Corvert

0.1 mg/mL (10 mL) injection

1.0 mg IV over 10 min; repeat × 1 if needed

Not applicable

Dofetilide

(Tikosyn)

125, 250, 500 mcg capsules

 

CrCl > 60 mL/min = 500 mcg bid; 40-60 mL/min = 250 mcg bid; 20-39 mL/min = 125 mcg bid; < 20 mL/min = not recommended

Class IV: calcium channel blockers

Verapamil

Calan, Calan SR, Isoptin SR, Covera-HS, Verelan, Verelan-PM

40, 80, 120 mg tablets 120, 180, 240 mg tablets 180, 240 mg tablets 120, 180, 240, 360 mg capsules 100, 200, 300 mg capsules 2.5 mg/ml injection

2.5-10 mg IV over 2 min

PO: 120-360 mg/d IV: 5-15 mg/h Calan, Isoptin: tid-qid Calan SR, Isoptin SR, Covera-HS, Verelan: qd

Diltiazem

Cardizem, Cardizem CD, Cardizem Monovial, Cardizem Lyo-Ject, Cardizem SR, Cartia XT, Dilacor XR, Diltia XT, Tiazac, Cardizem LA

30, 60, 90, 120 mg tablets 5 mg/mL injection 120, 180, 240, 300, 360 mg capsules 100 mg/mL injection 25 mg injection 60, 90, 120 mg capsules 120, 180, 240, 300 mg capsules 120, 180, 240 mg capsules 120, 180, 240, 300 mg capsules 120, 180, 240, 300, 360, 420 mg tablets

20 mg IV over 2 min

IV: 5-15 mg/h PO: 120-360 mg/d Cardizem: qid Cardizem SR: bid Cardizem CD, Cardizem LA, Dilacor XR, Tiazac: qd

Miscellaneous

Atropine

 

0.1, 0.3, 0.4, 0.5, 0.6, 0.8, 1.0 mg/mL injection

0.5-1.0 mg q 5 min up to 3 mg total

 

Adenosine

Adenocard

3 mg/mL injection

 

Initial dose: 6 mg IV bolus; if necessary, can be followed by 12 mg q 2 min as IV bolus; flush IV line after each administration

Digoxin

Lanoxin, Lanoxicaps

125, 250, 500 mcg tablets

IV and PO: 0.25 mg q 2 h up to 1.5 mg

IV and PO: 0.125-0.375 mg qd

   

50 mcg/mL elixir 100, 250 mcg/mL injection 50, 100, 200 mcg capsules

   

Table 10-5. Pharmacokinetics of Antiarrhythmic Drugs

Drug

Bioavailability (%)

Protein binding (%)

Primary route of elimination

Substrate for

Inhibitor of

Half-life

Therapeutic range (mg/L)

Quinidine

70-80

80-90

Hepatic

CYP3A4

CYP2D6, CYP3A4, P-gp

5-9 h

2-6

Procainamide

75-95

10-20

Hepatic and renal

NAT

 

2.5-5.0 h

4-15

Disopyramide

70-95

50-80

Hepatic and renal

CYP3A4

 

4-8 h

2-6

Moricizine

34-38

92-95

Hepatic

   

1-6 h

 

Lidocaine

20-40

65-75

Hepatic

CYP3A4, CYP2D6, CYP1A2

CYP1A2

60-180 min

1.5-5.0

Tocainide

90-95

10-30

Hepatic

   

12-15 h

4-10

Mexiletine

80-95

60-75

Hepatic

CYP2D6, CYP1A2

CYP1A2

6-12 h

0.8-2.0

Flecainide

90-95

35-45

Hepatic and renal

CYP2D6

CYP2D6

13-20 h

0.2-1.0

Propafenone

11-39

85-95

Hepatic

CYP2D6, CYP1A2, CYP3A4

CYP2D6

3-25 h

 

Amiodarone

22-88

95-99

Hepatic

CYP3A4, CYP1A2, CYP2C19, CYP2D6

CYP1A2, CYP2C9, CYP2D6, CYP3A4, CYP2C19, P-gp

15-100 d

1.0-2.5

Sotalol

90-95

30-40

Renal

   

12-20 h

 

Ibutilide

 

40

Hepatic

   

3-6 h

 

Dofetilide

> 90

60-70

Renal

CYP3A4

 

6-10 h

 

Digoxin

60-85 (90-100) for Lanoxicaps

20-30

Renal

P-gp

 

34-44

0.5-2.2 ng/mL

Diltiazem

35-50

70-85

Hepatic

CYP3A4, CYP2C9, CYP2D6

CYP3A4, CYP2C9, CYP2D6, P-gp

4-10 h

 

Verapamil

20-40

95-99

Hepatic

CYP3A4, CYP1A2, CYP2C9

CYP3A4, CYP1A2, CYP2C9, CYP2D6, P-gp

4-12 h

 

Note: CYP = cytochrome P450 isoenzyme; NAT = N-acetyltransferase; P-gp = P-glycoprotein.

Table 10-6. Antiarrhythmic Drug Interactions and Significant Adverse Effects

Drug

Effect of disease/drugs on antiarrhythmic drug concentrations

Effect of antiarrhythmic on other drug concentrations

Common or severe adverse effects

Quinidine

Elevated: cimetidine, amiodarone, verapamil, diltiazem, ketoconazole, urine alkalinization

Reduced: enzyme inducers

Elevated: warfarin, digoxin, β-blockers, disopyramide, procainamide, propafenone, mexiletine, flecainide

QTc prolongation, torsades de pointes, diarrhea, fever, hepatitis, thrombocytopenia

Procainamide

Elevated: cimetidine, trimethoprim, amiodarone

 

Lupus-like syndrome, QTc prolongation, torsades de pointes, hypotension, gastrointestinal (GI) distress, agranulocytosis

Disopyramide

Reduced: enzyme inducers

Elevated: erythromycin, protease inhibitors, cimetidine

 

Anticholinergic side effects, decreased cardiac contractility, heart failure, QTc prolongation, torsades de pointes, hypoglycemia

Moricizine

Elevated: cimetidine

Elevated: theophylline

Dizziness, nausea, tremor, ataxia, paresthesias, proarrhythmia

Lidocaine

Increased: with decreased cardiac output

 

Central nervous system (CNS) toxicity: paresthesias, dizziness, muscle twitching, confusion, nausea and vomiting, slurred speech, seizures, sinus arrest

Tocainide

Decreased: cimetidine, enzyme inducers

 

GI distress; CNS: dizziness, paresthesias, confusion, seizures; pulmonary fibrosis or pneumonitis; agranulocytosis

Mexiletine

Reduced: enzyme inducers

Elevated: quinidine, amiodarone, ritonavir

Elevated: theophylline

GI distress; CNS: tremor, dizziness, confusion, vertigo, nystagmus, diplopia, tremor, ataxia; hypotension, sinus bradycardia, AV block

Flecainide

Elevated: cimetidine, amiodarone

Elevated: digoxin

Proarrhythmia, prolonged PR interval and QRS complex; dizziness, blurred vision, headache, tremor, heart failure

Propafenone

Reduced: enzyme inducers

Elevated: cimetidine, quinidine

Elevated: warfarin, digoxin, cyclosporine, theophylline

Metallic/bitter taste; CNS: dizziness, paresthesias, fatigue; GI distress; heart failure, liver injury, bradycardia, AV block, proarrhythmia

Amiodaronea

 

Elevated: quinidine, procainamide, warfarin, digoxin, phenytoin, cyclosporine, lovastatin, simvastatin, atorvastatin

IV: phlebitis; general: corneal microdeposits, photophobia, increased liver enzymes, photosensitivity, blue-gray skin discoloration, pulmonary fibrosis, hyper- and hypothyroidism, polyneuropathy

Sotalol

   

β-blocking effects: bradycardia, fatigue, dyspnea, bronchospasm, heart failure; QTc prolongation, torsades de pointes

Ibutilide

   

QTc prolongation, torsades de pointes

Dofetilide

Elevated: verapamil, cimetidine, ketoconazole, trimethoprim, megestrol, prochlorperazine

 

QTc prolongation, torsades de pointes

Digoxin

Elevated: quinidine, amiodarone, verapamil, diltiazem

   

Diltiazem

Elevated: cimetidine

Elevated: cyclosporine, carbamazepine, digoxin

Hypotension, bradycardia, heart failure

Verapamil

Reduced: rifampin, phenobarbital

Elevated: theophylline, digoxin, carbamazepine, cyclosporine, simvastatin, lovastatin

Hypotension, bradycardia, heart failure, constipation

a. See

Table 10-7.

Table 10-7. Suggested Monitoring Guidelines for Amiodarone

Test

Baseline

 

6 months

12 months

Electrocardiogram

 

Pulmonary function tests

Routine monitoring is controversial; may repeat tests if patient becomes symptomatic.

   

Ophthalmologic examination

Periodic exam is recommended.

Chest x-ray

Repeat earlier if patient becomes symptomatic.

Thyroid function tests

 

Liver enzymes

 

Table 11-1. Cardiac Enzymes and ECG Changes: UA versus NSTEMI/STEMI

 
 

UA

NSTEMI/STEMI

 

Cardiac enzymes

Negative

Positive

 

ECG changes: ST-segment, T-wave changes

If present, are transient

Always present

 
           

Table 11-2. Morphine, Oxygen, Nitrates, and Aspirin Therapy

Medication

Details

Morphine

Vasodilatory properties on both arterial and venous sides decrease both preload and afterload. Pain relief decreases tachycardia, along with decrease in preload and afterload; all work to decrease myocardial O2 demand.

Increments of 2-4 mg IV are given every 5-15 minutes until pain is relieved.

Nausea, vomiting, hypotension, sedation, and respiratory depression may occur.

Morphine produces a vagotonic effect that may be contraindicated in patients with bradycardia. Watch closely for hypotension, respiratory depression, and allergic reactions.

Meperidine

Meperidine can be used in patients who are intolerant of morphine. It has vagolytic effects, so it is the analgesic of choice in patients who are bradycardic; 25-75 mg IV.

Oxygen

Supplemental O2 2-4 L/min by nasal cannula is recommended to correct and avoid hypoxia, particularly within the first 2-3 hours. More aggressive ventilatory support should be considered and given as needed.

Nitroglycerin

All patients should receive NTG as a sublingual tablet or spray, followed by IV administration as needed for the relief of ischemia.

Long-acting nitrates (oral, transdermal) should be used as secondary prevention in patients who do not tolerate β-blockers and CCBs. These nitrates can be used in patients who have continual chest pain despite the use of β-blockers and CCBs.

Aspirin (ASA)

Nonenteric-coated aspirin 162-325 mg should be given at the onset of chest pain unless contraindicated. Chew and swallow the first dose.

A dose of 75-162 mg should be taken daily for life.

Poststent, aspirin 162-325 mg is used in combination with clopidogrel for at least 1 month after BMS, 3 months after sirolimus-eluting stents, and 6 months after paclitaxel-eluting stents. With the newer DES, everolimus, and zotarolimus, a minimum of 75 mg of aspirin daily is acceptable immediately after PCI. After this initial period, the dose of aspirin can be reduced to 75-162 mg daily.

Clopidogrel may be substituted if a true aspirin allergy is present or if the patient is considered unresponsive to ASA.

Table 11-3. STEMI versus UA or NSTEMI

STEMI

NSTEMI

Totally occlusive thrombus is found.

Platelet-rich thrombi, which do not completely block coronary blood flow, are found.

More extensive damage occurs.

Smaller, less extensive damage occurs.

STEMI results in an injury that affects the entire thickness of the myocardial wall.

NSTEMI involves only the subendocardial myocardium.

Occlusion persists long enough to compromise myocardial function and leads to myocardial necrosis.

Unstable angina is ischemia; NSTEMI may still result in necrosis, but not to the extent of STEMI.

ST-segment elevation on ECG is present.

ST depression or no ST elevation on ECG is present.

Lytic therapy or primary reperfusion is a main treatment strategy.

Antiplatelets and anticoagulants are used to target platelet-rich thrombus.

     

Table 11-4. Pharmacologic Properties and Doses of Nitrates

Drug

Route

Onset

Duration of action

Dose

Nitroglycerin sublingual tablet (Nitrostat, Nitroquick)

Sublingual

1-3 min

30-60 min

0.2-0.6 mg every 5 min. Seek emergency treatment if chest pain is unrelieved after 1 dose.

Nitroglycerin spray (Nitrolingual)

Translingual

2 min

30-60 min

0.4 mg every 5 min. Seek emergency treatment if chest pain unrelieved after 1 spray.

Nitroglycerin transmucosal tablets (Nitroguard)

Buccal

1-2 min

3-5 hours

Insert 1 tablet into cheek every 3-5 hours.

Nitroglycerin ointment (Nitrobid, Nitrol)

Topical

30-60 min

2-12 hours

1-2 inches every 8 hours up to 4-5 inches every 4 hours.

Nitroglycerin transdermal patches (Nitro-dur, Transderm Nitro, Nitrek, Nitrodisc, Deponit, Minitran)

Topical

30-60 min

Up to 24 hours

Starting dose: 0.2-0.4 mg/hour. Apply and allow patch to stay in place for 12 hours. Remove the patch after 12 hours to allow a nitrate-free interval.

Nitroglycerin sustained-release tablets or capsules (Nitrong, Nitroglyn, Nitro-Time)

Oral

20-45 min

3-8 hours

Starting dose: 2.5 mg tid-qid. Increase the dose by 2.5 mg two to four times daily to reach effective dose.

Nitroglycerin intravenous (Tridil, Nitro-Bid IV)

IV

1-2 min

3-5 min

Starting dose: 5 mcg/min. Titrate to response.

Isosorbide mononitrate (Ismo, Monoket)

Oral

30-60 min

No data

20 mg bid (given 7 hours apart). May need to start with 5 mg bid for low-weight patients.

Isosorbide mononitrate, extended-release (Imdur, Isotrate ER)

Oral

30-60 min

No data

Starting dose: 30-60 mg daily. Maximum dose: 240 mg daily.

Isosorbide dinitrate (Isordil Titradose, Sorbitrate)

Oral

20-40 min

4-6 hours

Starting dose: 5-20 mg q6h. Maintenance dose: 10-40 mg q6h.

Isosorbide dinitrate, sustained-release tablets or capsules (Isordil Tembids, Dilatrate-SR)

Oral

Up to 4 hours

6-8 hours

Initial dose: 40 mg q8h. Maintenance dose: 40-80 mg q8-12 h.

Table 11-5. Nitrate Adverse Reactions

Type

Reaction

Tolerance

Tolerance to the vasodilatory effects can develop if dosing does not allow for a nitrate-free interval (10-12 hours).

CNS

Headache (up to 50%), dizziness, anxiety, and nervousness can occur.

Cardiovascular

Hypotension, tachycardia, palpitations, and syncope can occur.

Gastrointestinal

Nausea, vomiting, and dyspepsia can occur.

Dermatologic

Rash or dermatitis can occur.

Other

Blurred vision, muscle twitching, perspiration, edema, and arthralgia can occur.

           

Table 11-6. Nitrate Drug-Drug Interactions

Interacting medication

Effect

Sildenafil (Viagra), vardenafil (Levitra), tadalafil (Cialis)

Significant reduction of systolic and diastolic blood pressure may occur. Do not give sildenafil or vardenafil within 24 hours of nitrate use. Do not give tadalafil within 48 hours of nitrate use.

Calcium channel blockers

Marked symptomatic hypotension may occur.

Alcohol

Severe hypotension may occur.

Table 11-7. Ranolazine Adverse Drug Reactions

 

Type

Reaction

 

CNS

Dizziness, headache, asthenia

 

Cardiovascular

Bradycardia, palpitations, hypotension, orthostatic hypotension

 

Gastrointestinal

Nausea, abdominal pain, vomiting, dry mouth, constipation

 

Other

Tinnitus, vertigo, dyspnea, peripheral edema

 
       

Table 11-8. Ranolazine Drug-Drug Interactions

Interacting medication

Effect

Strong CYP3A inhibitors: ketoconazole, itraconazole, clarithromycin, nefazodone, ritonavir, nelfinavir, indinavir, saquinavir

Medication increases average steady-state plasma concentration of ranolazine 3.2-fold, which can precipitate QTc prolongation. Concomitant use is contraindicated.

Moderated CYP3A inhibitors: diltiazem, verapamil, erythromycin, fluconazole, grapefruit juice

Medication increases ranolazine steady-state plasma concentrations about twofold, which can precipitate QTc prolongation. Concomitant use is cautioned.

P-glycoprotein inhibitors: cyclosporine

Increased ranolazine concentrations can occur; use lower doses of ranolazine.

CYP3A and P-glycoprotein inducers: rifampin, rifabutin, phenobarbital, phenytoin, carbamazepine, St. John's Wort

Medication decreases plasma concentrations of ranolazine by up to 95% (rifampin).

Simvastatin

Plasma levels of simvastatin, a CYP3A4 substrate, are increased approximately twofold.

Table 11-9. Aspirin Adverse Reactions

Type

Reaction

Cardiovascular

Hypotension, edema, tachycardia

CNS

Fatigue, nervousness, dizziness

Dermatologic

Rash, urticaria, angioedema

Gastrointestinal

Nausea, vomiting, dyspepsia, gastrointestinal ulceration, gastric erosion, duodenal ulcers

Hematologic

Bleeding, anemia

Otic

Hearing loss, tinnitus

Renal

Renal impairment, increased serum creatinine, proteinuria

Respiratory

Asthma, bronchospasm, dyspnea, tachypnea, respiratory alkalosis

     

Table 11-10. Thienopyridine Adverse Reactions

Type

Reaction

Clopidogrel

Chest pain, headache, dizziness, abdominal pain, vomiting, diarrhea, arthralgia, back pain, upper respiratory infections, flu-like symptoms; < 1% blood dyscrasias, bleeding, rash

Ticlopidine

Rash, nausea, dyspepsia, diarrhea; 2.4% neutropenia; < 1% blood dyscrasias, thrombotic thrombocytopenic purpura, bleeding

Table 11-11. Thienopyridine Drug-Drug Interactions

 

Interacting medication

Effect

 

Antiplatelet agents, anti-coagulants, NSAIDs, and celecoxib

Combination may increase the risk of bleeding.

 

CYP4502C9 substrates (phenytoin, fluvastatin, NSAIDs, losartan, irbesartan, valsartan)

Medication may increase serum levels.

 
       

Table 11-12. Pharmacologic Properties of Glycoprotein IIb/IIIa Receptor Inhibitors

Drug

Chemical nature

Duration of effect (hours)

Renal elimination

Renal dosing adjustment

Abciximab (ReoPro)

Antibody

>12a

No

No

Eptifibatide (Integrilin)

Nonpeptide

4-8

Yes

Yes

Tirofiban (Aggrastat)

Peptide fragment

4

Yes

Yes

a. Action can be reversed by a platelet infusion.

Table 11-13. Indications and Doses of the Glycoprotein IIb/IIIa Receptor Inhibitors

Drug

Indication

Dose

Abciximab (ReoPro)

Adjunct to PCI or when PCI is planned within 24 hours

0.25 mg/kg IV bolus, 0.125 mg/kg infusion continued for 12 hours postprocedure; maximum length of infusion: 18-24 hours

Eptifibatide (Integrilin)

Adjunct to PCI

180 mcg/kg IV bolus × 2, 10 min apart; 2 mcg/kg/min infusion (creatinine clearance < 50 mL/min; 1 mcg/kg/min) started after the first bolus and continued for 18-24 hours postprocedure (minimum of 12 hours)

 

Patients with ACS managed with or without PCI

180 mcg/kg IV bolus, 2 mcg/kg/min infusion (creatinine clearance < 50 mL/min; 1 mcg/kg/min) continued until discharge, up to 72 hours; or if post-PCI for 18-24 hours; maximum length of infusion: 96 hours

Tirofiban (Aggrastat)

Adjunct to PCI

0.4 mcg/kg/min IV bolus for 30 min, 0.1 mcg/kg/min infusion (creatinine clearance < 30mL/min; bolus and infusion are reduced by 50%) for 12-24 hours postprocedure

 

Patients with ACS managed with or without PCI

10 mcg/kg IV bolus over 3 min followed by 0.15 mcg/kg/min infusion for 36 hours or 0.4 mcg/kg IV bolus over 30 min, 0.1 mcg/kg/min infusion for 72 hours (creatinine < 30 mL/min, bolus and infusion are reduced by 50%)

             

Table 11-14. Properties of Low Molecular Weight Heparin versus Unfractionated Heparin

Drug

Half-life (hours)

Molecular weight (daltons)

Anti-Xa: Anti-IIa

Renal elimination

Enoxaparin

4.5

4,500

2.7:1.0

Yes

UFH

1

15,000

1.0:1.0

No

Table 11-15. Thrombolytic Doses

Drug

Dose

Streptokinase (Streptase)

1.5 million units in 50 mL of normal saline or D5W given over 60 min

Tissue plasminogen activator (Alteplase)

15 mg IV bolus, followed by 0.75 mg/kg IV infusion over 30 min (not to exceed 50 mg); then 0.5 mg/kg IV infusion over 1 hour (not to exceed 35 mg)

Reteplase (Retevase)

10 units IV push over 2 min, followed in 30 min by a repeat 10 units IV bolus over 10 min

Tenecteplase (TNKase)

< 60 kg, give 30 mg IV bolus; 60-69.9 kg, give 35 mg IV bolus; 70-79.9 kg, give 40 mg IV bolus; 80-89.9 kg, give 45 mg IV bolus; > 90 kg, give 50 mg IV bolus; each bolus given over 5 seconds

           

Table 12-1. Classification of Lipids

 

Type

Classification

 

LDL cholesterol (primary target of therapy)

 

< 100 mg/dL

Optimal

 

100-129 mg/dL

Near optimal or above optimal

 

130-159 mg/dL 3

Borderline high

 

160-189 mg/dL

High

 

≥ 190 mg/dL

Very high

 

Total cholesterol

 

< 200 mg/dL

Desirable

 

200-239 mg/dL

Borderline high

 

≥ 240 mg/dL

High

 

HDL cholesterol

 

< 40 mg/dL

Low

 

≥ 60 mg/dL

High

 

Triglycerides (secondary target of therapy)

 

< 150 mg/dL

Normal

 

150-199 mg/dL

Borderline high

 

200-499 mg/dL

High

 

> 500 mg/dL

Very high

 

Table 12-2. Risk Categories, Lipid Goals, and Risk of Event

Risk category

LDL goal

Risk of event

CHD and CHD risk equivalenta

< 100 mg/dL

> 20% over 10 years

Multiple risk factors (2+)

< 130 mg/dL

10-20% over 10 years

0-1 risk factor

< 160 mg/dL

< 10% over 10 years

a. CHD risk equivalent = clinical CHD, symptomatic carotid artery disease, peripheral arterial disease, abdominal aortic aneurysm, and diabetes.

         

Table 12-3. Drug Products and Dosage

Generic name

Trade name

Dosage range and schedule

Dosage form and strength

Statins

     

Atorvastatin

Lipitor

10-80 mg/d qhs

10-, 20-, 40-, and 80-mg tablet

Fluvastatin

Lescol

20-80 mg/d qhs

20- and 40-mg capsule; 80-mg XL tablet

Lovastatin

Mevacor

20-80 mg/d qhs

10-, 20-, 40-mg tablet

Lovastatin extended-release

Altoprev

10-60 mg/d qhs

10-, 20-, 40-, and 60-mg tablet

Pravastatin

Pravachol

20-80 mg/d qhs

10-, 20-, 40-, and 80-mg tablet

Simvastatin

Zocor

20-80 mg/d qhs

5-, 10-, 20-, 40-, and 80-mg tablet

Rosuvastatin

Crestor

5-40 mg/d hs

5-, 10-, 20-, and 40-mg tablet

Bile acid sequestrants

     

Cholestyramine

Questran

4-16 g/d divided

Powder

Colestipol

Colestid

5-20 g/d divided

Powder or tablet

Colesevelam

WelChol

2.6-3.8 g/d (once or bid)

625-mg tablet

Nicotinic acid

     

Immediate release

Niacor

1.5-3 g/d (divided tid)

500-mg tablet

Sustained release

Slo-Niacin

1-2 g/d qhs

250-, 500-, and 750-mg tablet

Extended release

Niaspan

1-2 g/d qhs

500-, 750-, and 1,000-mg tablet

Fibric acids

     

Gemfibrozil

Lopid

600 mg before meals bid

600-mg tablet

Fenofibrate

Tricor

48-145 mg/d

48- and 145-mg tablet

Cholesterol inhibitors

     

Ezetimibe (Zetia)

 

10 mg/d

10-mg tablet

Omega-3 fatty acids

     

Omega-3 fatty acid

Lovaza

4 g qd or 2 g bid

1-g capsule

Combinations

     

Aspirin + pravastatina

Pravigard PAC

81/20-325/80 mg qhs

81/20-, 81/40-, and 81/80-mg tablets; 325/20-, 325/40-, and 325/80-mg tablets

Ezetimibe + simvastatin

Vytorin

10/10-10/80 mg qhs

10/10-, 10/20-, 10/40-, and 10/80-mg tablets

Lovastatin + Niaspan

Advicor

20/500-40/2,000 mg/d

20/500-, 20/750-, and 20/1,000-mg tablets

a. Aspirin tablets and pravastatin tablets are separate tablets within the PAC.

Table 12-4. Efficacy of Drugs Used to Treat Hyperlipidemia

 

Drug class

Lipid and lipoprotein effect

 

Statins

LDL ¯18-55%

HDL ­5-15%

TG ¯7-30%

 

Resins

LDL ¯15-30%

HDL ­3-5%

TG (no change)

 

Nicotinic acid

LDL ¯5-25%

HDL ­15-35%

TG ¯20-50%

 

Fibric acids

LDL ¯5-20%

HDL ­10-20%

TG ¯20-50%

 

Cholesterol inhibitors

LDL ¯17%

HDL ¯1.3%

TG ¯6%

 

Omega-3 fatty acid (Lovaza)

LDL ­25-31%

HDL ­4-13%

TG ¯45%

 
           

Table 12-5. Pharmacotherapeutic Options for Treatment of Hyperlipidemia

Lipid target

Pharmacotherapy

LDL

Statin most potent and effective for large LDL reductions

Niacin and resins effective for moderate LDL reductions

Combination of statin + niacin

Combination of statin + ezetimibe

Combination of statin + resin

LDL + TG

Combination of statin + niacin

Combination of statin + fibric acid

TG

Fibric acid or niacin

Table 12-6. Nutrient Makeup of the TLC Diet

Nutrient

Recommended intake

Saturated fat

< 7% of total calories

Polyunsaturated fat

Up to 10% of total calories

Monounsaturated fat

Up to 20% of total calories

Total fat

25-35% of total calories

Carbohydrate

50-60% of total calories

Fiber

20-30 g/d

Protein

About 15% of total calories

Cholesterol

< 200 mg/d

Total calories

Individualize to balance energy intake and expenditure to maintain desirable weight or prevent weight gain.

     

000070
Figure 13-1. Estimated Age-Adjusted Total Prevalence of Diabetes in People 20 Years or Older, by Race and Ethnicity: United States, 2005 Source: For American Indians/Alaska Natives, the estimate of total prevalence was calculated using the estimate of diagnosed diabetes from the 2003 outpatient database of the Indian Health Service and the estimate of undiagnosed diabetes from the 1999-2002 National Health and Nutrition Examination Survey. For the other groups, 1999-2002 NHANES estimates of total prevalence (both diagnosed and undiagnosed) were projected to year 2006.

* Graph and information obtained from CDC (Centers for Disease Control and Prevention) website at http://www.cdc.gov/diabetes/pubs/estimatesDS.html#prev4 on December 1, 2006.

Table 13-1. Summary of Recommendations for Adults with Diabetes

 

Area

Recommended goal

 

Glycemic control:

 
 

A1C

< 7.0%a

 
 

Preprandial capillary plasma glucose

70-130 mg/dL

 
 

Peak postprandial capillary plasma glucoseb

< 180 mg/dL

 

Blood pressure:

< 130/80 mmHg

 

Lipids:c

   
 

LDL

< 100 mg/dLd

 
 

Triglycerides

< 150 mg/dL

 
 

HDL

> 40 mg/dLe

 

Key concepts in setting glycemic goals:

    • A1C is the primary target for glycemic control.

    • Goals should be individualized.

    • More or less stringent glycemic goals may be appropriate for individual patients.

    • Postprandial glucose may be targeted if A1C goals are not met despite reaching preprandial glucose goals.

 

a. Referenced to a nondiabetic range of 4.0-6.0% using a Diabetes Control and Complications Trial-based assay.

 

b. Postprandial glucose measurements should be made 1-2 hours after the beginning of the meal—generally peak levels in patients with diabetes.

 

c. Current National Cholesterol Education Program-Adult Treatment Panel III guidelines suggest that in patients with triglycerides ≥ 200 mg/dL, the "non-HDL cholesterol" (total cholesterol - HDL) be used. The goal is 130 mg/dL.

 

d. In individuals with overt cardiovascular disease, a lower LDL cholesterol goal of < 70 mg/dL is an option.

 

e. For women, it has been suggested that the HDL goal be increased by 10 mg/dL.

 

Source: Adapted from American Diabetes Association. Standards of medical care in diabetes—2009. Diabetes Care. 2009: 32(suppl 1):S13-61.

 

Table 13-2. Sulfonylureas

Drug

Trade name

Strength

Daily dose

Duration of action

Comments

First generation

         

Acetohexamide

Dymelor

250, 500 mg

250-1,500 mg

Up to 16 hours

Active metabolite excreted by kidney

Chlorpropamide

Diabinese

100, 250 mg

100-500 mg

Up to 72 hours

Contraindicated in renal insufficiency

Tolazamide

Tolinase

100, 250, 500 mg

100-1,000 mg

Up to 10 hours

 

Tolbutamide

Orinase

250, 500 mg

500-3,000 mg qd-bid

Up to 10 hours

 

Second generation

         

Glipizide

Glucotrol, Glucotrol XL

5, 10 mg

5-40 mg qd-bid 5-20 mg qd (XL)

Up to 20 hours

Given with or without meal; do not cut XL tab

Glyburide

DiaBeta, Micronase

1.25, 2.50, 5.00 mg

1.25-20.00 mg qd-bid

Up to 24 hours

3 mg Glynase = 5 mg glyburide

Glyburide micronized

Glynase

1.5, 3.0, 4.5, 6.0 mg

1.5-12.0 mg qd

Up to 24 hours

 

Glimepiride

Amaryl

1, 2, 4 mg

1-8 mg qd

24 hours

Begin with 1 mg in renal insufficiency

Meglitinides and phenylalanines

         

Repaglinide

Prandin

0.5, 1.0, 2.0 mg

0.5-4.0 mg before each meal; maximum dose = 16 mg/d

Peak effect: ~ 1 hour; duration: ~ 2-3 hours

Skip dose if meal skipped; do not give in combination with sulfonylureas

Nateglinide

Starlix

60, 120 mg

60-120 mg before each meal

Peak effect: ~ 1 hour; duration: ~ 4 hours

Efficacy: Prandin > Starlix

             

Table 13-3. Biguanides

Drug

Trade name

Strength

Daily dose

Duration of action

Comments

Metformin

Glucophage

500, 850, 1,000 mg

1,000-2,550 mg (adult) up to 2,000 mg (10 years and older)

≥ 24 hours

 

Metformin extended release

Glucophage XR Glumetza

500, 750 mg 500, 1,000 mg

2,000 mg qpm; may take 1 g bid if qd dosing causes GI symptoms

 

Do not cut, crush, or chew

Table 13-4. Thiazoladinediones

Drug

Trade name

Strength

Daily dose

Duration of action

Comments

Rosiglitazone

Avandia

2, 4, 8 mg

4-8 mg qd or 2-4 mg bid

24 hours

May be more effective when given bid

Pioglitazone

Actos

15, 30, 45 mg

30-45 mg qd

24 hours

 
                 

Table 13-5. Alpha-Glucosidase Inhibitors

Drug

Trade name

Strength

Daily dose

Duration of action

Comments

Acarbose

Precose

50, 100 mg

25-100 mg tid

1-3 hours

Maximum dose: < 60 kg = 50 mg tid; > 60 kg = 100 mg tid

Miglitol

Glyset

25, 50, 100 mg

25-100 mg tid

1-3 hours

 

Table 13-6. Dipeptidyl Peptidase-4 Inhibitors

Drug

Trade name

Strength

Daily dose

Duration of action

Comments

Sitagliptin

Januvia

25, 50, 100 mg

100 mg qd

24 hours

CrCl 30-50: 50 mg qd; CrCl < 30: 25 mg qd

                     

000144
Figure 13-2. Combination Oral Agents

Table 13-7. Sample Titration Schedules for Basal and Prandial Insulin

Basal insulin titration

Prandial insulin titration

Fasting blood glucose levels for 3 consecutive days

Adjust basal insulin dose (units)

Preprandial or bedtime glucose levels for 3 consecutive days

Adjust rapid-acting insulin dose (units)

≥ 180 mg/dL

+8

≥ 180 mg/dL

+3

160-180 mg/dL

+6

140-180 mg/dL

+2

140-160 mg/dL

+4

140-180 mg/dL

+2

120-140 mg/dL

+2

120-140 mg/dL

+1

100-120 mg/dL

+1

100-120 mg/dL

No change

80-100 mg/dL

No change

80-100 mg/dL

-1

60-80 mg/dL

- 2

60-80 mg/dL

-2

< 60 mg/dL

-4

< 60 mg/dL

-4

Note: To increase fasting glucose, adjust basal dose only. Increase preprandial or bedtime glucose levels as follows: (1) if increase at lunchtime, adjust breakfast prandial insulin; (2) if increase at dinnertime, adjust lunchtime prandial insulin; (3) if increase at bedtime, adjust dinnertime prandial insulin.

Table 13-8. Insulin Products

Insulin type

Trade name

Device availability

Onset of action

Time of peak

Duration of action

Rapid acting:

 

Glulisine

Apidra

OptiClick pen, SoloSTAR

15-30 min

30-90 min

1-3 hours

 

Aspart

Novolog

NovoPen

10-15 min

30-90 min

3-5 hours

 

Lispro

Humalog

Lilly pen, HumaPen MEMOIR, Luxura HD pen

10-15 min

30-90 min

 

Intermediate acting:

 

Human NPH

Novolin N

NovoPen, InnoLet

1-3 hours

4-12 hours

10-18 hours

   

Humulin N

Lilly pen

1-3 hours

4-12 hours

10-18 hours

 

Lente human

   

2-5 hours

7-15 hours

24 hours

Basal:

 

Glargine

Lantus

OptiClick pen, SoloSTAR

1-2 hours

Peakless

24 hours

 

Detemir

Levemir

NovoPen

1-2 hours

6-8 hours

18-24 hours

Premixed:

 

NPH + regular

Novolin 70/30

NovoPen, InnoLet

     
   

Humulin 70/30

Lilly pen

     
   

Humulin 50/50

Lilly pen

     
 

Insulin protamine + analogs

Novolog 70/30

NovoPen

     
   

Novolog 50/50

NovoPen

     
   

Humalog 75/25

Lilly pen

     
   

Humalog 50/50

Lilly pen

     

Note: Most common available concentration = 100 units per mL. Concentration used in severe insulin resistance = 500 units per mL.

                 

Table 13-9. Incretin Mimetics

Drug

Trade name

Strength

Daily dose

Duration of action

Exenitide

Byetta

5, 10 mcg pen

5-10 mcg bid

~ 8-10 hours

Table 13-10. Amylin Mimetics

Drug

Trade name

Strength

Daily dose

Duration of action

Comments

Pramlintide

(Symlin)

0.6 mg/mL-5 mL vial

Type 1 DM: 15-60 mcg tid with meals; type 2 DM: 60-120 mcg tid with meals

4-6 hours

Dosed using an insulin syringe: 30 mcg = 5 units, 60 mcg = 10 units, 120 mcg = 20 units

Table 13-11. Comparison of Type 1 and Type 2 Diabetes Mellitus

   

Type 1

Type 2

Previous names

Insulin-dependent diabetes mellitus; juvenile-onset diabetes

Non-insulin-dependent diabetes mellitus; adult-onset diabetes

Percentage of DM cases

5-10

90-95

Age of occurrence

< 30 years (usually childhood or adolescence); at any age following autoimmune stimulus (e.g., virus)

> 30 years; increasing in childhood andadolescence in association with obesity and inactivity

Onset

Rapid

Gradual

Primary etiology

Autoimmune-mediated mechanism with genetic predisposition

Genetic and environmental (e.g., family history, ethnicity, obesity, inactivity)

Pathogenesis

Destruction of β-cells resulting in absolute insulin deficiency and abnormal glucose control

Increasing resistance of tissue (liver and skeletal muscle) to insulin; impaired insulin secretion resulting in relative deficiency of insulin; increased hepatic glucose production

Signs and symptoms

Polyuria, polydipsia, polyphagia, unexplained weight loss, fatigue, blurred vision, possibly ketoacidosis

Polyuria, polydipsia, polyphagia, obesity, fatigue, blurred vision, possibly asymptomatic

Ketoacidosis

Ketosis prone (DKA)

Not ketosis prone because of residual insulin (hyperglycemic hyperosmolar nonketotic syndrome)

Treatment:

   
 

Nondrug therapy

Medical nutrition therapy and physical activity approved by physician

Essential adjunct to oral antidiabetic therapy; may be sufficient as monotherapy to control blood glucose

 

Drug therapy

Insulin monotherapy or rarely oral antidiabetic drugs as adjunct to insulin therapy (if accompanied by insulin resistance)

MNT monotherapy or oral antidiabetic drugs or oral antidiabetic drugs in combination therapy or insulin monotherapy or insulin and oral antidiabetic drugs

Table 14-1. Thyroid Preparations for the Treatment of Hypothyroidism

Trade name

Generic name

Dosage forms

Usual dosage range

Synthroid, Levothroid, Levoxyl, Unithroid, Thyro-Tabs

Levothyroxine sodium (T4)

Tablets: 0.025, 0.05, 0.075, 0.088, 0.1, 0.112, 0.125, 0.137, 0.15, 0.175, 0.2, 0.3 mg

Injection: 200, 500 mcg

0.1-0.15 mg po qd for hypothyroidism (dosage is individualized); higher doses used in treating thyroid cancer

Armour Thyroid, Nature-Throid, Westhroid

Desiccated thyroid USP

Tablets: 15, 30, 32.4, 60, 64.8, 65, 90, 120, 129.6, 130, 180, 194.4, 195, 240, 300 mg

60-120 mg po qd for hypothyroidism (dosage is individualized); higher doses used in treating thyroid cancer

Cytomel, Triostat

Liothyronine (T3)

Tablets: 5, 25, 50 mcg

Injection: 10 mcg

25 mcg po qd for hypothyroidism

Thyrolar

Liotrix (T4 and T3 in a 4:1 ratio)

Tablets: 3.1/12.5 mcg, 6.25/25 mcg, 12.5/50 mcg, 25/100 mcg, 37.5/150 mcg

60-120 mg po qd for hypothyroidism

           

Table 14-2. Antithyroid Medications

Drug name

Drug contains

Dosage forms

Usual dosage range

PTU

Propylthiouracil

Tablets: 50 mg

150-300 mg po daily at 8-hour intervals

Tapazole

Methimazole

Tablets: 5, 10 mg

5-40 mg po in single daily dose or divided

Lugol's solution

Strong iodine solution

Solution: 5% iodine and 10% potassium iodide; delivers 6.3 mg iodine per drop

0.1-0.3 mL (3-5 drops) po tid

SSKI

Saturated solution of potassium iodide

Solution: 1 g/mL; delivers 38 mg iodine per drop of saturated solution

1-5 drops po tid in water or juice

Table 14-3. Drugs for Cushing's Syndrome

Trade name

Generic name

Dosage forms

Usual dosage range

Nizoral

Ketoconazole

Tablets: 250 mg

800-1,200 mg po qd

Cytadren

Aminoglutethimide

Tablets: 250 mg

250 mg po q6h

Lysodren

Mitotane

Tablets: 500 mg

9-10 g/d po in divided doses

Metopirone

Metyrapone

Capsules: 250 mg

1-6 g/d po in 4-6 divided doses

           

Table 14-4. Corticosteroids and Dose Equivalents

Trade name

Generic name

Anti-inflammatory potency

Sodium-retaining potency

Equivalent dose (mg)

Half-life

Cortone

Cortisone

0.8

2

25

Short

Cortef, Hydrocortone, Solu-Cortef

Hydrocortisone

1.0

2

20

Short

Deltasone, Liquid Pred

Prednisone

4.0

1

5

Medium

Prelone, Pediapred, Delta-Cortef

Prednisolone

4.0

1

5

Medium

Medrol, Solu-Medrol, Depo-Medrol, A-Methapred

Methylprednisolone

5.0

0

4

Medium

Aristocort, Kenacort, Kenalog

Triamcinolone

5.0

0

4

Medium

Decadron, Dexameth, Dexone, Hexadrol

Dexamethasone

30.0

0

0.75

Long

Celestone

Betamethasone

25.0

0

0.75

Long

Florinef

Fludrocortisone

15.0

150

2

Medium

Table 14-5. ACTH and Cosyntropin

Trade name

Generic name

Dosage forms

Usual dosage range

Cortrosyn

Cosyntropin

Injection: 0.25 mg

0.25-0.75 mg for testing

Acthar (ACTH)

Corticotropin

Injection: 25, 40 units

10-25 units for testing

H.P. Acthar Gel

 

Repository injection: 40, 80 units/mL

40-80 units of repository injection every 1-3 days

Table 14-6. Vasopressin and Desmopressin

Trade name

Generic name

Dosage forms

Usual dosage range

Pitressin

Vasopressin

Injection: 20 units/mL

10-20 units intramuscular, subcutaneous, or IV daily at 3- to 4-hour intervals or as a continuous infusion

Stimate (DDAVP)

Desmopressin

Tablets: 0.1, 0.2 mg

Nasal solution: 0.1 mg/mL, 1.5 mg/mL

Injection: 4 mcg/mL

Nocturnal enuresis: 0.2-0.6 mg po qhs

Diabetes insipidus: 0.1-0.2 mg po bid, 0.1-0.4 mL intranasally in single or divided doses

Table 14-7. Androgens and Anabolic Steroids

Trade name

Generic name

Dosage forms

Usual dosage range

Testoderm

Androderm

Testosterone transdermal system

Patch: 2.5, 4, 5, 6 mg/24 h

Patch: 2.5-6 mg for 24 h

AndroGel 1%, Testim

Testosterone

1% gel

5 grams applied once daily

Depo-Testosterone

Testosterone cypionate (in oil)

Injection in oil: 100 mg/mL, 200 mg/mL

50-400 mg every 2-4 weeks

Delatestryl

Testosterone enanthate (in oil)

Injection in oil: 100 mg/mL, 200 mg/mL

50-400 mg every 2-4 weeks

Testopel

Testosterone

Pellet for subcutaneous implantation: 75 mg

150-450 mg every 3-6 months

Striant

Testosterone

Buccal tablet: 30 mg

30 mg every 12 h

Methitest

Methyltestosterone

Tablets: 10, 25 mg

10-50 mg once daily

Testred, Android

 

Capsules: 10 mg

 

Halotestin, Androxy

Fluoxymesterone

Tablets: 2, 5, 10 mg

5-10 mg once daily

Anadrol-50

Oxymetholone

Tablets: 50 mg

50-100 mg once daily

Winstrol

Stanozolol

Tablets: 2 mg

2 mg qd tid

Oxandrin

Oxandrolone

Tablets: 2.5, 10 mg

2.5-10 mg qd

Deca-Durabolin

Nandrolone decanoate

Injection: 100, 200 mg/mL (in oil)

100-200 mg once weekly

             

Table 15-1. Selected Hormone Replacement Therapy Products

Medication

Available strengths and dosing

Oral estrogen products

 

Conjugated equine estrogens (CEE) (Premarin)

0.3, 0.45, 0.625, 0.9, 1.25, 2.5 mg daily

Synthetic conjugated estrogens (Cenestin, Enjuvia)

0.3 mg, 0.45 mg, 0.625 mg, 0.9 mg, 1.25 mg daily

Micronized estradiol (Estradiol, Estrace, Gynodiol)

0.5, 1, 1.5, 2 mg daily

Estrone sulfate (Estropipate, Ortho-Est, Ogen)

0.625, 1.25, 2.5, 5 mg daily

Esterified estrogens (Estratab, Menest)

0.3, 0.625, 1.25, 2.5 mg daily

17-β-Estradiol

2 mg daily

Synthetic conjugated estrogen

0.3, 0.625, 0.9, 1.25 mg daily

Transdermal products

 

Estradiol transdermal patch (Estraderm, Esclim, Alora, Vivelle)

Apply twice weekly

Estradiol transdermal patch (Climara, Fempatch, Menostar)

Apply once weekly

Estradiol and levonorgestrel (Climara Pro)

Apply once weekly

Estradiol and norethindrone (CombiPatch)

Apply twice weekly

Estradiol topical emulsion (Estrasorb)

Apply daily

17-β-estradiol micronized gel (Estrogel)

Apply daily

17-β-estradiol transdermal spray (Evamist)

Apply one spray daily

Vaginal estrogen products

 

Estrace vaginal cream (local effects)

0.1 mg estradiol/g; dose: 2-4 g daily for 1-2 weeks; maintenance dose: 1 g 1-3 times/week

Premarin vaginal cream (local effects)

0.625 mg conjugated estrogen/g; dose: 0.5-2 g daily for 3 weeks, then 1 week off

Estring vaginal ring, 17-β-estradiol (local effects)

2 mg estradiol ring releases 7.5 mcg/24 hr; ring remains in vagina for 3 months

Vagifem vaginal tablet (local effects)

25 mcg estradiol/tablet; dose: 1 tablet once daily for 2 weeks; maintenance dose: 1 tablet twice/week

Femring vaginal ring, estradiol acetate (systemic absorption)

0.05 mg/d or 0.1 mg/d

Oral combination estrogen-progestin products

 

Activella

Estradiol/norethindrone: 1 mg/0.5 mg or 0.5 mg/0.1 mg

Femhrt

2.5 or 5 mcg ethinyl estradiol, 0.5 or 1 mg norethindrone acetate

Prempro

0.3 mg/1.5 mg, 0.45/1/5 mg, 0.625 mg/2.5 mg, or 0.625 mg/5 mg or conjugated estrogen/medroxyprogesterone

Premphase

0.625 mg conjugated estrogen, 5 mg medroxyprogesterone (2 weeks of estrogen alone, 2 weeks of combination)

Combination estrogen-androgen products

 

Estratest HS, Covaryx HS

0.625 mg esterified estrogens, 1.25 mg methyltestosterone

Estratest, Covaryx HS

0.625 mg esterified estrogens, 2.5 mg methyltestosterone

Adapted from Pharmacist's Letter 2008; Kalantaridou, Davis, Calis 2008.

Table 15-2. Prescription Contraceptive Products

Product

Estrogen

Progestin

Progestin-only oral contraceptives

Micronor, Errin, Nor-QD, Nora-BE, Camila

-

Norethindrone 0.35 mg

Monophasic low-dose estrogen oral contraceptives

Aviane, Lessina, Levlite

Ethinyl estradiol 20 mcg

Levonorgestrel 0.1 mg

Loestrin 1/20, Loestrin Fe 1/20, Microgestin Fe 1/20

Ethinyl estradiol 20 mcg

Norethindrone 1 mg

Yasmin

Ethinyl estradiol 30 mcg

Drospirenone 3 mg

Levlen, Levora, Nordette, Portia

Ethinyl estradiol 30 mcg

Levonorgestrel 0.15 mg

Cryselle, Lo/Ovral, Low-Ogestrel

Ethinyl estradiol 30 mcg

Norgestrel 0.3 mg

Apri, Desogen, Ortho-Cept

Ethinyl estradiol 30 mcg

Desogestrel 0.15 mg

Ovcon-35

Ethinyl estradiol 30 mcg

Norethindrone 0.4 mg

Brevicon, Modicon, Necon 0.5/35, Nortrel 0.5/35

Ethinyl estradiol 35 mcg

Norethindrone 0.5 mg

Necon 1/35, Norinyl 1+35, Nortrel 1/35, Ortho-Novum 1/35

Ethinyl estradiol 35 mcg

Norethindrone 1 mg

Monophasic high-dose estrogen oral contraceptives

Ogestrel 0.5/50

Ethinyl estradiol 50 mcg

Norgestrel 0.5 mg

Demulen 1/50, Zovia 1/50

Ethinyl estradiol 50 mcg

Ethynodiol diacetate 1 mg

Ovcon-50

Ethinyl estradiol 50 mcg

Norethindrone 1 mg

Necon 1/50, Norinyl 1+50, Ortho-Novum 1/50

Mestranol 50 mcg

Norethindrone 1 mg

Biphasic oral contraceptives

Ortho-Novum 10/11, Necon 10/11

Ethinyl estradiol 35 mcg

Norethindrone 0.5 mg × 10 days; 1 mg × 11 days

Mircette, Kariva

Ethinyl estradiol 20 mcg × 10 days, placebo × 2 days, then 10 mcg × 5 days

Desogestrel 0.15 mg × 21 days

Triphasic oral contraceptives

Enpresse, Tri-Levlen, Triphasil, Trivora

Ethinyl estradiol 30 mcg × 6 days, 40 mcg × 5 days, 30 mcg × 10 days

Levonorgestrel 0.05 mg × 6 days; 0.075 mg × 5 days; 0.125 mg × 10 days.

Tri-Norinyl, Leena, Aranelle

Ethinyl estradiol 35 mcg × 21 days

Norethindrone 0.5 mg × 7 days, 1 mg × 9 days, 0.5 mg × 5 days

Necon 7/7/7, Ortho-Novum 7/7/7, Nortrel 7/7/7

Ethinyl estradiol 35 mcg × 21 days

Norethindrone 0.5 mg × 7 days, 0.75 mg × 7 days, 1 mg × 7 days

Cyclessa, Velivet

Ethinyl estradiol 25 mcg × 21 days

Desogestrel 0.1 mg × 7 days, 0.125 mg × 7 days, 0.15 mg × 7 days

Ortho Tri-Cyclen Lo

Ethinyl estradiol 25 mcg × 21 days

Norgestimate 0.18 mg × 7 days, 0.215 mg × 7 days, 0.25 mg × 7 days

Ortho Tri-Cyclen, Trinessa

Ethinyl estradiol 35 mcg × 21 days

Norgestimate 0.18 mg × 7 days, 0.215 mg × 7 days, 0.25 mg × 7 days

Estrostep Fe

Ethinyl estradiol 20 mcg × 5 days, 30 mcg × 7 days, 35 mcg × 9 days

Norethindrone 1 mg × 21 days

Extrended-cycle oral contraceptives

Loestrin-24 FE

Ethinyl estradiol 20 mcg

Norethindrone 1 mg

Seasonale, Jolessa, Quasense

Ethinyl estradiol 30 mcg

Levonorgestrel 0.15 mg

Yaz

Ethinyl estradiol 20 mcg

Drospirenone 3 mg

Continuous-cycle oral contraceptives

Lybrel

Ethinyl estradiol 30 mcg

Levonorgestrel 90 mg

Transdermal contraceptive system

Ortho Evra

Ethinyl estradiol 20 mcg per 24 hours

Norelgestromin 0.15 mg per 24 hours; applied weekly

Vaginal ring contraceptive system

NuvaRing

Etonogestrel 0.12 mg per 24 hours; insert for 3 weeks, then remove 1 week

Contraceptive implants

Implanon

Etonogestrel subdermal rod; release rate varies over time

Contraceptive injection

Depo-Provera CI

Medroxyprogesterone acetate 150 mg intramuscular q 3 months

Depo-SubQ Provera

Medroxyprogesterone acetate 104 mg subcutaneous q 3 months

Intrauterine contraceptive systems

Mirena

Levonorgestrel 20 mcg/day × 5 years

Adapted from Dickerson et al. 2008; Pharmacist's Letter 2007.

       

Table 15-3. Potential Hormonal Effects Associated with an Imbalance in Estrogen or Progestin

Type of imbalance

Effect

Estrogen excess

    • Breast tenderness, fullness

    • Nausea

    • Edema and bloating

    • Hypertension

    • Melasma

    • Headache

Progestin excess

    • Acne or oily scalp

    • Breast tenderness

    • Depression or irritability

    • Hypomenorrhea

    • Increased appetite and weight gain

    • Fatigue

    • Constipation

Estrogen deficiency

    • Breakthrough bleeding (early or midcycle)

    • Hypomenorrhea

    • Vasomotor symptoms

Progestin deficiency

    • Amenorrhea

    • Breakthrough bleeding (late)

    • Hypermenorrhea

Adapted from Dickerson et al. 2008; Pharmacist's Letter 2007.

Table 15-4. Select Calcium Supplement Products

 

Product

Calcium (mg)

 

Calcium citrate (24% calcium content)

 

Citracal

Tablet: 200; liquitab: 500

 

Citracal + vitamin D

200-315 plus 200 IU vitamin D

 

Calcium carbonate (40% calcium content)

 

Caltrate 600

600

 

Titralac

Chewable: 168, 300; liquid: 400/5 mL

 

Tums

Chewable: 200, 300, 400, 500

 

Viactiv chews

500 plus 200 IU vitamin D

 

Mylanta Supreme liquid

160 mg/5 ml

 

Calcium carbonate + vitamin D

 

Caltrate 600 + D

600 plus 200 IU

 

Calcilyte + vitamin D

500 plus 200 IU

 

Oscal + vitamin D

500 plus 125 IU

 

Calcium phosphate tribasic (39% calcium content)

 

Posture

600

 

Posture-D

600 plus 125 IU

 

Adapted from O'Connell, Vondracek 2008; www.nof.org.

 
       

Table 15-5. Antiresorptive Agents

Medication

Dosing

FDA indication, availability

Bisphosphonates

Alendronate (Fosamax)

Prevention: 5 mg daily or 35 mg weekly

Prevention and treatment of postmenopausal osteoporosis

 

Treatment: 10 mg daily or 70 mg weekly

Osteoporosis in men and glucocorticoid-induced osteoporosis

   

Available as tablet, liquid, and tablet plus vitamin D

Risedronate (Actonel)

Prevention: 5 mg daily

Prevention and treatment of postmenopausal osteoporosis

 

Treatment: 5 mg daily or 35 mg po weekly, 75 mg po daily × 2 consecutive days monthly, or 150 mg po monthly

Osteoporosis in men

Glucocorticoid-induced osteoporosis

Available as tablets and tablets plus calcium

Ibandronate (Boniva)

2.5 mg po daily, 150 mg po monthly, 3 mg IV Q 3 months

Prevention and treatment of postmenopausal osteoporosis

Zoledronic acid (Reclast)

5 mg IV infusion over 15 minutes once yearly

Treatment of postmenopausal osteoporosis

Selective estrogen receptor modulator

Raloxifene (Evista)

60 mg daily

Prevention and treatment of postmenopausal osteoporosis

Other agents

Calcitonin (Miacalcin)

Intranasal: 200 IU daily, alternating nostrils

Intramuscular or subcutaneous: 100 IU every other day

Treatment of postmenopausal osteoporosis in women at least 5 years postmenopause

Teriparatide (Forteo)

Injection: 20 mcg daily

Treatment of postmenopausal women with osteoporosis who are at high risk for fractures or who have failed or are intolerant to other therapies

Treatment of men with primary or hypogonadal osteoporosis who are at high risk for fractures

Adapted from O'Connell, Vondracek 2008; www.nof.org; MacLaughlin, Raehl 2008.

Table 16-1. Drug-Induced Causes of Kidney Disease

 

Clinical syndrome

Causative drugsa

 

Prerenal kidney disease

ACEIs, ARBs, COX-2 inhibitors, cyclosporine, diuretics, NSAIDs, radiocontrast dye, renin inhibitors, and tacrolimus

 

Intrinsic kidney disease

   

Vascular

Amphetamines, cisplatin, cyclosporine, and mitomycin C

 

Glomerular

Gold, heroin, lithium, NSAIDs, and phenytoin

 

Interstitial nephritis

Analgesic combinations, aristolochic acid (Chinese herbs), cyclosporine, lithium, NSAIDs, penicillins, sulfonamides, and tacrolimus

 

Acute tubular necrosis

Aminoglycosides, amphotericin B, chemotherapeutic agents, cidofovir, cocaine, foscarnet, ifosfamide, radiocontrast dye, and tacrolimus

 

Postrenal kidney disease

   

Obstructive

Acyclovir, methotrexate, oxalate, sulfonamides, and uric acid

 

Nephrolithiasis

Allopurinol, indinavir, sulfadiazine, and triamterene

 

a. This list does not include all potential nephrotoxins.

 
         

Table 16-2. Laboratory Findings to Differentiate Prerenal and Intrinsic Kidney Disease

Diagnostic test

Prerenal kidney disease

Intrinsic kidney disease

BUN:Cr ratio

> 20:1

< 15:1

Urinalysis

Normal with few cells or casts (hyaline casts normal)

Granular casts with tubular epithelial cells

Urine osmolality

> 500 mOsm/kg

≤300-350 mOsm/kg

Urinary Cr:Plasma Cr ratio

> 40:1

< 20:1

Specific gravity

> 1.020

< 1.015

Urine sodium

< 20 mEq/L

> 40 mEq/L

FENa

< 1%

> 2%

Note: BUN, blood urea nitrogen; CR, creatinine; FENa, fractional excretion of sodium.

Table 16-3. Diuretics as Drug Therapy for AKI by Drug Classification

Generic name

Trade name

Daily dosage range

Dosage forms

Frequency of administration

Loop diureticsa

       

Furosemide

Lasix

20-400 mg

po

q 6-12 hours

   

20-200 mg (up to 1-3 g/d in AKI)

IV

 

Bumetanide

Bumex

0.5-10 mg

po, IV

q 12-24 hours

Torsemide

Demadex

10-200 mg

po, IV

q 24 hours

Ethacrynic acid

Edecrin

50-400 mg

po

q 8-12 hours

   

50-100 mg

IV

 

Osmotic diuretics

       

Mannitol

Osmitrol, Resectisol

Initial test dose: 12.5-25 g over 3-5 minutes; maintenance dose: 0.25-0.5 g/kg (20-200 g/d)

IV

q 4-6 hours

Thiazide

       

Hydrochlorothiazide

Microzide

25-200 mg

po

qd, bid

Chlorothiazide

Diuril

500 mg-2 g

po

qd, bid

   

250-1,000 mg

IV

 

Thiazide-like diuretics

       

Metolazone

Zaroxolyn

5-20 mg

po

qd

a. Loop diuretics are also administered as a continuous infusion. Higher dose ranges for intermittent dosing are reserved for patients who are unresponsive to initial smaller doses.

           

Table 16-4. Stages of Chronic Kidney Disease

Stage

Description

GFR (mL/min/1.73 m2)

Action

Increased risk

≥ 90 (with CKD risk factors)

Screening and CKD risk reduction

1

Kidney damage with normal or increased GFR

≥ 90

Diagnosis and treatment, treatment of comorbid conditions, slowing of progression, and cardiovascular disease risk reduction

2

Kidney damage with mildly decreased GFR

60-89

Estimation of progression

3

Moderately decreased GFR

30-59

Evaluation and treatment of complications

4

Severely decreased GFR

15-29

Preparation for kidney replacement therapy

5

Kidney failure (defined as ESRD if renal replacement therapy is needed)

< 15 (or need for renal replacement therapy)

Renal replacement therapy (if uremia is present)

Table 16-5. Definitions of Proteinuria and Albuminuria

 

Total protein

Albumin

Condition

24-hour collection (mg/d)

Spot urine dipstick (mg/dL)

Spot urine protein: Cr ratio (mg/g)

24-hour collection (mg/d)

Spot urine dipstick (mg/dL)

Spot urine albumin: Cr ratio (mg/g)

Normal

< 300

< 30

< 200

< 30

< 3

< 17 (men); < 25 (women)

Microalbuminuria

n.a.

n.a.

n.a.

30-300

> 3

17-250 (men); 25-355 (women)

Albuminuria or clinical proteinuria

> 300

> 30

> 200

> 300

n.a.

> 250 (men); > 355 (women)

Note: n.a., not applicable.

Table 16-6. Estimated Starting Doses of Darbepoetin Alfa Based on Previous Epoetin Alfa Dose

 
 

Darbepoetin alfa dose (mcg/wk)

 

Epoetin alfa dose (units/wk)

Adult

Pediatric

 

< 1,500

6.25

a

 

1,500-2,499

6.25

6.25

 

2,500-4,999

12.5

10.0

 

5,000-10,999

25.0

20.0

 

11,000-17,999

40.0

40.0

 

18,000-33,999

60.0

60.0

 

34,000-89,999

100.0

100.0

 

≥90,000

200.0

200.0

 

a. Insufficient data.

 

Table 16-7. Erythropoietic Stimulating Agents

Generic name

Trade name

Starting dose

Route of administration

Frequency of administration

Epoetin alfa

Epogen, Procrit

50-100 units/kg

IV or SC

1-3 doses per week

Darbepoetin alfa

Aranesp

0.45 mcg/kg

IV or SC

Once weekly or once every other week (may prolong interval to every 3-4 weeks)

             

Table 16-8. Iron Supplements

Generic name

Trade name

Dose

Dosage forms

Frequency of administrationa

Ferrous sulfate

Fer-In-Sol, Feosol, Slow FE

200 mg elemental iron per day

po

bid-tid

Ferrous fumarate

Femiron, Vitron-C

200 mg elemental iron per day

po

bid-tid

Ferrous gluconate

Fergon

200 mg elemental iron per day

po

bid-tid

Polysaccharide iron

Hytinic, Niferec

200 mg elemental iron per day

po

qd-bid

Heme iron polypeptide

Proferrin

200 mg elemental iron per day

po

tid-qid

Sodium ferric gluconate

Ferrlecit

62.5-125.0 mg

IV

Weekly, three times per week, or monthlyb

Iron sucrose

Venofer

20-200 mg

IV

Weekly, three times per week, or monthlyb

Iron dextran

InFeD, Dexferrum

25-1,000 mg

IV

Weekly, three times per week, or monthlyb

Ferumoxytol

Feraheme

510 mg × 1 followed by 2nd 510 mg dose 3-8 days after 1st dose

IV

As needed to treat iron deficiency in CKD.

a. For oral formulations, frequency of administration depends on the amount of elemental iron per unit; 200 mg elemental iron per day is necessary.

b. Three times per week is common in iron-deficient hemodialysis patients.

Table 16-9. Phosphate Binding Agents

Generic name

Trade name

Starting dosage rangea

Calcium carbonate (40% elemental calcium)

Tums, Os-Cal-500, Nephro-Calci, Caltrate 600, CalCarb HD, CaCO3 (multiple preparations)

0.8-2.0 g elemental calcium

Calcium acetate (25% elemental calcium)

Phos-Lo

1,334-2,001 mg

Sevelamer carbonate

Renvela

800-1,600 mg

Sevelamer hydrochloride

Renagel

800-1,600 mg

Lanthanum carbonate

Fosrenol

250-500 mg

Aluminum hydroxide

AlternaGel, Alu-Cap, Alu-tab, Amphojel, Basaljel

300-600 mg

Magnesium carbonate

Mag-Carb

70 mg

Magnesium hydroxide (milk of magnesia)

Various

300-400 mg

Note: All agents are taken orally and should be taken with meals.

a. Dose per meal.

           

Table 16-10. Vitamin D Therapy

Generic name

Trade name

Dosage range

Dosage forms

Frequency of administration

Vitamin D precursor

       

Ergocalciferol

Drisdol

400-50,000 IU

po

Daily, weekly, or monthly

Ergocalciferol

Calciferol

400-50,000 IU

po or IV

Daily, weekly, or monthly

Active vitamin D

       

Calcitriol

Calcijex

0.5-5 mcg

IV

Three times per week

Calcitriol

Rocaltrol

0.25-5 mcg

po

Daily, every other day, or three times per week

Vitamin D analogs

       

Paricalcitol

Zemplar

1-4 mcg

po

Daily or three times per week

   

2.5-15 mcg

IV

Three times per week

Doxercalciferol

Hectorol

5-20 mcg

po

Daily or three times per week

   

2-8 mcg

IV

Three times per week

IU, international units.

Table 16-11. Water-Soluble Vitamin Supplements for Dialysis Patients

 

Generic name

Trade name

 

Vitamin B complex, vitamin C, and folic acid

Nephrocaps, Nephrovite, Nephrovite Rx, Renavite, Biotin Forte

 

Vitamin B complex, vitamin C, folic acid, and iron

Nephrovite Rx + Iron, NephrPlex Rx

 

Vitamin B complex

Allbee with C

 

Note: All these supplements are taken orally, 1 capsule or tablet once per day.

 
             

Table 17-1. Selected Drug Therapy Based on Guidelines for Use in ICU Patients

Generic name

Trade name

Dosage range

Formsa

Scheduleb

Notes on usage

Morphine sulfate

 

0.5-10.0 mg

IV, IM, po

Continuous; q6h

General opiate of choice

Hydromorphone

Dilaudid

0.3-1.5 mg

IV

Continuous; q6h

Used in morphine intolerance, hemodynamic instability, or renal dysfunction

Fentanyl

Sublimaze

50-200 mcg/h

IV

Continuous

Used in morphine intolerance, hemodynamic instability, or renal dysfunction

Acetaminophen

Tylenol

Up to 4 g/d

po, PR

q4-6h

NSAIDs may be added to opiates

Ketorolac

Toradol

10-30 mg

IV, IM, po

q6h

Maximum use 5 days

Lorazepam

Ativan

0.5-4.0 mg

IV, po

Continuous; q6h

Long-term sedation (> 24-72 hours)

Midazolam

Versed

1-5 mg

IV

Continuous; q2h

Acute and short term (< 24-72 hours)

Propofol

Diprivan

1-5 mg/kg/h

IV

Continuous

Used when rapid awakening needed

Haloperidol

Haldol

2-5 mg

IV, po

q1-4h

Drug of choice for delirium

Pancuronium

Pavulon

0.05-0.1 mg/kg

IV

Continuous; q2h

General NMB agent of choice (lowcost); causes tachycardia

Vecuronium

Norcuron

0.05-0.1 mg/kg

IV

Continuous; q1h

Used in hemodynamic instability, renal dysfunction, cardiac disease

Cisatracurium

Nimbex

0.05-0.10 mg/kg

IV

Continuous; q1h

Used in renal and hepatic dysfunction

a. Long-acting drugs and dosage forms generally not used in ICU (e.g., fentanyl patch, controlled-release morphine, doxacurium).

b. Continuous analgesia and sedation with frequent titration (patient-controlled analgesia pump, IV infusion, or scheduled) preferred to prn therapy alone. NMB agents used prn are preferred.

Table 17-2. Drug and Nondrug Therapy for Prevention of Venous Thromboembolism

Patient group

Recommended therapya

Medical conditions

 

General medical patient with risk factor

LDUH or LMWH; alternatives: IPC, ES

Acute myocardial infarction

LDUH or full-dose IV heparin

Ischemic stroke

LDUH or LMWH; alternatives: IPC, ES

General surgery (begin preoperatively; generally continue until patient is ambulatory or discharged)

 

Low risk

 
 

Minor procedure without risk factors

Early ambulation

Moderate risk

 
 

Minor procedure + risk factor or > 40 years old; major procedure

LDUH, LMWH, or fondaparinux; alternatives: IPC, ES

High risk

 
 

Major procedure + multiple risk factors or > 40 years old; minor procedure + multiple risk factors or > 60 years old

LDUH, LMWH, or fondaparinux plus IPC, ES (combine drug + mechanical), or both

Orthopedic surgery or trauma (recommended duration if available)

 

Hip replacement (28-35 days)

LMWH or fondaparinux or warfarin (INR 2-3) ± IPC or ES

Knee replacement (minimum 10 days); hip fracture (28-35 days)

LMWH or fondaparinux or warfarin (INR 2-3); alternative: IPC

Neurosurgery

IPC ± ES; add LDUH or LMWH when bleeding is stopped

Major trauma (until discharge)

LMWH; alternative: IPC ± ES if bleeding risk; may use warfarin (INR 2-3) during rehabilitation if major impairment

Acute spinal cord injury (throughout rehabilitation)

LMWH ± IPC, ES; convert to warfarin (INR 2-3) in rehabilitation

a. ES (elastic compression stockings) may add to efficacy of drugs. IPC (intermittent pneumatic compression) may add to efficacy of drugs but noncompliance is high. LDUH (low-dose unfractionated heparin [generic]) dosing is 5,000 units SC q8-12h. Fondaparinux (Arixtra) dosing is 2.5 mg SC qd. LWMH (low molecular weight heparin) dosing is as follows: for dalteparin (Fragmin), 2,500-5,000 units SC qd; for enoxaparin (Lovenox), 30 mg SC q12h or 30-40 mg SC qd. In case of major trauma, start therapy within 36 hours of injury; routine vena cava filter placement is not recommended.

               

Table 17-3. Vasopressors and Inotropes Used in Severe Sepsis and Septic Shock

Name

Dosage range

Adrenergic-receptor activity

Comments

Dopamine

< 5 mcg/kg/min

Increased renal perfusion (dopaminergic receptors)

Preferred agent; use of low-dose "renal tonic" dopamine is not recommended.

 

5-10 mcg/kg/min

Increased cardiac output/HR (β1) > increased BP (α1)

 
 

10-20 mcg/kg/min

Increased cardiac output/HR and BP

 

Norepinephrine

0.01-3 mcg/kg/min

Increased BP (α1) > increased cardiac output/HR (β1)

Preferred agent.

Epinephrine

0.01-0.5 mcg/kg/min

Increased cardiac output/HR and BP (all receptors)

Second-line agent (because of tachycardia, gut ischemia).

Phenylephrine

0.01-5 mcg/kg/min

Increased BP only (α1)

 

Dobutamine

5-20 mcg/kg/min

Increased cardiac output/HR (β1)

 

Vasopressin

0.01-0.04 units/min (0.03 most studied)

None; acts on vasopressin receptors

Add to catecholamine vasopressor in nonresponsive patients. Do not exceed maximum dose.

Immunomodulator used in severe sepsis and septic shock

Drotrecogin alfa (Xigris)

Dosing regimen: 24 mcg/kg/h × 96 h IV infusion

 

Add to antimicrobial therapy within 48 hours of onset of severe sepsis; decreases mortality. Limit use to highly severe illness (i.e., APACHE II score > 25); monitor for bleeding; very expensive but likely cost-effective.

Note: All catecholamine vasopressors are given as continuous IV infusions and are titrated to effect. APACHE = Acute Physiology, Age, and Chronic Health Evaluation.

Table 19-1. Tissue Origin of Malignant Tumor Types

 

Origin

Tissue type

Malignant tumor

 

Epithelial

Surface epithelium

Carcinoma

 
 

Glandular tissue

Adenocarcinoma

 

Connective

Fibrous

Fibrosarcoma

 
 

Bone

Osteosarcoma

 
 

Smooth or striated muscle

Leiomyosarcoma or rhabdomyosarcoma

 
 

Fat

Liposarcoma

 

Lymphoid

Bone marrow

Leukemia

 
 

Lymphoid

Hodgkin and non-Hodgkin lymphoma

 
 

Plasma cell

Multiple myeloma

 

Neural

Glial

Glioblastoma and astrocytoma

 
 

Nerve sheath

Neurofibrosarcoma

 
 

Melanocytes

Malignant melanoma

 

Mixed

Gonadal tissue

Teratocarcinoma

 

Source: Adapted from Balmer et al., 2002.

 
           

Table 19-2. Alkylating Agents

Generic name

Trade name

Dosage range

Dosage form

Frequency

Diseasesa

Nitrogen mustard

Mechlorethamine

Mustargen

6-10 mg/m2

IV

Days 1, 8 q 4 wk

HL, NHL

Cyclophosphamide

Cytoxan, Neosar

500-2,000 mg/m2, 40-100 mg/m2

IV, po

q 3 wk, qd 2-14 days

ALL, CLL, HL, NHL, myeloma, testis, neuroblastoma, breast, ovary, lung, cervix

Ifosfamide

Ifex

1.2 g/m2

IV

qd × 5 d q 3 wk

HL, NHL, lung, bladder, sarcoma

Melphalan

Alkeran

16 mg/m2, 6 mg/m 2

IV, po

q 4 wk, qd 4 days q 4 wk

Myeloma, breast, ovary

Chlorambucil

Leukeran

0.1-0.2 mg/kg

po

qd × 3-6 wk

CLL, HL, NHL

Bendamustine

Treanda

100-120 mg/m 2

IV

qd × 2 d, q 21-28 d

CLL, NHL

Ethylenimines and methylmelamines

Altretamine

Hexalen

260 mg/m2

po

qd × 14-21 d

Bladder, breast, ovarian, HL, Ovarian

Thiotepa

Thioplex

10-20 mg/m2

IV

q 3-4 wk

NHL

Alkyl sulfonates

Busulfan

Myleran, Busulfex

4-8 mg/kg

IV, po

qd

CML, BMT

Nitrosureas

HL, NHL, brain, myeloma

Carmustine

BiCNU

150-200 mg/m2

IV

q 6 wk

Islet cell carcinoma

Streptozocin

Zanosar

500 mg/m2

IV

qd 5 d q 6 wk

Glioblastoma multiforme

Polifeprosan 20 with carmustine implant

Gliadel

7.7 mg

Implant

n.a.

 

ALL, acute lymphocytic leukemia; BMT, bone marrow transplant; CLL, chronic lymphocytic leukemia; CML, chronic myelogenous leukemia; HL, Hodgkin lymphoma; n.a., not applicable; NHL, non-Hodgkin lymphoma.

a. Appearance of disease in list does not indicate U.S. Food and Drug Administration approval for drug's use in treatment of that disease, but does indicate use of that drug in that disease in clinical practice.

Table 19-3. Antimetabolites

Generic name

Trade name

Dosage range

Dosage form

Frequency

Diseasea

Folic acid antagonists

Pemetrexed

Alimta

500-600 mg/m2

IV

q 21 d

Malignant mesothelioma, NSCLC, breast, NHL, sarcoma, ALL

Methotrexate

Rheumatrex

10-12 mg, 1-10 g/m2, 25 mg/m2, 10 mg/m2

Intrathecal, IV, IM, po

q wk, q 3 wk, q wk, q wk

 

Pyrimidine analogs

Azacitidine

Vidaza

75-100 mg/m2

SC, IV

qd × 7 d q 4 wk

Myelodysplastic syndrome

Fluorouracil, 5-FU

Adrucil

450 mg/m2

IV

qd × 5 d

Colorectal, breast, head, neck

Cytarabine

Cytosar-U, DepoCyt

3 gm/m2, 100-200 mg/m2, 50 mg

IV, Continuous IV, intrathecal

q 12 hr days 1, 3, 5 q 6 w, qd × 7 d, q 14 d

ALL, AML, CML

Capecitabine

Xeloda

2,500 mg/m2

po

qd × 14 d, q 3 wk

Breast, colorectal

Gemcitabine

Gemzar

1,000-1,250 mg/m2

IV

q wk

Pancreatic, NSCLC, bladder

Decitabine

Dacogen

15 mg/m2

IV

q8h × 3 d, q 6 wk

Myelodysplastic syndrome

Purine analogs

Clofarabine

Clolar

52 mg/m2

IV

qd × 5d q 4 wk

ALL (pediatric)

Mercaptopurine

Purinethol

1.5-2.5 mg/kg

po

Qd

ALL

Thioguanine

Tabloid

2-3 mg/kg

po

Qd

ALL, AML

Pentostatin

Nipent

4 mg/m2

IV

q 2 wk

CLL, hairy cell leukemia, ALL

Cladribine

Leustatin

0.09-0.10 mg/kg

IV

qd × 7 d

NHL, hairy cell leukemia, CLL

Fludarabine

Fludara

25 mg/m2

IV

qd × 5 d q 4 wk

CLL, NHL

Guanosine analogs

Nelarabine

Arranon

Children: 650 mg/m2/d

IV

qd × d, q 21 d

T-cell ALL or NHL

   

Adults: 1,500 mg/m2/d

IV

d 1, 3, 5, q 21 d

 

ALL, acute lymphocytic leukemia; AML, acute myelogenous leukemia; CLL, chronic lymphocytic leukemia; CML, chronic myelogenous leukemia; NHL, non-Hodgkin lymphoma; NSCLC, non-small cell lung cancer.

a. Appearance of disease in list does not indicate U.S. Food and Drug Administration approval for drug's use in treatment of that disease, but does indicate use of that drug in that disease in clinical practice.

                 

Table 19-4. Antitumor Antibiotics

Generic name

Trade name

Dosage range

Dosage form

Frequency

Diseasea

Anthracyclines

Doxorubicin

Adriamycin, Doxil (liposomal)

60-75 mg/m2, 20-50 mg/m2(liposomal)

IV

q 3 wk

ALL, AML, NHL, HL, solid tumors of every major organ

Daunorubicin

Cerubidine, Daunoxome (liposomal)

45 mg/m2, 40 mg/m2(liposomal)

IV

qd × 3 d, q 2 wk

ALL, AML, NHL

Epirubicin

Ellence, Pharmarubicin

60-120 mg/m2

IV

q 3 wk

Breast, bladder, lung, ovarian, gastric

Idarubicin

Idamycin

12-13 mg/m2

IV

qd × 3 d

AML, ALL, breast

Mitoxantrone

Novantrone

12-14 mg/m2

IV

q 3 wk

Prostate, NHL, AML, breast

Valrubicin

Valstar

800 mg

Intravesical

q wk × 6 wk

Bladder

Alkylating-like

Mitomycin

Mutamycin

10-20 mg/m2

IV, intravesical

q 6-8 wk

Bladder, breast, NSCLC, cervix, pancreatic, colon

Chromomycin

Dactinomycin

Cosmegen

12-15 mcg/kg

IV

qd × 5 d

Wilms' tumor, testis, sarcoma

Miscellaneous

Bleomycin

Blenoxane

10-20 USP units/m2/wk

IM, IV, and SC

q wk

HL, NHL, testis, head, neck, lung, skin

ALL, acute lymphocytic leukemia; AML, acute myelogenous leukemia; HL, Hodgkin lymphoma; NHL, non-Hodgkin lymphoma; NSCLC, non-small cell lung cancer.

a. Appearance of disease in list does not indicate U.S. Food and Drug Administration approval for drug's use in treatment of that disease, but does indicate use of that drug in that disease in clinical practice.

Table 19-5. Hormones and Antagonists

Generic name

Trade name

Dosage range

Dosage form

Frequency

Diseasea

Adrenocorticoids

Aminoglutethimide

Cytadren

250 mg

po

qd

Adrenal, breast, prostate

Progestins

Megestrol acetate

Megace

40 mg, 40-320 mg

po

qid, qd divided

Breast, endometrial

Medroxyprogesterone acetate

Provera, Depo-Provera

400-1,000 mg

IM

q wk

Endometrial

Estrogens

Ethinyl estradiol

Estinyl

150 mcg-3 mg, 100 mcg to 1 mg

po

qd

Prostate, breast

Antiestrogen

Tamoxifen

Nolvadex

20-40 mg

po

qd

Breast

Fulvestrant

Faslodex

250 mg

IM

q mo

Breast

Toremifene

Fareston

60 mg

po

qd

Breast

Third Generation

Aromatase inhibitors

Exemestane

Aromasin

25 mg

po

qd

Breast

Anastrozole

Arimidex

1 mg

po

qd

Breast

Letrozole

Femara

2.5 mg

po

qd

Breast

Androgens

Testosterone propionate

Delatestryl

200-400 mg

IM

qd

Breast

Fluoxymesterone

Halotestin

10-40 mg

po

q 2-4 wk

Breast

Antiandrogens

Flutamide

Eulexin

250 mg

po

tid

Prostate

Bicalutamide

Casodex

50 mg

po

qd

Prostate

Nilutamide

Nilandron

300 mg, 150 mg

po

qd × 30 days, qd

Prostate

LHRH agonists

Triptorelin

Trelstar

3.75, 11.25 mg

IM

q 28 d, q 84 d

Prostate

Leuprolide

Lupron, Eligard

7.5, 22.5, 30.0, 45, 65 mg

IM and SC

q mo, q 3 mo, q 4 mo, q 6 mo, q 12 mo

Prostate, breast

Goserelin

Zoladex

3.6, 10.8 mg

SC

q mo, q 3 mo

Prostate, breast

GNRH antagonist

Degarelix

 

240 mg, 80 mg

SC

First month, then q 28 d

Prostate

GNRH, gonadotropin-releasing hormone; LHRH, luteinizing hormone-releasing hormone.

a. Appearance of disease in list does not indicate U.S. Food and Drug Administration approval for drug's use in treatment of that disease, but does indicate use of that drug in that disease in clinical practice.

                     

Table 19-6. Plant Alkaloids

Generic name

Trade name

Dosage range

Dosage form

Frequency

Diseasea

Taxanes

Docetaxel (gastric)

Taxotere

60-100 mg/m2

IV

q 3 wk

NSCLC, breast, ovarian, head, neck, gastric

Paclitaxel

Taxol

135-175 mg/m2

IV

q 3 wk

NSCLC, breast, ovarian, head

Paclitaxel

Abraxane

260 mg/m2

IV

q 3 wk

Breast

Epothilones

Ixabepilone

Ixempra

40 mg/m2(maximum 88 mg)

IV

q 3 wk

Breast

Epipodophyllotoxins

Etoposide

VePesid

100 mg/m2, 50 mg/m2

IV, po

qd × 3-5 d q 3 wk, qd × 21 d q 4 wk

SCLC, testis, NSCLC

Teniposide

Vumon

165 mg/m2

IV

q wk × 4 doses

ALL, SCLC

Camptothecins

Irinotecan

Camptosar

100-125 mg/m2

IV

q wk

Colorectal, NSCLC, SCLC

Topotecan

Hycamtin

1.5 mg/m2

IV

qd × 5 d q 21 d

Ovarian, lung, AML, cervical

Vinca alkaloids

Vincristine

Oncovin

1.4 mg/m2

IV

q wk

ALL, HL, NHL, CLL

Vinblastine

Velban

6 mg/m2

IV

q 2-3 wk

HL, NHL, testis

Vinorelbine

Navelbine

25-30 mg/m2

IV

q wk

NSCLC, breast, ovarian

ALL, acute lymphocytic leukemia; AML, acute myelogenous leukemia; CLL, chronic lymphocytic leukemia; HL, Hodgkin lymphoma; NHL, non-Hodgkin lymphoma; NSCLC, non-small cell lung cancer; SCLC, small cell lung cancer.

a. Appearance of disease in list does not indicate U.S. Food and Drug Administration approval for drug's use in treatment of that disease, but does indicate use of that drug in that disease in clinical practice.

Table 19-7. Biologic Response Modifiers and Monoclonal Antibodies

Generic name

Trade name

Dosage range

Dosage form

Frequency

Diseasea

Immune therapies

Aldesleukin

Proleukin

600,000 units/kg

IV

q 8 h × 14 doses

Metastatic renal cell, metastatic melanoma

Interferon alfa-2b

Intron A

20 × 106units/m2, 10 × 106 units/m2, 2 × 106 units

IV, SC, SC

qd × 5 d per wk × 4 wk,b3 × wk × 11 mo, 3 × wk × 6 mo

Malignant melanoma and hairy cell leukemia

Thalidomide

Thalomid

200 mg

po

qd

Multiple myeloma, erythema nodosum leprosum

Lenalidomide

Revlimid

10 mg

po

qd

Myelodysplastic syndrome

   

25 mg

po

qd d 1-21, q 28 d

Multiple myeloma

Monoclonal antibodies

Rituximab

(Rituxan)

375 mg/m2

IV

q wk × 4-8 doses, q 3 wk

NHL, CLL

Trastuzumab

(Herceptin)

2-6 mg/kg

IV, SC

q wk

Metastatic breast

Gemtuzumab

(Mylotarg)

9 mg/m2

IV

q 2 wk

AML

Alemtuzumab

(Campath)

3-10 mg

IV

qd, then 30 mg 3 × wk

B-cell CLL

Bevacizumab

(Avastin)

5-15 mg/kg

IV

q 2 wk or q 3 wk

Colorectal, NSCLC, breast, glioblastoma, renal cell carcinoma

Cetuximab

(Erbitux)

250-500 mg/m2

IV

q 1-2 wk

Colorectal, head and neck

Denileukin diftitox

(Ontak)

9 or 18 mcg/kg

IV

qd × 5 d q 21 d

T-cell lymphoma

Ibritumomab tiuxetan

(Zevalin)c

     

NHL

Tositumomab

(Bexxar)c

     

NHL

AML, acute myelogenous leukemia; CLL, chronic lymphocytic leukemia; NHL, non-Hodgkin lymphoma; NSCLC, non-small cell lung cancer.

a. Appearance of disease in list does not indicate U.S. Food and Drug Administration approval for drug's use in treatment of that disease, but does indicate use of that drug in that disease in clinical practice.

b. Induction dose.

c. See package insert for range, form, and frequency of dosing.

               

Table 19-8. Miscellaneous Agents

Generic name

Trade name

Dosage range

Dosage form

Frequency

Diseasea

Platinum compounds

Cisplatin

Platinol-AQ

50-100 mg/m2

IV

q 3-4 wk

NSCLC, ovarian, testis, bladder, head, neck, lung

Carboplatin

Paraplatin

300-400 mg/m2, AUC 6

IV

q 3-4 wk

Ovarian, testis, NSCLC, head, neck, lung

Oxaliplatin

Eloxatin

85-130 mg/m2

IV

q 2 wk

Colorectal

Enzymes

Asparaginase

Elspar

6,000 IU/m2

IM

3 × wk

ALL

 

Oncaspar

2,500 IU/m2

IM

Q 14 d

ALL

Cell-specific

Hydroxyurea

Hydrea

20-30 mg/kg

po

qd

CML, AML, head, neck

MTOR inhibitors

Temsirolimus

Torisel

25 mg

IV

q wk

Renal cell carcinoma

Tyrosine kinase inhibitor

Imatinib mesylate

Gleevec

400-600 mg

po

qd

CML, gastrointestinal stromal tumors

Erlotinib

Tarceva

150 mg

po

qd

NSCLC

Gefitinib

Iressa

250-500 mg

po

qd

NSCLC

Sunitinib

Sutent

50 mg

po

qd × 28 d, 14 d off

Kidney, gastrointestinal stromal tumors

Dasatinib

Sprycel

70 mg

po

bid

CML or AML resistant to or intolerant to imatinib

Sorafenib

Nexavar

400 mg

po

bid

renal cell, hepatocellular carcinoma

Lapatinib

Tykerb

1,250 mg

po

qd × 21 d

Breast

Nilotinib

Tasigna

400 mg

po

q12h

CML

26S Proteasome inhibitor

Bortezomib

Velcade

1.3 mg/m2

IV

Days 1, 4, 8, 11

Multiple myeloma, mantle cell lymphoma

AML, acute myelogenous leukemia; CML, chronic myelogenous leukemia; MTOR, mammalian target of rapamycin; NSCLC, non-small cell lung cancer.

a. Appearance of disease in list does not indicate U.S. Food and Drug Administration approval for drug's use in treatment of that disease, but does indicate use of that drug in that disease in clinical practice.

Table 19-9. Common Toxicities of Chemotherapeutic Agents

Toxicity

Causative drugsa

Recommended therapy

Alopecia

Cyclophosphamide, doxorubicin, paclitaxel, mechlorethamine

n.a.

Cardiac toxicity

Anthracyclines, trastuzumab

Limit cumulative doses

Diarrhea

Irinotecan, fluorouracil

Premedicate with atropine (irinotecan); treat with loperamide

Edema

Docetaxel

Administer prophylactic dexamethasone

Extravasation

Anthracyclines, mitomycin, vinca alkaloids, paclitaxel, mechlorethamine

Treat with heat packs for vincas and with cold compresses for all other drugs

Hemorrhagic cystitis

Cyclophosphamide, ifosfamide

Premedicate with hydration therapy, mesna

Hepatotoxicity

Asparaginase, cytarabine, mercaptopurine, methotrexate, imatinib, erlotinib

n.a.

Hypersensitivity

Paclitaxel, asparaginase, cisplatin, carboplatin, etoposide, teniposide

Premedicate with ranitidine or cimetidine, diphenhydramine, dexamethasone, or test dose; treat with emergency resuscitation

Infertility

Cyclophosphamide, chlorambucil, melphalan, mechlorethamine

n.a.

Myelosuppression

Alkylating agents, fluorouracil, methotrexate, lomustine, cyclophosphamide, methotrexate

Treat with G-CSF, platelet transfusions, red blood cell transfusions, erythropoietin-stimulating agents (unless cancer is curable)

Nausea and vomiting

Cisplatin, cyclophosphamide, cytarabine, dacarbazine, ifosfamide, melphalan, mitomycin, mechlorethamine

Premedicate with dexamethasone, phenothiazines (e.g., Compazine), 5-HT3-receptor antagonists (e.g., granisetron), and neurokinin-1 antagonists

Neurotoxicity

Paclitaxel, cisplatin, cytarabine, methotrexate, vincristine, asparaginase

Dose reductions

Pulmonary toxicity

Bleomycin, busulfan, carmustine, mitomycin, trastuzumab

Treat with corticosteroids

Renal toxicity

Cisplatin, ifosfamide, methotrexate, streptozocin

Premedicate with hydration therapy

Stomatitis

Fluorouracil, methotrexate

Hold ice chips in mouth; administer paliferminb

n.a., not applicable.

a. Adverse effects are not limited to the listed drugs.

b. Use for hematologic malignancies that need myelotoxic therapy requiring hematopoietic agents only.

               

Table 19-10. Pharmacologic Management for the Prevention of Acute Chemotherapy-Induced Nausea and Vomiting

Generic name

Trade name

Dosage range

Dosage forma

Frequency

Side effects

5-HT3 receptor antagonists

Dolasetron

Anzemet

100-200 mg

IV, po

30 min before treatment

Headache, dizziness, constipation, blurred vision, elevated liver enzymes

Granisetron

Kytril

1-2 mg

IV, po

30 min before treatment

Headache, dizziness, constipation, blurred vision, elevated liver enzymes

Ondansetron

Zofran

8-16 mg

16-24 mg

IV po

30 min before treatment

Headache, dizziness, constipation, blurred vision, elevated liver enzymes

Palonosetron

Aloxi

0.25, 0.5 mg

IV, po

Day 1 (not to be repeated within 7 d)

Diarrhea, headache, fatigue, insomnia, arrhythmias

Phenothiazines

Prochlorperazine

Compazine

10-25 mg

IV, po, PR

q4h prn

Sedation, hypotension, extrapyramidal effects, lethargy

Chlorpromazine

Thorazine

25-50 mg

po

q4-6h prn

Sedation, hypotension, extrapyramidal effects, lethargy

Promethazine

Phenergan

12.5-25 mg

IV, po, PR

q4-6h prn

Sedation, hypotension, extrapyramidal effects, lethargy

Butyrophenones

Droperidol

Inapsine

1.25-2.5 mg

IM, slow IV

q4h prn

Sedation, tachycardia, hypotension

Haloperidol

Haldol

2 mg

IV, IM, po

q4-6h prn

Sedation, tachycardia, hypotension

Corticosteroids

Dexamethasone

Decadron

4 mg, 10-20 mg

IV, po

Varies

Anxiety, insomnia, GI upset, psychosis

Cannabinoids

Dronabinol

Marinol

10-20 mg

po

q3-6h

Drowsiness, euphoria, dry mouth

Nabilone

Cesamet

1-2 mg

po

bid

Drowsiness, euphoria, dry mouth

Benzodiazepines

Lorazepam

Ativan

2 mg

po

q6h

Sedation, amnesia

Benzamides

Metoclopramide

Reglan

20 mg

po

tid-qid

Diarrhea, sedation, agitation

Neurokinin-1 antagonist

Aprepitant

Emend

80-125 mg

po

Day 1 (125 mg); days 2-3 (80 mg daily)

Somnolence, fatigue, diarrhea

a. Most agents are available in more than one dosage form. Because of space limitations, oral dosing has been given preference.

Table 19-11. American Cancer Society Screening Recommendations

Diseasea

Sex

Age (years)

Procedure

Frequency

Colorectal

M and F

50+

Fecal occult blood test

Every year

 

M and F

50+b

Flexible sigmoidoscopy, colonoscopy, double contrast barium enema, CT colonography

Every 5 years (flexible sigmoidoscopy, CT colonography, and double contrast barium enema, followed by colonoscopy if positive result), every 10 years (colonoscopy)

Breast

F

20+

Breast self-exam

Every month

 

F

20-39 or 40+

Clinical breast exam

Every 3 years or every year

 

F

40+

Mammography

Every year

Cervical

F

21+c

Pap smear and pelvic exam

Every year

Prostate

M

50+

Digital rectal exam

Every year

 

M

50+

Prostate-specific antigen test

Every year

Adapted from the American Cancer Society, 2009.

a. No specific screening recommendations have been made for lung, skin, and testicular cancer in patients with average risk. However, after age 40, it is recommended that all men and women receive health counseling and a physical exam every year.

b. Screening should be done earlier if there is a strong family history of prostate cancer.

c. Screening should be done earlier if patient is sexually active.

                 

Table 19-12. Common Tumor Markers and Associated Cancers

Tumor marker

Abnormal level

Cancer

Alpha-fetoprotein (AFP)

> 20 ng/mL

Hepatocellular, ovarian

β-2 microglobulin (β2M)

> 3 ng/mL

Multiple myeloma, lymphoma

CA 15-3

> 25 U/mL

Breast

CA 125

> 30 U/mL

Ovarian

CA 19-9

> 37 U/mL

Pancreatic, colorectal

Calcitonina

> 70 pg/mL

Thyroid

Carcinoembryonic antigen (CEA)

> 5 U/mL

Colorectal, breast, non-small cell lung

Chromogranin A

> 76 ng/mL (males); > 51 (females)

Neuroendocrine, lung, prostate

Gamma globulin

> 2-3 g/100 mL

Multiple myeloma

HER2/neu

> 450 fmol/mL

Breast

Human chorionic gonadotropin (HCG)

> 5 mIU/mL

Testicular

Prostate-specific antigen (PSA)a

> 4-10 ng/mL

Prostate

Thyroglobulin

> 10 ng/mL

Thyroid

a. PSA can be used to diagnose early disease.

Table 20-1. Kaplan-Meier Patient and Graft Survival Rates for Transplant Recipients

 

Organ

Patient survival (%)

Graft survival (%)

 

Heart

     
 

1 year

87.8

87.3

 
 

3 years

80.2

79.3

 

Intestinal

     
 

1 year

81.0

73.4

 
 

3 years

67.4

54.3

 

Kidney: cadaveric

     
 

1 year

94.8

90.0

 
 

3 years

88.4

78.9

 

Kidney: living

     
 

1 year

98.0

95.1

 
 

3 years

94.7

88.5

 

Liver: cadaveric

     
 

1 year

86.9

82.3

 
 

3 years

78.9

73.7

 

Liver: living

     
 

1 year

90.6

84.1

 
 

3 years

83.8

77.1

 

Lung:

     
 

1 year

84.0

82.3

 
 

3 years

68.0

65.4

 

Pancreas

     
 

1 year

96.7

80.1

 
 

3 years

91.9

55.9

 

Based on data from U.S. Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients as of May 1, 2007.

 
             

Table 20-2. Immunosuppressant Drugs

Generic name

Trade name

Dosage forms

Dose

Generic products

Calcineurin inhibitors

       

Cyclosporine USP

Sandimmune

Injection: 50 mg/mL; oral solution: 100 mg/mL; capsules: 25, 50, 100 mg

Intravenous: 5-6 mg/kg/d; oral: 8-14 mg/kg/d divided q12h; adjusted to desired trough concentration

Injection: 50 mg/mL; capsules: 25, 100 mg

Cyclosporine USP (modified)

Neoral

Oral solution 100 mg/mL; capsules: 25 and 100 mg

Oral: 5-10 mg/kg/d divided q12h; adjusted to desired trough concentration

Oral solution: 100 mg/mL; capsules: 25, 100 mg

Tacrolimus

Prograf

Injection: 5 mg ampoules; capsules: 0.5, 1.0, and 5.0 mg

Intravenous: 0.03-0.05 mg/kg/d as continuous infusion; oral: 0.1-0.2 mg/kg/d divided q12h; adjusted to desired trough concentration

Not available

MTOR inhibitor

       

Sirolimus

Rapamune

Oral solution: 1 mg/mL; tablets: 1, 2 mg

Initial: 6-15 mg po; maintenance: 2-5 mg po qd; adjusted to desired trough concentration

Not available

Antiproliferative agents

       

Azathioprine

Imuran

Injection: 100 mg vial; tablets: 50 mg

Initial: 3-5 mg/kg IV or po; maintenance: 1-2 mg/kg IV or po qd

Injection: 100 mg vial; tablets: 50 mg

Mycophenolate mofetil

CellCept

Injection: 500 mg vial; oral suspension: 200 mg/mL; capsules: 250 mg; tablets: 500 mg

Maintenance: adults: 2-3 g/d divided q8-12h IV or po; children: 1,200 mg/m2divided q8-12h IV or po

Capsules: 250 mg; tablets: 500 mg

Mycophenolate sodium

Myfortic

Tablets: 180, 360 mg

Maintenance: adults: 720 mg po q12h; children: 400 mg/m2 po q12h (maximum dose of 720 mg po q12h)

Not available

Monoclonal antibodies

       

Muromonab-CD3

Orthoclone OKT 3

Injection: 5 mg ampoules

Induction:a 2.5-5.0 mg IV qd × 7-10 d; acute rejection: 2.5-5.0 mg IV qd × 10-14 d

Not available

Basiliximab

Simulect

Injection: 10 and 20 mg vials

Induction: adults and children > 35 kg: 20 mg IV on day 0 and day 4; children < 35 kg: 10 mg IV on day 0 and day 4

Not available

Daclizumab

Zenapax

Injection: 25 mg vials

Induction: 1 mg/kg IV q 2 wk for a total of 5 doses

Not available

Polyclonal antibodies

       

Antithymocyte globulin (equine)

Atgam

Injection: 50 mg vials

Induction:a 15 mg/kg IV qd × 7-14 d; acute rejection: 10-15 mg/kg IV qd × 14 d

Not available

Antithymocyte globulin (rabbit)

Thymoglobulin

Injection: 25 mg vials

Induction:a 1.5 mg/kg IV qd × 3-7 d; acute rejection: 1.5 mg/kg IV qd × 7-14 d

Not available

a. Medication is not FDA-approved for induction.

Table 20-3. Drug Interactions Leading to Altered Exposure of CYP450 3A Isoenzyme Substrates

CYP450 3A4 enzyme inducersa

CYP450 3A4 enzyme inhibitorsb

Anticonvulsants: phenytoin, phenobarbital, carbamazepine

Antidepressants: nefazodone

Antimicrobial agents: rifampin, rifabutin

Antiviral agents: delavirdine, indinavir, nelfinavir, ritonavir, saquinavir

Antiviral agents: nevirapine, efavirenz

Azole antifungal agents: voriconazole, posaconazole, ketoconazole, fluconazole, itraconazole, clotrimazole

Herbal products: St. John's wort

Calcium channel blockers: diltiazem, nicardipine, verapamil

Macrolide antimicrobial agents: erythromycin, clarithromycin

Food-drug interaction: grapefruit juice

Note: The table shows examples only. Numerous other interactions are associated with CYP450 3A4 substrates. See current journals or drug interaction texts for a more detailed list.

a. Inducers result in increased metabolism and decreased bioavailability of substrates of the same system.

b. Inhibitors result in decreased metabolism and increased bioavailability of substrates of the same system.

Table 20-4. Drug Interactions Leading to Altered Exposure of Other Drugs by Cyclosporine

Mechanism

Drug

Comment

CYP450 3A4 enzyme substrates

HMG-CoA reductase inhibitors: lovastatin, simvastatin, atorvastatin

Coadministration of these agents with CsA results in significant increases in HMG-CoA reductase inhibitor exposure and may place patients at increased risk of rhabdomyolysis.

CYP450 3A4 enzyme substrates

Sirolimus

Simultaneous administration increased Cmaxand area under the curve of sirolimus by 120-500% and 140-230%, respectively; administration 4 hours apart increased Cmaxand area under the curve of sirolimus by 30-40% and 35-80%, respectively.

Alteration in enterohepatic recycling

Mycophenolate mofetil

CsA coadministration inhibits MPAG excretion via hepatocytes, thus interfering with MPA enterohepatic recycling and leading to reduced exposure of the active metabolite, MPA.

Note: The table shows examples only. Numerous other interactions are associated with CYP450 3A4 substrates. See current journals or drug interaction texts for a more detailed list. CsA, cyclosporine A; HMG-CoA, 3-hydroxy-3-methyglutaryl coenzyme A; MPA, mycophenolic acid; MPAG, phenolic glucuronide of MPA.

Table 21-1. Selected Medications Used in Peptic Ulcer Disease

Generic name

Trade name

Classification

Dosage range and frequency

Dosage forms

Omeprazole

Prilosec

Proton pump inhibitor

20-40 mg qd

C, G

Omeprazole

Prilosec OTC

Proton pump inhibitor

20 mg qd × 14 days

T

Omeprazole + sodium bicarbonate

Zegerid

Proton pump inhibitor and antacid

20-40 mg qd

C, P

Esomeprazole

Nexium

Proton pump inhibitor

20-40 mg qd

C, IV, G

Lansoprazole

Prevacid, Prevacid SoluTab

Proton pump inhibitor

15 mg qd-30 mg bid

C, ODT, L, ST

Dexlansoprazole

Kapidex

Proton pump inhibitor

30-60 mg qd

C

Rabeprazole

Aciphex

Proton pump inhibitor

10-20 mg qd

T

Pantoprazole

Protonix

Proton pump inhibitor

40-80 mg qd

T, G, IV

Cimetidine

Tagamet

H2-receptor blocker

300 mg qid-800 mg hs

T, L, IV

Ranitidine

Zantac

H2-receptor blocker

150 mg bid-300 mg hs

T, L, IV, C, EfT

Nizatidine

Axid

H2-receptor blocker

150 mg bid-300 mg hs

C, L, T

Famotidine

Pepcid

H2-receptor blocker

20 mg bid-40 mg hs

T, C, P, IV

Clarithromycin

Biaxin

Antibacterial

500 mg bid × 10-14 d

T, G

Amoxicillin

Amoxil

Antibacterial

1 g bid × 10-14 d

C, P, CT

Metronidazole

Flagyl

Antibacterial

500 mg tid × 10-14 d

T, C, IV,

Tetracycline

Various trade names

Antibacterial

500 mg qid × 10-14 d

C

Sucralfate

Carafate

Cytoprotective

1 g qid

T, L

C, capsule; CT, chewable tablet; EfT, effervescent tablet; G, granules for oral suspension; IV, intravenous; L, liquid; ODT, orally disintegrating tablet; P, powder for oral suspension; ST, SoluTab; T, tablet.

             

Table 21-2. Selected Antacids and Absorbents

Generic name

Trade name

Classification

Dosage range and frequency

Dosage forms

Magnesium hydroxide

Milk of magnesia

Antacid

15-30 mL prn

T, L

Aluminum hydroxide

Amphojel, ALternaGEL

Antacid

15-30 mL prn

T, L

Aluminum carbonate

Basaljel

Antacid

15-30 mL prn

T, L

Magnesium hydroxide + aluminum hydroxide

Maalox

Antacid

15-30 mL prn

T, L

Magaldrate

Riopan

Antacid

15-30 mL prn

T, L

Calcium carbonate

Tums, Titralac

Antacid

15-30 mL prn

T, L

Sodium bicarbonate

Various trade names

Antacid

15-30 mL prn

T, L

Alginic acid + aluminum hydroxide + magnesium hydroxide

Gaviscon

Absorbent + antacid

15-30 mL prn; 2 after meals

T, L

L, liquid; T, tablet.

Table 21-3. Selected Medications Used in Inflammatory Bowel Disease

Generic name

Trade name

Classification

Dosage range and frequency

Dosage forms

Sulfasalazine

Azulfidine

Aminosalicylate

4-6 g/d

T

Mesalamine

Asacol

Aminosalicylate

2.4-4.8 g/d

DT

Mesalamine

Pentasa, Rowasa

Aminosalicylate

2-4 g/d

DC

Mesalamine

Salofalk, Claversal

Aminosalicylate

1-4 g/d

EN, SU

Mesalamine

Lialda

Aminosalicylate

2.4-4.8 g/d

DT

Mesalamine

Canasa

Aminosalicylate

500-1,000 mg

SU

Balsalazide

Colazal

Aminosalicylate

6.75 g/d

DC

Metronidazole

Flagyl

Antibacterial

10-20 g/d (Crohn's disease)

T, IV

Ciprofloxacin

Cipro

Antibacterial

500 mg bid (Crohn's disease)

T, IV

Prednisone

Various trade names

Corticosteroid

40-60 mg/d

T

Methylprednisolone

Solu-Medrol

Corticosteroid

16 mg q8h

IV

Budesonide

Entocort EC

Corticosteroid

9 mg qd

C

Azathioprine

Imuran

Immunosuppressive

1.0-2.5 mg/kg/d

T, IV

6-mercaptopurine

Purinethol

Immunosuppressive

1.5 mg/kg/d

T

Methotrexate

Abitrexate

Antimetabolite

25 mg/wk

IM, SC

Infliximab

Remicade

Immunomodulator

Induction: 5 mg/kg at 0, 2, and 6 wks; maintenance: 5 mg/kg q 8 wks

IV

Adalimumab

Humira

Immunomodulator

Induction: 160 mg as 4 injections over 1-2 days then 80 mg 2 wks later; maintenance: 40 mg q other wk starting on day 29

SC

Certolizumab pegol

Cimzia

Immunomodulator

Induction: 400 mg (given as 2 separate doses of 200 mg each) at 0, 2, and 4 wks; maintenance: 400 mg q 4 wks

SC

Natalizumab

Tysabri

Immunomodulator

300 mg over 1 h every 4 wks

IV

Cyclosporine

Neoral, Sandimmune

Immunosuppressive

4 mg/kg/d

IV, C, L

C, capsule; DT, delayed-release tablet; DC, delayed-release capsule; EN, enema; IV, intravenous; IM, intramuscular; L, liquid; SC, subcutaneous; SU, suppository; T, tablet.

Table 21-4. Selected Medications Used in Irritable Bowel Syndrome

Generic name

Trade name

Classification

Dosage range and frequency

Dosage forms

Dicyclomine

Bentyl

Antispasmodic, anticholinergic

10-20 mg qid prn

T, C, L

Hyoscyamine

Various trade names

Anticholinergic

0.25-0.5 mg bid-qid

T, L

Amitriptyline

Elavil

Tricyclic antidepressant

10-50 mg qhs

T

Paroxetine

Paxil

SSRI

10-60 mg/d

T, L, DT

Tegaserod

Zelnorm

Serotonin (5-HT4) receptor antagonist

6 mg bid

T

Lactulose

Various trade names

Osmotic laxative

30-45 mL bid-qid prn

L

Polycarbophil

Fibercon

Bulking agent

1 g qd-qid prn

T

Polyethylene glycol

Various trade names

Osmotic laxative

250 mL q 10 min up to 4 L

L

Alosetron

Lotronex

Serotonin (5-HT3) receptor antagonist

1 mg qd-bid

T

Lubiprostone

Amitiza

C-2 chloride channel activator

8 mcg bid

C

Loperamide

Imodium

Antidiarrheal

2 mg after each loose stool; maximum 16 mg/d

T, C, L

Diphenoxylate/atropine

Lomotil

Antidiarrheal

15-20 mg/d of diphenoxylate in 3-4 divided doses

T, L

C, capsule; DT, delayed-release tablet; L, liquid; T, tablet.

Table 22-1. Disease-Modifying Antirheumatic Drugs

Generic name

Trade name

Dosage range

Administration schedule

Dosage forms

Nonbiologic

       

Hydroxychloroquine

Plaquenil

200-400 mg

1-2 doses per day

po

Sulfasalazine

Azulfidine

2,000-4,000 mg

2-3 doses per day

po

Methotrexate

Rheumatrex

7.5-25.0 mg

Once weekly

po, IM, SC, IV

Gold sodium thiomalate

Myochrysine

25-50 mg

Every 2-4 weeks

IM

Auranofin

Ridaura

3-6 mg

1-2 doses per day

po

Azathioprine

Imuran

50-150 mg

1-2 doses per day

po, IV

Penicillamine

Cuprimine

250-750 mg

2-3 doses per day

po

Minocycline

Minocin

100-200 mg

2 doses per day

po

Leflunomide

Arava

10-20 mg

1-2 doses per day

po

Biologic

       

Etanercept

Enbrel

25 mg

Twice weekly or 50 mg once weekly

SC

Infliximab

Remicade

3 mg/kg

Weeks 0, 2, and 6, then every 8 weeks

IV

Anakinra

Kineret

100 mg

1 dose per day

SC

Adalimumab

Humira

40 mg

Every other week

SC

Abatacept

Orencia

< 60 kg = 500 mg; 60-100 kg = 750 mg; > 100 kg = 1,000 mg

Weeks 0, 2, and 4, then every 4 weeks

IV

Rituximab

 

1,000 mg IV

Every 2 weeks for two doses

IV

               

000048
Figure 22-1. Nonbiologic DMARD Use Note: DMARD, disease-modifying antirheumatic drug; HCQ, hydroxychloroquine; LEF, leflunomide; MTX, methotrexate; SSZ, sulfasalazine; MIN, minocycline; 000042, see text; 000153, includes functional limitation (defined using standard measurement scales such as Health Assessment Questionnaire score or variations of this scale), extra-articular disease (presence of rheumatoid nodules, secondary Sjogren's syndrome, RA vasculitis, Felty's syndrome, and RA lung disease), rheumatoid factor positivity, positive anticyclic citrullinated peptide antibodies, or bony erosions by radiography; 000168, patients with high disease activity and poor prognosis; ||, patients with moderate disease activity and high disease activity without features of poor prognosis; #, patients with high disease activity without features of poor prognosis.

Source: Reprinted with permission from American College of Rheumatology. Recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum. 2008;59:762-84.

000195
Figure 22-2. Biological DMARD Use Note: DMARD, disease-modifying antirheumatic drug; MTX, methotrexate; SSZ, sulfasalazine; TNF, tumor necrosis factor; 000042, see text; 000153, includes functional limitation (defined using standard measurement scales such as Health Assessment Questionnaire score or variations of this scale), extra-articular disease (presence of rheumatoid nodules, secondary Sjogren's syndrome, RA vasculitis, Felty's syndrome, and RA lung disease), rheumatoid factor positivity, positive anticyclic citrullinated peptide antibodies, or bony erosions by radiography; 000168, patients with high disease activity and poor prognosis; ||, patients with moderate disease activity and high disease activity without features of poor prognosis; #, patients with high disease activity without features of poor prognosis.

Source: Reprinted with permission from American College of Rheumatology. Recommendations for the Use of Nonbiologic and Biologic Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis. Arthritis Rheum. 2008;59:762-84.

Table 22-2. Drug Therapy with Nonsteroidal Anti-Inflammatory Drugs

Generic name

Trade name

Dosage range

Administration schedule (doses/d)

Available dosage forms

Acetic acids

       

Diclofenac

Voltaren

150-200 mg/d

3-4

po, ophthalmic, topical gel

 

Votaren XR

100-200 mg/d

1-2

po

Etodolac

Lodine

600-1,200 mg/d

2-4

po

 

Lodine XL

400-1,000 mg/d

1

po

Indomethacin

Indocin

100-200 mg/d

2-3

po, IV, suppository

 

Indocin SR

75-150 mg/d

1-2

po

Nabumetone

Relafen

1,000-2,000 mg/d

1-2

po

Tolmetin

Tolectin

600-1,800 mg/d

3

po

Sulindac

Clinoril

300-400 mg/d

2

po

Propionic acids

       

Fenoprofen

Nalfon

900-3,200 mg/d

3-4

po

Flurbiprofen

Ansaid

200-300 mg/d

2-4

po

Ibuprofen

Motrin

1,200-3,200 mg/d

3-4

po

Ketoprofen

Orudis

150-300 mg/d

3-4

po

Ketoprofen SR

Oruvail

100-200 mg/d

1

po

Naproxen

Naprosyn

500-1,500 mg/d

2-3

po

Oxaprozin

Daypro

1,200-1,800 mg/d

1

po

Fenamates

       

Meclofenamate

Meclomen

200-400 mg/d

3-4

po

Oxicams

       

Piroxicam

Feldene

10-20 mg/d

1-2

po

COX-2 selective

       

Celecoxib

Celebrex

200-400 mg/d

1-2

po

000013
Figure 22-3. Ribose-Uric Acid Pathway

Table 22-3. Drugs for the Treatment of Gout

Generic name

Trade name

Classification

Normal dose

Comments

Dosage forms

Colchicine

 

Anti-inflammatory

1.2 mg po followed by 0.6 mg 1 hour later. Maximum dose is 1.8 mg over 1 hour.

Drug may be used for chronic suppressive therapy; dose must be adjusted for renal insufficiency.

po, IV

Probenecid

Benemid

Uricosuric agent

250-500 mg bid

Avoid salicylates; take with plenty of water.

po

Sulfinpyrazone

Anturane

Uricosuric agent

50-200 mg bid

Avoid salicylates; take with plenty of water.

po

Allopurinol

Zyloprim

Xanthine oxidase inhibitor

100-300 mg qd or divided dose

Drug may cause rash; reduce dosage in renal failure.

po

Indomethacin

Indocin

NSAID

50 mg tid

Drug may cause fluid retention, GI bleeding.

po, IV, suppository


Figure 23-1. Algorithm for Comprehensive Evaluation and Management of Chronic Pain Reproduced with permission from the Pain Management Center of Paducah.


Figure 23-2. The WHO's Three-Step Hierarchy for Analgesic Pain Management in Cancer Patients Reproduced with permission from WHO 1996.

Table 23-1. Starting Doses for Strong Opioids for Severe Pain in Adults: Mu Agonists

     

Equianalgesic dose

 

Generic name

Common product name and strength

Dosing interval

IV

po

Oral starting dose

Fentanyl (synthetic)

Injection

Sublimaze 50 mcg/mL

0.5-2 hours IM or IV

0.1 mg

Not applicable

 

Transdermal

Duragesic 12, 25, 50, 75, 100 mcg/h

q 2-3 days

     

Transmucosal lozenge

Actiq 200, 400, 600, 800, 1,200, 1,600 mcg

prn

   

100 to 200 mcg

Disintegrating tablet

Fentora 100, 200, 400, 600, 800 mcg

prn

   

100 mcg

Hydromorphone (semisynthetic)

Tablet

Dilaudid 2, 4, 8 mg

4-6 hours po; 6-8 hours IM, SC, or IV

1.5 mg

7.5 mg

4-8 mg

Liquid

Dilaudid 1 mg/mL; HP 10 mg/mL

       

Injection

Dilaudid 1, 2, 4 mg/mL

       

Levorphanol (semisynthetic)

Tablet

Levo-Dromoran 2 mg

6-8 hours po; 3-4 hours IV; 6-8 hours IM or SC

2 mg

4 mg

2-4 mg

Injection

Levo-Dromoran 2 mg/mL

       

Meperidine (synthetic)

Tablet

Demerol 50, 100 mg

3-4 hours po; 3-4 hours IM or SC

75 mg

300 mg

50-150 mg (not recommended)

Liquid

Demerol 10 mg/mL

       

Injection

Demerol 25, 50, 75, 100 mg/mL

       

Methadone (synthetic)

Tablet

Dolophine 5, 10 mg; Methadose 5, 10 mg; 40 mg dispersible

3-8 hours po; 4-12 hours IM, SC, or IV

Acute: 10 mg acute; chronic: 2-4 mg

Acute: 20 mg; chronic: 2-4 mg

2.5-10.0 mg

Liquid

Methadose 10 mg/mL; methadone hydrochloride (HCl) 1, 2, 10 mg/mL

       

Injection

Methadone HCl 10 mg/mL

       

Morphine (natural)

Immediate-release tablet

MSIR 15, 30 mg

2-4 hours po; 4 hours IM, SC, or IV; 4 hours per rectum

10 mg

30 mg

5-30 mg

Liquid

MSIR 2, 4, 20 mg/mL; morphine sulfate 2, 5 mg/mL; Roxanol 20 mg/mL

       

Injection

Duramorph, Astramorph PF 0.5, 1 mg/mL

       

Suppository

RMS 5, 10, 20, 30 mg

       

Controlled-release tablet

Avinza 30, 45, 60, 75, 90, 120 mg

24 hours po

     
 

Kadian 10, 20, 30, 50, 60, 80, 100, 200 mg

12-24 hours po

     
 

MsContin 15, 30, 60, 100, 200 mg

8-12 hours po

     
 

Oramorph SR 15, 30, 60, 100 mg

8-12 hours po

     

Oxycodone (semisynthetic)

Tablet

Roxicodone 5, 15, 30 mg

4-6 hours po

Not applicable

20 mg

5-30 mg

Capsule

OxyIR 5 mg

       

Liquid

Roxicodone 1, 20 mg/mL; OxyFast 20 mg/mL

       

Tablet (oxycodone/acetaminophen)

Magnacet 2.5/400, 5/400, 7.5/400, 10/400 mg

       

Tablet (oxycodone/acetaminophen)

Roxicet 5/325, 5/500 mg; Percocet 2.5/325, 5/325, 7.5/325, 10/325 mg

       

Capsule (oxycodone/acetaminophen)

Tylox 5/500 mg

       

Liquid (oxycodone/acetaminophen)

Roxicet 5/325 per 5 ml

       

Controlled-release tablet

Oxycontin 10, 15, 20, 40, 80 mg

12 hours po

     

Oxymorphone (semisynthetic)

Injection

Oxymorphone HCl 1, 1.5 mg/ml; Opana 1 mg/ml

4-6 hours po; 4 hours IM, SC, or IV

1 mg

10 mg

5-20 mg

Immediate-release tablet

Opana 5, 10 mg

12 hours po

     

Controlled-release tablet

Opana ER 5, 7.5, 10, 15, 20, 30, 40 mg

       

Table 23-2. Opioid Dosing for Mild to Moderate Pain in Adults

Generic name

Common product name and strength

Dosing interval

IV starting dose

Oral starting dose

Moderate-mild opioids

Codeine (natural)

       

Tablet

Codeine sulfate 15, 30, 60 mg (CII)

4-6 hours

15-30 mg

15-60 mg

Injection

Codeine phosphate 15, 30 mg/mL

     

Tablet (codeine/acetaminophen)

Tylenol with Codeine #1 (300/7.5 mg), #2 (300/15 mg), #3 (300/30 mg), #4 (300/60 mg)

     

Liquid (codeine/acetaminophen)

Tylenol with Codeine Elixir 8/160 mg per 5 mL

     

Hydrocodone (semisynthetic)

Tablet (hydrocodone/acetaminophen)

Vicodin 5/500 mg; Vicodin ES 7.5/750 mg; Vicodin HD 10/660 mg; Norco 5/325, 7.5/325, 10/325 mg; Lortab 2.5/500, 5/500, 7.5/500, 10/500 mg; Lorcet 10/650 mg

4-6 hours

Not applicable

5-10 mg

Liquid (hydrocodone/acetaminophen)

Hycet 7.5/325 mg per 15 mL; Lortab Elixir 7.5/500 mg per 15 mL

     

Tablet (hydrocodone/ibuprofen)

Zydone 5/400, 7.5/400, 10/400 mg; Vicoprofen 7.5/200 mg; Reprexain 2.5/200, 5/200, 10/200 mg

     

Propoxyphene (synthetic)

       

Tablet (propoxyphene/acetaminophen)

Darvocet N 50 (50/325 mg); Darvocet N 100 (100/650 mg)

4-6 hours

Not applicable

65-130 mg; maximum 600 mg/d

Capsule (propoxyphene/acetaminophen)

Darvon 65 mg

     

Agonists-antagonists

Pentazocine

       

Tablet (pentazocine/naloxone)

Talwin NX 50/0.5 mg

4 hours

 

50-100 mg; maximum 600 mg/d

Tablet (pentazocine/aspirin)

Talwin Compound 12.5/325 mg

6-8 hours

30 mg IM, SC, or IV; maximum 360 mg/d

12.5-25 mg

Injection

Talwin 30 mg/mL

3-4 hours

   

Butorphanol

       

Injection

Stadol 1, 2 mg/mL

3-4 hours

0.5-2 mg

 

Nasal spray

Butorphanol tartrate 1 mg/spray

   

1 spray in 1 nostril

Nalbuphine injection

Nalbuphine HCl 10, 20 mg/mL

3-6 hours

10 mg

 

Buprenorphine injection

Buprenex 0.3 mg/mL

6-8 hours

0.3-0.6 mg

 

Miscellaneous

Tablet

Ultram 50 mg

4-6 hours

 

50-100 mg; maximum 400 mg/d

Controlled-release tablet

Ultram ER, Ryzolt 100, 200, 300 mg

24 hours

 

100 mg; maximum 300 mg/d

Tablet (tramadol/acetaminophen)

Ultracet 325/37.5 mg

     

Table 23-3. Opioid Antagonists

Generic name

Common product name and strength

Dosing interval

IV starting dose

Oral starting dose

Naloxone injection

Naloxone HCl 0.4 mg/mL

Every 2-3 min

Opioid overdose: 0.4-2 mg; postoperative narcotic depression: 0.1-0.2 mg

 

Naltrexone

Tablet

Revia 50 mg; naltrexone HCl 25, 50, 100 mg

qd, qod, q3d

 

Alcoholism: 50 mg qd; narcotic addiction: 50 mg qd, 100 mg qod, or 150 mg q3d

Injection

Vivitrol 380 mg/vial

Monthly

Alcoholism: 380 mg monthly

 

Table 23-4. CYP450 2D6 Enzyme Activity

 

Substrates

Inhibitors

Inducers

 

Codeine

Celecoxib

Carbamazepine

 

Hydrocodone

Cimetidine

Ethanol

 

Meperidine

Citalopram

Phenobarbital

 

Methadone

Fluoxetine

Phenytoin

 

Oxycodone

Methadone

Rifampin

 

Propoxyphene

Paroxetine

   

Tramadol

Propoxyphene

   
 

Sertraline

   
               

Table 23-5. Agents Used in Migraine Treatment

Drug

Common brand names and strengths

Maximum daily dose (weekly maximum)

Dosing instructions

Ergot alkaloids

     

Ergotamine sublingual tablet

Ergomar 2 mg

6 mg (10 mg) po

1 tablet at onset; then 1 every 30 min prn

Ergotamine/caffeine tablet

Cafergot 1/100 mg

Ergotamine 6 mg (10 mg)

2 tablets at onset; then 1 every 30 min prn

Ergotamine/caffeine suppository

Migergot 2/100 mg; Cafergot 2/100 mg

Ergotamine 4 mg (10 mg)

Insert 1 at onset; repeat in 1 hour prn

Dihydroergotamine

Injection: 1 mg/mL DHE 45 Nasal spray: Migranal 4 mg/mL

DHE 2 mg (6 mg IV or 3 mg IM)

0.5-1.0 mg IV or IM every hour as needed

   

DHE 2 mg (6 mg)

Administer 1 spray (0.5 mg) in each nostril, followed in 15 min by an additional spray in each nostril

Miscellaneous agents

     

Isometheptene/dichloralphenazone/acetaminophen capsule

Midrin 65/100/325 mg

5 capsules within a 12-hour period

2 capsules at once, followed by 1 capsule every hour until headache is relieved

Isometheptene/acetaminophen/caffeine capsule

Migraten 65/325/100 mg

5 capsules within a 12-hour period

2 capsules at once, followed by 1 capsule every hour until headache is relieved

Table 23-6. Selective Serotonin Receptor Agonists (Triptans)

Drug

Brand name

Available strengths

Dosage (maximum daily dose)

Half-life

Onset

Metabolism

Almotriptan

Axert

Tablet: 6.25, 12.5 mg

12.5 mg; repeat in 2 hours (25 mg)

3.5 hours

60 min

CYP450; MAO

Sumatriptan

Imitrex

Tablet: 25, 50, 100 mg

50-100 mg; repeat in 2 hours (200 mg)

2.5 hours

60-120 min

MAO

   

Nasal: 5, 20 mg

5 or 20 mg; repeat in 2 hours (40 mg)

 

15-20 min

 
   

Injection: 6 mg/mL; Statdose injection: 4, 6 mg/mL

4 or 6 mg; repeat in 1 hour (12 mg)

 

10-15 min

 

Eletriptan

Relpax

Tablet: 20, 40 mg

20 mg; repeat in 2 hours (80 mg)

5 hours

60 min

CYP450 3A4

Frovatriptan

Frova

Tablet: 2.5 mg

2.5 mg; repeat in 2 hours (7.5 mg)

25 hours

60-120 min

Renal 50%

Rizatriptan

Maxalt

Tablet or wafer: 5, 10 mg

5 or 10 mg; repeat in 2 hours (30 mg)

2-3 hours

30 min

MAO

Zolmitriptan

Zomig

Tablet or wafer: 2.5, 5 mg

2.5 or 5 mg; repeat in 2 hours (10 mg)

2.5-4 hours

45 min

CYP450; MAO

   

Nasal: 5 mg

5 mg; repeat in 2 hours (10 mg)

3 hours

10-15 min

CYP450; MAO

Naratriptan

Amerge

Tablet: 1, 2.5 mg

1 or 2.5 mg; repeat in 4 hours (5 mg)

6 hours

60 min

Renal 70%; CYP450

Miscellaneous agents

           

Sumatriptan/naproxen

Treximet

Tablet: 85/500 mg

1 tablet; may repeat in 2 hours (2 tablets)

The safety of treating more than 5 migraines in a 30-day period has not been established.

Sumatriptan 2 hours/naproxen 19 hours

60-120 min

Sumatriptan: MAO; naproxen: no significant CYP450 induction

Table 23-7. Selected Migraine Preventive Treatments

Drug

Recommended dose/day

Selected side effects

β-adrenergic receptor antagonists

Propranolol

80-240 mg

Reduced energy, tiredness, postural symptoms

Metoprolol

100-200 mg

 

Timolol

20-30 mg

 

Atenolol

100 mg

 

Antidepressants

Amitriptyline

25-150 mg

Drowsiness

Fluoxetine

10-20 mg

Headache, nausea, nervousness, insomnia, drowsiness

Serotonin antagonists

Methysergide

1-6 mg (treatment must be discontinued for 1 month every 6 months)

Drowsiness, leg cramps, hair loss, retroperitoneal fibrosis

Calcium channel blockers

Diltiazem

90-180 mg

Headache

Verapamil

160-320 mg

Constipation, peripheral edema, cardiac conduction disturbances

Anticonvulsants

Divalproex

400-600 mg

Drowsiness, weight gain, tremor, hair loss, hematologic and liver abnormalities, teratogenicity

Valproate

500-1500 mg

 

Gabapentin

900-2400 mg

Somnolence, dizziness

Topiramate

100 mg

Confusion, paresthesias, weight loss

Adapted from Goadsby P, Lipton R, Ferrari M 2002; D'Amico D, Tepper J 2008.

Table 24-1. Seizures Caused by Anticonvulsants

 

Seizure type

Anticonvulsant

Absence

Generalized tonic-clonic

Myoclonic

Carbamazepine (Tegretol, Carbitrol)

Causes

Causes

Causes

Phenytoin (Dilantin, Phenytek)

Causes

   

Phenobarbital

Causes

   

Table 24-2. Dosage Forms, Normal Maintenance Doses, and Dosing Interval for Older Anticonvulsants

Generic name

Trade name

Dosage form

Adult oral maintenance dosea

Intervalb

Carbamazepine

Carbatrol, Equetro

Extended-release capsule: 100, 200, 300 mg

800-1,200 mg/d

bid

 

Epitol

200 mg

   
 

Tegretol

Suspension: 100 mg/5 mL (5, 10, 450 mL) Chewable tablet: 100 mg Tablet: 200 mg

 

Suspension: qid Chewable tablet: tid-qid Tablet (200 mg): bid

 

Tegretol XR

Extended-release tablet: 100, 200, 400 mg

 

Extended-release tablet: bid

Ethosuximide

Zarontin

Capsule: 250 mg

25-1,500 mg/d

bid

Fosphenytoin

Cerebyx

Injection:c 150 mg/2 mL; 750 mg/10 mL

NA

NA

Phenobarbital

Variety of generics

Elixir: 20 mg/5 mL (5, 7.5, 15, 480 mL) Tablet (15, 30, 60, 100 mg) Injection: 60, 65, 130 mg/mL (1 mL)

30-120 mg/d

bid-tid

Phenytoin

Dilantin

Suspension: 125 mg/5 mL (240 mL)

100-600 mg/d

bid-tid

   

Chewable tablet: 50 mg

 

bid-tid

   

Prompt-release capsule: 30, 100 mg

 

bid-tid

   

Extended-release capsule: 30, 100 mg

 

qd

   

Injection: 50 mg/mL

   
 

Phenytek

Extended-release capsule: 200 mg, 300 mg

   
 

Generic

Suspension: 100 mg/4 mL (4 mL); 125 mg/5 mL (240 mL)

Prompt-release capsule: 100 mg

Extended-release capsule: 100 mg

Injection: 50 mg/mL

   

Primidone

Mysoline

Suspension: 250 mg/5 mL

250-750 mg/d

tid-qid

   

Tablet: 50, 125, 250 mg

   
   

Chewable tablet: 125 mg

   

Valproic acid

Depacon

Injection: 100 mg/mL (5 mL)

NA

NA

 

Depakene

Syrup: 250 mg/5 mL (5, 10, 480 mL)

250-4,000 mg/d

bid-qid

   

Gel capsule: 250 mg

   
 

Stavzor

Gel capsule: 125, 250, 500 mg

   

Divalproex sodium

Depakote Sprinkles

Capsule: 125 mg

 

bid

 

Depakote

Delayed-release tablet: 125, 250, 500 mg

 

bid

 

Depakote ER

Extended-release tablet: 250, 500 mg

 

qd

NA, not applicable.

a. With the exception of the intravenous dosage forms, these anticonvulsants are begun at low doses and slowly titrated to a dose that will control the patient's seizures.

b. Interval may either decrease or increase in the presence of medications that induce or inhibit metabolism, respectively.

c. 150 mg of fosphenytoin = 100 mg phenytoin.

Table 24-3. Dosage Forms, Normal Maintenance Doses, and Dosing Intervals for the Newer Anticonvulsants

Generic name

Trade name

Dosage form

Adult oral maintenance dosea

Intervalb

Felbamate

Felbatol

Suspension: 600 mg/5 mL (240, 960 mL) Tablets: 400, 600 mg

1,200-3,600 mg/d

tid-qid

Gabapentin

Neurontin

Capsules:100, 300, 400 mg

900-3,600 mg/dc

tid

   

Oral solution: 250 mg/mL (480 mL)

   
   

Tablets: 100, 300, 400, 600, 800 mg

   

Lacosamide

Vimpat

Tablets: 50,100, 150, 200 mg Injection: 200 mg/20mL

200-400 mg/d

bid

Lamotrigine

Lamictal

Chewable tablets: 2, 5, 25 mg

50-400/d

bid

   

Tablets: 25, 100, 150, 200 mg

 

bid

 

Lamictal ODT

Tablets: 25, 50, 100, 200 mg

 

bid

 

Lamictal XR

Tablets: 25, 50, 100, 200 mg

 

qd

Levetiracetam

Keppra

Tablets: 250, 500, 750 mg

1,000-3,000 mg/d

bid

   

Solution: 100 mg/mL

   
 

Keppra XR

Extended release: 500 mg

 

Extended release: qd

Oxcarbazepine

Trileptal

Tablets: 150, 300, 600 mg

600-2,400 mg/d

bid

   

Suspension: 300 mg/5mL (250 mL)

   

Pregabalin

Lyrica

Tablets: 100, 150, 200, 225, 300 mg

300-600 mg/d

bid-tid

Tiagabine

Gabitril

Tablets: 2, 4, 12, 16 mg

4-56 mg/d

bid-qid

Topiramate

Topamax

Sprinkle capsules:15, 25 mg

200-400 mg/dd

bid

   

Tablets: 25, 50, 100, 200 mg

   

Rufinamide

Banzel

Tablets: 200, 400 mg

45 mg/kg/d

bid

Vigabatrin

Sabril

Tablets: 500 mg

400-600 mg/d

bid

Zonisamide

Zonegran

Capsules: 25, 50, 100 mg

100-600 mg/d

qd

a. With the exception of gabapentin, these anticonvulsants are begun at low doses and slowly titrated over weeks to a dose that will control the patient's seizures.

b. Interval may either decrease or increase in the presence of medications that induce or inhibit metabolism, respectively.

c. Much larger doses have been given.

d. The recommended maintenance doses for initial monotherapy and adjunctive therapy are 400 mg/d and 200-400 mg/d, respectively. Doses > 400 mg are no more effective than doses ≤ 400 mg.

           

Table 24-4. Treatment of Status Epilepticus

As soon as possible

    • Assess cardiorespiratory status; insert oral airway and administer oxygen as needed.

    • Place secure IV and start infusion of normal saline.

    • Obtain medical history; perform neurological examination.

    • Obtain the following tests: if the patient has been on anticonvulsants as an outpatient, obtain blood for serum drug concentrations and a chemistry panel including electrolytes, glucose, blood urea nitrogen, and urine drug screen.

    • Administer 25 g of glucose and 100 mg of thiamine IV.

If still seizing

    • Administer either diazepam or lorazepam up to maximum dosage until seizure stops.

If still seizing

    • Load with IV phenytoin (provided patient was not on phenytoin at home or has low serum concentrations) and begin maintenance doses.

    • Monitor blood pressure and EEG.

If still seizing

    • Load with IV phenobarbital or begin a continuous infusion of midazolam.

If still seizing

    • Begin medically induced coma.

    • Adjust EEG to burst suppression.

    • Avoid hypotension during infusion of the barbiturate.

Table 25-1. Typical (Conventional or Older) Antipsychotics

Drug and form

Trade name

Form

Potency

Dosage range

Equivalent oral dose

Clinical pearls

Chlorpromazine

Thorazine

10, 25, 50, 100, 200 mg tablets; 30, 75, 150, 200, 300 mg sustained release capsules; 10 mg/5 mL syrup; 30 mg/mL, 100 mg/mL concentrate; 25 mg, 100 mg rectal suppository; 25 mg/mL injection

Low

50-2000 mg/d

100 mg

First antipsychotic used clinically; contributed to deinstitutionalization of many patients in the 1950s; 100 mg of chlorpromazine is equivalent to 2 mg of haloperidol.

Thioridazine

Mellaril

10, 15, 25, 50, 100, 150, 200 mg tablets; 25 mg/5 mL, 100 mg/5 mL suspension; 30 mg/mL, 100 mg/mL concentrate

Low

50-800 mg/d

100 mg

Pigmentary retinopathy at daily doses > 800 mg/d; black box warning: QT prolongation

Perphenazine

Trilafon

2, 4, 8, 16 mg tablets; 5 mg/mL injection

Medium

4-64 mg/d in divided doses

10 mg

Moderate sedation, extrapyramidal symptoms; low anticholinergic effect, orthostasis

Fluphenazine

Prolixin

1.0, 2.5, 5.0, 10.0 mg tablets; 25 mg/mL decanoate injection; 2.5 mg/mL injection; 2.5 mg/5 mL elixir; 5 mg/mL concentrate

High

1-65 mg/d po; 12.5-75 mg IM (decanoate) every 2 weeks

2 mg

Decanoate injection every 2 weeks; immediate-release injection, 5-10 minutes onset

Haloperidol

Haldol

0.5, 1.0, 2.0, 5.0, 10.0, 20.0 mg tablets; 2 mg/mL concentrate; 50, 100 mg/mL decanoate injection; 5 mg/mL injection

High

1-100 mg/d po; 50-300 mg IM (decanoate) every 4 weeks

2 mg

Decanoate injection every 4 weeks; immediate-release injection, 5-10 min onset

Table 25-2. Adverse Effects of Typical Antipsychotic Medications

Drug

Extrapyramidal symptoms

Sedation

Orthostasis

Weight gain

Anticholinergic effect

Chlorpromazine

+++

++++

++++

++

+++

Thioridazine

+++

++++

++++

+

++++

Perphenazine

++++

++

+

+

++

Fluphenazine

++++

+

+

+

+

Haloperidol

++++

+

+

+

+

Table 25-3. Atypical Antipsychotics

Drug

Trade name

Form

Usual dose

Adverse effects

Clinical pearls

Clozapine

Clozaril, FazaClo (disintegrating clozapine tablets)

25, 100 mg tablets

12.5 mg titrated up to 300-900 mg/d

Sedation, weight gain, hypersalivation, black box: seizure risk (> 600 mg/d), agranulocytosis, orthostasis, myocarditis, respiratory and cardiac arrest; no EPS or TD

Indicated for refractory schizophrenia only.

Weekly CBC with differential is required; if WBC < 3,500 or ANC < 1,500, patient must discontinue medication; if stable CBC with differential for 6 months, patient may go to biweekly dosage; if still stable for additional 6 months, patient may go to every-4-weeks dosage.

Procyclidine [Kemadrin] 5 mg may help with hypersalivation.

Risperidone

Risperdal

0.25, 0.5, 1.0, 2.0, 3.0, 4.0 mg tablets; 1 mg/mL concentrate

1 mg bid up to 4-6 mg/d; maximum dose 16 mg/d

Dose-related EPS (> 8 mg/d), +/- weight gain, +/- sedation, prolactin elevation, orthostasis, Sedation, weight gain, possible dose-related EPS

Available in concentrate; do not mix with teas or colas; used commonly in dementia (0.25-1 mg); patient must overlap Consta with oral risperidone for at least 3 weeks.

 

Risperdal-M (disintegrating risperidone tablets)

0.5, 1.0, 2.0 mg

     
 

Risperdal Consta (long-acting injection)

25.0, 37.5, 50.0 mg

     

Olanzapine

Zyprexa

2.5, 5, 7.5, 10, 15, 20 mg tablets

10-20 mg/d; higher doses have been reported

Sedation, orthostasis, weight gain

Olanzapine is also indicated for acute manic episodes of bipolar disorder; Zyprexa Zydis is useful for patients who are unable to swallow or are "cheeking" medications.

 

Zyprexa Zydis (disintegrating olanzapine tablets)

5, 10, 15, 20 mg tablets

     
 

Zyprexa IntraMuscular

10 mg/mL injection

10 mg IM × 1; may repeat in 2 and 4h; maximum IM daily dose 30 mg

Sedation, orthostasis

 

Quetiapine

Seroquel

25, 100, 200, 300, 400 mg tablets

300-800 mg/d; higher doses have been reported

Sedation, dizziness, headache

Low EPS and prolactin elevation risk; cataract risk: do lens test at baseline and every 6 months.

 

Seroquel XR (extended-release tablets)

200, 300, 400 mg

     

Ziprasidone

Geodon

20, 40, 60, 80 mg capsules; 20 mg/mL injection

40-200 mg/d po; 20 mg IM × 1 dose (may repeat in 4 h; maximum IM daily dose 40 mg)

+/- sedation, +/- weight gain, QT prolongation warning in package insert

Use caution with other medications that prolong QT interval.

Aripiprazole

Abilify

2, 5, 10, 15, 20, 30 mg tablets; 1 mg/mL concentrate; 7.5-mg/mL injection

10-30 mg/d po; 5.25-15 mg/d IM; maximum IM daily dose 30 mg

Possible insomnia, +/-weight gain

Once-daily dosing benefit; partial dopamine agonist

 

Abilify Discmelt (disintegrating tablets)

10, 15 mg

     

Paliperidone

Invega

3, 6, 9 mg extended release tablets

6 mg/d; maximum dose 12 mg/d

Headache, tachycardia, somnolence, anxiety

Sustained release tablet: do not crush or chew; tablet shell may be seen in stool.

ANC, absolute neutrophil count; CBC, complete blood count.

Table 25-4. Mood Stabilizers

Drug

Trade name

Form

Usual dose

Adverse effects

Clinical pearls

Lithium

Lithobid, Eskalith CR

150, 300, 600 mg caplets; 300 mg, 450 mg (CR) tablets; 300 mg (SR) tablets; syrup, as citrate 300 mg/5 mL (Cibalith-S)

Starting: 900-1,200 mg in divided doses; titrate to desired response or level

Tremor, polydipsia or polyuria, nausea or diarrhea, weight gain, hypothyroidism, mental dulling

Many drug interactions; toxicity is a concern (pregnancy category D); monitor blood levels—acute: 0.6-1.2 mEq/L, maintenance: 0.8-1.0 mEq/L

Divalproex sodium

Depakote

125, 250, 500 mg tablets; 250, 500 mg (ER) tablets

Starting: 500 mg bid-tid or 15 mg/kg; maximum dose 60 mg/kg/d; ER dosed daily

GI upset, sedation, tremor, weight gain, alopecia, transient elevation in LFTs

Black box warnings: hepatotoxicity, hemorrhagic pancreatitis, teratogenicity (pregnancy category D); monitor blood levels—50-125 mcg/mL

Carbamazepine

Tegretol

200 mg tablets; 100 mg chew tablets; 100, 200, 400 mg ER tablets; 100 mg/5 mL suspension

Starting: 200 mg bid; increase to 800-1,200 mg/d (tid-qid doses); usual range 400-1,600 mg/d

Ataxia, dizziness, sedation, slurred speech, aplastic anemia

See text for contraindications; many drug interactions (pregnancy category C); monitor blood levels—4-12 mcg/mL

Lamotrigine

Lamictal

25, 100, 150, 200 mg tablets; 2, 5, 25 mg chew tablets

Starting: 25 mg/d weeks 1 and 2; 50 mg/d week 5; 200 mg/d week 6; 200 mg/d usual dose

Dizziness, headache, ataxia, nausea, diplopia, rash

Black box warning: severe rashes such as Stevens-Johnson syndrome; start at 25 mg and titrate to 200 mg over 6 weeks to help prevent rash

CR, controlled release; ER, extended release; GI, gastrointestinal.

Table 25-5. Drug Interactions with Lithium

 

Increase level of lithium

Decrease level of lithium

 

Nonsteroidal anti-inflammatory

Theophylline

 

drugs

Caffeine

 

Angiotensin-converting enzyme inhibitors

Pregnancy

 

Fluoxetine

Osmotic diuretics (mannitol and urea)

 

Metronidazole

   

Diuretics (e.g., thiazides)

   

Sodium depletion:

   
 

Low sodium diet

   
 

Excessive exercise or sweating

   
 

Vomiting or diarrhea

   
 

Salt deficiency

   
             

Table 25-6. Lamotrigine Dose Titration

Timing

Patients not taking carbamazepine (or other enzyme-inducing drugs) or valproate (orange color)

Patients taking valproate (blue color)

Patients taking carbamazepine (or other enzyme-inducing drugs) and not taking valproate (green color)

Weeks 1 and 2

25 mg daily

25 mg every other day

50 mg daily

Weeks 3 and 4

50 mg daily

25 mg daily

100 mg daily, in divided doses

Week 5

100 mg daily

50 mg daily

200 mg daily, in divided doses

Week 6

200 mg daily

100 mg daily

300 mg daily, in divided doses

Week 7

200 mg daily

100 mg daily

Up to 400 mg daily, in divided doses

Table 25-7. Tricyclic Antidepressants

Drug

Trade name

Form

Indications

Initial dose

Dose range

Amitriptyline

Elavil

10, 25, 50, 75, 100, 150 mg tablets; 10 mg/mL injection (pregnancy category D)

Depression, chronic and neuropathic pain, migraine prophylaxis, peripheral neuropathy

50-75 mg/d

75-300 mg

Nortriptyline

Pamelor, Aventyl

10, 25, 50, 75 mg capsules; 10 mg/5 mL injection (pregnancy category D)

Depression, chronic pain

25-50 mg/d

40-200 mg

Imipramine

Tofranil

75, 100, 125, 150 mg pamoate capsule

Depression, childhood enuresis, chronic and neuropathic pain

50-75 mg/d

75-300 mg

 

Tofranil-PM

10-, 25-, 50-mg tablets; 12.5-mg/mL injection (pregnancy category D)

     

Doxepin

Sinequan

10, 25, 50, 75, 100, 150 mg capsules; 10 mg/mL concentrate; 5% cream (pregnancy category C)

Depression; anxiety; unlabeled: chronic and neuropathic pain

75 mg/d (in divided doses)

75-300 mg

Clomipramine

Anafranil

25, 50, 75 mg (pregnancy category C)

Obsessive-compulsive disorder; depression; panic attacks; chronic pain

25-100 mg qd, titrated up for 1-2 weeks

Usual effective dose 200-250 mg/d; maximum dose 250 mg because of dose-related increased risk of seizure

Desipramine

(Norpramin)

10, 25, 50, 75, 100, 150 mg tablets (pregnancy category C)

Depression; chronic pain; unlabeled: peripheral neuropathy

50-75 mg/d

75-300 mg

Table 25-8. Monoamine Oxidase Inhibitors

Drug

Trade name

Form

Initial dose

Dose titration

Dose range

Phenelzine

Nardil

15 mg tablets

15 mg tid (>16 years old)

Increase by 15 mg/wk

60-90 mg/d

Tranylcypromine

Parnate

10 mg tablets

30 mg/d in divided doses

Increase by 10 mg/d every 1-3 weeks

30-60 mg/d

Table 25-9. Selective Serotonin Reuptake Inhibitors

Drug

Trade name

Form

Initial dose

Usual dose

Clinical pearls

Citalopram

Celexa

10, 20, 40 mg tablets; 10 mg/5 mL syrup

10 mg

20-40 mg/d; maximum dose 60 mg/d

Used in geriatric patients; fewer drug interactions

Escitalopram

Lexapro

5, 10, 20 mg tablets

10 mg

10-20 mg/d

S-isomer of citalopram; 40 mg Celexa = 10 mg Lexapro

Fluvoxamine

Luvox

50, 100 mg tablets

50 mg

100-300 mg/d

Available in generic; primarily used for obsessive-compulsive disorder drug interactions

Paroxetine

Paxil

10, 20, 30, 40 mg tablets; 10 mg/5 mL suspension

10-20 mg

10-40 mg; maximum dose 50 mg/d

Least-activating SSRI

Paroxetine

Paxil CR

12.5, 25.0, 37.5 mg tablets

12.5-25.0 mg

25.0-37.5 mg

Controlled-release formulation associated with fewer side effects; 10.0 mg Paxil = 12.5 mg Paxil CR

Fluoxetine

Prozac, Sarafem

10, 20, 40 mg capsules; 10, 20 mg tablets; 20 mg/5 mL syrup; 90 mg capsules

10-20 mg

20-80 mg/d

Longer half-life, so tapering unnecessary; 90 mg formulation given once weekly

Sertraline

Zoloft

25, 50, 100 mg tablets; 20 mg/mL concentrate

25-50 mg

50-100 mg/d; maximum dose 200 mg/d

Used in geriatric patients; fewer drug interactions

Table 25-10. Serotonin-Norepinephrine Reuptake Inhibitors

Drug

Trade name

Form

Initial dose

Maximum dose

Clinical pearls

Venlafaxine

Effexor

25.0, 37.5, 50.0, 75.0, 100.0 mg capsules

37.5 mg bid

375 mg/d in divided doses

Take with food; monitor blood pressure

 

Effexor XR

37.5, 75.0, 150.0, 225.0 mg capsules

75 mg/d

225 mg/d

Less GI upset than immediate release formulation; monitor blood pressure

Desvenlafaxine

Pristiq

50, 100 mg extended release tablets

50 mg daily

50 mg/d; CrCl < 30 mL/min every other day

Less drug interactions due to conjugation; monitor blood pressure

Duloxetine

Cymbalta

20, 30, 60 mg capsules

30 mg daily

120 mg/d

Also used for diabetic peripheral neuropathy; monitor blood pressure

CrCl, creatinine clearance

Table 25-11. Benzodiazepines

Drug

Trade name

Time to peak plasma concentration (h)

Half-life (h)

Usual daily dose (mg/d)

Metabolic pathway

Alprazolam

Xanax, Niravam

1-2

12-15

0.5-4.0

Oxidation

Chlordiazepoxide

Librium

2-4

5-30

5-200

Oxidation

Clonazepam

Klonopin

1-2

18-50

1-3

Nitro reduction

Clorazepate

Tranxene

1-2

Not significant

15-60

Oxidation

Diazepam

Valium

0.5-2

20-80

2-40

Oxidation

Estazolam

ProSom

2

10-24

0.5-2.0

Oxidation

Flurazepam

Dalmane

0.5-2

Not significant

15-30

Oxidation

Halazepam

Paxipam

1-3

7-14

80-160

Oxidation

Lorazepam

Ativan

1-6

10-20

2-6

Conjugation

Oxazepam

Serax

2-4

5-20

30-120

Conjugation

Prazepam

Centrax

6

1.2

20-60

Oxidation

Quazepam

Doral

2

25-41

7.5-30

Oxidation

Temazepam

Restoril

2-3

10-40

15-30

Conjugation

Triazolam

Halcion

1

1.5-5.0

0.125-0.5

Oxidation

Table 26-1. Topical Antimicrobials

 

Generic name

Trade name

Form

 

Clindamycin

Cleocin-T

Liquid

 

Erythromycin

Theramycin Z

Liquid

 
 

Benzamycin 2%

Gel

 
 

Emgel 2%

Gel

 

Table 26-2. Retinoids

Generic name

Trade name

Form and strength

Tretinoin

Retin-A

0.025%, 0.05%, 0.1% cream; 0.1% gel; 0.025% lotion

 

Retin-A Micro

0.04%, 0.1% gel

 

Renova

0.02% cream

 

Avita

0.025% cream and gel

Adapalene

Differin

0.1% cream

Tazarotene

Tazorac

0.1%, 0.3% alcohol-free gel; 0.5%, 0.1% gel and cream

Alitretinoin

Panretin

0.1% gel

         

Table 26-3. Oral Antimicrobials

Generic name

Trade name

Dosage and form

Tetracycline

Achromycin, Sumycin

500 mg qd or bid capsules

Erythromycin

E.E.S., Erythrocin

250-500 mg qd or bid tablets

Doxycycline

Vibramycin

100 mg qd capsules or tablets

Minocycline

Minocin

50 mg bid capsules

Table 26-4. Prescription Topical Antifungals

 

Generic name

Trade name

 

Econazole

Spectazole cream

 

Naftifine

Naftin gel, cream

 

Ciclopirox

Loprox gel, cream, lotion; Penlac solution

 

Butenafine

Mentax cream, Lotrimin Ultra

 
       

Table 26-5. Typical Pharmaceutical Ingredients

Relative potency

Generic name

Trade name

Strength

Low

Hydrocortisone (OTC)

Cortaid, Cortizone

1% (OTC)

   

Allercort, Hytone, Synacort, Emo-Cort

2.5% (prescription only)

Medium

Desonide

Tridesilon Des Owen

0.05%

 

Fluocinolone acetonide

Synalar

0.01-0.025%

 

Flurandrenolide

Cordran

0.025-0.05%

 

Hydrocortisone butyrate

Locoid

0.1%

 

Hydrocortisone valerate

Westcort

0.2%

 

Triamcinolone acetonide

Aristocort

0.025%

High

Betamethasone valerate

Valisone, Dermabet

0.1%

 

Fluocinolone

Synalar, Synemol

0.025%

 

Triamcinolone acetonide

Aristocort

0.1%

Very high

Desoximetasone

Topicort

0.25%

 

Diflorasone diacetate

Maxiflor

0.05%

 

Fluocinonide

Lidex

0.01-0.05%

 

Halcinonide

Halog

0.1%

Ultra-high

Betamethasone dipropionate

Diprosone, Maxivate

0.05%

 

Betamethasone dipropionate (in optimized vehicle)

Diprolene AF

0.05%

 

Clobetasol propionate

Temovate

0.05%

 

Diflorasone diacetate

Psorcon

0.05%

 

Halobetasol propionate

Ultravate

0.05%

Table 27-1. Selected Examples of Nonprescription Cough Products

Type of product

Generic name

Action

Trade name

Expectorant

Guaifenesin

Immediate release

Robitussin Syrup (100 mg/5 mL)

   

Extended release

Mucinex (600 or 1,200 mg)

Humibid sprinkle (30 mg)

Cough suppressant

Dextromethorphan

Immediate release

Benylin Adult Cough Formula Liquid (15 mg/mL)

   

Extended release

Delsym Suspension (30 mg/5 mL)

Combination expectorant and cough suppressant

Guaifenesin and dextromethorphan

 

Robitussin DM (guaifenesin 100 mg and dextromethorphan 10 mg/5 mL)

Combination expectorant and decongestant

Guaifenesin and pseudoephedrine

 

Robitussin PE (guaifenesin 100 mg and pseudoephedrine 30 mg/5 mL)

             

Table 27-2. Selected Nonprescription Antihistamine Products

 

Generic name

Trade name

Adult dosage (maximum daily dose)

 

Chlorpheniramine

Chlor-Trimeton

4 mg q4-6h (24 mg)

 

Brompheniramine

Lodrane

4 mg q4-6h (24 mg)

 

Diphenhydramine

Benadryl

25-50 mg q6h (200 mg)

 

Clemastine

Tavist

1.34 mg bid (2.68 mg)

 

Triprolidine

Zymine

2.5 mg q6h (10 mg)

 

Loratadine

Claritin, Alavert

10 mg qd

 

Cetirizine

Zyrtec

10 mg qd

 

Table 27-3. Selected Nonprescription Oral Decongestant Products

Generic name

Products

Comments

Side effects

Adult dosage (maximum daily dose)

Phenylephrine

Combination products

Weakest oral decongestant

+

10 mg q4h (60 mg)

Pseudoephedrine

Sudafed

Less central nervous system stimulation

++

60 mg q4-6h (240 mg)

Note: + and ++ indicate the amount of side effects.

               

Table 27-4. Selected Nonprescription Cold, Allergy, and Sinus Combination Products

Product

Trade name

Primary ingredients

Decongestant and analgesic

Alka-Seltzer Plus Cold and Sinus

Phenylephrine 5 mg + acetaminophen 250 mg

 

Aleve-D Sinus & Cold

Pseudoephedrine 120 mg + naproxen 220 mg

 

Sudafed Sinus & Cold

Pseudoephedrine 30 mg + acetaminophen 325 mg

Antihistamine, decongestant, and analgesic

Vicks Dayquil Liquicaps

Phenylephrine 5 mg + acetaminophen 325 mg + dextromethorphan 10 mg

 

Advil Allergy Sinus Caplets

Chlorpheniramine 6 mg + pseudoephedrine 30 mg + ibuprofen 200 mg

Antihistamine and decongestant

Actifed Cold and Allergy

Chlorpheniramine 4 mg + phenylephrine 10 mg

 

Drixoral Cold and Allergy

Dexbrompheniramine 6 mg + pseudoephedrine 120 mg

 

Zyrtec D

Cetirizine 5 mg + pseudoephedrine 120 mg

 

Claritin-D 24 hour

Loratadine 10 mg + pseudoephedrine 240 mg

Table 27-5. Common Causes of Constipation

Daily habits

Diseases

Medications

Inadequate fluid intake

Parkinson's Disease

Antacids containing Al or Ca

Inadequate fiber intake

Multiple sclerosis

Anticholinergics

Lack of physical exercise

Cerebrovascular disease

Phenothiazines

 

Irritable bowel syndrome

Tricyclic antidepressants

 

Hemorrhoids

Opiates

 

Polyps and tumors

Antihistamines

 

Diabetes

ACE inhibitors

 

Hypothyroidism

CCB (especially Verapamil)

   

Sucralfate

   

Iron

         

Table 27-6. Additional Nonprescription Treatments of Constipation Not Listed in Text

 

Medication class

Generic name

Brand name

 

Bulk-forming laxatives

Psyllium seed

Metamucil

 
 

Methylcellulose

Citrucel

 
 

Calcium polycarbophil

FiberCon

 
 

Barley malt extract

Maltsupex

 

Emollient laxatives

Docusate sodium

Colace, Correctol

 
 

Docusate calcium

Surfak

 
 

Docusate potassium

Dialose

 

Saline laxatives

Magnesium hydroxide

Milk of Magnesia

 
 

Magnesium citrate

Citroma

 
 

Magnesium sulfate

Epsom salts

 
 

Sodium phosphate

Fleet Phospho-Soda

 

Combination products

Senna + psyllium

Perdiem

 
 

Senna + docusate

Senokot-S

 

Table 27-7. Common Causes of Diarrhea

Common Causes

Infection

Medications

Diet

Viral:

Antibiotics

Allergies

 

Norwalk

Laxatives

Spicy foods

 

Rotavirus

Magnesium-containing antacids

High carbohydrate load

Bacterial:

   
 

Food-borne illness

Contaminated water

Traveler's diarrhea

Cytotoxic agents

Lactose intolerance

Protozoal

   
             

Table 27-8. Common Causes of Nausea and Vomiting

Irritation of chemoreceptor trigger zone

Vestibular disorders

CNS disorders

GI disorders

Chemotherapy

Motion sickness

Psychogenic vomiting

Obstruction

Narcotics

Otitis interna

Migraines

Gastroparesis

Theophylline

Meniere's syndrome

Increased intracranial pressure

Gastroenteritis

Digoxin

 

Psychogenic vomiting

Infection

Antibiotics

 

Migraines

 

Drug withdrawal

 

Increased intracranial pressure

 

Alcohol

     

NSAIDs

     

Antibiotics

     

Ketoacidosis

     

Uremia

     

Pregnancy

     

Electrolyte imbalances

     

Table 27-9. Nonprescription Drugs of Choice for Prevention of Motion Sickness

   

Dosage

Generic name

Trade name

Adults (maximum daily dose)

Children age 6-12 (maximum daily dose)

Children age 2-6 (maximum daily dose)

Dimenhydrinate

Dramamine

50-100 mg q4-6h (400 mg)

25-50 mg q6-8h (150 mg)

12.5-25 mg q6-8h (75 mg)

Diphenhydramine

Benadryl

25-50 mg q4-6h (300 mg)

12.5-25 mg q4-6h (150 mg)

6.25 mg q4-6h (37.5 mg)

Cyclizine

Marezine

50 mg q4-6h (200 mg)

25 mg q6-8h (75 mg)

Not recommended

Meclizine

Bonine

25-50 mg qd (50 mg)

Not recommended

Not recommended

               

Table 27-10. Selected Analgesic and Antipyretic Products

   

Dosage

Generic name

(Trade name)

Adults (maximum daily dose)

Children (maximum daily dose)

Acetaminophen

Tylenol, Tempra

325-1,000 mg q4-6h (4,000 mg)

10-15 mg/kg q4-6h (5 doses)

Aspirin

Bayer

650-1,000 mg q4-6h (4,000 mg)

10-15 mg/kg q4-6h (80 mg/kg)

Ibuprofen

Motrin, Advil

200-400 mg q4-6h (1,200 mg OTC)

5-10 mg/kg q6-8h (40 mg/kg)

Naproxen sodium

Aleve

220 mg q8-12h (660 mg)

Not recommended < 12 years of age; ≥ 12 years of age: use adult dosage

Table 27-11. Pharmacologic Treatment of Dry Eyes

Product

Common preparations

Comments

Artificial tearsa

Cellulose derivatives (carboxymethylcellulose)

Bion Tears, Celluvisc, Clear Eyes CLR

Has enhanced duration compared to other products; tends to form dry crusts, which may be easily washed off with warm water

Polyvinyl alcohol (glycerin, propylene glycol, polyethylene glycols, polysorbate 80)

Moisture Eyes, Hypo Tears, Murine Tears, Tears Plus

Has shorter duration; has no crust formation

Povidone and dextran 70

AquaSite

Can cause transient stinging or burning

Ocular emollientsb

Lanolin, mineral oil, petrolatum, white ointment, white wax, or yellow wax

Moisture Eyes PM, Lacri-Lube SOP, Refresh PM

 

a. Artificial tears act as demulcents to mimic mucin. Use twice daily as suggested.

b. Ointments have longer contact and are more likely to cause blurred vision.

         

Table 27-12. Ophthalmic Vasoconstrictors

Product

Common preparations

Key points

Phenylephrine

Prefrin Liquifilm Relief

Can precipitate angle-closure glaucoma

Naphazoline

Clear Eyes, Clear Eyes ACR, Allerest, All Clear, All Clear AR

Is ocular decongestant of choice

Tetrahydrozoline

Visine, Vision Clear, Visine Advanced Relief, OptiClear

Is less likely to alter pupil size; may cause stinging on instillation

Oxymetazoline

Visine LR

Is relatively free of ocular or systemic side effects

Table 27-13. Causes of Error in Home Pregnancy Testing

 

False positives

False negatives

 

Miscarriage within previous 8 weeks

Test performed first day of a missed cycle

 

Childbirth within previous 8 weeks

Refrigerated urine not allowed to come to room temperature

 

Use of fertility medications (Pergonal, Profasi)

Wax cups or household containers with soap residues used for test

 
         

Table 27-14. The "5 A's" Clinicians Should Use to Assist Patients in Smoking Cessation

Ask about tobacco use.

Identify and document tobacco use status for every patient at every visit.

Advise to quit.

In a clear, strong, and personalized manner, urge every tobacco user to quit.

Assess willingness to make a quit attempt.

Is the tobacco user willing to make a quit attempt at this time?

Assist in quit attempt.

For the patient willing to make a quit attempt, use counseling and pharmacotherapy to help him or her quit.

Arrange follow-up.

Schedule follow-up contact, preferably within the first week after the quit date.

Table 27-15. Drugs versus Dietary Supplements

 

Drug

Dietary supplement

 

Active ingredient is identified.

Active ingredient may not be identified.

 

Safety and efficacy are proven by manufacturer.

No proof of efficacy is required; FDA must provide proof if unsafe.

 

Purity and contents are regulated.

No standards exist for quality or purity.

 

Claims to treat, cure, or prevent disease are made.

No claims to treat, cure, or prevent specific disease are made.

 
       

Table 27-16. Natural Products Associated with Serious Toxicity

Common name

Promoted benefit or ailment helped

Associated conditions

Blue cohosh

Uterotonic, diuretic

Vasoconstriction, GI spasms

Comfrey

Gout, arthritis, infections

Obstruction of blood flow to the liver possibly resulting in death

Chinese weight-loss preparations (Aristolochia fangchi mistaken for Stephania tetrandra)

Primarily weight loss

Kidney cancer (referred to as Chinese-herb nephropathy)

Ephedra (ma huang)

Weight loss, energy, decongestion

Hypertension, arrhythmias, seizures, stroke, myocardial infarction, death

Kava-kava

Stress reduction

Liver failure

Licorice root

Peptic ulcers, expectorant

Pseudoaldosteronism

Yohimbe

Aphrodisiac

Weakness, paralysis, anxiety, death (overdose)

Table 27-17. Selected Nonprescription Products for Insomnia

 

Drug or drug combination

Trade name

 

Diphenhydramine

Compoz, Sominex

 

Diphenhydramine + acetaminophen

Tylenol PM, Excedrin PM

 

Diphenhydramine + aspirin

Bayer PM

 

Diphenhydramine + ibuprofen

Advil PM

 
         


Figure 28-1. Classification of Asthma Severity (Ages ≥ 12 and Adults)


Figure 28-2. Stepwise Approach for Managing Infants and Young Children (0-4 Years of Age)


Figure 28-4. Stepwise Approach for Managing Asthma ≥ 12 Years of Age and Adults: Treatment


Figure 28-3. Stepwise Approach for Managing Asthma in Children 5-11 Years of Age: Treatment

Table 28-1. Long-Term Asthma Control Medications

Generic name

Trade name

Usual dosage range

Dosage form

Schedulea

Inhaled corticosteroids

Beclomethasone HFA 40 mcg/puff; 80 mcg/puff

QVAR

80-480 mcg/d

MDI

Twice daily

Budesonide 200 mcg/inhalation

Pulmicort

1-3 inhalations/d

DPI (Flexhaler)

Twice daily

Budesonide-formoterol combination (each inhalation 4.5 mcg formoterol + budesonide 80.0 mcg or 160.0 mcg)

Symbicort

2 puffs

MDI

Twice daily

Budesonide 0.25 and 0.50 mg

Respules

0.5-2.0 mg/d

Nebulized

Twice daily

Flunisolide 250 mcg/puff

Aerobid

1-8 puffs/d

MDI

Twice daily

Fluticasone 44, 110, 220 mcg/puff

Flovent

88-660 mcg/d

MDI

Twice daily

Fluticasone 50, 100, 250

Flovent Diskus

100-500 mcg/d

DPI

Twice daily

Fluticasone-salmeterol combination (each dose 50 mcg salmeterol + 100, 250, or 500 mcg fluticasone)

Advair Diskus (Advair 100, 250, 500)

1 inhalation

DPI (Diskus)

Twice daily

Fluticasone-salmeterol combination (each puff 21 mcg salmeterol + 45, 115, or 230 mcg fluticasone)

Advair HFA (Advair HFA 45, 115, 230)

2 inhalations/dose

MDI

Twice daily

Mometasone 220 mcg/inhalation

Asmanex Twisthaler

1-2 inhalations/d

DPI

At bedtime

Triamcinolone 75 mcg/puff

Azmacort

4-20 puffs/d

MDI/spacer

Twice daily

Leukotriene modifiers

Montelukast

Singulair

4 mg (12-23 months)

Oral granules

Every night

   

4 mg (age 2-5 years)

Chewable tab

Every night

   

5 mg (age 6-14 years)

Chewable tab

Every night

   

10 mg (adult) tablet

Tablet

Every night

Zafirlukast

Accolate

20-40 mg/d tablet

Tablet

Twice daily

Zileuton

Zyflo

600 mg/tablet

Tablet

Four times daily

 

Zyflo CR

600 mg controlled release tablet (2 tablets/dose)

Controlled release tablet

Twice daily

Mast cell stabilizers

Cromolynb

Intal

1-4 puffs MDI

MDI

Four times daily

 

Intal

20 mg

Nebulizer solution

Four times daily

Long-acting inhaled β2 agonists

Formoterolc

Foradil Aerolizer

1 inhalation

DPI

Twice daily

Salmeterolc

Serevent Diskus

1 inhalation

DPI

Twice daily

Methylxanthines

Theophylline (numerous products)

Uniphyl

10 mg/kg/d up to 300 mg maximum in adults to start; aim for 5-15 mcg/mL steady state

Tablet

Daily; 5:00 or 6:00 pm

Note: MDI, metered dose inhaler; DPI, dry powder inhaler (breath activated). See EPR-3 and FDA-approved product literature for pediatric doses for each drug product.

a. Usual schedule (some patients do well on once-daily dosing).

b. Since the release of EPR-3, cromolyn nebulizer solution and nedocromil MDI became unavailable in the United States in 2008. Cromolyn MDI may be available in the United States through the end of 2009.

c. Use only in combination with ICS.

d. Complex, high-risk drug to dose; see references cited for details; do not use unless competent in dosing and monitoring serum theophylline concentrations. See EPR-3 for pediatric doses (<1 year of age and >1 year of age).

Table 28-2. Quick-Relief Asthma Medications

Generic name

Trade name

Usual dosagea

Dosage form

Schedule

Short-acting inhaled β2 agonistsb

Albuterol HFA

Ventolin, Proventil, Proair

2 puffs

MDI

Every 4 hours as needed

   

2.5 mg

Nebulizer solution

Every 4 hours as needed

Pirbuterol

Maxair Autohaler

2 puffs

MDI

Every 4 hours as needed

Anticholinergics

Ipratropium

Atrovent

2 puffs

MDI

Every 6 hours

   

0.25 mg

Nebulizer solution

Every 6 hours

Ipratropium with albuterol

Combivent

2 puffs

MDI

Every 6 hours

   

3 mL

Nebulizer solution

Every 6 hours

Systemic corticosteroidsc

Methylprednisolone

Medrol

1 mg/kg/d

Tablets

Daily

Prednisone

 

1 mg/kg/d

Tablets or liquid

Daily

Prednisolone

 

1 mg/kg/d

Tablets

Daily

Note: See EPR-3 and FDA-approved product literature for pediatric doses for each drug product.

a. Usual dosage for routine home use. (Dose in emergency department is higher and more frequent.)

b. For prevention of exercise-induced asthma, inhale 2 puffs 5-15 minutes before exercise. Increasing use indicates poor asthma control; increase anti-inflammatory therapy and reassess environmental control. (Good asthma control is indicated by infrequent need for quick-relief therapy.)

c. Short courses are used for < 2 weeks.

               


Figure 28-5. Management of Asthma Exacerbations: Emergency Department and Hospital-Based Care


Figure 28-6. Steps for Using an Inhaler

Table 28-3. Directions for Use of Peak Flow Meter

1. Stand while using the meter.

2. Position the indicator at the bottom of the scale.

3. Hold the peak flow meter so your fingers do not block the opening.

4. Inhale as deeply as possible, place the mouthpiece well into your mouth, and make sure your lips form a tight seal around it.

5. Blow out as fast and as hard as possible!a BLAST! (Emphasize to the patient that the maneuver is highly effort dependent.)

6. Repeat steps 2-5 two more times, and record the highest of the three readings along with the date and time.

Note: If a short-acting inhaled β2 agonist is required in the early morning, remember to check the peak expiratory flow before using the drug and record the value; then repeat PEF testing 15 minutes later.

a. Do not accelerate air with your tongue (i.e., use a spitting motion). This incorrect maneuver will give false elevation in PEF.

Table 28-4. Factors Affecting Serum Theophylline Levels

Factor

Decreases Theophylline Concentrations

Increases Theophylline Concentrations

Recommended Action

Food

¯ or delays absorption of some sustained-release theophylline (SRT) products

­ rate of absorption (fatty foods) products

Select theophylline preparation that is not affected by food.

Diet

­ metabolism (high protein)

¯ metabolism (high carbohydrate)

Inform patients that major changes in diet are not recommended while taking theophylline.

Systemic, febrile viral illness (e.g., influenza)

 

¯ metabolism

Decrease theophylline dose according to serum concentration level. Decrease dose by 50 percent if serum concentration measurement is not available.

Hypoxia, cor pulmonale, and decompensated congestive heart failure, cirrhosis

 

¯ metabolism

Decrease dose according to serum concentration level.

Age

­ metabolism (1 to 9 years)

¯ metabolism (< 6 months, elderly)

Adjust dose according to serum concentration level.

Phenobarbital, phenytoin, carbamazepine

­ metabolism

 

Increase dose according to serum concentration level.

Cimetidine

 

¯ metabolism

Use alternative H2 blocker (e.g., famotidine or ranitidine).

Macrolides: TAO, erythromycin, clarithromycin

 

¯ metabolism

Use alternative antibiotic or adjust theophylline dose.

Quinolones: ciprofloxacin, enoxacin, pefloxacin

 

¯ metabolism

Use alternative antibiotic or adjust theophylline dose. Circumvent with ofloxacin if quinolone therapy is required.

Rifampin

­ metabolism

 

Increase dose according to serum concentration level.

Ticlopidine

 

¯ metabolism

Decrease dose according to serum concentration level.

Smoking

­ metabolism

 

Advise patient to stop smoking; increase dose according to serum concentration level.

*This list is not all-inclusive; for discussion of other factors, see package inserts.

Reproduced from NIH Expert Panel Report 2.

TAO, triacetyloleandomycin.

Table 29-1. Empiric Treatment of Meningitis

Age of patient

Most likely organism

Empiric treatment

Newborn to 1 month

Gram-negative enterics (Escherichia coli), group B streptococci, or Listeria monocytogenes

Ampicillin and aminoglycoside, cefotaxime, or Ceftriaxone

1 month to 4 years

Haemophilus influenzae, Neisseria meningitidis, or Streptococcus pneumoniae

Cefotaxime or ceftriaxone, plus vancomycin

5-29 years

N. meningitidis, S. pneumoniae, or H. influenzae

Cefotaxime or ceftriaxone, plus vancomycin

30-60 years

S. pneumoniae or N. meningitidis

Cefotaxime or ceftriaxone, plus vancomycin

> 60 years

S. pneumoniae, Gram-negative enterics (E. coli), or L. monocytogenes

Cefotaxime, ceftriaxone, or ampicillin and aminoglycoside-vancomycin

Table 29-2. Therapy for Endocarditis

Organism

Therapy

Duration (weeks)

Penicillin-susceptible streptococci

Penicillin G alone

4

 

Penicillin G with gentamicin

2

 

Ceftriaxone alone

4

 

Vancomycin (if allergic to penicillin)

4

Streptococci relatively resistant to penicillin

Penicillin G alone

4

 

Penicillin G with gentamicin

2

 

Vancomycin (if allergic to penicillin)

4

Staphylococcus without prosthetic material (methicillin sensitive)

Nafcillin or oxacillin (3-5 days of gentamicin may be added)

4-6

 

Cefazolin (with or without gentamicin)

4-6

 

Vancomycin (if allergic to penicillin)

4-6

Staphylococcus without prosthetic material (methicillin resistant)

Vancomycin (if allergic to penicillin)

4-6

         

Table 29-3. Treatment of Acute and Chronic Bronchitis

 

Illness

Treatment (7-10 days usual duration)

 

Acute (rare; for severe disease only)

Erythromycin, clarithromycin, azithromycin (drugs used for treatment of chronic disease may be used)

 

Chronic

Amoxicillin, amoxicillin-clavulanate, TMP-SMX, erythromycin, clarithromycin, azithromycin, doxycycline, cefuroxime, cefaclor, cefprozil

 

Table 29-4. Empiric Treatment of Pneumonia

Age or type

Usual organisms

Empiric treatments

Neonatal

Group B streptococci, Listeria monocytogenes, Escherichia coli

Ampicillin and gentamicin or cefotaxime and gentamicin

1-3 months

Chlamydia trachomatis, Bordetella spp.

Erythromycin, clarithromycin, or cefuroxime

3 months to 5 years

Streptococcus pneumoniae, C. trachomatis

Clarithromycin, cefuroxime, or cefotaxime

5-18 years

Mycoplasma pneumoniae, S. pneumoniae, Chlamydia pneumoniae

Clarithromycin, erythromycin, or cefuroxime

Adult, community-acquired

S. pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae, M. pneumoniae

Ambulatory: oral macrolide (azithromycin, clarithromycin, erythromycin) or fluoroquinolone (levofloxacin, gatifloxacin or moxifloxacin)

Hospitalized: cefotaxime or ceftriaxone with or without macrolide or fluoroquinolone alone (levofloxacin, gatifloxacin, moxifloxacin)

Adult, hospital-acquired

K. pneumoniae, Enterobacter aerogenes, Serratia spp., Acinetobacter spp., Pseudomonas aeruginosa, Staphylococcus aureus

Aminoglycoside (tobramycin, amikacin, gentamicin) plus one of the following: cefotaxime, ceftriaxone, cefepime, ticarcillin-clavulanic acid, piperacillin-tazobactam, meropenem, or imipenem; vancomycin to be added if methicillin-resistant S. aureus suspected

Adult, aspiration

Mouth anaerobes

Uncomplicated: penicillin G, clindamycin

Hospital-acquired: ticarcillin-clavulanic acid, piperacillin-tazobactam

         

Table 29-5. Treatment of Tuberculosis

 

Disease stage

Treatment

Duration

 

Latent (probably isoniazid sensitive)

Isoniazid

9 months (6 months possible except for children and HIV-positive persons)

 

Latent (probably isoniazid resistant)

Rifampin + pyrazinamide

2 months

 

Active disease

Isoniazid + rifampin + pyrazinamide

2-4 months

 

Table 29-6. Treatment of Infectious Diarrhea

Symptoms

Organism

Treatment

Violent presentation 1-6 hours after eating high-protein foods (eggs)

Staphylococcus aureus

Supportive

Indolent presentation with mild fever after eating meat, vegetables, or eggs

Bacillus cereus

Supportive

Mild to severe presentation 8-16 hours after eating canned products

Clostridium perfringens

Supportive

Mild to severe presentation with mild fever; may be associated with meat or egg contamination or other foods contaminated with contaminated water

Escherichia coli

Supportive, if outpatient; if hospitalized, fluoroquinolones or TMP-SMX

Mild to severe presentation with mild fever, chills, and cramping; associated with other foods contaminated with contaminated water; carrier state possible

Salmonella spp.

Treatment only if febrile (fluoroquinolones or TMP-SMX)

Bloody mucoid diarrhea with fever and cramps

Shigella spp.

TMP-SMX

Mild indolent presentation, often thought to be "flu"; transmitted by contaminated water

Campylobacter

Macrolides or fluoroquinolones

Severe presentation with fever and abdominal pain associated with seafood ingestion

Yersinia enterocolitica

Fluoroquinolones

Mild presentation with fever and abdominal pain associated with seafood ingestion

Vibrio parahaemolyticus

Tetracycline or fluoroquinolones

Severe, explosive presentation associated with contaminated water

Vibrio cholerae

Tetracycline or fluoroquinolones

Mild to severe presentation associated with travel, 6-10 days after exposure, with cramping and low-grade fever

Escherichia coli

Mostly supportive; severe prophylactic regimens

           

Table 29-7. Treatment of Skin and Soft Tissue Infections

Infection

Organisms

Treatments

Cellulitis

Group A streptococcus; Staphylococcus aureus

Outpatient: dicloxacillin, cefadroxil, cephalexin, erythromycin

Inpatient: cefazolin, erythromycin

Severe cases: vancomycin

Diabetic foot infections

Proteus spp., Escherichia coli, S. aureus, Bacteroides fragilis, anaerobic streptococci

Clindamycin or cephalexin

Severe cases: ticarcillin-clavulanic acid or other β-lactamase inhibitor; vancomycin may be needed if methicillin-resistant S. aureus suspected

Decubitus ulcers

Gram-negative bacilli, Pseudomonas aeruginosa, anaerobes

Same as for diabetic foot infections

Table 29-8. Treatment of Urinary Tract Infections

Diagnosis

Organisms

Treatments

Acute uncomplicated cystitis

Escherichia coli, Staphylococcus saprophyticus

TMP-SMX × 3 days or quinolone × 3 days

Acute pyelonephritis

E. coli, Proteus mirabilis, Klebsiella pneumoniae, Enterococcus spp.

Quinolone × 14 days or TMP-SMX × 14 days; if severe, parenteral therapy with quinolone and extended-spectrum penicillin plus aminoglycoside should be used

Prostatitis

E. coli, Proteus spp., K. pneumoniae

Quinolone × 4-6 weeks or TMP-SMX × 4-6 weeks

         

Table 29-9. Treatment of Gonorrhea and Syphilis

Type

Gonorrhea

Syphilis

Uncomplicated adult presentation

Ceftriaxone 125 mg IM × 1 dose or spectinomycin 2 g IM q12h × 2 doses

Benzathine penicillin G 2.4 million units IM × 1 dose

Infant born of untreated mother

Cefotaxime 25 mg/kg q12h × 7 days

Penicillin G 50,000-75,000 units/kg q12h × 10-21 days

Disseminated infections

Ceftriaxone 1 g qd × 10 days

Secondary or latent disease: benzathine penicillin G 2.4 million units IM q week × 3 doses

Tertiary disease: penicillin G 2 million to 4 million units q4h for 10-14 days

Table 29-10. Treatment of Tick-Borne Systemic Febrile Syndromes

Disease

Causative agent

Primary treatment

Alternative treatment

Lyme disease

Borrelia burgdorferi

Doxycycline

Cefuroxime

Rocky Mountain spotted fever

Rickettsia rickettsii

Doxycycline

Chloramphenicol

Ehrlichiosis

Ehrlichia phagocytophila

Doxycycline

Tetracycline

Tularemia

Francisella tularensis

Gentamicin or tobramycin

Chloramphenicol; possibly ciprofloxacin

           

Table 29-11. Treatment of Systemic Fungal Infections

Disease

Organism

Treatments

Invasive pulmonary disease

Aspergillosis spp.

Amphotericin B, itraconazole, caspofungin, voriconazole

Cutaneous, pulmonary, or extrapulmonary disease

Blastomyces dermatitidis

Itraconazole, amphotericin B, fluconazole

Bloodstream infection

Candida albicans

Fluconazole, amphotericin B

Primary pulmonary disease

Coccidioides immitis

Itraconazole, fluconazole

Meningitis

Cryptococcus neoformans

Amphotericin B + flucytosine, fluconazole

Pulmonary, disseminated, or localized

Histoplasma capsulatum

Itraconazole (moderate disease), amphotericin B (severe disease)

Table 29-12. Treatment of Hepatitis

 

Organism

Presentation

Therapy

 

Hepatitis B

Chronic

Lamivudine + interferon alfa-2b

 

Hepatitis C

Chronic

Interferon alfa-2b + ribavirin

 

Hepatitis C

Acute

Interferon alfa-2b

 
           

Table 29-13. Treatment of Influenza

 

Organism

Treatment type

Therapy

 

Influenza A

Prophylaxis

Oseltamivir, rimantadine, amantadine

 

Influenza A

Treatment

Zanamivir, oseltamivir, rimantadine, amantadine

 

Influenza B

Prophylaxis

Oseltamivir

 

Influenza B

Prophylaxis

Zanamivir, oseltamivir

 

Table 29-14. Treatment of Herpes Virus Infections

Organism

Disease

Treatment

Herpes simplex

Initial episode

Acyclovir

 

Recurrence

Famciclovir

 

Chronic suppression

Valacyclovir

 

Immunocompromised

Acyclovir

 

Resistant to acyclovir

Foscarnet

Cytomegalovirus

Retinitis, colitis, esophagitis

Ganciclovir, valganciclovir, foscarnet, cidofovir, fomivirsen

Varicella zoster

Chickenpox, shingles

Acyclovir

Varicella zoster

Immunocompromised, resistant to acyclovir

Foscarnet

           

Table 30-1. Aminoglycosides

Generic name

Trade name

Dosage forms

Normal dose

Elimination

Amikacin

Amikin

IV, IM

15-20 mg/kg/d

Renal

Gentamicin

Garamycin

IV, IM

3 mg/kg/d conventional dose, 7 mg/kg/d extended interval

Renal

Kanamycin

 

IV, po

15 mg/kg/d

Renal

Neomycin

 

po

50-100 mg/kg/d

Renal

Streptomycin

 

IM

15 mg/kg/d

Renal

Tobramycin

 

IV, IM

3 mg/kg/d conventional dose, 7 mg/kg/d extended interval

Renal

Note: Use ideal or adjusted body weight for all aminoglycoside dosing.

Table 30-2. Spectrum of Activity of the Penicillins

Category

Spectrum

Natural penicillins

Natural penicillins are effective against all viridans streptococci and Streptococcus pyogenes and against 60% of S. pneumoniae, mouth anaerobes, and Clostridium perfringens (gas gangrene).

 

Because natural penicillins are readily hydrolyzed by penicillinases (β-lactamases), they are ineffective against Staphylococcus aureus and other organisms that resist penicillin.

 

Penicillin G is 5-10 times more active than penicillin V against Gram-negative organisms and some anaerobic organisms.

Penicillinase-resistant penicillins

These agents are used to treat methicillin-sensitive staphylococci, streptococci (not enterococci species).

Aminopenicillins

Aminopenicillins have greater penetration of the outer membrane of Gram-negative rods and higher affinity for penicillin-binding proteins.

 

They cover most enterococci, Listeria, and Proteus mirabilis.

 

They cover 60% of Streptococcus pneumoniae, Haemophilus influenzae, Escherichia coli, and some Salmonella and Shigella.

Carboxypenicillins and ureidopenicillins

The spectrum is like that of ampicillin, but these drugs provide less Gram-positive coverage. They cover Proteus (including P. vulgaris), Klebsiella (not ticarcillin), Enterobacter, and Pseudomonas (piperacillin > ticarcillin). Add an aminoglycoside for synergy for serious Gram-negative infections.

 

Ureidopenicillins possess better in vitro activity against Pseudomonas and other Gram-negative organisms. Ureidopenicillins have in vitro activity against streptococci, enterococci, most Enterobacteriaceae, Pseudomonas, and many anaerobes, including Bacteroides fragilis, Fusobacterium, Clostridium, and peptostreptococci; β-lactamase-producing staphylococci and Haemophilus influenzae are resistant to the ureidopenicillins.

β-lactamase inhibitors (clavulanic acid, sulbactam, and tazobactam)

β-lactamase inhibitors are active against some chromosomally produced β-lactamases of Staphylococcus aureus, Haemophilus influenzae, Moraxela catarrhalis, Bacteroides, Escherichia coli, and other Enterobacteriaceae.

 

They are not active against the chromosomally produced β-lactamases of Enterobacter, Citrobacter, Serratia, and Pseudomonas.

Amoxicillin-clavulanic acid

This combination is active against Haemophilus influenzae, Moraxela catarrhalis, Klebsiella pneumoniae, methicillin-sensitive Staphylococcus aureus, and anaerobes.

Ticarcillin-clavulanic acid

This combination has more activity against Haemophilus influenzae, Moraxela catarrhalis, Klebsiela pneumoniae, methicillin-sensitive Staphylococcus aureus, and anaerobes.

Piperacillin-tazobactam

This combination provides more Gram-positive, Gram-negative, and anaerobic coverage than ticarcillin-clavulanic acid; monotherapy treatment fails against Pseudomonas.

           

Table 30-3. Dosing of Penicillins

Type and generic name

Trade name

Elimination route

Administration route

Common doses

Natural penicillins

Penicillin G

Pfizerpen

Renal

IV, IM, po

2 million to 4 million units IV q4h

Penicillin G procaine

Wycillin

Renal

IM

300,000-600,000 units/d

Penicillin G benzathine

Bicillin LA

Renal

IM

Strep throat: 1.2 million units; syphilis: 2.4 million units

Penicillin V (phenoxymethyl penicillin)

Pen-Vee-K, Veetids

Renal

po

250-500 mg po bid-qid (250 mg bid for prophylaxis)

Penicillinase-resistant penicillins

Oxacillin

Prostaphlin, Bactocill

Hepatic

po, IV, IM

1-2 g IV q4-6h

Nafcillin

Nafcil, Unipen

Hepatic

IV, IM

1-2 g IV q4-6h

Cloxacillin

Cloxapen

Renal

po

200-500 mg q6h

Dicloxacillin

Dynapen, Dycill

Renal

po

250-500 mg po q6h

Aminopenicillins

Ampicillin

Omnipen, Principen

Renal

po, IM, IV

1-2 g IV q6h

Amoxicillin

Amoxil, Trimox, Moxatag

Renal

po

250-500 mg po q8h 775 mg (ER) po q24h

Ureidopenicillins

Piperacillin

Pipracil

Renal

IV, IM

3-4 g IV q4-6h

Penicillin plus β-lactamase inhibitors

Amoxicillin-clavulanic acid

Augmentin

Renal

po

250-500 mg po tid, 500-875 mg po bid

Ampicillin-sulbactam

Unasyn

Renal

IV, IM

1.5 g or 3 g IV q6-8h

Piperacillin-tazobactam

Zosyn

Renal

IV

2.25 to 4.5 g IV q6h

Ticarcillin-clavulanic acid

Timentin

Renal

IV

3.1 g IV q4-6h

Table 30-4. Cephalosporins

Generic name

Trade name

Dosage forms

Dose

Elimination

Notes

First-generation

More Gram-positive than Gram-negative activity

Cefadroxil

Duricef, Ultracef

po

1-2 g/d

Renal

 

Cefazolin

Ancef, Kefzol

IV

250-1,000 mg q8h

Renal

 

Cephalexin

Keflex

po

250-500 mg q6h

Renal

 

Second-generation

Enhanced Gram-negative activity versus first-generation drugs

Cefaclor

Ceclor

po

250-500 mg q8h

Renal

 

Cefotetan

Cefotan

IV, IM

1-2 g q12h

Renal

Anaerobic activity, N-methylthiotetrazole side-chain

Cefoxitin

Mefoxin

IV

1-2 g q6-8h

Renal

Anaerobic activity

Cefprozil

Cefzil

po

250-500 mg q12-24h

Renal

Anaerobic activity

Cefuroxime

Ceftin, Zinacef

IV, IM

750-1,500 mg q8h

Renal

 

Third-generation

More Gram-negative than Gram-positive activity; cerebrospinal fluid penetration

Cefdinir

Omnicef

po

300 mg q12h

Renal

 

Cefixime

Suprax

po

400 mg/d

Renal

 

Cefotaxime

Claforan

IV

1-2 g q6-8h

Renal

 

Cefpodoxime

Vantin

po

100-400 mg q12h

Renal

Anaerobic activity

Ceftazidime

Fortaz, Tazicef

IV, IM

1-2 g q8-12h

Renal

Antipseudomonal activity

Ceftibuten

Cedax

po

400 mg/d

Renal

 

Ceftriaxone

Rocephin

IV, IM

1-2 g/d

Renal or biliary

 

Fourth-generation

Gram-positive and Gram-negative activity

Cefepime

Maxipime

IV, IM

1-2 g q12h

Renal

Antipseudomonal activity

               

Table 30-5. Gram-Positive Antibiotics

Generic name

Trade name

Dosage forms

Dose

Elimination

Notes

Linezolid

Zyvox

IV, po

600 mg q12h

Renal

 

Quinupristin-dalfopristin

Synercid

IV

7.5 mg/kg q8h

Hepatic

 

Vancomycin

Vancocin

IV, po

15-20 mg/kg q12h IV; 125-250 mg po q6h

Renal

Adjust dose per serum concentrations.

Daptomycin

Cubicin

IV

4-6 mg/kg q24h IV

Renal

Monitor creatine phosphokinase weekly.

Table 30-6. Fluoroquinolones and Nonfluorinated Quinolones

Generic name

Trade name

Dosage forms

Normal dose

Elimination

Notes

Fluoroquinolones

Ciprofloxacin

Cipro

IV

po

400 mg q12h

500 mg q12h

Renal

Ciprofloxacin has less Gram-positive activity and enhanced antipseudomonal activity versus other fluoroquinolones.

Levofloxacin

Levaquin

IV, po

500 mg q24h

Renal

 

Moxifloxacin

Avelox

po

400 mg bid

Hepatic

 

Norfloxacin

Noroxin

po

400 mg qd

Hepatic

 

Ofloxacin

Floxin

po, IV

100-400 mg/d

Renal

 

Gemifloxacin

Factive

po

320 mg qd

Renal or biliary

Decrease dose if creatinine clearance < 40 mL/min.

Nonfluorinated quinolones

Nalidixic acid

NegGram

po

1 g q6h

Renal

Nalidixic acid has no Gram-positive activity and is effective only in the genitourinary and GI tracts.

Table 30-7. Macrolides and Ketolide

Generic name

Trade name

Dosage forms

Normal dose

Elimination

Notes

Macrolides

         

Azithromycin

Zithromax

po, IV

250 mg/d

Hepatic

po dose = IV dose

Clarithromycin

Biaxin, Biaxin XL

po

250 mg bid

Renal

XL = qd dosing

Erythromycin

Various

po

250-500 mg q6h

Hepatic

Erythromycin base, ethyl succinate, and stearate

   

IV

500-1,000 mg q6h

Hepatic

Erythromycin lactobionate

Ketolides

         

Telithromycin

Ketek

po

800 mg/d

Hepatic

Treatment duration: 5 days for bronchitis, 7-10 days for community-acquired pneumonia; hepatotoxicity

Table 30-8. Tetracyclines and Glycylcyclines

Generic name

Trade name

Dosage forms

Common doses

Primary mode of elimination

Tetracyclines

       

Demeclocycline

Declomycin

po

300-1,000 mg/d

Renal

Doxycycline

Vibramycin and others

po

100-200 mg q12h

Renal

Minocycline

Minocin

po, IV

100-200 mg q12h

Hepatic

Tetracycline

Achromycin V, Sumycin, Tetracyn, and others

po, IV, IM

1-2 g/d

Renal

Glycylcyclines

       

Tigecycline

Tygacil

IV

100 mg once, then 50mg q12h IV

Hepatic

               

Table 30-9. Sulfonamides

Generic name

Trade name

Dosage forms

Dose

Elimination

Notes

Sulfadiazine

 

IV, po

2-4 g/d

Renal

 

Sulfamethoxazole

Septra

IV, po

1-3 g/d

Hepatic

Combined with trimethoprim (Septra)

Sulfisoxazole

Gantrisin

IV, po

2-8 g/d

Renal

 

Table 30-10. Miscellaneous Antibiotics

Generic name

Trade name

Dosage forms

Dose

Elimination

Notes

Clindamycin

Cleocin

IV, po

300 mg q6h po; 600-900 mg q8h IV

Hepatic

Only po for Clostridium difficile

Carbapenems

         

Imipenem-cilastatin

Primaxin

IV, IM

250 mg q6h; 500 mg or 1 g q6h or q8h, depending on whether the organism is fully or moderately susceptible

Renal

 

Doripenem

Doribax

IV

500mg q8h

Renal

 

Meropenem

Merrem

IV

500-2,000 mg q8h

Renal

 

Ertapenem

Invanz

IV, IM

1,000 mg q24h

Renal

 

Monobactams

         

Aztreonam

Azactam

IV, IM

1-2 g q6h to q12h, depending on the severity of infection

Renal

Not for Pseudomonas

Table 30-11. Antifungal Agents

Generic name

Trade name

Dosage forms

Dose

Elimination

Notes

Amphotericin B

Fungizone

IV

0.5-1 mg/kg/d

Unknown

Dose should not exceed 1.5 mg/kg/d.

Amphotericin B (Liposomal, lipid, and cholesterol complex)

Ambisome, Abelcet, Amphotec

IV

3-7 mg/kg/d

Unknown

Drug is 20-30% less nephrotoxic than conventional amphotericin B.

Caspofungin

Cancidas

IV

70 mg once and then 50 mg/d

Hepatic

Dose adjustment is needed for patients with hepatic dysfunction.

Micafungin

Mycamine

IV

100 mg/d

Hepatic

 

Anidulafungin

Eraxis

IV

200 mg once and then 100 mg/d

Chemical degradation

 

Fluconazole

Diflucan

IV, po

100-800 mg/d

Renal

 

Flucytosine

Ancobon

po

50-150 mg/kg/d

Renal

 

Griseofulvin

Fulvicin P/G

po

500 mg

Hepatic

 

Itraconazole

Sporanox

po

200-600 mg/d

Hepatic

Capsules require acid environment for dissolution and absorption.

Ketoconazole

Nizoral

po, topical

200-400 mg bid

Hepatic

Drug requires acidic environment for dissolution and absorption.

Nystatin

Mycostatin

Topical

 

Fecal

 

Terbinafine

Lamisal

po

250 mg/d

Hepatic

Pulse therapy is also effective.

Voriconazole

Vfend

IV, po

200 mg q12h po; 4-6 mg/kg q12h IV

Renal

 

Posaconazole

Noxafil

po

200 mg qid initially and then 400mg bid

Hepatic

Dose limits absorption.

Table 30-12. Antitubercular Agents

Generic name

Trade name

Dosage forms

Normal dose

Elimination

Notes

Aminosalicylic acid

Paser

po

150 mg/kg/d

Renal

Maximum dose: 12 g/d

Capreomycin

Capastat

IM

15 mg/kg/d

Renal

Maximum dose: 1 g/d

Cycloserine

Seromycin

po

15-20 mg/kg/d

Renal

Maximum dose: 1 g/d

Ethambutol

Myambutol

po

15-25 mg/kg/d

Hepatic

 

Ethionamide

Trecator-SC

po

500-1,000 mg/d

Hepatic

 

Isoniazid

Various

po

5-10 mg/kg/d

Hepatic

Maximum dose: 300 mg/d

Pyrazinamide

Various

po

15-30 mg/kg/d

Hepatic

Maximum dose: 2 g/d

Rifampin

Various

po, IV

10-20 mg/kg/d

Hepatic

Maximum dose: 600 mg/d

Table 31-1. Indications for the Initiation of Antiretroviral Therapy in the Chronically HIV-1 Infected Patient

Clinical category

Recommendation

History of AIDS-defining illness

Antiretroviral therapy should be initiated.

CD4 count < 200 cells/mm3

 

CD4 count 200-350 cells/mm3

 

Pregnant women

 

Persons with HIV-associated nephropathy

 

Persons co-infected with hepatitis B virus (HBV), when HBV treatment is indicated

 

Patients with CD4 count > 350 cells/mm3 who do not meet any of the specific conditions listed above

The optimal time to initiate therapy in asymptomatic patients with CD4 cell counts > 350 cells/mm3 is not well defined. Patient scenarios and comorbidities should be taken into consideration.

Table 31-2. Antiretroviral Regimens for Treatment of HIV Infection in Antiretroviral-Naive Patients

Type of regimen

NNRTI-PI treatment

NRTI combinations

Preferred

    • Efavirenza

    • Atazanavirb-ritonavir once daily

    • Darunavir-ritonavir once daily

    • Fosamprenavir-ritonavir twice daily

    • Lopinavir-ritonavir (coformulated) once or twice daily

    • Tenofovir + emtricitabine (coformulated)

Alternative

    • Nevirapinec

    • Atazanavirb (unboosted) once daily

    • Fosamprenavir (unboosted) twice daily

    • Fosamprenavir-ritonavir once daily

    • Saquinavir-ritonavir twice daily

    • Abacavird-lamivudine (coformulated)

    • Didanosine + lamivudine or emtricitabine

    • Zidovudine-lamivudine (coformulated)

Note: Combine one PI or one NNRTI with two NRTIs to complete a highly active regimen from the table.

a. Efavirenz is not recommended for use in first-trimester pregnancy or in women with a high pregnancy potential.

b. Atazanavir must be boosted with ritonavir if used with tenofovir.

c. Use caution in women with CD4 cell counts > 250 cells/mm3 and men with CD4 cell counts > 400 cells/mm3 because of increased risk of nevirapine-associated toxicity.

d. Only use abacavir in patients who have tested negative for HLA-B*5701.

       

Table 31-3. Nucleoside Reverse Transcriptase Inhibitors

 

Zidovudine (AZT, ZDV)

Lamivudine (3TC)

Abacavir (ABC)

Didanosine (ddI)

Stavudine (d4T)

Tenofovir (TDF)

Emtricitabine (FTC)

Trade name

Retrovir

Epivir

Ziagen

Videx EC, Videx

Zerit

Viread

Emtriva

Form

100 mg caps; 300 mg tabs; also available in combination productsa; available as generic

150, 300 mg tabs; 10 mg/mL oral solution; also available in combination productsa

300 mg tabs; 20 mg/mL oral solution; also available in combination productsa

Videx EC caps: 125, 200, 250, 400 mg; Videx buffered tabs: 25, 50, 100, 150, 200 mg; Videx buffered powders: 100, 167, 250 mg; available as generic: didanosine DR

15, 20, 30, 40 mg caps

300 mg tabs; also available in combination productsb

200 mg tabs; also available in combination productsb

Dosing recommendations

300 mg twice daily; 200 mg every 8 hours

150 mg twice daily; 300 mg daily (pediatric dosage based on weight)

300 mg twice daily; 600 mg daily

> 60 kg: 400 mg daily; with tenofovir DF ÂŻddI to 250 mg; < 60 kg: 250 mg daily; with tenofovir DF: appropriate ddI dose not known

> 60 kg: 40 mg twice daily; < 60 kg: 30 mg twice daily

300 mg once daily

200 mg once daily

Food effect

Take without regard to meals

Take without regard to meals

Take without regard to meals

Take 0.5 hour before or 2.0 hours after meals

Take without regard to meals

Take without regard to meals

Take without regard to meals

Adverse events

Bone marrow suppression (macrocytic anemia or neutropenia); gastrointestinal intolerance, headache, insomnia, asthenia

Minimal toxicity

Hypersensitivity reaction testing for HLA-B*5701 should be done before start to evaluate patients risk for hypersensitivity; only negative patients should start abacavir. Hypersensitivity symptoms include rash, fever, nausea and vomiting, malaise or fatigue, loss of appetite; respiratory symptoms include sore throat, cough, shortness of breath

Pancreatitis, peripheral neuropathy, nausea, diarrhea

Pancreatitis; peripheral neuropathy; lipodystrophy, hyperlipidemia; rapidly progressive ascending neusomuscular weakness (rare)

Renal insufficiency, asthenia, headache, diarrhea, nausea, or vomiting

Minimal toxicity; hyperpigmentation of palms of hands and soles of feet (rare)

Drug interactions

Ribavirin, stavudine, methadone; with high dose: ganciclovir, TMP-SMX, other medications that can cause bone marrow suppression

No clinically significant drug interactions

Alcohol increases abacavir levels by 41%.

Methadone, ribavirin, tenofovir, ganciclovir, alcohol; medications that need acidic environment for absorption—buffered forms; use caution with other medications that can cause peripheral neuropathy.

Use with caution with other medications that can cause peripheral neuropathy

Didanosine, atazanavir, cidofovir, ganciclovir, valganciclovir

No clinically significant drug interactions

Monitoringc

Complete blood count, liver function tests

None necessary

Signs and symptoms of hypersensitivity reaction

Complete blood count, liver function tests, amylase, uric acid; signs and symptoms of above side effects

Signs and symptoms of above side effects

Renal function

None necessary

a. Combivir: zidovudine 300 mg + lamivudine 150 mg; 1 tablet twice daily. Trizivir: zidovudine 300 mg + lamivudine 150 mg + abacavir 300 mg; 1 tablet twice daily. Epzicom: abacavir 600 mg + lamivudine 300 mg; 1 tablet daily.

b. Truvada: tenofovir 300 mg + emtricitabine 200 mg; 1 tablet daily. Atripla: tenofovir 300 mg + emtricitabine 200 mg + efavirenz 600 mg; 1 tablet at or before bedtime.

c. Monitor all for signs and symptoms of NRTI class toxicities, lactic acidosis, and hepatic steatosis; incidence is higher with stavudine than with other NRTIs.

Table 31-4. Non-nucleoside Reverse Transcriptase Inhibitors

 

Efavirenz (EFV)

Nevirapine (NVP)

Etravirinea (ETR)

Delavirdine (DLV)

Trade name

Sustiva

Viramune

Intelence

Rescriptor

Form

50, 100, 200 mg caps; 600 mg tabs; also available in combination productb

200 mg tab; 10 mg/mL oral suspension

100 mg tabs

100, 200 mg tabs

Dosing recommendations

600 mg at or before bedtime

200 mg daily × 14 days, then 200 mg twice (note CD4 cell count)c

200 mg twice daily as tablets or dissolved in water to form a slurry to drink

400 mg every 8 hours as tablets or dissolved in water to form a slurry to drink

Food effect

Take on an empty stomach

Take without regard to meals

Take following a meal

Take without regard to meals

Adverse events

Central nervous system (CNS) side effects,drash,e 足 liver function tests (LFTs), false-positive cannabinoid test, teratogenic in monkeys

Rash,f symptomatic hepatitis, including fatal hepatic necrosis

Rash,e nausea

Rash,e 足 LFTs, headaches

Drug interactions

CYP450-3A4, CYP450-2C19 inhibitor; CYP450-3A4 inducer (see

Tables 31-5 and

31-6)

CYP450-3A4 inducer (see Tables 31-5 and 31-6)

CYP450-3A4, CYP450-2C9, CYP450-2C19 substrate; CYP450-3A4 inducer; CYP450-2C9, CYP450-2C19 inhibitor (see Tables 31-5 and 31-6)

CYP450-3A4, CYP450-2D6 inhibitor (see Tables 31-5 and 31-6); separate dosing with buffered didanosine or antacids by 1 hour

Monitoringf

CNS side effects, LFTs, rash

LFTs 2, 4, and 6 weeks, and then monthly for the first 18 weeks

LFTs, rash, nausea

LFTs, rash

a. Etravirine effective in patients with resistance (K103N) to other NNRTIs.

b. Atripla: tenofovir 300 mg + emtricitabine 200 mg + efavarenz 600 mg; one tablet at or before bedtime.

c. Because of the increased risk of symptomatic hepatic events, nevirapine should not be started in women with baseline CD4 cell counts of greater than 250 cells/mm3 or men with baseline CD4 cell counts greater than 400 cells/mm3; it is not recommended in patients with moderate-to-severe hepatic impairment (Child-Pugh B or C).

d. CNS side effects include dizziness, somnolence, insomnia, abnormal dreams, confusion, abnormal thinking, impaired concentration, amnesia, agitation, depersonalization, hallucinations, and euphoria. Use caution in patients with a psychiatric history or previous addictions.

e. Rare cases of Stevens-Johnson syndrome have been reported with the use of NNRTIs; the highest incidence is seen with nevirapine use.

f. Monitor all for signs and symptoms of NNRTI class toxicities, rash, and hepatic toxicity.

                 

Table 31-5. Drugs That Should Not Be Used with NNRTIs

Drug category

Efavirenz

Nevirapine

Etravirine

Delavirdine

Calcium channel blockers

None

None

None

None

Cardiac

None

None

None

None

Lipid-lowering agents

None

None

None

Simvastatin, lovastatin

Antimycobacterials

Rifapentine

Rifapentine

Rifampin, rifapentine

Rifampin, rifapentine, rifabutin

Antihistamines

Astemizole, terfenadine

None

None

Astemizole, terfenadine

Gastrointestinal drugs

Cisapride

None

None

Cisapride, histamine-2 blockers, proton pump inhibitors

Psychotropics

Midazolam, triazolam

None

None

Alprazolam, midazolam, triazolam

Ergot alkaloids (vasoconstrictor)

Ergotamine derivatives

None

None

Ergotamine derivatives

Herbs

St. John's wort

St. John's wort

St. John's wort

St. John's wort

Other

Voriconazole at standard doses

Ketoconazole

Unboosted protease inhibitors, ritonavir-boosted atazanavir, fosamprenavir or tipranavir, other NNRTIs, carbamazepine, phenobarbital, phenytoin

Fosamprenavir, carbamazepine, phenobarbital, phenytoin

Table 31-6. Drug Interactions with NNRTIs Requiring Dose Modifications or Cautious Use

 

Drug class

Drug

 

Antiarrhythmics (etravirine only)

Quinidine (delavirdine only)

 

Antifungals

Itraconazole, ketoconazole, posaconazole, voriconazole

 

Anticoagulants

Warfarin

 

Anticonvulsants

Carbamazepine, phenobarbital, phenytoin

 

Antimicrobials

Clarithromycin, rifabutin, rifampin

 

Benzodiazepines

Alprazolam, diazepam, midazolam, triazolam

 

Erectile dysfunction agents

Various

 

Hormonal contraceptives

Various

 

HMG-CoA reductase inhibitors

Atorvastatin, lovastatin, simvastatin, pravastatin, rosuvastatin

 

Narcotic analgesics

Methadone

 
           

Table 31-7. Protease Inhibitors

 

Lopinavir + ritonavir (LPV/r)

Nelfinavir (NFV)

Atazanavir (ATV)

Fosamprenavir (FPV)

Saquinavir (SQV); SQV-hard gel capsule (HGC)

Darunavir (DRV)

Tipranavir (TPV)

Ritonavir (RTV)

Indinavir (IDV)

Trade name

Kaletra

Viracept

Reyataz

Lexiva

Invirase

Prezista

Aptivus

Norvir

Crixivan

Form

200 mg lopinavir + 100 mg ritonavir tabs; 400 mg lopinavir + 100 mg ritonavir per 5 mL oral solution

250, 625 mg tabs; 50 mg/g oral powder

100, 150, 200, 300 mg caps

700 mg tabs, 50 mg/mL oral suspension

200 mg caps, 500 mg tabs

300, 400, 600 mg tabs

250 mg caps

100 mg caps; 80 mg/mL oral solution

200, 333, 400 mg caps

Dosing recommendations

400 mg lopinavir + 100 mg ritonavir twice daily; 800 mg lopinavir + 200 mg ritonavir once daily (once daily only in treatmentnaive patients)

1,250 mg twice daily; 750 mg every 8 hours

ATV 300 mg + RTV 100 mg once daily or 400 mg once daily (unboosted only for PI-naive patients)

ART-naive patients: FPV 1,400 mg twice daily; or FPV 1,400 mg + RTV 100-200 mg once daily; or FPV 700 mg + RTV 100 mg twice daily

PI-experienced patients: FPV 700 mg + RTV 100 mg twice daily

SQV 1,000 mg + RTV 100 mg twice daily

ART-naive patients: DRV 800 mg + RTV 100 mg once daily

ART-experienced patients: DRV 600 mg + RTV 100 mg twice daily

TPV 500 mg + RTV 200 mg twice daily

RTV 100-400 mg 1 or 2 times daily with other PIs for boosting; RTV 600 mg twice daily as single PI

IDV 800 mg every 8 hours or IDV 800 mg + 100-200 mg RTV every 12 hours

Food effect

Tablet: no food effect

Liquid: take with food

Take with food

Take with food

Take with or without food

Take within 2 hours of a meal

Take with food

Take with or without food

Take with food

Unboosted, take 1 hour before or 2 hours after meals; may take with skim milk or low-fat meal; when boosting can take with or without food

Adverse eventsa

GI intolerance, asthenia, ­LFTs

Diarrhea, ­LFTs

Increased indirect hyperbilirubinemia, prolonged PR interval (some patients experienced asymptomatic first-degree atrioventricular block); use with caution in patients with underlying conduction defects or on concomitant medications that can cause PR prolongation, nephrolithiasis

Skin rash, GI intolerance, headache, ­LFTs

GI intolerance, headache, ­LFTs

Rash, hepatotoxicity, GI intolerance, headache, ­LFTs

Hepatotoxicity, skin rash, intracranial hemorrhage (rare); patients with risk factors for intracranial hemorrhages are at highest risk

GI intolerance, paresthesias, hepatitis, pancreatitis, asthenia, taste perversion

Nephrolithiasis, GI intolerance, ­bilirubinemia, headache, asthenia, blurred vision, dizziness, rash, metallic taste, thrombocytopenia, alopecia, hemolytic anemia

Drug interactions

CYP450-3A4 inhibitor and substrate (see

Tables 31-10 and

31-11)

CYP450-3A4 inhibitor and substrate (see Tables 31-10 and 31-11)

CYP450-3A4 inhibitor and substrate (see

tables 31-9 and 31-10)

CYP450-3A4 inhibitor, inducer, and substrate (see Tables 31-10 and 31-11)

CYP450-3A4 inhibitor and substrate (see Tables 31-10 and 31-11)

CYP 450-3A4 inhibitor and substrate

CYP450 3A4 inducer and substrate; net effect when combined with RTV; CYP-3A4 and CYP-2D6 inhibitor

CYP450 3A4 and 2D6 inhibitor CYP450 substrate (CYP-3A4 greater than CYP-2D6)

CYP450 3A4 inhibitor

Storage

Tablets: room temperature

Refrigerated liquid stable until date on label; stable for 2 months at room temperature

Room temperature

Room temperature

Room temperature

Room temperature

Room temperature

Refrigerated capsules stable until date on label; stable for 60 days at room temperature

Refrigerated capsules stable until date on label; stable for 1 month at room temperature

Room temperature

Additional information

Oral solution contains 42% alcohol

Needs 500 kcal of food for absorption; take after eating; boosting with RTV not effective

Reduced incidence of hyperlipidemia; must use boosted regimen with tenofovir or efavirenz; needs normal GI acid concentrations for absorption; drug interactions with proton pump inhibitors, histamine-2 blockers, and antacids

Sulfonamide, caution in patients with history of sulfa allergy

Unboosted SQV not recommended

DRV has a sulfonamide moiety; use with caution in patients with known sulfonamide allergy. Unboosted DRV not recommended.

Clinical hepatitis including hepatic decompensation has been reported; monitor closely, especially in patients with underlying liver diseases.

TPV has a sulfonamide moiety; use with caution in patients with known sulfonamide allergy.

Primary role is for boosting of other PIs; most potent CYP450 inhibitor in the class; when used as a single PI, dose should be titrated to above target dose

Patients should drink ≥ 48 oz of water daily to reduce incidence of kidney stones; boosted indinavir increases incidence of kidney stones and requires additional monitoring for signs and symptoms of kidney stones, indirect bilirubin, and platelets

a. PI class side effects: fat maldistribution, hyperglycemia, hyperlipidemia, hypertriglyceridemia, possible increased bleeding episodes in hemophiliacs.

Table 31-8. Drugs That Should Not Be Used with PIs

Drug category

Indinavir

Ritonavir

Saquinavir-ritonavir

Darunavir-ritonavir

Tipranavir-ritonavir

Nelfinavir

Fosamprenavir

Lopinavir-ritonavir

Atazanavir

Calcium channel blockers

None

Bepridil

None

None

Bepridil

None

Bepridil

None

Bepridil

Cardiac

Amiodarone

Amiodarone, flecainide, propafenone, quinidine

None

None

Amiodarone, flecainide, propafenone, quinidine

None

None

Flecainide, propafenone

None

Lipid-lowering agents

Simvastatin, lovastatin

Simvastatin, lovastatin

Simvastatin, lovastatin

Simvastatin, lovastatin

Simvastatin, lovastatin

Simvastatin, lovastatin

Simvastatin, lovastatin

Simvastatin, lovastatin

Simvastatin, lovastatin

Antimycobacterials

Rifampin, rifapentine

Rifapentine

Rifampin, rifapentine

Rifampin, rifapentine

Rifampin, rifapentine

Rifampin, rifapentine

Rifampin, rifapentine

Rifampin, rifapentine

Rifampin, rifapentine

Antihistamines

Astemizole, terfenadine

Astemizole, terfenadine

Astemizole, terfenadine

Astemizole, terfenadine

Astemizole, terfenadine

Astemizole, terfenadine

Astemizole, terfenadine

Astemizole, terfenadine

Astemizole, terfenadine

GI drugs

Cisapride

Cisapride

Cisapride

Cisapride

Cisapride

Cisapride

Cisapride

Cisapride

Cisapride

Neuroleptics

Pimozide

Pimozide

Pimozide

Pimozide

Pimozide

Pimozide

Pimozide

Pimozide

Pimozide

Psychotropics

Midazolam, triazolam

Midazolam, triazolam

Midazolam, triazolam

Midazolam, triazolam

Midazolam, triazolam

Midazolam, triazolam

Midazolam, triazolam

Midazolam, triazolam

Midazolam, triazolam

Ergot alkaloids (vasoconstrictor)

Ergot derivatives

Ergot derivatives

Ergot derivatives

Ergot derivatives

Ergot derivatives

Ergot derivatives

Ergot derivatives

Ergot derivatives

Ergot derivatives

Herbs

St. John's wort

St. John's wort

St. John's wort, garlic supplements

St. John's wort

St. John's wort

St. John's wort

St. John's wort

St. John's wort

St. John's wort

Other

Atazanavir

Voriconazole (with RTV ≥ 400 mg bid), fluticasone, alfuzosin

Fluticasone

Carbamazepine, phenobarbital, phenytoin, fluticasone

Fluticasone

Proton pump inhibitors

Delavirdine, fluticasone, oral contraceptives

Fluticasone

Fluticasone, indinavir, irinotecan, proton pump inhibitors (not recommended for unboosted ATV)

Table 31-9. Drug Interactions with PIs Requiring Dose Modifications or Cautious Use

 

Drug class

Drug

 

Antacids (ATV, TPV-RTV)

Various

 

Antiarrhythmics

Quinidine

 

Antifungals

Itraconazole, ketoconazole, posaconazole, voriconazole

 

Anticoagulant

Warfarin

 

Anticonvulsants

Carbamazepine, phenobarbital, phenytoin

 

Antidepressants

Desipramine (RTV), trazodone (RTV)

 

Antimicrobials

Clarithromycin, rifabutin

 

Benzodiazepines

Alprazolam, diazepam

 

Calcium channel blockers

Dihydropyridines, diltiazem

 

Corticosteroids

Dexamethasone (SQV)

 

Erectile dysfunction agents

Various

 

Histamine-2 receptor antagonists (ATV-RTV, ATV, FPV)

Various

 

Hormonal contraceptives

Various

 

HMG-CoA reductase inhibitors

Atorvastatin, pravastatin (DRV/RTV), rosuvastatin

 

Narcotic analgesics

Methadone

 

Proton pump inhibitors (ATV-RTV, SQV-RTV, TPV-RTV)

Various

 

Selective serotonin reuptake inhibitors

Paroxetine (DRV/RTV), sertraline (DRV/RTV)

 

Xanthine derivatives

Theophylline (RTV)

 

Other

Grapefruit juice (IDV, SQV), vitamin C > 1 gram daily (IDV)

 

Table 31-10. Integrase and Entry Inhibitors

 

Raltegravir (RAL)

Maraviroc (MVC)

Enfuvirtide (T20)

Trade name

Isentress

Selzentry

Fuzeon

Classification

Integrase inhibitor

Entry inhibitor: CCR5 antagonist

Entry inhibitor: fusion inhibitor

Form

400 mg tablets

150, 300 mg tablets

Injectable, in lyophilized powder to be reconstituted with sterile water

Dosing recommendations

RAL 400 mg twice daily

MVC 150 mg po every 12 hours when giving with strong CYP3A4 inhibitors (most PIs)

MCV 300 mg po every 12 hours when giving with enfuvirtide, tipranavir-ritonavir, nevirapine, or weak CYP3A4 inhibitors

MCV 600 mg po every 12 hours when giving with CYP3A4 inducers (efavirenz, rifampin, etc.)

T20 90 mg/mL injected subcutaneously twice daily; powder should be reconstituted with 1.1 mL sterile water for injection

Food effect

Take with or without food.

Take with or without food.

Take with or without food.

Adverse events

Nausea, headache, diarrhea, pyrexia, CPK elevation

Abdominal pain, cough, dizziness, musculoskeletal symptoms, pyrexia, rash, upper respiratory tract infections, hepatotoxicity, orthostatic hypotension

Local injection site reactions, increased bacterial pneumonia, hypersensitivity reactions

Drug interactions

UGT1A1 mediated glucuronidation. Do not give with rifampin. Dose adjustments may be necessary with other medications metabolized by UGT1A1.

CYP540 3A4 substrate. Do not use with St. John's wort. Dose adjustments needed with itraconazole, ketoconazole, voriconazole, carbamazepine, phenobarbital, phenytoin, clarithromycin, rifabutin, rifampin.

Catabolism

Storage

Room temperature

Room temperature

Room temperature; reconstituted solution should be refrigerated and used within 24 hours

Additional information

 

Trofile testing should be done before using marivoric to determine patient's tropism—must be CCR5 tropic only.

 

Table 31-11. AIDS Clinical Trials Group 076 Guidelines: Dosing of Zidovudine for Prevention of Vertical Transmission

Period

Guideline

Prepartum

Initiation at 14-34 weeks gestation and continued throughout pregnancy

Preferred regimen: zidovudine 100 mg 5 times daily

Acceptable alternative regimens:

    • AZT 200 mg 3 times daily

    • AZT 300 mg 2 times daily

Intrapartum

During labor, AZT 2 mg/kg IV over 1 hour, followed by a continuous infusion of 1 mg/kg/h IV until delivery

Postpartum

Oral administration of AZT to the newborn: AZT syrup 2 mg/kg every 6 hours for the first 6 weeks of life, beginning 8-12 hours after birth

Table 31-12. Recommended HIV PEP Treatment Options

Exposure type

HIV-positive, class 1a

HIV positive, class 2b

Source of unknown HIV status

Unknown source

HIV negative

Recommended HIV PEP for percutaneous injuries

         

Less severe (example: solid needle or superficial injury)

Basic 2-drug PEP is recommended.

Expanded ≥ 3 drug PEP is recommended.

Generally, no PEP is warranted; however, consider basic 2-drug PEP for source with HIV risk factors.

Generally, no PEP is warranted; however, consider basic 2-drug PEP in settings where exposure to HIV-infected persons is likely.

No PEP is warranted.

More severe (example: large-bore hollow needle, deep puncture, visible blood on device, or needle used in patient's artery or vein)

Expanded 3-drug PEP is recommended.

Expanded ≥ 3-drug PEP is recommended.

Generally, no PEP is warranted; however, consider basic 2-drug PEP for source with HIV risk factors.

Generally, no PEP is warranted; however, consider basic 2-drug PEP in settings where exposure to HIV-infected persons is likely.

No PEP is warranted.

Recommended HIV PEP for mucous membrane exposures and nonintact skin exposures

         

Small volume (example: a few drops)

Basic 2-drug PEP should be considered.

Basic 2-drug PEP is recommended.

Generally no PEP is warranted.

Generally no PEP is warranted.

No PEP is warranted.

Large volume (example: major blood splash)

Basic 2-drug PEP is recommended.

Expanded ≥ 3-drug PEP is recommended.

Generally, no PEP is warranted; however, consider basic 2-drug PEP for source with HIV risk factors.

Generally, no PEP is warranted; however, consider basic 2-drug PEP in settings where exposure to HIV-infected persons is likely.

No PEP is warranted.

a. HIV-positive class 1 asymptomatic HIV infection or known low viral load (< 1,500 copies/mL).

b. HIV-positive class 2 symptomatic HIV infection, AIDS, acute seroconversion, or known high viral load.

Table 31-13. Regimens for PEP

Type of regimen

Basic 2-drug PEP

Expanded 3-drug PEP

Preferred

    • Zidovudine + lamivudine or emtricitabine

    • Tenofovir + lamivudine or emtricitabine

Basic regimen plus:

    • Lopinavir-ritonavir

Alternative

    • Stavudine + lamivudine or emtricitabine

    • Didanosine + lamivudine or emtricitabine

Basic regimen plus:

    • Atazanavir +/- ritonavir

    • Fosamprenavir +/- ritonavir

    • Indinavir +/- ritonavir

    • Saquinavir-ritonavir

    • Nelfinavir

    • Efavirenz


Figure 31-1. Algorithm for Evaluation and Treatment of Nonoccupational Exposure

Table 31-14. nPEP Antiretroviral Regimens

Type of regimen

Substantial exposure risk

Negligible exposure risk

Preferred

    • Zidovudine + lamivudine or emtricitabine

    • Tenofovir + lamivudine or emtricitabine

    • Lopinavir-ritonavir

    • Efavirenz

Alternative

    • Stavudine + lamivudine or emtricitabine

    • Didanosine + lamivudine or emtricitabine

    • Abacavir + lamivudine or emtricitabine

    • Atazanavir +/- ritonavir

    • Fosamprenavir +/- ritonavir

    • Indinavir +/- ritonavir

    • Saquinavir-ritonavir

    • Nelfinavir

Triple NRTI (only when other regimens cannot be used)

    • Abacavir + lamivudine + zidovudine

 

Table 31-15. Opportunistic Infections

Pathogen

Indication

First choice

Alternative regimens

Comments

Pneumocystis jiroveci pneumonia

Prophylaxis: CD4+ < 200/mm3; thrush; unexplained fever ≥ 2 weeks; history of PCP

TMP-SMX

Dapsone, atovaquone, or aerosolized pentamidine

Primary and secondary prophylaxis can be stopped for PCP on immune reconstitution (patients on HAART with CD4+ greater than 200/mm3 for > 3 months).

Pneumocystis jiroveci pneumonia

Acute infection

TMP 15-20 mg/kg/d + SMX 75-100 mg/kg/d po or IV × 21 d in 3-4 divided doses

Pentamidine IV, primaquine + clindamycin, dapsone + TMP, or atovaquone

Patients with PO2 < 70 mm Hg or A-a gradient > 35 mm Hg should receive a corticosteroid taper; treatment is for 21 days.

Candida

Treatment

Fluconazole, clotrimazole troches, nystatin suspension, itraconazole, posaconazole, amphotericin B, anidulafungin, caspofungin, micafungin, or voriconazole

Any of the preferred regimens

Thrush: treat for 10-14 days; CD4+.

Esophagitis: treat for 2-3 weeks.

Chronic use of azoles might promote development of resistance.

Cryptococcal meningitis

Induction therapy (for at least 2 weeks)

Amphotericin B or lipid formulation amphotericin + flucytosine

Amphotericin B + fluconazole, amphotericin B alone, or fluconazole

Condition is spread through inhalation of soil contaminated with bird droppings.

It is very important to manage increased intracranial pressures.

Cryptococcal meningitis

Consolidation therapy (for at least 8 weeks)

Fluconazole

Itraconazole

 

Cryptococcal meningitis

Maintenance therapy

Fluconazole

Itraconazole

Maintenance therapy is lifelong or until CD4+ ≥ 200/mm3 for > 6 months as a result of ART.

Toxoplasmosis

Treatment (for at least 6 weeks)

Pyrimethamine + leucovorin + sulfadiazine

Pyrimethamine + leucovorin + clindamycin or atovaquone or azithromycin, TMP-SMX, atovaquone alone, or atovaquone + sulfadiazine

Condition is spread through raw or undercooked meat (lamb, beef, pork) and by contact with infected cat feces.

Dexamethasone may be required if significant cerebral edema is present.

Toxoplasmosis

Chronic maintenance therapy

Pyrimethamine + leucovorin + sulfadiazine

Pyrimethamine + leucovorin + clindamycin or atovaquone

Maintenance therapy is lifelong or until CD4+ ≥ 200/mm3 for > 6 months as a result of ART and patient is free of signs and symptoms.

Histoplasmosis

Induction therapy (treat for at least 2 weeks)

Liposomal amphotericin B or itraconazole

Amphotericin B, amphotericin B lipid complex, or posaconazole

Condition is spread through inhalation of dust particles. Histoplasmosis is found in soils heavily contaminated by avian or bat feces. The Ohio and Mississippi River valleys are endemic areas in the United States.

Histoplasmosis

Maintenance therapy (for at least 12 months)

Itraconazole

Posaconazole

Maintenance therapy can be stopped after 12 months of treatment, CD4+ ≥ 150/mm3, ART for > 6 months, urine and serum antigen < 4.1 units.

Mycobacterium avium complex

Treatment and maintenance therapy

Clarithromycin + ethambutol +/- rifabutin

Azithromycin + ethambutol

Alternative third drugs: amikacin, streptomycin, ciprofloxacin, levofloxacin, moxifloxacin

Maintenance therapy may be discontinued after 12 months of treatment, CD4 > 100/mm3 for 6 months on ART after treatment, and patient is asymptomatic.

Mycobacterium avium complex

Primary prophylaxis: generally recommended at CD4 counts < 50/mm3

Azithromycin or clarithromycin

Rifabutin or azithromycin + rifabutin

It may be possible to discontinue treatment when CD4 count > 100/mm3 for > 6 months in patients on ART.

Cytomegalovirus retinitis

Treatment (for 21 days)

Intraocular ganciclovir, valganciclovir, foscarnet, or ganciclovir

Cidofovir

Oral ganciclovir should not be used as sole induction therapy.

Optimization of ART is an important part of initial therapy.

Cytomegalovirus retinitis

Maintenance

Valganciclovir or intraocular ganciclovir

Ganciclovir, foscarnet, or cidofovir

Maintenance therapy can be stopped with inactive disease, CD4 > 100-150/mm3 for 3-6 months in patients on ART.


Figure 31-2. Guidelines for the Treatment of Anemia in the HIV Patient

Table 32-1. Guidelines for Tetanus Wound Management

 

Clean minor wounds

All other wounds

Vaccination history

Td or Tdapa

TIG

Td or Tdapa

TIG

Unknown or < 3 years since last dose

Yes

No

Yes

Yes

Three or more years since last dose

Nob

No

Noc

No

Td, tetanus-diphtheria vaccine; Tdap, tetanus-diphtheria-pertussis vaccine; TIG, tetanus immune globulin.

a. Tdap should be used if the patient has not previously received Tdap and is 10 years or older.

b. Yes, if > 10 years since last dose.

c. Yes, if > 5 years since last dose.

Table 33-1. Proportionality Constant for Calculation of Creatinine Clearance Using the Schwartz Equationa

 

Age

k

 

Low birth weight ≤ 1 year

0.33

 

Full term ≤ 1 year

0.45

 

1-12 years

0.55

 

14-21 years (female)

0.55

 

14-21 years (male)

0.70

 

a. Schwartz et al. 1987.

 
           

Table 33-2. Treatment Options for Otitis Media

Severity of illness

First-line therapy

Therapy for penicillin allergy

Nonsevere illness: At diagnosis (initial antibiotic therapy)

Amoxicillin (80-90 mg/kg/day)

Non-type I: Cefdinir (14 mg/kg/day in 1 or 2 doses), cefuroxime (30 mg/kg/day in 2 doses), or cefpodoxime (10 mg/kg/day once daily)

Type I: Azithromycin (10 mg/kg day 1, 5 mg/kg days 2-5) or clarithromycin (15 mg/kg/day in 2 doses)

Severe illness: At diagnosis (initial antibiotic therapy)

Amoxicillin-clavulanate (90 mg/kg/day amoxicillin, 6.4 mg/kg/day clavulanate)

Ceftriaxone (50 mg/kg/day for 1 or 3 days)

Nonsevere illness: Treatment failure at 48-72 hours (initial observation option)

Amoxicillin (80-90 mg/kg/day)

Non-type I: Cefdinir (14 mg/kg/day in 1 or 2 doses), cefuroxime (30 mg/kg/day in 2 doses), or cefpodoxime (10 mg/kg/day once daily)

Type I: Azithromycin (10 mg/kg day 1, 5 mg/kg days 2-5) or clarithromycin (15 mg/kg/day in 2 doses)

Severe illness: Treatment failure at 48-72 hours (initial observation option)

Amoxicillin-clavulanate (90 mg/kg/day amoxicillin, 6.4 mg/kg/day clavulanate)

Ceftriaxone (50 mg/kg/day for 1 or 3 days)

Nonsevere illness: Treatment failure at 48-72 hours (initial antibiotic therapy)

Amoxicillin-clavulanate (90 mg/kg/day amoxicillin, 6.4 mg/kg/day clavulanate)

Non-type I: Cefriaxone (50 mg/kg/day for 3 days)

Type I: Clindamycin (30-40 mg/kg/day in 3 doses)

Severe illness: Treatment failure at 48-72 hours (initial antibiotic therapy)

Ceftriaxone (50 mg/kg/day for 3 days)

Tympanocentesis: Clindamycin (30-40 mg/kg/day in 3 doses)

AAP/AAFP Clinical Practice Guideline, 2004.

Note: Observation option must have follow-up at 48-72 hours and access to antibiotics if symptoms persist or worsen. Nonsevere illness manifests as mild otalgia and fever < 39°C or 102.2°F. Severe illness manifests as moderate to severe otalgia or fever of ≥ 39°C or 102.2°F.

Table 33-3. Drug Therapy for Cystic Fibrosis

Therapeutic category

Indication and mechanism of action

Comments

Pancreatic enzymes: microencapsulated (Creon, Pancrease, Pancrelipase, Ultrase); Tablet (Viokase); Powder (Viokase)

Supplementation or replacement of pancreatic enzymes (treatment of malabsorption syndrome); aid in digestion of proteins, carbohydrates, and fats

Products differ by enzyme content (units of lipase, protease, and amylase) and dosage form.

Primary enzyme component is lipase.

Dose is typically whole dose with meals and half dose with snacks.

Adequate replacement decreases bowel movements and improves stool consistency.

Fat-soluble vitamins

Supplementation of fat-soluble vitamins A, D, E, and K

Vitamins may be dosed individually, through the use of 1 or 2 multivitamins daily, or with a water-miscible combination preparation.

Nebulization therapy

Liquefaction of pulmonary secretions

Nebulization therapy can be accomplished with normal saline or sterile water with or without other therapies.a

N-acetylcysteine (Mucomyst)

Lowered mucus viscosity through sulfhydryl group, which opens the disulfide bond in mucoproteins

Bad taste and odor are present.

Significant efficacy has not been documented.

Recombinant human DNase (dornase alfa, Pulmozyme)

Contribution of DNA in mucus to viscosity; mechanism of action through cleavage of DNA (thereby decreasing mucus viscosity)

Product is expensive, reduces viscosity, improves pulmonary function, and may decrease respiratory exacerbations.

Ursodeoxycholic acid (ursodiol, Actigall)

Bile acid that suppresses hepatic synthesis and secretion of cholesterol; inhibits intestinal cholesterol absorption; solubilizes cholesterol

Product aids in dissolution of stones with cholelithiasis.

Bronchodilators (β2-agonists, theophylline)

Bronchodilator in reversible or obstructive airway disease

Bronchodilators may benefit patients with component of reactive airway disease; patients should use β2-agonist before theophylline because of pharmacokinetic issues.

Response (improvement in FEV1) should be documented before initiating long-term therapy.

Antibiotics

Treatment of infection

Altered pharmacokinetics may affect and complicate therapy.

Ibuprofen

Nonsteroidal anti-inflammatory; controls airway inflammation

Ibuprofen is not used routinely; it may have an effect on slowing pulmonary disease.

High dosages are needed to achieve good concentrations (requires therapeutic drug monitoring).

Corticosteroids

Anti-inflammatory

Corticosteroids are not used routinely; they have positive effects on pulmonary function but negative effects on growth and development, glucose sensitivity, and bone health.

a. Other therapies include N-acetylcysteine and recombinant human DNase.

       

Table 33-4. Drug Therapy for Attention-Deficit/Hyperactivity Disorder

Therapeutic category

Indication and mechanism of action

Comments

Stimulants (first-line therapy)

   

Short-acting: methylphenidate (Ritalin, Methylin); intermediate-acting: methylphenidate (Ritalin SR, Metadate ER, Methylin ER); long-acting: methylphenidate (Concerta, Metadate CD, Ritalin LA, Daytrana); short-acting amphetamine (Dexedrine, Dextrostat); intermediate-acting amphetamine (Adderall, Dexedrine Spansule); long-acting amphetamine (Adderall-XR)

Reuptake blockade of catecholamines (norepinephrine and dopamine) in presynaptic nerve endings

Because of concern of sudden death and stroke, methylphenidate should not be used in children or adults with structural cardiac abnormalities.

Do not give after 4:00 pm because later doses may cause insomnia.

Spansules may be opened and contents sprinkled on applesauce.

Methylphenidate is not labeled for use in children < 6 years of age.

Daytrana is a transdermal patch and should be applied every morning to alternating hips and worn for 9 hours.

Amphetamines are not labeled for use in children < 3 years of age.

Adderall can be crushed.

Drug holidays are recommended (e.g., summer is a good time to see if patient is outgrowing disease).

Products are not addictive in children with ADHD, but some parents or siblings may abuse child's medications.

Antidepressants (second-line therapy)

   

Tricyclics (imipramine, desipramine)

Reuptake blockade of norepinephrine and serotonin presynaptically

Tricyclics may be used in patients who fail to respond or are intolerant to stimulants.

Tricyclics are drug of choice in ADHD with depression.

They have longer duration of action.

No rebound or wearing-off effect occurs.

Rapid onset occurs in ADHD; effect can be noticed in 3-4 days. Taper off patient's dosage over 2 to 3 weeks.

Baseline and follow-up ECGs are needed.

Bupropion (Wellbutrin, Wellbutrin SR, Wellbutrin XL)

Indirect dopamine agonist and nonadrenergic effects

Products may induce seizures.

Other agents (not currently supported by most recent AAP Guidelines, 2001)

 

D-threo-enantiomer of racemic methylphenidate, dexmethylphenidate (Focalin)

Blockade of dopamine and norepinephrine in presynaptic nerve endings

D-enantiomer is thought to be the more active enantiomer.

Atomoxetine (Strattera)

Noradrenergic-specific reuptake inhibitor

Product is a nonstimulant agent; discontinue in patients who develop jaundice or laboratory evidence of liver injury.

Clonidine

α2-noradrenergic agonist

Clonidine is a good drug to use with ADHD and coexisting conditions such as sleep disturbances.

Pemoline (Cylert)

Blockade of dopamine and norepinephrine in presynaptic nerve endings

Product was withdrawn by manufacturer; previously, it was rarely used secondary to association with fatal hepatic failure (not dose or time related).

Table 34-1. Anticholinergic Drugs That Can Worsen Alzheimer's Disease

Class

Drugs

Antidepressants

Highest effects: amitriptyline, amoxapine, clomipramine, protriptyline; moderate effects: bupropion, doxepin, imipramine, maprotiline, trimipramine

Antiparkinsonian agents

Benztropine, trihexyphenidyl

Antipsychotics

Highest effects: clozapine, mesoridazine, olanzapine, promazine, triflupromazine, thioridazine; moderate effects: chlorpromazine, chlorprothixene, pimozide

Antispasmodics

Atropine, belladonna alkaloids, dicyclomine, glycopyrrolate, hyoscyamine, methscopolamine, oxyphencyclimine, propantheline, oxybutynin, flavoxate, terodiline

Antihistamines

Highest effects: carbinoxamine, clemastine, diphenhydramine, promethazine; moderate effects: azatadine, brompheniramine, chlorpheniramine, cyproheptadine, dexchlorpheniramine, triprolidine, hydroxyzine

Antiemetic-antivertigo agents

Meclizine, scopolamine, dimenhydrinate, trimethobenzamide, prochlorperazine

Other agents with some anticholinergic activity

Paroxetine

       

Table 34-2. Drugs Used to Treat Alzheimer's Disease

Generic name

Trade name

Usual dosage

Dosage forms

Adverse effects

Tacrine

Cognex

10-20 mg bid

Capsules

Nausea and vomiting, hepatotoxicity

Donepezil

Aricept

5-10 mg at bedtime

Tablets, oral solution, disintegrating tablets

Nausea and vomiting

Rivastigmine

Exelon

1.5-6 mg bid

Capsules, transdermal patch

Nausea and vomiting, anorexia, weight loss

Galantamine

Razadyne

4-12 mg bid

Tablets, extended-release capules, oral solution

Nausea and vomiting

Memantine

Namenda

10 mg bid

Tablets, oral solution

Headache, constipation, dizziness, hypertension

Table 34-3. The Stages of Parkinson's Disease

Stage

Characteristics

1

Only unilateral involvement, with minimal or no functional impairment

2

Bilateral involvement without impairment of balance

3

Mild to moderate bilateral disease, with some postural instability (patient can maintain independence)

4

Severe disability (patient is unable to live alone independently)

5

Inability to walk or stand without assistance

           

Table 34-4. Drugs for Treating Parkinson's Disease

Generic name

Trade name

Mechanism of action

Dosage and available strengths and forms

Carbidopa-levodopa

Sinemet

Increases dopamine (levodopa); prevents metabolism (carbidopa)

Give 25/100 mg/d at breakfast; increase to 25/100 mg tid. Dosage may be increased to 25/250 mg qid. Sustained-release 25/100 mg and 50/200 mg tablets are available.

Bromocriptine

Parlodel

Directly stimulates dopamine receptors

Give 1.25 mg bid with meals; increase by 2.5 mg/d every day, up to 100 mg/d. 2.5 mg and 5 mg tablets are available.

Pramipexole

Mirapex

Directly stimulates dopamine receptors

Give 0.125 mg tid; increase weekly to 0.5-1.5 mg tid. 0.125, 0.25, 1, and 1.5 mg tablets are available.

Ropinirole

Requip

Directly stimulates dopamine receptors

Give 0.25 mg tid; increase gradually to a maximum of 24 mg/d. 0.25, 0.5, 1, 2, 4, and 5 mg tablets are available.

Apomorphine

 

Directly stimulates dopamine receptors

Give 0.2-0.6 ml (2-6 mg) SC for acute attacks. Oral antiemetic (trimethobenzamide) given concurrently.

Selegiline

(Eldepryl, Carbex, Atapryl, Zelapar)

Inhibits monoamine oxidase B; increases dopamine and serotonin

Initially give 5 mg at breakfast; increase to 5 mg at breakfast and lunch. 5 mg capsules, 5 mg tablets, and 1.25 mg oral disintegrating tablets (Zelapar) are available.

Rasagiline

(Azilect)

Inhibits monoamine oxidase B; increases dopamine and serotonin

Initial monotherapy is 0.5 mg once daily, as adjunct to levodopa 0.5 mg to 1 mg daily. 0.5 mg and 1 mg tablets are available.

Entacapone

(Comtan)

Inhibits catecholamine O-methyl transferase (COMT), increasing dopamine

Give 200 mg with each dose of carbidopa-levodopa; maximum is 1,600 mg/d. 200 mg tablets are available.

Tolcapone

(Tasmar)

Inhibits COMT, increasing dopamine

Give 100 mg tid; discontinue if no benefits in 3 weeks. 100 and 200 mg tablets are available.

Amantadine

Symmetrel

May increase presynaptic release of dopamine; blocks reuptake

Give 100 mg bid; maximum is dose 400 mg/d. 100 mg tablets, 100 mg capsules, and 50 mg/5 mL syrup are available.

Benztropine

Cogentin

Blocks acetylcholine; may balance dopamine

Give 1-2 mg po, IM, or IV at bedtime or 0.5-6 mg/d in divided doses. 0.5, 1, and 2 mg tablets and 1 mg/mL injection are available.

Trihexyphenidyl

Artane

Blocks acetylcholine; may balance dopamine

Give 1 mg/d up to 5 mg/d (divided doses); 2 and 5 mg tablets and 2 mg/5 mL elixir are available.

Carbidopa-entacapone-levodopa

Stalevo

Combined effects of all three agents

Dosage is individualized, up to 8 tablets per day. Three dosage combinations are available.

IM, intramuscular; IV, intravenous; SC, subcutaneous.

Table 34-5. Adverse Effects of Medications Used to Treat Parkinson's Disease

Drug

Adverse effects

Dopaminergics: levodopa, pramipexole, bromocriptine, ropinirole, amantadine

Nausea and vomiting, agitation, confusion, depression, psychoses, orthostatic hypotension, dyskinetic movements, "sleep attacks," and "pathologic gambling" (dopamine agonists)

MAO-B inhibitors: selegiline, rasagiline

Nausea and vomiting, insomnia, dizziness, agitation, confusion, dyskinetic movements, anorexia

Amantadine

Confusion, dizziness, depression, anxiety, psychoses, insomnia

COMT inhibitors: tolcapone, entacapone

Nausea and vomiting, diarrhea, dyskinesia, urine coloration, liver toxicity (tolcapone)

Anticholinergics: benztropine, trihexyphenidyl

Dry mouth, blurred vision, constipation, urinary retention, confusion, agitation, psychoses

Table 34-6. Drug-Drug Interactions with Medications Used to Treat Parkinson's Disease

Medication

Interacting drug

Outcome

Dopamine agonists (e.g., bromocriptine, ropinirole)

Dopamine antagonists (e.g., haloperidol, metoclopramide)

Inhibition of benefits with worsening parkinsonism

Levodopa

Dopamine antagonists

Inhibition of benefits with worsening parkinsonism

Apomorphine

Ondansetron, other serotonin-receptor antagonists

Severe hypotension and loss of consciousness

Selegiline

Serotonergics, selective serotonin reuptake inhibitors, buspirone, mirtazapine

Serotonin syndrome (confusion, agitation, tremor, seizures, coma)

COMT inhibitors

Nonselective MAO inhibitors: phenelzine

Serotonin syndrome; hypertensive crisis secondary to increased catecholamines


Figure 34-1. Algorithm for the Treatment of Open-Angle Glaucoma

Table 34-7. Medications for the Treatment of Glaucoma

Generic name

Trade name

Form

Usual dosage

Comments

Nonselective β antagonists

Nonselective β antagonists are often the first choice for open-angle glaucoma.

Timolol

Timoptic

0.25% and 0.50% solution and gel-forming solution

1 drop twice daily; gel solution used once daily

 

Carteolol

Ocupress

1% ophthalmic solution

1 drop twice daily

 

Levobunolol

Betagen

0.25% and 0.50% solution

1 or 2 drops 1-4 times daily

 

Metipranolol

Optipranolol

0.3% solution

1 drop twice daily

 

Selective β1 antagonists

 

Betaxolol

Betoptic

0.25% and 0.50% solution

1 or 2 drops twice daily

Drug is cardioselective. It has less effect on heart rate and blood pressure.

Levobetaxolol

Betaxon

0.50% solution

1 drop twice daily

Drug is cardioselective.

Carbonic anhydrase inhibitors

 

Acetazolamide

Diamox

125 and 250 mg tablets, 500 mg extended-release capsules

250 mg 1-4 times daily; extended-release 1 or 2 times daily

Do not use with sulfa allergy.

Dorzolamide

Trusopt

2.0% solution

1 drop 3 times daily

Do not use with sulfa allergy.

Brinzolamide

Azopt

1.0% solution

1 drop 3 times daily

Do not use with sulfa allergy.

Methazolamide

Neptazane

25 and 50 mg tablets

15-50 mg 1-3 times daily

Do not use with sulfa allergy.

Prostaglandin analogues

 

Latanoprost

Xalatan

0.005% solution, refrigerated

1 drop at bedtime

Drug can change blue eyes to brown.

Bimatoprost

Lumigan

0.03% solution

1 drop at bedtime

Drug can cause darkening of eyelids and eyelashes.

Travoprost

Travatan

0.004% solution

1 drop at bedtime

Ocular hyperemia frequently occurs.

Unoprostone

Rescula

0.15% solution

1 drop twice daily

If used with another drop, wait 5 minutes.

α2-adrenergic agonists

 

Brimonidine

Alphagan

0.15% solution

1 drop 3 times daily

Wait at least 15 minutes after using before placing soft contacts.

Dipivefrin

Propine

0.1% solution

1 drop twice daily

Dipivefrin is a prodrug of epinephrine.

Cholinergics (miotics)

 

Pilocarpine

Pilocar

0.5%, 1%, 2%, 3%, 4%, 6%, 8% solution, 4% gel

1 or 2 drops 3-4 times daily; 1/2 inch gel at bedtime

A once weekly dose form called Ocuserts is available.

Table 34-8. Classification, Mechanism of Action, and Adverse Effects of Glaucoma Medications

Medication class

Mechanism of action

Adverse effects

β-adrenergic antagonists (timolol, metipranolol, carteolol, levobunolol, etc.)

Decrease in aqueous humor formation with slight increase in outflow (β selective)

Adverse cardiac effects, worsening pulmonary disease, depression, dizziness

Miotics (cholinergics) (pilocarpine, carbachol)

Increase in aqueous humor outflow

Miosis, brow ache, dizziness, nausea, flushing, itching, sweating, confusion

Carbonic anhydrase inhibitors (dorzolamide, brinzolamide)

Decrease in aqueous humor formation

Lethargy, decreased appetite, GI upset, urinary frequency

Prostaglandin analogues (latanoprost, travoprost, bimatoprost)

Increased uveoscleral outflow without effect on aqueous humor formation

Iris pigmentation, eyelid darkening, macular edema

α2-adrenergic agonists (apraclonidine, brimonidine)

Decrease in aqueous humor formation

Tachycardia, dry mouth, eyelid elevation, central nervous system effects in the old and very young

Other α-adrenergic agonists (epinephrine, dipivefrin)

Increase in aqueous humor outflow

Tachycardia, increased blood pressure, allergic responses

             

Table 35-1. Ranking of Most Frequent Poisonings from U.S. Poison Centers and Emergency Departments, 2006

 

Cases from poison centersa

Cases from emergency departmentsb

 

Analgesics

Alcohol, alone or in combination

 

Cosmetics and personal care products

Cocaine

Marijuana

 

Cleaning substances

Anxiolytics and sedatives

 

Sedative drugs

Opioid analgesics

 

Foreign bodies

Nonopioid analgesics

 

Cough and cold drugs

Heroin

 

Topical drugs

Antidepressant drugs

 

Pesticides

Amphetamines

 

Antidepressant drugs

Antipsychotic drugs

 

Bites and envenomations

Muscle relaxant drugs

 

Cardiovascular drugs

Cardiovascular drugs

 

Alcohols

   

a. Categories are listed in decreasing order of frequency and are based on 2,403,539 poison exposures. Source: Bronstein AC, Spyker DA, Cantelina LR, et al. 2006 annual report of the American Association of Poison Control Centers' National Poison Data System (NCDS). Clin Toxicol. 2007;45:815-917.

b. Categories are listed in decreasing order of frequency and are based on cases of substance abuse, poisoning, overmedication, and attempted suicide in 2006. Source: Office of Applied Studies, Substance Abuse and Mental Health Services Administration. Drug Abuse Warning Network, 2006. DHHS publication SMA 08-4339. Rockville, Md.: Substance Abuse and Mental Health Services Administration; 2008.

 

Table 35-2. First Aid for Poisoning Emergencies

Type of emergency

First-aid response

Inhaled poison

Immediately get the person to fresh air. Avoid breathing fumes. Open doors and windows wide.

Poison on the skin

Remove any contaminated clothing, and flood skin with water for at least 15 minutes.

Poison in the eye

Remove contact lenses. Flood the eye with water, pouring it from a large glass 2-3 inches from the eye. Repeat for a total of 15-30 minutes. Do not force the eyelid open.

Swallowed poison

Unless the victim is unconscious, is having convulsions, or cannot swallow, give a small glassful (2-4 oz) of water immediately. Call a poison center for advice about whether other actions are needed.

       

Table 35-3. Selected Drugs of Abuse and Addictive Substances

Substance

Slang names

Methods of abuse

Major or unique health effects

Androgenic anabolic steroids

Roids

These drugs are taken orally or injected, typically in cycles of weeks or months ("cycling"). Users often combine several different types of steroids ("stacking").

Anabolic steroids are synthetic derivatives of testosterone. Abuse can lead to serious health problems, some irreversible.

Men: Shrinking of the testicles, reduced sperm count, infertility, baldness, gynecomastia, and increased risk for prostate cancer can occur.

Women: Growth of facial hair, male-pattern baldness, changes in or cessation of the menstrual cycle, enlargement of the clitoris, and deepened voice can occur.

Adolescents: Stunted growth by premature skeletal maturation and accelerated puberty changes can occur.

Other major side effects include jaundice, fluid retention, high blood pressure, and severe acne. Extreme mood swings, including manic-like symptoms leading to violence and depression, are often experienced when drugs are stopped, and such symptoms may contribute to dependence.

Barbiturates

Barbs, downers

Barbiturates can be ingested or injected.

Barbiturates are CNS depressants that at high doses can become general anesthetics.

With high doses, coma, ataxia, depressed reflexes, hypotension, and respiratory depression can occur.

CNS depressants should not be combined with any medication or substance that causes sedation, including prescription pain medicines, certain over-the-counter cold and allergy medications, or alcoholic drinks. The effects of the drugs can combine to slow breathing or to slow both the heart and respiration, which can be fatal.

Discontinuing prolonged use of high doses of barbiturates can lead to withdrawal.

Cocaine

Snow, crack (the street name given to cocaine that has been processed from cocaine hydrochloride to the free base for smoking), rock

Cocaine can be sniffed or snorted, injected, or smoked (free-base and crack cocaine). It is poorly absorbed orally.

Cocaine is a CNS stimulant that produces euphoric effects and hyper-stimulation such as dilated pupils, increased temperature, tachycardia, and hypertension.

Prolonged cocaine snorting can result in ulceration of the mucous membranes of the nose and can damage the nasal septum enough to cause it to collapse.

Cocaine-related deaths are often a result of cardiac arrest or seizures followed by respiratory arrest.

Tolerance to the euphoric effects develops.

When addicted individuals stop using cocaine, they often become depressed.

Dextromethorphan

DXM, DM, robo, velvet, rojo

This drug is taken orally by drinking dextromethorphan-containing cough syrups. Availability of the powdered form has led to repackaging as capsules or tablets and to snorting.

Dextromethorphan is the dextro isomer of levomethorphan. It has no analgesic, opiate-like, dependence-producing properties. A behaviorally active metabolite, dextrorphan is structurally related to PCP (phencyclidine) and ketamine and may contribute to its abuse potential.

The typical clinical presentation of intoxication involves hyperexcitability, lethargy, ataxia, slurred speech, sweating, hypertension, and nystagmus. Abusers report a heightened sense of perceptual awareness, altered time perception, and visual hallucinations.

The majority of abuse occurs among teenagers and young adults who use dextromethorphan alone or mixed with other drugs. It has been sold as "ecstasy." It has been identified as a filler in confiscated samples of bogus heroin and bogus ketamine.

Procedures to extract dextromethorphan from cough syrups are described on the Internet, which has led to the availability of powdered forms.

Ethanol

Various names and alcoholic drinks

Ethanol is ingested.

Ethanol is a CNS depressant that at high doses can lead to hypotension, hypoglycemia, respiratory depression, and death. Acute intoxication leads to ataxia, sedation, emesis, and slurred speech.

Chronic abuse leads to many medical complications such as esophageal varices, hepatic failure with ascites, and malnutrition.

Tolerance, dependence, and withdrawal develop with chronic abuse.

Gamma-hydroxybutyrate (GHB)

Liquid ecstasy, soap, easy lay, Georgia home boy, somatomax, scoop, grievous bodily harm

GHB is ingested.

GHB is a CNS depressant abused for euphoric, sedative, and anabolic (body-building) effects.

Coma and seizures are likely; increased risk of seizures occurs when combined with methamphetamine.

Use with alcohol causes nausea and difficulty breathing.

GHB and two of its precursors, gamma-butyrolactone (GBL) and 1,4-butanediol (BD) have been involved in poisonings, overdoses, date rapes, and deaths. They are produced by illicit laboratories.

GHB may produce withdrawal effects.

Heroin

Smack, H, skag, junk

Heroin can be injected, snorted, or smoked.

Abuse is associated with fatal overdose, spontaneous abortion, collapsed veins, and infectious diseases, including HIV/AIDS and hepatitis.

Effects include euphoria ("rush") followed by an alternately wakeful and drowsy state ("on the nod").

CNS depression, respiratory depression, miosis (pinpoint pupils), and pulmonary edema can occur.

Street heroin may have additives.

With regular use, tolerance develops and withdrawal is possible.

Inhalants

Various names

Inhalants are sniffed or huffed.

Inhalants include a variety of breathable chemical vapors that produce psychoactive effects. They are found in industrial or household solvents or solvent-containing products, including paint thinners or solvents, degreasers, dry-cleaning fluids, gasoline, and glues.

Nearly all abused inhalants produce short-term intoxicating and CNS depressant effects similar to anesthetics.

Intoxication usually lasts only a few minutes. Successive inhalations lead to loss of inhibition and control. Continued use can lead to coma.

In some cases, heart failure and death occur within minutes of a session of prolonged use ("sudden sniffing death").

Injected drugs

Various names

Such drugs are injected, which is referred to as "shooting up" or "mainlining."

Injecting drug users are at risk for transmitting or acquiring HIV/AIDS, hepatitis, bacterial infections, and fungal infections if needles or other injection equipment are shared. Chronic users may develop collapsed veins, infection of the heart lining and valves, skin abscesses, cellulitis, and liver disease.

Because some abusers dissolve the tablets in water and inject the mixture, emboli can form from the insoluble materials in the tablets.

Ketamine

K, special K, cat Valium, vitamin K

Ketamine is injected or snorted.

Ketamine is an anesthetic that has been approved for human and veterinary use.

Certain doses can cause dream-like states and hallucinations.

At high doses, ketamine can cause delirium, amnesia, impaired motor function, hypertension, depression, and potentially fatal respiratory depression.

Lysergic acid diethylamide (LSD)

Acid, L, blotter, cubes, sugar, dots

LSD is ingested. It is often added to absorbent paper, such as blotter paper, and divided into small decorated squares ("blotter acid") or placed on dot-like candy ("dots") or sugar cubes ("cubes," "sugar").

LSD is a hallucinogen sold on the street in tablets, capsules, and liquid form.

Effects are unpredictable. Physical effects include mydriasis (dilated pupils), elevated temperature, tachycardia, hypertension, sweating, loss of appetite, sleeplessness, dry mouth, and tremors.

Sensations and feelings change more dramatically than do the physical signs. In sufficient doses, the drug produces delusions and visual hallucinations.

Some users experience severe, terrifying thoughts and feelings; fear of losing control; fear of insanity and death; and despair. Fatal accidents have occurred during intoxication. Many users experience flashbacks.

Marijuana

Pot; herb; weed; grass; widow; ganja; hash; and trademarked varieties of cannabis, such as Bubble Gum, Northern Lights, Juicy Fruit, Afghani #1, and a number of Skunk varieties

Marijuana is smoked as a cigarette ("joint," "nail"), in a pipe ("bong"), or in blunts (cigars that have been emptied of tobacco and refilled with marijuana, often in combination with another drug). It is also ingested when mixed in food or brewed as a tea.

Main active chemical in marijuana is THC (delta-9-tetrahydrocannabinol).

Delirium, conjunctivitis, and food craving are typical. Short-term effects include problems with memory and learning, distorted perception, difficulty in thinking and problem solving, loss of coordination, and tachycardia.

Risk of heart attack more than quadruples in the first hour after smoking marijuana.

Users experience the same respiratory problems as cigarette smokers (see nicotine); burning and stinging of the mouth and throat, often accompanied by a heavy cough, can occur.

Drug craving and withdrawal effects can occur.

3-4,-methylene-dioxy-methamphetamine (MDMA)

Ecstasy, Adam, XTC, hug, beans, love drug

MDMA is ingested, snorted, injected, or used in suppository form.

MDMA is a synthetic, psychoactive drug with both stimulant and hallucinogenic properties. It increases pulse and blood pressure.

In high doses, it can cause malignant hyperthermia leading to rhabdomyolysis (muscle breakdown with kidney and cardiovascular system failure).

Psychological difficulties, which include confusion, depression, sleep problems, drug craving, severe anxiety, and paranoia, occur during use and sometimes for weeks afterward.

Physical symptoms include muscle tension, involuntary teeth clenching, nausea, blurred vision, nystagmus, faintness, chills, or sweating.

Content of the MDMA pills also varies widely, and may include caffeine, dextromethorphan, heroin, and mescaline. In some areas, the MDMA-like substance paramethoxyamphetamine (PMA) has led to death when mistaken for true MDMA; deaths were due to complications from hyperthermia.

Methamphetamine

Crank, meth, speed, chalk, ice, crystal, glass

Methamphetamine can be ingested, snorted in the powder form, or injected. The clear, chunky crystals resembling ice can be smoked and are referred to as "ice," "crystal," and "glass."

Methamphetamine is an addictive stimulant chemically related to amphetamine.

It produces euphoria, irritability, insomnia, confusion, tremors, convulsions, anxiety, paranoia, and aggressiveness. Higher doses lead to hypertension, tachycardia, stroke, arrhythmias, cardiovascular collapse, and death. Hyperthermia and convulsions can result in death.

Prolonged use leads to extreme anorexia and is associated with tooth decay and skin lesions.

Methamphetamine is made in illegal laboratories and may contain contaminants and by-products.

The potential for abuse and dependence is high.

Nicotine

Various names and products

Nicotine is smoked with tobacco in cigarettes, cigars, and pipes. It also is in chewing tobacco.

Nicotine is a highly addictive CNS stimulant and sedative. Stimulation is followed by depression and fatigue, leading the user to seek more nicotine.

Women who smoke and take oral contraceptives are more prone to cardiovascular and cerebrovascular diseases, especially those older than 30. Pregnant women have an increased risk of having stillborn or premature infants or infants with low birth weight.

Respiratory problems include daily cough and phlegm production, more frequent acute respiratory illness, a heightened risk of lung infections, and a greater tendency toward obstructed airways and cancer of the respiratory tract and lungs.

Tar in cigarettes is associated with a higher rate of lung cancer, emphysema, and bronchial disorders.

Carbon monoxide in the smoke increases the chance of cardiovascular diseases.

Nicotine tolerance, dependence, and withdrawal symptoms occur.

Opioids

Various names

Opioids are ingested or injected.

Opioids include morphine; codeine; oxycodone (Oxycontin, MS Contin); propoxyphene (Darvon); hydrocodone (Vicodin); hydromorphone (Dilaudid); and meperidine (Demerol).

They cause drowsiness and constipation. Large single doses cause coma, hypotension, respiratory depression, and in some cases seizures and death. Mixing with alcohol and other CNS depressants increases the risk of coma and death.

Chronic use of opioids produces tolerance, physical dependence, and withdrawal symptoms.

Phencyclidine (PCP)

Angel dust, ozone, wack, rocket fuel; killer joints or crystal supergrass when combined with marijuana

PCP is snorted, smoked, or eaten. For smoking, PCP is often applied to a leafy material such as mint, parsley, oregano, or marijuana

PCP is an addictive hallucinogen and sedative that often leads to psychological dependence, craving, and compulsive PCP-seeking behavior. Users often become violent or suicidal and are very dangerous to themselves and others.

At low to moderate doses, effects include slight tachypnea, more pronounced tachycardia and hypertension, shallow respirations, and profuse sweating. Generalized numbness of the extremities and muscular lack of coordination also may occur. Psychological effects include distinct changes in body awareness, similar to those associated with alcohol intoxication.

At high doses, effects include decreased blood pressure, pulse, and respirations; nausea and vomiting; blurred vision and nystagmus; drooling; ataxia; and seizures, coma, and death (though death more often results from accidental injury or suicide during PCP intoxication). Psychological effects at high doses include illusions, hallucinations, and effects that mimic the full range of symptoms of schizophrenia.

Interactions with other CNS depressants, such as alcohol and benzodiazepines, can lead to coma.

PCP is illegally manufactured in illicit laboratories.

Flunitrazepam (Rohypnol)

Rophie, roofies, roche, roach, rope, the date rape drug, forget-me

Rohypnol is ingested.

Rohypnol, a trade name for flunitrazepam, is a benzodiazepine that is not sold in the United States, but is smuggled into it. It produces sedative-hypnotic effects, including muscle relaxation and amnesia. It can also produce physical and psychological dependence.

When mixed with alcohol, Rohypnol can incapacitate victims, can prevent them from resisting sexual assault, and can produce anterograde amnesia. It may also be lethal when mixed with alcohol or other CNS depressants.

Clonazepam (Klonopin) and alprazolam (Xanax) are being abused like Rohypnol.

Stimulants, amphetamines, and related compounds

Speed, dexies, uppers

These drugs are ingested. Tablets can also be crushed and snorted.

These substances are CNS stimulants that increase alertness, attention, and energy, as well as increase blood pressure, pulse, and respiration.

High doses can lead to arrhythmias; hypertension; hyperthermia; and potential for cardiovascular failure, stroke, or lethal seizures.

Taking high doses of some stimulants repeatedly over a short period of time can lead to hostility or feelings of paranoia in some individuals.

Stimulants such as dextroamphetamine (Dexedrine) and methylphenidate (Ritalin) can be addictive when misused.

Sources: National Institute on Drug Abuse, National Institutes of Health, 2009; Diversion Control Program, Drug Enforcement Administration, U.S. Department of Justice, 2009. Available at: www.deadiversion.usdoj.gov/drugs_concern/index.html.

Table 35-4. Commonly Used Antidotes

Toxin

Antidote (trade name)

Adult dose

Pediatric dose

Acetaminophen

Acetylcysteine (Mucomyst)

Oral loading dose: 140 mg/kg; maintenance dose: 70 mg/kg every 4 hours for 17 doses

Same as adult dose regimen

 

Acetylcysteine (Acetadote)

IV infusion: 150 mg/kg in 200 mL D5W over 1 hour, then 50 mg/kg in 500 mL 5% dextrose in water (D5W) over 4 hours, followed by 100 mg/kg in 1,000 mL D5W over 16 hours

Same as adult dose regimen

Anticholinergic compounds

Physostigmine salicylate (Antilirium)

1-2 mg slow IV infusion over 3-5 minutes titrated to effect

0.02 mg/kg slow IV infusion over 3-5 minutes titrated to effect

Arsenic

Succimer (Chemet)

10 mg/kg orally 3 times per day

Same as adult dose regimen

 

Dimercaprol, also called British antilewisite (BAL in Oil), only if unable to tolerate oral succimer

3-5 mg/kg intramuscular every 4-6 hours

3-5 mg/kg intramuscular every 4-6 hours

Benzodiazepines

Flumazenil (Romazicon)a

0.2 mg IV bolus titrated to effect or total dose of 3 mg

0.01 mg/kg IV bolus titrated to effect or total dose of 1-3 mg

β-blockers

Glucagon (GlucaGen)

5-10 mg IV bolus, followed by 5-10 mg/h IV infusion titrated to effect

0.15 mg/kg mg IV bolus, followed by 0.1 mg/h IV infusion titrated to effect

Calcium channel blockers

Calcium chloride 10%

10-20 mL IV bolus; repeat doses and IV infusions common

0.1-0.2 mL/kg IV bolus; repeat doses and IV infusions common

 

Glucagon (GlucaGen)

5-10 mg IV bolus, followed by 5-10 mg/h IV

0.15 mg IV bolus, followed by 0.1 mg/h IV infusion titrated to effect

Carbamates

Atropine

2-4 mg IV bolus, repeat doses titrated to effect

1 mg/kg IV bolus, repeat doses titrated to effect

Cyanide

Cyanide antidote kit composed of sodium nitrite 3% and sodium thiosulfate

Sodium nitrite: 300 mg slow IV infusion; sodium thiosulfate: 12.5 g IV infusion

Sodium nitrite: 0.15-0.33 mL/kg to maximum of 300 mg slow IV infusion; sodium thiosulfate: 400 mg/kg up to 12.5 g IV infusion

 

Hydroxocobalamin (CyanoKit)b available since 2007

5 g IV infusion over 15 min; up to 5 g more based on response

70 mg/kg IV infusion based on use outside the United States

Digoxin

Digoxin immune Fab (Digibind, DigiFab)

Empiric dosing: 10-20 vials IV bolus for life-threatening toxicity (see package insert for other dosing regimens)

Empiric dosing: same as adult dose regiment (see package insert for other dosing regimens)

Ethylene glycol, methanol

Ethanol 10%

Loading dose 10 mL/kg IV or orally, followed by maintenance dose 1-2 mL/kg/h IV infusion or oral dose

Same as adult dose regimen

 

Fomepizole (Antizol)

15 mg/kg IV bolus; smaller repeat doses may be necessary

Same as adult dose regimen

Iron

Deferoxamine (Desferal)

5-15 mg/kg/h IV infusion titrated to effect

Same as adult dose regimen

Isoniazid

Pyridoxine, also called vitamin B6

1 g per gram ingested or empiric dosing of 5 g IV bolus

1 g per gram ingested or empiric dosing of 75 mg/kg IV bolus up to 5 g

Lead

Succimer (Chemet)

10 mg/kg orally 3 times per day; repeat doses common

Same as adult dose regimen

 

Dimercaprol (also called British antilewisite [BAL]), only for lead encephalopathy (BAL in Oil)

3-5 mg/kg intramuscularly or 50-75 mg/m2 intramuscularly

Same as adult dose regimen

 

Calcium disodium ethylene-diaminetetraacetic acid (Calcium Disodium Versenate)

20-30 mg/kg diluted in 250 mL IV infusion over 12-24 hours (start 4 hours after BAL administration)

Same as adult dose regimen

Methemoglobinemia

Methylene blue

1-2 mg/kg slow IV infusion; repeat doses common

Same as adult dose regimen

Opioids

Naloxone (Narcan)

0.4-2.0 mg IV titrated to effect

Same as adult dose regimen

Organophosphates

Atropine

2-4 mg IV bolus; repeat doses titrated to effect

0.1 mg/kg IV bolus; repeat doses titrated to effect

 

Pralidoxime hydrochloride (Protopam)

1-2 g slow IV infusion followed by 500 mg/h continuous infusion or 1 g every 4 hours

20-40 mg/kg slow IV infusion, followed by 5-10 mg/kg/h continuous infusion or 20 mg/kg every 4 hours

Salicylate

Sodium bicarbonate

150 mEq with 40 mEq KCl in 1 L of D5W infused to maintain urine output at 1-2 mL/kg/h and a urine pH approximately 7.5

Same as adult dose regimen

Snake envenomation, crotalineb (rattlesnakes, cottonmouth, copperhead)

Crotalidae polyvalent immune Fab, ovine (CroFab)

Empiric dose: 4-6 vials IV infusion over 1 hour; additional doses depend on patient response (see package insert for dosing)

Same as adult dose regimen

Tricyclic antidepressants, agents with type 1a antiarrhythmic effects

Sodium bicarbonate

1-2 mEq/kg IV bolus; repeat boluses titrated to QRS duration (do not exceed arterial pH of 7.55)

Same as adult dose regimen

Warfarin, superwarfarins

Fresh-frozen plasma

Fresh-frozen plasma for life-threatening hemorrhage

Same as adult indication

 

Vitamin K1 (Mephyton, AquaMEPHYTON)

10-50 mg slow IV infusion or taken subcutaneously or orally

0.6 mg/kg slow IV infusion or taken subcutaneously or orally

Source: Based on American College of Emergency Physicians. Clinical policy for the initial approach to patients presenting with acute toxic ingestion or dermal or inhalation exposure. Ann Emerg Med. 1999;33:735-61.

Note: The table lists common antidotes that may need to be used emergently for patients presenting with acute toxic ingestion or dermal or inhalation exposure. Dosages are derived from standard texts and references and are given as convenience references. These should not be considered specific treatment guidelines; consult appropriate resources.

a. Potential risks may exceed the benefits because of precipitation of intractable seizures.

b. Information updated by author January 2009.

         

Table 35-5. Biological Agents That May Be Used in a Terrorist Attack

Biological agent and description

Clinical features

Treatment

Smallpox is caused by the variola virus and may be spread by aerosol or direct contact with infected persons or fluids.

Early symptoms resemble a mild viral illness, with a 2- to 4-day nonspecific prodrome of fever and myalgias before rash onset. Pustules form, and then scabs form and fall off, leaving pitted scars. When all the scabs have fallen off (in about 3 weeks), patients are no longer contagious. Smallpox rash is typically most prominent on the face and extremities, and lesions form at the same time.a

No specific treatment exists. A live-virus vaccine of vaccinia virus (Dryvax) is primarily preventive for close contacts, but vaccination within 4 days of exposure may prevent or lessen disease.

Anthrax is caused by Bacillus anthracis, a Gram-positive spore-forming rod. It has 3 major forms (cutaneous, inhalation, and gastrointestinal), and none are contagious.

Cutaneous: This form begins as a small papule and progresses to a vesicle in 1-2 days, followed by a necrotic, normally painless ulcer. Victim may have fever, malaise, headache, and regional lymphadenopathy.

Inhalation: This form initially resembles a viral illness with sore throat, mild fever, muscle aches, and malaise. It often has minimally productive cough, nausea or vomiting, and chest discomfort, which may progress to respiratory failure and shock, with meningitis frequently developing.b

Gastrointestinal: This form causes severe abdominal or oropharyngeal distress, followed by fever and signs of septicemia, bloody vomit, and diarrhea.

Ciprofloxacin and doxycycline are FDA-approved for postexposure prophylaxis (PEP) of children and adults, while levofloxacin is approved for adults 18 years of age and older. Ciprofloxacin and doxycycline are FDA-approved for treatment. Amoxicillin or penicillin may be used if hypersensitivity or other risks are present. Persons at risk for inhalation anthrax need 60 days of prophylactic antibiotics.

Anthrax Vaccine Adsorbed (BioThraxT) given intramuscularly is indicated for active immunization for the prevention of disease caused by Bacillus anthracis in persons age 18-65 at high risk of exposure.

Plague, caused by Yersinia pestis, has several forms, with pneumonic plague being the most virulent.

Clinical features of aerosolized pneumonic plague include fever, cough with mucopurulent sputum, hemoptysis, and chest pain with signs consistent with severe pneumonia 1-6 days after exposure. Septic shock and high mortality can occur within 2-4 days of symptom onset without early treatment. Y. pestis-caused bubonic plague is less likely to be weaponized.

Early treatment for pneumonic plague with streptomycin or gentamicin is advised. Other antibiotics may also be effective. A vaccine is no longer manufactured.

Botulism, caused by Clostridium botulinum, may be foodborne or airborne.

Clinical features include acute symmetric descending paralysis in a proximal to distal pattern; prominent bulbar palsies such as diplopia, dysarthria, dysphonia, and dysphagia that typically present 12-72 hours postexposure; and respiratory dysfunction from respiratory muscle paralysis or upper airway obstruction without sensory deficits.

Antitoxin (most effective within 24 hours of exposure) is maintained and dispensed by the CDC. Most patients recover after supportive care, often with mechanical ventilation for weeks to months.

Tularemia, caused by Francisela tularensis, is one of the most infectious bacteria known.

Inhalation exposure causes an abrupt onset of a nonspecific febrile illness beginning 3-5 days postexposure, with incipient pneumonia, pleuritis, and hilar lymphadenopathy. Without treatment, respiratory failure, shock, and death are possible. Like botulism and anthrax, tularemia is not contagious, so patients who have tularemia do not need to be isolated.

Prompt treatment with streptomycin, gentamicin, chloramphenicol, doxycycline, or ciprofloxacin is advised, as is early PEP use of doxycycline or ciprofloxacin.

Viral hemorrhagic fevers (VHFs) include filoviruses, arenaviruses, bunyaviruses, and flaviviruses. (Other VHFs exist but are not considered a serious bioterrorism risk.) Filoviruses and arenaviruses are most virulent, but all viruses listed here are considered serious biological threats; exposure is by all routes, including direct and aerosol.

With filoviruses (Ebola and Marburg types), an abrupt onset of an undifferentiated febrile illness with high fever occurs 2-21 days after exposure. A maculopapular rash, prominent on the trunk, develops about 5 days later, with progressive bleeding symptoms such as petechiae, ecchymosis, disseminated intravascular coagulation, and hemorrhages.

With arenaviruses (Lassa and multiple New World arenaviruses, including Machupo, which causes Bolivian hemorrhagic fever), symptoms and onset are similar to filoviruses, but with a gradual onset of rash, hemorrhagic diathesis, and shock.

Bunyaviruses cause Rift Valley fever (< 1% develop hemorrhagic fever).

Flaviviruses cause yellow fever, Omsk hemorrhagic fever, and Kyasanur Forest disease.

The mainstay of treatment is supportive to maintain fluid and electrolyte balance, circulatory volume, and blood pressure. There are no FDA-approved antiviral drugs or vaccines.

Ricin, from castor beans, is cytotoxic through inhibition of protein synthesis; abrin is a similar toxalbumin agent.

Within a few hours of inhalation, victims develop cough and dyspnea, with the lungs rapidly becoming severely inflamed and filled with fluid. Skin might turn blue from cyanosis or flush red. Ingestion causes internal bleeding of the stomach and intestines. Injection kills the closest muscles and lymph nodes before spreading to other organs. Death can occur within 36-48 hours of all types of exposure from multiple organ failure.

No antidote is available. The mainstay of treatment is supportive, varying with the route of exposure. If victims survive more than 5 days, survival is likely.

a. In contrast, chickenpox rash is prominent on the trunk and develops in groups of lesions over several days.

b. In contrast, influenza patients rarely have a runny nose and usually have an abnormal chest x-ray and high white-blood-cell count.

Table 35-6. Chemical Agents That May Be Used in a Terrorist Attack

Chemical agents

Clinical features

Treatment

Nerve agents:

    G agents: sarin (GB), soman (GD), tabun (GA), cyclohexyl sarin (GF)

    V agents: VX

These nerve agents are organophosphates that attach to and inhibit acetylcholinesterase at muscarinic and nicotinic receptors, causing cholinergic crisis with miosis; vomiting; diarrhea; excessive bronchial, lacrimal, dermal, nasal, and salivary secretions; bradycardia or tachycardia; skeletal muscle fasciculations; paralysis; seizures; and respiratory failure. They are well absorbed through all routes of exposure. Symptoms occur within minutes after significant exposure and up to 18 hours after liquid exposure.

Rapid, thorough decontamination is needed. Antidotes include atropine to reverse muscarinic symptoms and pralidoxime early to restore acetylcholinesterase before permanent deactivation (aging) of the enzyme. Also give diazepam or lorazepam for seizures.

Blister agents:

    Mustards and nitrogen mustards

    Lewisites

    Chloroarsines

    Mustard-lewisite combinations

    Phosgene oxime (CX)

Mustards are vesicants that cause blistering of the skin and mucous membranes on contact, damaging skin, eyes, and lungs. Damage is immediate, but symptoms can be delayed 2-24 hours. Liquid forms are more likely to cause burns and scarring than will gas. All forms are absorbed through the skin and distributed systemically. Nitrogen mustards cause bone marrow suppression in 3-5 days. Sulfur mustards have garlic, onion, mustard, or no odor. Nitrogen mustards can smell fishy, musty, soapy, or fruity.

Lewisites and chloroarsines are arsenical vesicants that cause immediate pain and damage to the eyes, skin, and respiratory tract, although lesions may take hours to form. After absorption, they cause increased capillary permeability leading to hypovolemia, shock, and organ damage. Lewisite smells like geraniums. A mustard-lewisite combination is lewisite combined with distilled mustard.

Phosgene oxime is readily absorbed—causing immediate, painful corrosive and necrotic tissue damage—and has a disagreeable odor.

Sulfur and nitrogen mustards (thought to be alkylating agents that crosslink DNA strands) have no antidote. Avoiding contact or effecting rapid, thorough decontamination are the only preventions. Treatment is supportive. Exposure is not usually fatal (sulfur type < 5% fatal in World War I). No mustard is in tissue or blister fluids. British antilewisite is specific antidote for lewisite, used intramuscularly for systemic effects or topically as skin or eye ointment.

Chloroarsine treatment is similar, except atropine sulfate ointment is used for eyes.

No antidote exists for phosgene oxime.

Rapid decontamination and supportive treatment are used as for any corrosive agent.

Blood agents:

    Arsine (SA)

    Cyanide gases: hydrogen cyanide (AC), cyanogen chloride (CK)

    Cyanide solids: potassium (KCN), sodium (NaCN) cyanide

Arsine is a gas that causes nausea, vomiting, hemolysis, and secondary renal failure in 1-2 hours to 11 days. It has a garliclike odor.

Inhalation of highly concentrated cyanide causes an increased rate and depth of breathing in 15 seconds, convulsions in 30 seconds, cessation of respiration in 2-4 minutes, and cessation of heartbeat in 4-8 minutes. Progress and severity of symptoms after ingestion or inhalation of lower gas concentrations are slower and dose dependent. Gas may have odor of bitter almonds or peach kernels (AC); no odor; or irritating, lacrimating properties like riot control agents (CK).

For arsines, use symptomatic management of hemolysis, normally without chelation.

Cyanides bind to cytochrome oxidase. Two antidote kits are available. Cyanide Antidote Kit has a methemoglobin-forming agent (sodium nitrite) that binds cyanide and a sulfur donor to convert it to excretable sodium thiocyanate (sodium thiosulfate). CyanoKit combines hydroxocobalamin with cyanide to form nontoxic cyanocobalamin (vitamin B12). Fresh air, oxygen, and supportive treatment are essential.

Choking and pulmonary agents:

    Phosgene (CG)

    Diphosgene (DP)

    Ammonia

    Chlorine (CL)

    Hydrogen chloride

    Nitrogen oxide (NO)

    Perfluoroisobutylene (PHIB)

    Others

Phosgene gas causes eye, nose, throat, and pulmonary irritation, with serious pulmonary injury and edema delayed up to 48 hours, because it hydrolyzes to hydrochloric acid in moist conditions. It has a new-mown-hay odor. Phosgene is the prototype agent in the group. Other agents cause immediate irritation with potential for more severe delayed effects.

Ammonia hydrolyzes to caustic ammonium hydroxide.

Chlorine (pungent, greenish gas) hydrolyzes to hydrochloric acid.

Perfluoroisobutylene is a toxic pyrolysis product of Teflon.

Nitrogen oxides are components of blast weapons or fire.

Others include red (RP) and white phosphorus, sulfur trioxide-chlorosulfonic acid (FS), titanium tetrachloride (FM), and zinc oxide (HC).

Phosgene has no antidote. Good decontamination and symptomatic treatment are needed.

Treatment of other agents is similar because all agents in this class are gases with no antidotes. Thorough, rapid decontamination with fresh air is the best initial management, with thorough flushing of exposed eyes and skin and symptomatic treatment.

Incapacitating agents

These agents contain a variety of fast-acting central nervous system and respiratory depressants, often with hallucinogenic properties. The CDC list includes BZ/agent 15 (glycolate anticholinergic), cannabinoids, fentanyls and other opioids, LSD, and phenothiazines.

Management is decontamination with supportive treatment, and antidotes should be used when they exist (physostigmine for anticholinergics; naloxone for opioids).

Riot control and tear gases

Lacrimators include chloroacetophenone (CN) in several solvents and chloropicrin (PS), bromobenzylcyanide (CA), dibenzoxazepine (CR), and 2-chlorobenzalmalononitrile (CS) gases.

Treatment is symptomatic after decontamination. No antidotes are available.

Vomiting agents

These agents include adamsite (DM), diphenylchloroarsine (DA), and diphenylcyanoarsine (DC). They are rapidly incapacitating, irritant gases.

Symptomatic measures are used for sneezing, coughing, and vomiting (e.g., antiemetics).

Note: Military names are in parentheses.

Table 36-1. Drugs Used to Treat Iron Deficiency Anemia

Generic name

(trade name)

Elemental Fe (%)

Dose (mg)

Fe content (mg)

Ferrous sulfate

(Feosol, Fer-in-Sol)

20

325

65

Ferrous gluconate

(Fergon)

12

300

35

Ferrous fumarate

(Femiron, Fumerin, Feostat)

33

300

99

Table 36-2. Percentage of Patients Reporting Adverse Effects of Epoetin Alfa

 

Event

Patients treated with epoetin alfa (n = 200)

Patients on placebo (n = 135)

 

Hypertension

24%

19%

 

Headache

16%

12%

 

Arthralgias

11%

6%

 

Nausea

11%

9%

 

Edema

9%

10%

 

Fatigue

9%

14%

 

Vomiting

8%

5%

 

Chest pain

7%

9%

 

Skin reaction at site of administration

7%

12%

 

Asthenia

7%

12%

 

Dizziness

7%

13%

 

Clotted access

7%

2%

 

Significant adverse events:a

 

Seizure

1.1%

1.1%

 

Cerebrovascular accident-transient ischemic attack

0.4%

0.6%

 

Myocardial infarction

0.4%

1.1%

 

Death

0.0%

1.7%

 

a. Significant adverse events of concern in patients with chronic renal failure treated in double-blind, placebo-controlled trials occurred in the percentages of patients shown during the blinded phase of the studies.

Reproduced from Procrit package insert with permission of Ortho Biotech Products.

 
               

Table 37-1. Recommendations for VTE Prophylaxis

Medical condition

Recommended therapy

General medical

 

General medical patients with risk factors

LMWH, LDUH, or fondaparinux

Acute myocardial infarction

LDUH, IV UFH

Ischemic stroke

LDUH, LMWH; if anticoagulation prophylaxis is contraindicated, GCS or IPC

General surgery

 

Low risk:

 

    Patients undergoing minor procedures with no additional VTE risk factors

Early and frequent ambulation

Moderate risk:

 

    Major surgery for benign disease

LMWH, LDUH, or fondaparinux

    General surgery with multiple VTE risk factors

LMWH, LDUH tid, or fondaparinux

Higher risk:

 

    Major surgery for cancer

LMWH, LDUH tid, or fondaparinux combined with GCS ± IPC

    Major surgery for cancer or previous VTE

LMWH, LDUH tid, or fondaparinux

 

LMWH during hospitalization and continue up to 28 days post-discharge

    General surgery with high risk of bleeding

Mechanical prophylaxis with GCS or IPC until bleeding risk decreases, then use appropriate pharmacologic thromboprophylaxis

Gynecologic surgery

 

Low risk and no VTE risk factors or laparoscopic procedure

Early and frequent ambulation

Laparoscopic procedure with additional VTE risk factors

LMWH, LDUH, IPC, or GCS

Major surgery for benign disease without risk factors

LDUH, LMWH, or IPC starting just before surgery and continued until ambulating

Major surgery for malignancy and for patients with additional VTE risk factors

LMWH, LDUH tid, or IPC started before surgery and continued until ambulating; alternatively, LMWH, LDUH plus GCS or IPC, or fondaparinux

Select high-risk patients with major cancer surgery or a previous VTE

LMWH may be considered for up to 28 days after discharge

Urologic surgery

 

Transurethral or low-risk procedure

Early and frequent ambulation

Major or open urologic procedure

LDUH bid to tid, LMWH, fondaparinux, GCS and/or IPC

Highest-risk patients

LMWH or fondaparinux with GCS ± IPC started before surgery and continued until ambulating

Other

 

Elective total hip replacement

LMWH, fondaparinux, or warfarin for at least 10 days and up to 35 days; IPC is an alternative option with bleeding risk

Elective total knee replacement

LMWH, fondaparinux, or warfarin for at least 10 days and up to 35 days; IPC is an alternative option with bleeding risk

Hip fracture surgery

Fondaparinux, LMWH, warfarin, or LDUH for at least 10 days and up to 35 days

Neurosurgery

IPC, LDUH, or LMWH when risk of bleeding resolved

Trauma

LMWH, IPC, or GCS if bleeding occurs

Acute spinal cord injury

LMWH ± IPC or ES; convert to warfarin

Adapted with permission from Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest 2008;133(suppl 6):381S-453S.

Note: LMWH, low-molecular-weight heparin: enoxaparin 30 mg SC q 12 hours, enoxaparin 40 mg SC q 24 hours, dalteparin 5,000 units SC q 24 hours; LDUH, low-dose unfractionated heparin, 5,000 units SC q 8-12 hours; fondaparinux 2.5 mg SC q 24 hours; UFH, unfractionated heparin; GCS, graduated compression stocking; IPC, intermittent pneumatic compression device; warfarin, target INR 2.5, range 2.0-3.0.

Table 37-2. Guidelines for Anticoagulation: IV Unfractionated Heparin

 

Indication

Guidelines

 

VTE suspected

Obtain baseline aPTT, PT, and CBC count.

 
 

Check for contraindications to heparin therapy.

 
 

Order imaging study; administer IV bolus of heparin 80 IU/kg or 5,000 IU.

 

VTE confirmed

Rebolus with IV heparin 80 IU/kg and start maintenance infusion at 18 IU/kg/h.

 
 

Check aPTT at 6 hours to keep aPTT in a range that corresponds to a therapeutic blood heparin level.

 
 

Check platelet count between days 1 and 3.

 
 

Start warfarin therapy on day 1 at 5 mg, and adjust subsequent daily dose according to INR.

 
 

Stop heparin after at least 4-5 days of combined therapy when INR is ≥ 2.0 for 24 hours.

 
 

Anticoagulate with warfarin for at least 3 months at an INR of 2.5; range of 2.0-3.0.

 

Adapted with permission from Kearon C, Kahn SR, Agnelli G, et al. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest. 2008;133(suppl 6):454S-545S.

Note: For treatment with subcutaneous UFH, give 250 IU/kg SC q 12 hours to obtain a therapeutic aPTT in 6 hours.

 
       

Table 37-3. Guidelines for Anticoagulation: LMWH or Fondaparinux

 

Indication

Guidelines

 

VTE suspected

Obtain baseline aPTT, PT, and CBC.

 
 

Check for contraindications to LMWH or fondaparinux therapy.

 
 

Order imaging study; administer LMWH or fondaparinux.

 

VTE confirmed

Continue LMWH or fondaparinux.

 
 

Check platelet count between days 3 and 5.

 
 

Start warfarin therapy on day 1 at 5 mg, and adjust subsequent daily dose according to INR.

 
 

Stop LMWH or fondaparinux after at least 4-5 days of combined therapy when INR is ≥ 2.0 for 24 hours.

 
 

Continue warfarin for at least 3 months at an INR of 2.5; range of 2.0-3.0.

 

Adapted with permission from Kearon C, Kahn SR, Agnelli G, et al. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest. 2008;133(suppl 6):454S-545S.

Note: Dalteparin sodium 200 anti-Xa IU/kg per day SC; single dose should not exceed 18,000 IU. Enoxaparin 1 mg/kg SC q 12 hours or 1.5 mg/kg SC q 24 hours; single dose should not exceed 180 mg. Fondaparinux 5 mg for < 50 kg; 7.5 mg for 50-100 kg; 10 mg for > 100 kg SC q 24 hours.

 

Table 37-4. Duration of Anticoagulation Therapy

Indication

Duration of anticoagulation

VTE secondary to transient risk factor

Warfarin therapy for 3 months

First unprovoked VTE

Warfarin therapy for at least 3 months, but consider long-term therapy based on risk-benefit ratio

Second unprovoked VTE

Warfarin therapy long term

VTE and cancer

LMWH for the first 3-6 months of long-term anticoagulation therapy, followed by anticoagulation with LMWH or warfarin therapy long term or until cancer resolves

Adapted with permission from Kearon C, Kahn SR, Agnelli G, et al. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest. 2008;133(suppl 6):454S-545S.

       

Table 37-5. Body Weight-Based Dosing of IV Heparin

 

aPTT

Dose

 

Initial dose

80 IU/kg bolus, then 18 IU/kg per hour

 

< 35

80 IU/kg bolus, then 4 IU/kg per hour

 

35-45

80 IU/kg bolus, then 2 IU/kg per hour

 

46-70a

No change

 

71-90

Decrease infusion rate by 2 IU/kg per hour

 

> 90

Hold infusion 1 hour, then decrease infusion rate by 3 IU/kg per hour

 

Adapted from Raschke RA, Gollihare B, Peirce JC. The effectiveness of implementing the weight-based heparin nomogram as a practice guideline. Arch Intern Med. 1996;156:1645-49.

a. The therapeutic aPTT range of 46-70 seconds corresponded to antifactor Xa activity of 0.3-0.7 IU/mL at the time this study was performed. The therapeutic range at any institution should be established by correlation with antifactor Xa levels in this range.

 

Table 37-6. LMWH and Pentasaccharide Dosage Forms

Generic name

Trade name

Form and dose

LMWH

   

Dalteparin

Fragmin

2,500, 5,000, 7,5000 10,000, 12,500, 15,000, 17,500, and 18,000 unit syringe

Enoxaparin

Lovenox

30, 40, 60, 80, 100, 120, and 150 mg syringe

Tinzaparin

Innohep

20,000 anti-Xa IU/mL 2 mL vial

Pentasaccharide

   

Fondaparinux

Arixtra

2.5, 5, 7.5, and 10 mg syringe

         

Table 37-7. Pharmacokinetics of LMWHs and Pentasaccharides

Drug

Bioavailability (%)

Half-life (hours)

Xa:IIa binding ratio

Enoxaparin

92

3-6

1.9:1

Dalteparin

87

3-5

2.7:1

Tinzaparin

90

2-6

2:1

Fondaparinux

100

17-21

Only Xa binding

Table 37-8. Indications and Recommended Doses of LMWH and Fondaparinux

Indication

Enoxaparin

Dalteparin

Tinzaparin

Fondaparinux

Total hip replacement

30 mg SC q 12 hours or 40 mg SC q 24 hours

5,000 units SC 0-14 hours before surgery, then q 24 hours or 2,500 units SC 2 hours before surgery, then 5,000 units q 24 hours or 2,500 units SC 2 hours before surgery and 4-8 hours after, then 5,000 units q 24 hours

 

2.5 mg SC q 24 hours starting 6-8 hours after surgery

Total knee replacement

30 mg SC q 12 hours

   

2.5 mg SC q 24 hours starting 6-8 hours after surgery

Abdominal surgery

40 mg SC q 24 hours

2,500 units SC 1-2 hours before surgery, then 5,000 units q 24 hours

 

2.5 mg SC q 24 hours starting 6-8 hours after surgery

Hip fracture

     

2.5 mg SC q 24 hours starting 6-8 hours after surgery

Acute medical illness

40 mg SC q 24 hours

5,000 units SC q 24 hours

   

Trauma

30 mg SC q 12 hours

     

DVT treatment with or without PE

1 mg/kg SC q 12 hours or 1.5 mg/kg SC q 24 hours

 

175 units/kg SC q 24 hours

5 mg for < 50 kg; 7.5 mg for 50-100 kg; 10 mg for > 100 kg SC q 24 hours

VTE in patients with cancer

 

200 IU/kg SC daily for 1 month, followed by 150 IU/kg for 5 months

   

Unstable angina

1 mg/kg SC q 12 hours

120 units/kg SC q 12 hours

   
             

Table 37-9. Enoxaparin Dosage Regimens for Patients with Severe Renal Impairment (Creatinine Clearance < 30 mL/min)

Indication

Dosage regimen

Prophylaxis in abdominal surgery

30 mg SC once daily

Prophylaxis in hip or knee replacement surgery

30 mg SC once daily

Prophylaxis in medical patients during acute illness

30 mg SC once daily

Prophylaxis of ischemic complications of unstable angina and non-Q-wave myocardial infarction, when concurrently administered with aspirin

1 mg/kg SC once daily

Inpatient treatment of acute DVT with or without PE, when administered in conjunction with warfarin sodium

1 mg/kg SC once daily

Outpatient treatment of acute DVT without PE, when administered in conjunction with warfarin sodium

1 mg/kg SC once daily

Table 37-10. Recommended Therapeutic Ranges for Oral Anticoagulation

Indication

Target INR (INR range)

Prophylaxis of VTE (high-risk surgery)

2.5 (2.0-3.0)

Treatment of VTE

2.5 (2.0-3.0)

Unprovoked VTE in patients who desire less-intensive monitoring after 3 months of conventional therapy

(1.5-2.0) with less frequent monitoring

Prevention of thromboembolic events in patients with antiphospholipid syndrome with a lupus inhibitor

2.5 (2.0-3.0)

Patients with recurrent thromboembolic events with a therapeutic INR and a lupus inhibitor

3.0 (2.5-3.5)

Prevention of arterial embolism in atrial fibrillation

2.5 (2.0-3.0)

Prevention of arterial embolism with a bileaflet or Medtronic Hall tilting disk mechanical prosthetic heart valve in the aortic position who are in sinus rhythm without atrial enlargement

2.5 (2.0-3.0)

Prevention of arterial embolism in tilting disk or bileaflet mechanical prosthetic heart valve in the mitral position; caged ball or caged disk mechanical prosthetic valves

3.0 (2.5-3.5)

Mechanical prosthetic valve with additional risk factors such as atrial fibrillation, MI, left atrial enlargement, low ejection fraction, hypercoagulable state, or atherosclerotic vascular disease

3.0 (2.5-3.5) combined with low doses of aspirin 50-100 mg daily

Mechanical prosthetic valve with system embolism despite a therapeutic INR of 2.0-3.0

3.0 (2.5-3.5) ± low doses of aspirin 50-100 mg daily

Mechanical prosthetic valve with system embolism despite a therapeutic INR of 2.5-3.5

3.5 (3.0-4.0) ± low doses of aspirin 50-100 mg daily

Adapted with permission from Hirsh J, Guyatt G, Albers GW, et al. Executive summary: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest. 2008;133(suppl 6):71S-105S

     

Table 37-11. Drugs and Foods That Can Interact with Warfarin

Type of interaction

Interacting substance

Potentiation of anticoagulant effect

Acetaminophen, alcohol (acute use), anabolic steroids, cimetidine, clofibrate, disulfiram, piroxicam, omeprazole, simvastatin, sulfinpyrazone

Highly significant potentiation of anticoagulant effect

Amiodarone, ciprofloxacin, erythromycin, fluconazole, isoniazid, itraconazole, ketoconazole, levothyroxine, metronidazole, phenytoin, trimethoprim-sulfamethoxazole, vitamin E (high doses)

Reduction of anticoagulation effect

Alcohol (chronic use), dicloxacillin, griseofulvin

Highly significant reduction of anticoagulation effect

Barbiturates, carbamazepine, cholestyramine, enteral feeding, nafcillin, rifampin, vitamin K-containing foods (broccoli, brussels sprouts, cabbage, canola oil, cauliflower, coleslaw, collard greens, endive, green kale, lettuce, mayonnaise, mustard greens, soybean oil, spinach)

Table 37-12. Suggested Patient Risk Stratification for Perioperative Arterial or Venous Thromboembolism

Risk

Mechanical heart valve

Atrial fibrillation

VTE

High

Any mitral valve prosthesis

CHADS2 score of 5 or 6

Recent (within 3 months) VTE

 

Older (caged-ball or tilting disc) aortic valve prosthesis

Recent (within 6 months) stroke or transient ischemic attack

Recent (within 3 months) stroke or transient ischemic attack

Rheumatic valvular heart disease

Severe thrombophilia (e.g., deficiency of protein C, protein S, or antithrombin; antiphospholipid antibodies; or multiple abnormities)

Moderate

Bileaflet aortic valve prosthesis and one of the following: atrial fibrillation, prior stroke or transient ischemic attack, hypertension, diabetes, congestive heart failure, age > 75 years

CHADS2 score of 3 or 4

VTE within the past 3 to 12 months

Nonsevere thrombophilic conditions (e.g., heterozygous factor V Leiden mutation, heterozygous factor II mutation)

Recurrent VTE

Active cancer (treated within 6 months) or palliative

Low

Bileaflet aortic valve prosthesis without atrial fibrillation and no other risk factors for stroke

CHADS2 score of 0 or 2 (and no prior stroke or transient ischemic attack)

Single VTE occurred > 12 months ago and no other risk factors

CHADS2, congestive heart failure, hypertension, age, diabetes, stroke.

         

Table 37-13. Risk Stratification in AF Based on CHADS2 Score

Risk factors

Points

Previous stroke, transient ischemic attack

2

Congestive heart failure

1

Hypertension

1

Diabetes

1

Age > 75

1

Gage BF, Waterman AD, Shannon W, et al. Validation of clinical classification schemes for predicting stroke: Results from the National Registry of Atrial Fibrillation. JAMA 2001;285:2864-70.

Table 37-14. Stroke Rate Based on CHADS2 Score

 

CHADS2 score

Stroke riska

 

0

1.9%

 

1

2.8%

 

2

4.0%

 

3

5.9%

 

4

8.5%

 

5

12.5%

 

6

18.2%

 

Gage BF, Waterman AD, Shannon W, et al. Validation of clinical classification schemes for predicting stroke: Results from the National Registry of Atrial Fibrillation. JAMA 2001;285:2864-70.

a. Adjusted stroke rate per 100 person-years.

 
       

Table 37-15. Recommendations for Antithrombotic Therapy in AF

Risk category

Recommended therapy

No risk factors, age ≤ 75

Aspirin, 75-325 mg daily

One risk factor, age > 75, hypertension, diabetes, moderate or severe left ventricular systolic dysfunction, or heart failure

Aspirin, 75 to 325 mg daily, or warfarin with a target INR of 2.5 (INR range of 2.0-3.0)

Prior ischemic stroke, transient ischemic attack, or systemic embolism

Warfarin with a target INR of 2.5 (INR range of 2.0-3.0)

Two or more risk factors, age > 75, hypertension, diabetes, moderate or severe left ventricular systolic dysfunction, or heart failure

Warfarin with a target INR of 2.5 (INR range of 2.0-3.0)

Adapted with permission from Singer DE, Alberts GW, Dalen JE, et al. Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest. 2008;133(suppl 6):546S-92S.


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