THE APhA COMPLETE REVIEW FOR PHARMACY, 7th Ed

33. Pediatrics - Catherine M. Crill, PharmD, BCPS, BCNSP

33-1. Special Drug Therapy Considerations in Pediatric Patients

Pediatric Age Definitions

• Preterm: < 36 weeks gestation

• Term: ≥ 36 weeks gestation

• Neonate: < 1 month

• Infant: 1 month to < 1 year

• Child: 1-11 years

• Adolescent: 12-16 years

Absorption

Gastric pH

Infants may be considered to be in a relative state of achlorhydria (because of decreased basal acid secretion and total volume of secretions); however, they are capable of producing sufficient gastric acid with stimuli (e.g., in response to histamine or pentagastrin challenge, enteral feeding, or stress).

Gastric acid production reaches adult values by approximately age 3.

Implications for drug therapy

• Increased bioavailability of basic drugs

• Decreased bioavailability of acidic drugs

• Increased bioavailability of acid-labile drugs (e.g., penicillin G)

Gastric emptying time in pediatric patients

Gastric emptying time (GET) is longer for pediatric patients than for adults. GET is inversely related to postconceptional age.

GET is characterized by irregular and unpredictable peristalsis and decreased motility. Premature neonates have longer GET than term neonates and have a greater incidence of gastroesophageal reflux. GET is related to the type of feeding. Formula-fed infants exhibit longer transit time than do breast-fed infants.

Pediatric GET approaches adult function by 7-9 months. Stomach muscles are mature at 7 months. Stomach muscles are completely innervated at 9 months.

Implications for drug therapy

Absorption of sustained-release products (e.g., theophylline) is erratic. The rate of absorption in the small intestine, where most drugs are absorbed, is slower; peak drug concentrations are lower for children than for adults.

Pancreatic enzymes and bile salts

• Low levels of amylase and lipase

• Low intraluminal bile acid concentrations and synthesis

• Decreased proteolytic ability

Implications for drug therapy

• Erratic absorption of drugs requiring pancreatic enzymes for hydrolysis (e.g., chloramphenicol)

• Decreased absorption of lipid-soluble drugs

• Decreased fat absorption from enteral feedings

• Decreased absorption of fat-soluble vitamins

Gastrointestinal mucosa

• Functional integrity of intestinal mucosa is decreased.

• The surface area of the gastric mucosa is small compared to that of intestinal mucosa (most drugs are absorbed from the small intestine).

• Changes in splanchnic blood flow in the neonatal period may alter the concentration gradient across the intestinal mucosa.

Other absorption routes

Skin

Absorption through the skin is inversely related to the thickness of the stratum corneum and directly related to hydration of the skin. Neonates (particularly premature) have increased skin hydration. The stratum corneum of preterm infants is immature and ineffective as an epidermal barrier.

Premature neonates may develop drug toxicity if a drug is administered through the dermal route.

Buccal route

The buccal route is not typically used in pediatric patients.

Intramuscular route

Drug delivery is restricted by volume of medication and the pain associated with administration. Results are variable in premature neonates because of (1) blood flow and vasomotor instabilities and (2) insufficient muscle mass and tone, contraction, and oxygenation.

Rectal administration

Rectal administration is effective for drug delivery in older infants and children.

Administration through intraosseous route

This vessel-rich marrow (up to age 5) is a great site for drug delivery to the systemic circulation. It may be an acceptable route in emergency situations for children over age 5 (vessel-rich marrow is then replaced by yellow marrow).

Distribution

Protein binding

• Decreased albumin and α1-acid glycoprotein concentrations

• Lower binding capacity

• Qualitative differences in neonatal plasma proteins

• Competitive binding by endogenous substances (unconjugated bilirubin, free fatty acids)

• Risk of kernicterus (hypoalbuminemia, unconjugated hyperbilirubinemia, displacement by highly protein-bound drugs or free fatty acids)

• Exhibition of adult-like binding by 3-6 months of age; adult concentrations of albumin and α-acid glycoprotein at 10-12 months

Differences in body composition

• Vascular and tissue perfusion are altered.

• The brain and liver are the largest organs in children.

• Total body water is greater in neonates and infants.

• Extracellular fluid volume is greater in neonates and infants.

• There is a relative lack of adipose tissue in neonates and infants (adipose level increases into adulthood).

Implications for drug therapy in neonates and infants

• Increased free fraction of drugs can occur.

• Increased potential of drug displacement by endogenous substances is present.

• Potential risk of kernicterus with physiologic jaundice (unconjugated hyperbilirubinemia) is present.

• Hydrophilic drugs, which parallel water in the body (e.g., aminoglycosides), exhibit greater volume of distribution.

• Lipophilic drugs (e.g., diazepam) parallel body fat and will exhibit a smaller volume of distribution.

Liver Metabolism

Phase I reactions (nonsynthetic): Oxidation, reduction, hydrolysis, and hydroxylation

• The hepatic cytochrome P450 (CYP450) enzyme system is responsible for most phase I reactions.

• The capacity of isoenzymes in the CYP450 system at birth is 20-70% of adult capacity and increases with postnatal age.

• Full capacity for reduction is present at birth.

• Hydrolysis is most developed at birth, followed by the processes of oxidation and hydroxylation.

• Benzyl alcohol, a preservative present in certain medications, can accumulate in neonates because of underdeveloped alcohol dehydrogenase. Gasping syndrome (i.e., metabolic acidosis, respiratory failure, seizures, neurologic deterioration, and cardiovascular collapse) can result.

Phase II reactions (synthetic): Conjugation with glycine or glutathione, glucuronidation, sulfation, methylation, and acetylation

• The sulfation pathway is the most developed pathway at birth.

• Glucuronidation (i.e., UDP-glucuronosyltransferase [UGT] activity) begins around 2 months of age. It reaches adult capacity by age 2.

• Assumptions about substances primarily metabolized by glucuronidation (i.e., morphine, bilirubin, and chloramphenicol) are as follows:

• They are potentially toxic in neonates.

• They may exhibit long half-lives (e.g., toxicity with chloramphenicol).

• They may require greater dosing in infants (e.g., morphine conjugated to its more active metabolite).

• They may be metabolized by another pathway in infants (e.g., acetaminophen is primarily metabolized through sulfation in infants).

• Methylation is functional in infants but is not significantly expressed in adults. (Methylation is responsible for the conversion of theophylline to caffeine.)

Implications for drug therapy

• For drugs undergoing phase I and II reactions, the metabolism is reduced and the half-life is prolonged in infants and neonates.

• Insufficiency of one pathway may lead to metabolism through another.

• Adverse drug reactions are more likely in younger children (i.e., five times more likely in children under age 1 and three and one-half times more likely in children age 1-4).

• Drug metabolism, which is slower in the neonate, increases between 1 and 5 years of age and is similar to that in adults after puberty.

Renal Elimination

• Renal blood flow is only 5-6% of cardiac output at birth, compared with 15-25% in adults (12 mL/min versus 140 mL/min).

• Glomerular filtration rate is lower at birth and reaches adult values by 1-5 months of age in term infants.

• Tubular secretion is low at birth and reaches adult values by 7 months of age in term infants.

• Renal elimination is affected by prematurity and postconceptional age. It increases with maturity.

Estimation of creatinine clearance in pediatric patients

• The estimation of creatinine clearance (CrCl) is altered by differences in renal blood flow, glomerular filtration, tubular secretion, and muscle mass.

[

Table 33-1. Proportionality Constant for Calculation of Creatinine Clearance Using the Schwartz Equationa]

• It may be affected by the presence of maternal serum creatinine (SCr) over the first week of life (i.e., false underestimation of CrCl).

• The Schwartz equation may be used for calculation of CrCl:

   CrCl (mL/min/1.73 m2) = k × (length in cm)/SCr

   where k = proportionality constant that changes with age and sex (Table 33-1).

Other Pediatric Drug Issues

• Digoxin-like immunoreactive substance (DLIS) is produced in infants. DLIS may interfere with digoxin assays and falsely elevate concentrations.

• Di(2-ethylhexyl)phthalate (DEHP), a plasticizer contained in intravenous (IV) bags, is shown to have an effect on the male reproductive system. Pediatric patients at highest risk of DEHP exposure are neonates on extracorporeal membrane oxygenation, those receiving parenteral and enteral nutrition, and those receiving plasma exchange transfusions.

• Polyethylene glycol, an additive used to promote stability in certain IV medications, can cause hyperosmolarity in infants.

33-2. Specific Infections and Disease States in the Pediatric Population

Otitis Media

Otitis media is an inflammatory process of the middle ear.

Classification

• Acute otitis media is an inflammation of the area behind the eardrum (tympanic membrane) in the chamber called the middle ear. It is accompanied by the presence of fluid in the middle ear (effusion) and by the rapid onset of signs or symptoms of ear infection (also see the American Academy of Pediatrics [AAP] and American Academy of Family Physicians [AAFP] definition in section on diagnostic criteria).

• Recurrent otitis media is the diagnosis of three episodes of acute otitis media within a 6-month period or four episodes within a year.

• Otitis media with effusion is fluid in the middle ear (effusion) without the associated signs or symptoms of acute infection.

Clinical presentation

Signs and symptoms include fever, otalgia (often manifested as ear tugging or pulling), otorrhea (discharge from the ear), changes in balance or hearing, irritability, difficulty sleeping, lethargy, anorexia, vomiting, and diarrhea. Associated findings may be runny nose, congestion, or cough.

Pathophysiology

Eustachian tube dysfunction

The infant's eustachian tube is shorter and more horizontal than that of the adult, thus preventing drainage of middle ear secretions into the nasopharynx and promoting pooling of secretions in the middle ear. Anatomic abnormalities increase risk (e.g., cleft palate and adenoid hypertrophy). An immature immune system or altered host defenses also increase risk, as well as viral infections and allergies increase risk.

Risk factors include male gender; Native American, Canadian Eskimo, or Alaskan descent; family history of acute otitis media or respiratory tract infection; early age of first episode (earlier age is associated with greater severity and recurrence); day care environment; parental smoking; lack of breast-feeding in infancy; and pacifier use.

Complications include mastoiditis, meningitis, subdural empyema, hearing loss, and delayed speech and language development.

Microbial pathogens

Up to 50% of cases of acute otitis media may be viral in origin. The rest are bacterial:

• Streptococcus pneumoniae is responsible for 40-50% of bacterial otitis media. Resistance is becoming an increasing problem; bacterial resistance occurs primarily through alteration in penicillin-binding protein (decreased affinity for binding sites).

• Haemophilus influenzae (primarily nonencapsulated or nontypeable strains) is responsible for 20-30% of bacterial otitis media cases. Bacterial resistance occurs through β-lactamase production.

• Moraxella catarrhalis is responsible for 10-15% of bacterial otitis media. Almost all strains are β-lactamase producing.

Diagnostic criteria

For diagnosis of otitis media, the clinical presentation must show signs and symptoms consistent with infection.

In 2004, the AAP and AAFP published a clinical practice guideline on the diagnosis and management of acute otitis media. The guideline presented a revised definition of acute otitis media as follows: "diagnosis requires: (1) a history of acute onset of signs and symptoms, (2) the presence of middle ear fluid (by a bulging tympanic membrane, limited/absent mobility of or air-fluid level behind the tympanic membrane, or otorrhea), and (3) signs and symptoms of middle ear inflammation (distinct erythema of the tympanic membrane or distinct otalgia referable to the middle ear that interferes with normal sleep/activity)."

When middle ear disease is present, otoscopic examination determines color, translucency, and position. Redness or opacity of membrane, absence of light reflection, or bulging membrane will be observed.

Pneumatic otoscopic examination determines mobility of the tympanic membrane (i.e., presence or absence of effusion). The membrane will not move briskly with positive and negative pressure if effusion is present.

Tympanocentesis (i.e., a needle is inserted through the tympanic membrane to withdraw fluid) allows for culture and identification of the pathogen.

Treatment principles and goals

• Assess and control pain.

• Eradicate infection.

• Prevent complications.

• Avoid unnecessary antibiotic therapy.

• Improve compliance.

• Eliminate presence of effusion.

• Prevent recurrence.

Drug therapy

Many episodes of otitis media will have spontaneous resolution; however, because there is a risk of developing complications from untreated otitis media, antimicrobials remain the mainstay of therapy. Observation therapy may be appropriate in certain patients, depending on age, diagnostic certainty, and severity of illness and when follow-up can be ensured.

First-line therapy

Amoxicillin is the drug of choice for uncomplicated and nonsevere (mild otalgia and fever < 39°C or 102.2°F) acute otitis media. Amoxicillin has excellent in vitro activity against Streptococcus pneumoniae and most Haemophilus influenzae. It has the optimal pharmacodynamic profile of the available agents and reaches good concentrations in middle ear fluid.

Amoxicillin has an excellent safety and efficacy profile with narrow spectrum of activity. It is palatable and inexpensive. It may overcome drug-resistant S. pneumoniae with higher doses (i.e., achieves greater concentrations in middle ear fluid). It does not eradicate β-lactamase-producing organisms.

For penicillin-allergic patients (non-type I hypersensitivity), cefdinir, cefpodoxime, or cefuroxime may be used. In patients with type I reactions (urticaria or anaphylaxis), azithromycin, clarithromycin, trimethoprim-sulfamethoxazole (6-10 mg/kg/day of trimethoprim), or erythromycin-sulfisoxazole (50 mg/kg/day of erythromycin) may be substituted; however, resistance appears to be increasing with these agents. Depending on the severity of the illness, ceftriaxone therapy may be initiated. Clindamycin may be used when drug-resistant S. pneumoniae is suspected.

Amoxicillin-clavulanate should be used as first-line therapy, depending on the severity of illness (moderate to severe otalgia or fever ≥ 39°C or 102.2°F).

Other effective antimicrobial agents include other cephalosporins (cefprozil, cefaclor, and ceftibuten). Fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin) are thought to be effective, but they are not approved for use in pediatric patients.

Dosing issues and drug resistance

Treatment options are described in

Table 33-2.

Dosages are as follows:

• Amoxicillin: A high dose is recommended (80-90 mg/kg/day).

• Amoxicillin-clavulanate: A high dose is recommended (90 mg/kg/day of amoxicillin with 6.4 mg/kg/day of clavulanate). Maintain daily

[Table 33-2. Treatment Options for Otitis Media]

   clavulanate dose < 10 mg/kg/day to prevent diarrhea.

• Ceftriaxone: An intramuscular (IM) dose of 50 mg/kg/day (single dose versus three daily doses) is recommended.

Duration of therapy

Two courses of therapy are possible:

• Standard 10-day course

• Shorter course (1-7 days)

Advantages of the shorter course are improved compliance, decreased adverse effects of drug therapy, decreased risk of bacterial resistance, and lower costs. Disadvantages are delayed or no cure, increased risk of complications from untreated acute otitis media, and greater risk of recurrence.

A shorter course is not appropriate for the following:

• Children under age 2 (AAP and AAFP state under age 6)

• Children with severe disease

• Those in day care

• Those with underlying diseases

• Those with a history of recurrent otitis media

Other therapy

Antipyretics (acetaminophen and ibuprofen) or analgesics may be used. Use acetaminophen with caution in high doses to avoid hepatotoxicity. Use ibuprofen with caution in patients with vomiting, diarrhea, and poor fluid intake, because dehydration predisposes to ibuprofen-induced renal insufficiency. Avoid alternating antipyretic therapy. Encourage parents to choose one agent, inform them of any adverse effects, and educate them about symptoms of these effects (e.g., hepatotoxicity or renal insufficiency).

Narcotic analgesics may be used for moderate to severe pain not controlled with acetaminophen or ibuprofen.

Topical analgesics include otic solutions, such as antipyrine-benzocaine (Auralgan and Americaine Otic) and naturopathic agents (Otikon Otic Solution).

Topical antimicrobials may have a place in therapy, particularly with ruptured membranes (fluoroquinolone or fluoroquinolone and steroid combination otic suspensions [Floxin, Cipro HC, and Ciprodex]).

Antihistamines and decongestants are ineffective at eliminating effusion or relieving symptoms. Use them only if indicated for other signs or symptoms.

Patient instructions and counseling

• Complete the entire course of prescribed antibiotics.

• Shake bottle well before administering dose. Follow labeling regarding temperature for storage of medication.

• Contact the physician if patient develops a rash or has difficulty breathing, or if symptoms persist after 72 hours of initiating therapy.

Adverse drug events

• Gastrointestinal effects: Nausea and diarrhea; discoloration of stools (with cefdinir)

• Hypersensitivity: Rash and anaphylaxis

Drug interactions

Drug interactions may occur with macrolides, particularly erythromycin and clarithromycin.

Nondrug therapy

Local heat or cold therapy may be used (counsel the caregiver on appropriate use and technique to prevent burn injury).

Tympanostomy tubes decrease recurrent episodes, restore hearing, and relieve discomfort. Risks include anesthesia and permanent tympanic membrane scarring.

Observation therapy

Observation therapy is appropriate only when follow-up at 48-72 hours can be ensured and antimicrobials initiated if symptoms persist or worsen. This therapy is not appropriate for the following:

• Infants < 6 months of age

• Infants and children between 6 months and 2 years of age with a certain diagnosis (nonsevere or severe illness) or an uncertain diagnosis (severe illness)

• Children ≥ 2 years of age with a certain diagnosis and severe illness

nonsevere illness is mild otalgia and fever < 39°C or 102.2°F. A severe illness is moderate to severe otalgia or fever ≥ 39°C or 102.2°F.

Immunization and immunoprophylaxis

Pneumococcal conjugate vaccination should provide some protection against strains responsible for a majority of bacterial otitis media.

Haemophilus influenzae type B vaccination is of no benefit in otitis media. Most strains causing otitis media are nontypeable and not prevented by vaccination.

Killed and live-attenuated intranasal influenza vaccine may decrease episodes of acute otitis media during the respiratory season. Most children studied were less than 2 years of age.

Risk reduction

• Alter day care attendance (when possible).

• Adopt exclusive breast-feeding for 6 months.

• Avoid supine bottle feeding.

• Reduce or eliminate pacifier use after 6 months of age.

• Eliminate passive exposure to tobacco smoke.

Recurrent otitis media

Prophylaxis with half therapeutic dosing of amoxicillin or sulfisoxazole has been initiated in high-risk patients; however, this practice is no longer recommended because of concerns over emergence of drug-resistant organisms.

Otitis media with effusion

The AAP, AAFP, and the American Academy of Otolaryngology-Head and Neck Surgery published a clinical practice guideline on otitis media with effusion in 2004. It applies to infants and children (2 months to 12 years of age) with or without developmental disabilities or underlying conditions that predispose patients to otitis media with effusion. Recommendations include the following:

• Use pneumatic otoscopy as the primary diagnostic method.

• Distinguish otitis media with effusion from acute otitis media.

• Determine the risk of speech, language, and learning problems.

• At-risk children: More rapid evaluation and intervention

• Children not at risk: Watchful waiting for 3 months from date of onset or diagnosis

• No role exists for antihistamines, decongestants, antimicrobials, or corticosteroids.

• Hearing testing is recommended with effusion lasting ≥ 3 months or when language delay, learning problems, or hearing loss exists.

• For persistent otitis media with effusion (not at risk), perform evaluations every 3-6 months until effusion is resolved, hearing loss is identified, structural abnormalities are suspected, or the child becomes a surgical candidate (tympanostomy tube insertion is preferred).

Otitis Externa

Otitis externa is an inflammation of the outer ear canal, also referred to as swimmer's ear.

Clinical presentation

Patients present with itching, pain, otic exudate, and hearing impairment

Pathophysiology

Moisture is present in the ear canal and the integrity of the ear canal is disrupted. The most common organisms are Pseudomonas aeruginosa and Staphylococcus aureus. Other pathogens include fungi and Bacillus and Proteus species.

Therapy consists of antibiotic or steroid otic preparations such as neomycin, polymyxin, and hydrocortisone (Cortisporin Otic) or neomycin, colistin, and hydrocortisone (Coly-Mycin S Otic). Fluoroquinolone otic preparations such as ciprofloxacin (Cipro HC) and ofloxacin (Floxin) can also be used, as well as acetic acid and hydrocortisone otic preparations (VoSol HC Otic) or oral analgesics.

Preventive measures include drying ears after exposure to moisture; using drops containing isopropyl alcohol, with or without acetic acid to reduce pH; and avoiding cotton swabs.

According to a 1994 special report of the American Pharmaceutical Association, otic drops should be applied as follows:

1. Wash hands before and after administration.

2. Warm otic drops to room temperature by holding bottle in hands for several minutes. Avoid instilling cold or hot drops into the ear canal.

3. Shake the bottle if indicated on the label.

4. Tilt the child's head to the side or have the child lie down.

5. Pull the child's ear backward and upward and instill the drops in the ear canal. Do not put the dropper bottle inside the ear canal. To remain free from contamination it should not come into contact with the ear.

6. Press gently on the small flap over the ear to push the drops into the canal.

7. Have the child remain in the same position for the period of time indicated in the labeling. If this is not possible, place a cotton ball gently into the ear to prevent the drops from draining out of the ear canal.

8. Wipe excess medication from the outside of the ear.

Cystic Fibrosis

Cystic fibrosis is an autosomal recessive disease of exocrine gland function resulting in abnormal mucus production.

Genetic classification

Cystic fibrosis is the result of a gene mutation on the long arm of chromosome 7. The protein encoded by this gene, the cystic fibrosis transmembrane regulator (CFTR), is a channel involved in the transport of water and electrolytes.

Defects in processing

The most common genetic mutation involves a 3-base-pair deletion at position 508 (ΔF508). Patients homozygous for ΔF508 are pancreatic insufficient.

Prognosis is not as good as that for patients who are pancreatic sufficient. Defects exist in protein production, regulation, and conduction.

Clinical presentation

Pulmonary complications

Initial manifestations include chronic cough, wheezing, hyperinflation of lungs, or lower respiratory tract infections. Patients present with hypoxia, clubbing, labored breathing, and acute respiratory exacerbations (fever, sputum production, increased oxygen requirements, and dyspnea); changes in forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and residual volume; and the development of a chronic obstructive picture as the disease progresses.

Gastrointestinal complications

Gastrointestinal complications include poor digestion of proteins and fats, resulting in foul-smelling steatorrhea, and distal intestinal obstruction (commonly manifested as vomiting of bilious material, abdominal distension, and pain).

Infants may have meconium ileus and gastroesophageal reflux.

Other complications

Patients may also have the following complications:

• Cirrhosis and cholelithiasis

• Problems with pancreatic function

• Insulin insufficiency and diabetes mellitus

• Malnutrition

• Nasal polyps and sinusitis, anemia, arthritis, osteopenia, and osteoporosis

Pathophysiology

A defect exists in the chloride transport channel in secretory epithelial cells. Normally, chloride is transported out of blood followed by sodium and water. However, with cystic fibrosis, decreased chloride and water secretion and increased sodium absorption lead to thick, dehydrated secretions and mucus. Exocrine gland involvement includes pancreas, hepatobiliary ducts, gastrointestinal tract, and the lungs (secretions build up and block airways and pancreatic and hepatobiliary exocrine flow).

Pulmonary system

Initial obstruction of small airways with mucus plugging results in bronchiolitis and persistence of bacteria, as follows:

• Early bacterial pathogens: Staphylococcus aureus and Haemophilus influenzae present in younger patients.

• Later bacterial pathogens: Pseudomonas aeruginosa is the primary pathogen in late childhood.

• Other bacterial pathogens: Proteus and Klebsiella species, Stenotrophomonas maltophilia, and Burkholderia cepacia can be present.

Viral pathogens can also be present.

Chronic pulmonary infection and inflammation progress to large airway and eventual chronic obstructive disease.

Pancreatic system

Pancreatic enzyme insufficiency (trypsin, chymotrypsin, lipases, and amylase) and decreased bicarbonate secretion (necessary for optimal pancreatic enzyme activity) can occur. Thus, maldigestion of fats and proteins and fat-soluble vitamin deficiency may develop.

Insulin insufficiency (resistance and decreased secretion) leads to glucose intolerance and the development of diabetes mellitus (occurs later in the disease process and may be associated with increased morbidity and mortality).

Biliary system

Biliary cirrhosis or fatty infiltration may lead to portal hypertension, development of bleeding varices, hypersplenism, and cholelithiasis.

Sweat glands

A high concentration of sodium and chloride exists in sweat (representing the failure of sweat glands to reabsorb sodium and chloride).

Reproductive system

Male infertility is common because of bilateral absence of vas deferens. Female infertility is due to abnormal cervical mucus.

Diagnostic criteria

Laboratory confirmation of CFTR dysfunction should be obtained through sweat chloride analysis (i.e., administration of pilocarpine):

• Sweat is collected and electrolytes are measured.

• Chloride of 60 mEq/L or more is diagnostic (values of up to 80 mEq/L have been seen in non-cystic fibrosis patients).

• Levels of 50-60 mEq/L are indeterminate, and tests may need to be repeated.

Presence of clinical characteristics of cystic fibrosis should also be observed.

Treatment goals

• Halt or decrease disease progression.

• Maintain normal growth and development and nutrition status.

• Maintain pulmonary function.

• Optimize drug therapy for pharmacokinetic differences in cystic fibrosis patients.

Drug therapy

Drug therapy for cystic fibrosis is described in

Table 33-3.

Antibiotic therapy in acute exacerbations

Empiric therapy should be used initially. The patient should then be treated on the basis of sputum culture and sensitivity. Administer intravenously two antibiotics for 14-21 days in combination with aggressive therapy for clearance of secretions. Provide coverage for Staphylococcus aureus, Haemophilus influenzae, and Pseudomonas aeruginosa.

Double coverage of antibiotics is needed when Pseudomonas species are suspected, so typically use an antipseudomonal penicillin (piperacillin, mezlocillin, piperacillin-tazobactam, ticarcillin-clavulanate, ticarcillin, aztreonam, meropenem, or imipenem) or a cephalosporin (ceftazidime) plus an aminoglycoside (tobramycin).

Most S. aureus are β-lactamase producers, so use an extended spectrum penicillin—β-lactamase inhibitor combination (e.g., ticarcillin-clavulanate). Use vancomycin for methicillin-resistant S. aureus.

Burkholderia and Stenotrophomonas species are commonly resistant. Follow culture and sensitivity results. Antibiotics that may be effective include trimethoprim-sulfamethoxazole, chloramphenicol, ceftazidime (B. cepacia), doxycycline, and piperacillin (S. maltophilia).

Other agents include ciprofloxacin.

Antibiotic therapy and chronic suppression

Chronic inhaled antibiotic therapy with tobramycin

This therapy results in significant improvement in FEV1, decreased hospitalizations, and decreased need for IV antibiotics. Decreased systemic concentrations (i.e., less resistance) and high pulmonary concentrations appear. However, therapy is expensive.

Oral antibiotic therapy

Fluoroquinolones are the only oral antibiotics with good coverage against Pseudomonas.

Patient instructions and counseling

Compliance with therapeutic regimens is important.

Pancreatic enzyme supplementation

• Give immediately before or during snacks and meals.

• Capsule may be opened and contents sprinkled on applesauce or other acidic carrier.

• Contents should not be crushed or chewed.

Aminoglycosides

• Monitor urine output.

• Use ibuprofen with caution if dehydration, diarrhea, or decreased oral intake is present.

Adverse drug events

• Aminoglycosides: Nephrotoxicity and ototoxicity

• Ibuprofen: Renal insufficiency

• Fluoroquinolones: Arthropathy

[Table 33-3. Drug Therapy for Cystic Fibrosis]

Drug interactions

Pancreatic enzymes and acid suppression therapy may decrease inactivation of enzymes by gastric acid, thereby reducing dose requirement.

Monitoring parameters

Clinical status should be monitored:

• Fever and activity level

• Pulmonary function (as indicated by FEV1, FVC, residual volume, and chest radiography)

Pharmacokinetic considerations

Aminoglycosides

• Increased clearance and larger Vd, necessitating greater dosing

• Concentration-dependent killing

• Postantibiotic effect against Gram-negative organisms

• Higher doses (10 mg/kg/day tobramycin)

• Peak concentrations from 8-12 mcg/mL

• Trough concentrations of less than 2 mcg/mL

β-Lactams

• No change or increased clearance

• No change or increased Vd

• No postantibiotic effect or concentration-dependent killing

Fluoroquinolones

• Concentration-dependent killing

• Postantibiotic effect against Gram-negative organisms

Nondrug therapy

Pulmonary percussion therapy and postural drainage

The purpose of this therapy is to clear mucus and secretions from the pulmonary system. Therapy is conducted once or twice per day and up to five times daily or more. Percussion is usually conducted after nebulization therapy with or without bronchodilator or mucolytic. Therapy with handheld devices or oscillatory vests can be done.

Transplantation

Lung transplantation is an option. Liver-lung transplantation can be done if there is liver involvement.

Attention-Deficit/Hyperactivity Disorder

According to the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), attention-deficit/hyperactivity disorder (ADHD) is a behavioral disorder of childhood onset (by age 7) characterized by symptoms of inattentiveness and impulsive or hyperactive behavior.

Classification

DSM-IV makes the following classifications:

• Combined type: Criteria for inattention, hyperactivity, and impulsivity are met.

• Predominantly inattentive type: Criteria for inattention are met, but not for hyperactivity and impulsivity.

• Predominantly hyperactive and impulsive type: Criteria for inattention are not met, and criteria for hyperactivity and impulsivity are met.

• ADHD not otherwise specified.

Clinical presentation

• Inattention: The child has difficulty paying attention, daydreams frequently, is easily distracted and disorganized, and loses things frequently.

• Hyperactivity: The child has difficulty staying seated and talks too much.

• Impulsivity: The child acts and speaks out without thinking, and the child also interrupts others frequently.

Pathophysiology

ADHD results from an imbalance in catecholamine neurotransmission (specifically between dopamine and norepinephrine).

Genetic basis

Genetic studies have primarily evaluated genes involved in neurotransmission. ADHD is likely to be due to the interaction of many genes. Most evidence currently indicates that dopamine transmitter (DAT-1) and dopamine D2 and D4 receptors are responsible (dopamine and norepinephrine are potent agonists of the D4 receptor).

Diagnostic criteria

Diagnostic criteria must be met for accurate diagnosis. Diagnosis is based on DSM-IV criteria that six or more of the criteria for inattention or hyperactivity and impulsivity are met for at least 6 months "to a degree that is maladaptive and inconsistent with developmental level."

Some impairment should be present before age 7. Impairment should be present in at least two settings (e.g., home and school). Evidence of clinically significant impairment in functioning should also be present.

Symptoms must not be related to another illness (e.g., schizophrenia or mood disorder).

Treatment goals

• Educate the patient and family.

• Improve functioning and behavior.

• Achieve effective drug therapy with minimal side effects.

Drug therapy

Table 33-4 describes drug therapy for ADHD.

Patient counseling

Advise patients and caregivers of the need to store medications away from other children or siblings because of the potential for lethal overdose (tricyclic antidepressants) and for abuse (stimulants).

Adverse drug events

Stimulants cause anorexia, abdominal pain, headache, insomnia, jitteriness, social withdrawal, transient motor tics, and weight loss (not height dependent).

Methylphenidate is contraindicated in a seizure disorder according to the package insert (i.e., it lowers the seizure threshold). Canada has suspended marketing of Adderall XR because of concern over reports of sudden death and stroke in patients taking Adderall or Adderall XR.

Tricyclics carry cardiotoxicity risk (sudden death). Patients should undergo electrocardiogram (ECG) testing prior to initiation of therapy and periodically throughout therapy.

Bupropion may lower the seizure threshold. Seizures are associated with high doses and a previous history of seizure disorders. Minimize risk by dividing the daily dose or by using the extended-release formulation.

Labeling for all the stimulants and for atomoxetine includes warnings for an increased risk of psychosis or mania, aggression or violent behavior, and anxiety or panic attacks. Atomoxetine labeling includes warnings for an increased risk of suicidal ideation in children and adolescents and for the potential for severe liver injury.

Drug interactions

Methylphenidate

• Methylphenidate should not be given with monoamine oxidase (MAO) inhibitors (severe hypertension).

• Caffeine may enhance stimulant effects.

• Methylphenidate may inhibit metabolism of phenytoin, phenobarbital, warfarin, and tricyclics.

Tricyclics

• Multiple pharmacodynamic and pharmacokinetic drug interactions exist.

• Increased plasma concentrations of tricyclics could result in potential toxicity when certain antidepressants are added to the regimen (fluoxetine, sertraline, fluvoxamine, paroxetine) as well as with cimetidine, methylphenidate, diltiazem, quinidine, and verapamil.

• Decreased concentrations of tricyclics may be seen with concomitant administration of carbamazepine and phenytoin.

• Increased therapeutic effect and potential toxicity may occur with MAO inhibitors.

• Increased central nervous system depressant effects occur with alcohol and sedatives.

Recommendations for therapy and monitoring

The efficacy of therapy should be monitored. Assess behavior changes and evaluate feedback from teachers and parents.

Stimulants

Begin with a low dose, and titrate upward to optimal functioning ability. The patient may need a decreased dose if side effects occur or if no further improvement is seen with the larger dose.

No therapeutic drug monitoring or ECG monitoring is needed.

If one stimulant fails, try another stimulant for the patient. For children who fail two stimulants, try a third type of stimulant.

Tricyclics

Initial and periodic ECGs are needed.

Pharmacokinetic considerations

Methylphenidate does not distribute well into adipose tissue (dose on milligram basis instead of milligrams per kilogram).

Nondrug therapy

• Behavioral techniques (e.g., positive reinforcement, time out, response cost, and token economy)

• Environmental modifications

• Classroom management

Conjunctivitis

Conjunctivitis is an inflammation of the conjunctiva of the eye.

[Table 33-4. Drug Therapy for Attention-Deficit/Hyperactivity Disorder]

Classification

Conjunctivitis may be bacterial, viral, or allergic.

Clinical presentation

Conjunctivitis is characterized by redness of the eye, itching, ocular discharge, foreign body sensation, and crusting of the eye and eyelid. Patient may have altered vision because of the presence of discharge.

Pathophysiology

Conjunctivitis of the newborn

Inflammation of the conjunctiva often occurs in the first month of life. Causative agents include topical antimicrobial agents; bacteria (primarily Neisseria gonorrhoeae, Chlamydia trachomatis, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Escherichia coli, and other Gram-negative bacteria); and viruses (primarily herpes simplex).

Bacterial conjunctivitis (beyond first month of life)

The most common bacteria are Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, and Haemophilus influenzae (also gonococcal and chlamydial). Treat bacterial conjunctivitis with antibiotic therapy.

Viral conjunctivitis

Viral conjunctivitis, also known as pink eye, is contagious. Adenovirus is the most common causative agent.

This condition is commonly preceded by a cold or sore throat or exposure to another person with viral conjunctivitis.

Herpes simplex (corneal involvement may yield permanent visual damage) may also be seen.

Allergic conjunctivitis

Allergic conjunctivitis is caused by exposure to dander, pollen, or topical eye preparation. Most patients will exhibit itching of the eye.

Diagnostic criteria

Diagnosis is based on the patient's symptoms.

Treatment goals

• Eliminate or avoid the allergen (allergic conjunctivitis).

• Treat the underlying infection (bacterial conjunctivitis).

• Decrease severity and provide symptomatic relief (all forms).

Drug therapy

Neonatal

Preventive medicine includes prophylaxis after delivery with antibacterial ophthalmic ointment (erythromycin, tetracycline, silver nitrate, and povidone-iodine):

• Onset day 1: No treatment (secondary to prophylaxis after delivery)

• Onset days 2-4 (Neisseria gonorrhoeae): Penicillin G or ceftriaxone for 7 days

• Onset days 3-10 (Chlamydia trachomatis): Oral erythromycin + erythromycin ointment for 14 days

• Onset days 2-16 (herpes simplex): Possibly IV acyclovir

Bacterial (beyond first month of life)

Topical antibiotic therapy (bacitracin-polymyxin B, trimethoprim-polymyxin B, erythromycin, or fluoroquinolone [ciprofloxacin, gentamicin, or tobramycin]) should be used in combination with an antibiotic ointment (erythromycin or bacitracin) at bedtime for 5-7 days.

Gonococcal

Ceftriaxone should be used for one dose. With corneal ulceration, use systemic IV ceftriaxone therapy. Also treat for Chlamydia species.

Chlamydial

For adults, oral tetracycline or doxycycline is administered for 2-3 weeks. Administer a single dose of azithromycin to children.

Viral

Ocular lubricant (artificial tears) should be administered every 3-4 hours while the patient is awake.

Allergic

Remove allergen. Use ocular lubricant (artificial tears); ocular decongestants (phenylephrine, naphazoline, tetrahydrozoline, and oxymetazoline: α-adrenergic activity); antihistamines (olopatadine [Patanol]); antihistamine-decongestant combination products (pheniramine and naphazoline [Naphcon-A, Opcon-A, and Visine-A]); topical mast cell stabilizer (cromolyn sodium); combination mast cell stabilizer and antihistamine; or oral antihistamine therapy.

Adverse drug events

Ocular decongestants can cause rebound congestion of the conjunctiva. This reaction is less common with naphazoline and tetrahydrozoline.

Instilling of eye drops and ointment

Wash hands before and after administration. Tilt head back, grasp lower eyelid and pull away from eye, place dropper or ointment tube over eye, and have the child look up immediately before instilling the drop.

For ointment, use a sweeping motion and instill 0.25 to 0.5 inch of ointment inside eyelid. Close eye after instillation, and wait 1-2 minutes. Blot excess ointment or solution away from around the eye. Vision may be temporarily blurred with ointment administration.

Wait 5 minutes between drops for multiple drop therapy. For suspension, place that drop in the eye last. For use of both ointment and drops, instill drops first and wait 10 minutes before applying ointment.

Patient instructions and counseling

• Wash hands.

• Do not share towels or linens.

• Store products according to labeling instructions.

Nondrug therapy

Cold compresses are a helpful nondrug therapy.

Recent Pediatric Medication Issues and Labeling Changes

In October 2004, the U.S. Food and Drug Administration (FDA) mandated black box warnings for all antidepressants regarding the potential for increased suicidal behavior in children.

In January 2005, the FDA sent out a letter warning health care professionals that the use of promethazine is contraindicated in children under age 2 because of the risk of respiratory depression and death.

In July 2005, the FDA mandated black box warnings for the use of fentanyl. The FDA mandated that fentanyl should not be used in children under age 2 and should only be used in children 2 years of age or older if they are already using other opioid narcotic pain medicines (i.e., they are opioid tolerant).

In January 2006, the FDA requested the addition of boxed warnings to the labeling for Elidel Cream (pimecrolimus) and Protopic Ointment (tacrolimus) to notify patients about the possible risk of cancer. Use of these drugs in children under age 2 is not recommended.

In May 2006, the FDA requested labeling changes for Serevent Diskus (salmeterol xinafoate inhalation powder), Advair Diskus (fluticasone propionate and salmeterol inhalation powder), and Foradil Aerolizer (formoterol fumarate inhalation powder) to include a warning that these medicines may increase the risk of severe asthma attacks and death when these attacks occur.

In August 2007, a letter was sent out warning health care professionals about the concomitant use of ceftriaxone and IV calcium-containing products and the risk of ceftriaxone and calcium precipitation. Deaths attributable to intravascular and pulmonary precipitates have occurred in neonates. Ceftriaxone should not be used in neonates (≤ 28 days of age) if they are receiving or are expected to receive calcium-containing IV products.

In October 2007, the FDA recommended that over-the-counter cough and cold medicines not be used in infants and children under age 2 because of the risk of serious and potentially life-threatening side effects.

In January 2008, the FDA mandated labeling changes for antiepileptic agents to include a warning about the risk of suicidal thoughts or actions.

33-3. Key Points

• The pharmacokinetics and pharmacodynamics of medications are altered by developmental differences in absorption, distribution, metabolism, and elimination in pediatric patients.

• Pharmacotherapy should be adjusted according to the developmental differences to optimize therapeutic efficacy while minimizing the risk of toxicity.

• Although spontaneous resolution does occur in many cases of acute otitis media, antibiotic therapy is initiated to prevent complications such as meningitis and mastoiditis. The observation option is an acceptable initial treatment for select patients depending on age, certainty of diagnosis, and disease severity.

• The incidence of drug-resistant Streptococcus pneumoniae is increasing. Because of its safety profile, cost, and excellent pharmacodynamic profile against sensitive and drug-resistant S. pneumoniae, amoxicillin remains the drug of choice for uncomplicated and nonsevere acute otitis media. Higher doses should routinely be used.

• Therapy for cystic fibrosis should focus on halting the progression of the disease and maintaining pulmonary function. Appropriate therapies decrease mucus viscosity and increase clearance of secretions; manage acute infectious exacerbations; and by using appropriate pancreatic enzyme supplementation, maintain normal growth and development.

• Pharmacokinetics of medications in cystic fibrosis patients may be altered; therapeutic drug monitoring and dose alterations should be conducted to ensure efficacy and decrease toxicity.

• An accurate diagnosis of attention-deficit/hyperactivity disorder, a behavioral disorder of childhood onset characterized by inattentiveness, hyperactivity, and impulsivity, should be obtained prior to initiating drug therapy.

• Pharmacotherapy for ADHD is with stimulants (first line) and antidepressants (second line).

• ADHD pharmacotherapy should be titrated to the desired functional effect without increasing the risk of side effects.

• ADHD therapy should include behavioral modification. Monitoring of drug and nondrug therapy should include input from different environments (i.e., parents and teachers).

• Bacterial and viral conjunctivitis may occur in the first month of life. Antimicrobial ointment administration should be instituted after delivery for prophylaxis.

• Bacterial, viral, and allergic conjunctivitis should be treated with antimicrobial therapy (bacterial); symptomatic therapy (bacterial, viral, and allergic); and ocular antihistamines, decongestants, mast cell stabilizers, or combination products (allergic).

33-4. Questions

1.

J. S., a 4-day-old infant (37 weeks' gestation, birth weight 3.2 kg, length 52 cm), has been admitted to the hospital secondary to spiking temperatures. J. S. has demonstrated decreased oral intake and irritability since being discharged home from the newborn nursery 2 days ago. J. S. is started on IV fluid at maintenance volume and antimicrobial therapy with ampicillin 165 mg IV q6h and gentamicin 8 mg IV q8h. Cultures have been obtained and are pending from blood, urine, and CSF. Laboratory assessment includes the following: Na 142 mEq/L, K 3.5 mEq/L, Cl 108 mEq/L, HCO3 22 mEq/L, BUN 15 mg/dL, SCr 0.9 mg/dL, and Glc 88 mg/dL. What is J. S.'s estimated creatinine clearance (in milliliters per minute)?

A. 100

B. 80

C. 60

D. 50

E. 25

 

2.

Which of the following may affect the creatinine clearance estimate in this patient?

I. The presence of maternal serum creatinine

II. Decreased glomerular filtration rate

III. Increased tubular secretion rate

A. I only

B. III only

C. I and II only

D. II and III only

E. I, II, and III

 

3.

Aminoglycosides are hydrophilic compounds. Which of the following is true regarding aminoglycoside pharmacokinetic parameters in premature neonates compared with those in adults?

A. Increased clearance

B. Increased Vd

C. Decreased half-life

D. Unchanged elimination

E. Increased liver metabolism

 

4.

Which of the following may complicate phenytoin therapy in a 2-day-old infant with new-onset seizures?

I. Hypoalbuminemia

II. Physiologic jaundice

III. IV lipid therapy

A. I only

B. III only

C. I and II only

D. II and III only

E. I, II, and III

 

5.

A drug metabolized through which of the following reactions is a concern in the neonatal population?

A. Hydrolysis

B. Reduction

C. Sulfation

D. Glucuronidation

E. Methylation

 

6.

M. J., a 7-month-old female, is brought to your pharmacy by her mother, who describes the infant as having new onset of fever (102.5°F) and increased irritability in the past 24 hours. The mother states that she stayed home with M. J. today instead of sending her to day care. M. J. has been bottle-fed since birth. Family history is significant for an older sibling with a recent upper respiratory tract infection. Examination of her ear canal using a pneumatic otoscope reveals a bulging, red tympanic membrane with no mobility on negative or positive pressure. Computer records reveal she has been treated for acute otitis media twice since birth (at 3 and 5 months of age). Decisions for antimicrobial therapy in this patient should be based on coverage for which of the following pathogens?

A. Staphylococcus epidermidis, Streptococcus pneumoniae, and Pseudomonas aeruginosa

B. Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis

C. Haemophilus influenzae, Streptococcus pyogenes, and Pseudomonas aeruginosa

D. Streptococcus pneumoniae, Staphylococcus aureus, and Moraxella catarrhalis

E. Staphylococcus epidermidis, Pseudomonas aeruginosa, and Burkholderia cepacia

 

7.

The drug of choice for M. J.'s current episode of acute otitis media is

A. amoxicillin.

B. amoxicillin-clavulanate.

C. IM ceftriaxone.

D. cefixime.

E. trimethoprim-sulfamethoxazole.

 

8.

When the pharmacist is counseling M. J.'s mother about the antibiotic suspension prescribed by M. J.'s physician, which of the following should be discussed?

I. Risk factors for otitis media

II. Whether the suspension should be refrigerated

III. The need to shake the suspension vigorously prior to administration

A. I only

B. III only

C. I and II only

D. II and III only

E. I, II, and III

 

9.

Which of the following is a common side effect of amoxicillin-clavulanate therapy?

A. Hemolytic anemia

B. Liver function test abnormalities

C. Pancreatitis

D. Diarrhea

E. Headache

 

10.

Which of the following is a side effect that should be a concern in a child with acute otitis media and nausea and vomiting who is receiving ibuprofen for fever?

A. Stevens-Johnson syndrome

B. Renal insufficiency

C. Hyponatremia

D. Oral candidiasis

E. Liver failure

 

11.

How is otitis externa, or swimmer's ear, best treated?

A. Instill an antimicrobial and steroid solution into the ear canal.

B. Apply antimicrobial ointment into the ear canal with a cotton swab.

C. Instill an antihistamine solution into the ear canal.

D. Increase pH of the ear canal with administration of Burow's solution.

E. Decrease pH of ear canal with administration of dilute HCl solution.

 

12.

R. E., age 15, weighs 40 kg and has cystic fibrosis. R. E. is admitted to the hospital secondary to an acute pulmonary exacerbation. Home medications include Ultrase as directed, TOBI nebulization, ADEK qd, and dornase alfa (qd nebulization). She is started on ceftazidime 2 g IV q8h and tobramycin 130 mg IV q8h. Which of the following should be ordered in this patient?

A. Serum tobramycin peak concentration

B. Serum tobramycin trough concentration

C. Serum tobramycin peak and trough concentrations

D. Sputum ceftazidime concentration

E. Sputum ceftazidime and tobramycin concentrations

 

13.

Sputum cultures taken from R. E. shortly after hospital admission are positive for Staphylococcus aureus (non-methicillin sensitive). Which of the following agents should be initiated at this time?

A. Oxacillin

B. Ticarcillin

C. Piperacillin

D. Vancomycin

E. Amikacin

 

14.

Which of the following is a pancreatic enzyme supplement?

A. Actigall

B. Beractant

C. Creon

D. Diabinese

E. Pulmozyme

 

15.

Which of the following can be used to decrease the viscosity of pulmonary secretions?

A. Exosurf

B. Mucomyst

C. Protilase

D. Liquaemin

E. Serevent

 

16.

Counseling a patient on the use of pancreatic enzyme supplementation should include which of the following?

A. Capsules may be opened and sprinkled over any food.

B. Capsule contents should not be crushed or chewed.

C. The total daily dose may be given at one time in the evening.

D. Adequate supplementation will increase bowel movement frequency.

E. The supplementation dose should not change with diet changes.

 

17.

N. G., age 8, has newly diagnosed attention-deficit/hyperactivity disorder. Which of the following is not considered first-line therapy for N. G.?

A. Ritalin

B. Dexedrine

C. Wellbutrin

D. Adderall

E. Methylin

 

18.

Atomoxetine is associated with which of the following serious adverse effects?

A. Hepatic injury

B. Renal failure

C. Cardiovascular collapse

D. Anaphylaxis

E. Toxic epidermal necrolysis

 

19.

T. S., age 9, is being started on imipramine therapy after failing therapy for ADHD with several different stimulants. T. S. has two other siblings, a 15-year-old brother and a 3-year-old sister. The pharmacist instructs T. S.'s parents to keep the medicine away from siblings and in a safe place. What is the most likely reason for the pharmacist's concern?

I. Toxicity of imipramine with overdose

II. Abuse potential of imipramine

III. Stability of imipramine product

A. I only

B. III only

C. I and II only

D. II and III only

E. I, II, and III

 

20.

A decrease in seizure threshold is a side effect of which of the following agents used for ADHD?

I. Methylphenidate

II. Bupropion

III. Clonidine

A. I only

B. III only

C. I and II only

D. II and III only

E. I, II, and III

 

21.

Every spring, M. S. develops itchy, red eyes, which are often swollen and draining. Which of the following is the most likely cause of this ocular disorder?

A. Viral conjunctivitis

B. Bacterial conjunctivitis

C. Allergic conjunctivitis

D. Blepharitis

E. Episcleritis

 

22.

Which of the following therapies is not an appropriate recommendation for M. S.'s symptoms?

A. Ocular lubricant

B. Ocular decongestant

C. Ocular antihistamine

D. Ocular mast cell stabilizer

E. Ocular antimicrobial

 

23.

Which of the following is not commonly associated with conjunctivitis?

A. Chlamydia

B. Neisseria

C. Staphylococcus

D. Streptococcus

E. Clostridium

 

24.

Which of the following is a side effect of the prolonged use of ocular decongestants?

A. Peripheral vasodilation

B. Rebound conjunctival congestion

C. Development of arrhythmias

D. Development of tolerance

E. Development of allergy to product

 

33-5. Answers

1.

E. Using the Schwartz equation, J. S.'s estimated creatinine clearance is 26 mL/min (CrCl = 0.45 × 52/0.9).

 

2.

C. The presence of maternal serum creatinine that decreases in neonates over the first week of life may cause a false underestimate of creatinine clearance to be calculated during this time. If one assumes that by the end of the first week of life, J. S.'s SCr has decreased to within the normal infant range to 0.4 mg/dL, the estimated CrCl would be 59 mL/min (CrCl = 0.45 × 52/0.4). Other factors that affect creatinine clearance in the neonate and infant include a decreased glomerular filtration rate and a decreased tubular secretion rate.

 

3.

B. Aminoglycosides are hydrophilic compounds; they will exhibit larger volumes of distribution in patients with greater total body water. Neonates and infants have greater total body water, greater extracellular fluid volume, and a relative lack of adipose tissue.

 

4.

E. Phenytoin is a highly plasma protein-bound drug. The total and free concentrations of highly protein-bound drugs may be altered because of developmental differences in protein binding (decreased protein concentrations and altered binding capacity) and displacement by endogenous substances (e.g., free fatty acids and unconjugated bilirubin). Physiologic jaundice, as exhibited by increasing total and unconjugated bilirubin concentrations, may occur in the neonatal period. Unconjugated bilirubin may displace drugs from albumin binding sites. Additionally, one of the by-products of lipid metabolism, free fatty acids, may also displace drugs from albumin binding sites (thereby increasing the free drug concentration). Kernicterus (also known as yellow brain) may occur when unconjugated bilirubin displaced by drugs or other endogenous substances (i.e., free fatty acids) crosses the blood-brain barrier, where it can deposit in the brain and cause neurologic complications.

 

5.

D. UDPG (uridinediphosphoglucose)-glucuronyl transferase is responsible for conjugation of endogenous substances (bilirubin) and medications (morphine and chloramphenicol). The capacity for glucuronidation metabolism does not begin until around 2 months of age and reaches adult capacity by 2 years of age. Medications metabolized through this system are potential toxins in the neonatal population. An example would be the use of chloramphenicol in neonates and the development of "gray-baby syndrome" because of drug accumulation. Hydrolysis, reduction, sulfation, and methylation are functional in the neonatal period and should not pose drug therapy complications in this population.

 

6.

B. The most common pathogens in acute otitis media are Streptococcus pneumoniae (40-50%), Haemophilus influenzae (20-30%), and Moraxella catarrhalis (10-15%).

 

7.

B. Despite the emergence of drug-resistant Streptococcus pneumoniae, amoxicillin—because of its excellent pharmacodynamic profile, side effect profile, and cost—remains the drug of choice in uncomplicated and nonsevere acute otitis media. However, amoxicillin-clavulanate is now considered first-line therapy in patients with severe illness. This patient is considered to be in the high-risk group (age < 2 years, day care attendance, and recurrent otitis media) and should be treated with antibiotics. High-dose therapy with amoxicillin-clavulanate (90 mg/kg/day amoxicillin and 6.4 mg/kg/day clavulanate) should be used first line in this patient because of symptoms consistent with severe illness (moderate or severe otalgia or fever of 39°C or 102.2°F or greater).

 

8.

E. Counseling should include specific information about the antibiotic, its side effect profile, storage information, information about administering the medicine, dosage instructions, the importance of taking the full course, and the need to shake the bottle prior to administering the dose. In addition, a discussion of risk factors for acute otitis media and preventive measures (pneumococcal and flu immunization) is appropriate in a counseling session.

 

9.

D. The most common side effects with amoxicillin-clavulanate therapy include rash, urticaria, nausea, vomiting, and diarrhea. Although the other listed side effects may be seen with other antibiotic therapies, they do not typically occur with amoxicillin-clavulanate therapy.

 

10.

B. Dehydration, which may develop in a child who is vomiting, is a risk factor for ibuprofen-induced renal insufficiency. If ibuprofen is used as an antipyretic or analgesic in pediatric patients, the parents or caregivers should be counseled regarding this risk and the need to follow intakes and outputs during the period of acute illness (i.e., gastroenteritis) when the child may be receiving ibuprofen therapy.

 

11.

A. The treatment of otitis externa includes the instillation of an antibiotic and steroid otic solution into the ear canal. Cotton swabs should be avoided to prevent otitis externa. Antihistamine solutions are not indicated in the treatment of otitis externa. Otic solutions containing acetic acid may also be of benefit in otitis externa by decreasing (not increasing) the pH of the ear canal and lowering its bacteria-harboring potential. Hydrochloric acid in any form should not be used in the ear canal.

 

12.

C. Therapeutic drug monitoring is a critical part of the overall therapeutic plan in patients with cystic fibrosis. Patients with cystic fibrosis exhibit altered pharmacokinetic parameters of aminoglycosides, primarily increased clearance and greater volumes of distribution. Tobramycin peak concentrations should be obtained to make sure the dose being given is sufficient to reach concentrations of 8-12 mcg/mL, and trough concentrations should be obtained to ensure adequate renal clearance (cystic fibrosis patients receive higher milligram/kilogram doses).

 

13.

D. S. aureus is a common pathogen in cystic fibrosis patients. Methicillin-sensitive S. aureus may be treated with a number of agents (e.g., oxacillin); however, methicillin-resistant S. aureus should be treated with vancomycin.

 

14.

C. Creon is the brand name for a pancreatic enzyme supplement. Creon is available as a microencapsulated formulation.

 

15.

B. Mucomyst is the brand name for N-acetylcysteine, which lowers mucus viscosity (the sulfhydryl group opens the disulfide bond in mucoproteins).

 

16.

B. Pancreatic enzyme products are available in powder, tablet, and microencapsulated formulations. The microencapsulated formulations may be opened and the contents sprinkled over acidic foods (e.g., applesauce). Contents should not be crushed or chewed. Additionally, the dose should be based on the amount and type of food (i.e., full doses with meals or half-doses with snacks and light meals). Adequate replacement will actually decrease bowel movements and improve stool consistency (i.e., decrease steatorrhea).

 

17.

C. All of the listed products are stimulants, with the exception of Wellbutrin. Stimulants are considered first-line therapy for ADHD; antidepressants may be considered second-line agents.

 

18.

A. Atomoxetine's labeling has a warning about the potential for severe liver injury. Atomoxetine should be discontinued in any patient who develops jaundice or laboratory evidence of liver injury.

 

19.

A. Overdose of tricyclic antidepressants may be fatal because of the development of arrhythmias. Because T. S. has a younger sibling in the house, there is a potential for the child to get into her older brother's medicine. Stimulants may have the potential for abuse in patients who do not have ADHD (i.e., the 15-year-old brother), but tricyclic antidepressants are not associated with a high abuse potential. There are no stability issues with imipramine.

 

20.

C. Both bupropion and methylphenidate may lower the seizure threshold. Clonidine is not associated with seizure occurrence.

 

21.

C. Allergic conjunctivitis occurs after exposure to allergens, primarily dander or pollen. Patients suffering from allergic conjunctivitis will typically complain of eye itching.

 

22.

E. Antimicrobial therapy has no place in therapy for allergic conjunctivitis. Ocular lubricants, decongestants, antihistamines, mast cell stabilizers, or combinations of these products are appropriate options for allergic conjunctivitis.

 

23.

E. The most common pathogens in neonatal bacterial conjunctivitis are Neisseria gonorrhoeae, Chlamydia trachomatis, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, and Escherichia coli. Bacterial conjunctivitis beyond the first month of life is most commonly caused by Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, and Haemophilus influenzae. Clostridium, an anaerobe, is not a common bacterial pathogen in conjunctivitis.

 

24.

B. Not unlike reactions from prolonged use of nasal decongestants, prolonged use of ocular decongestants may cause rebound congestion of the conjunctiva. This effect is less pronounced with naphazoline and tetrahydrozoline.

 

33-6. References

American Academy of Child and Adolescent Psychiatry. Practice parameter for the use of stimulant medication in the treatment of children, adolescents, and adults. J Am Acad Child Adolesc Psychiatry. 2002;41(suppl 2):26S-49S.

American Academy of Family Physicians, American Academy of Otolaryngology-Head and Neck Surgery, American Academy of Pediatrics Subcommittee on Otitis Media with Effusion. Otitis media with effusion. Pediatrics. 2004;113: 1412-29.

American Academy of Pediatrics, Committee on Quality Improvement and Subcommittee on Attention-Deficit/Hyperactivity Disorder. Clinical practice guideline: Treatment of the school-aged child with attention-deficit/hyperactivity disorder. Pediatrics. 2001;108:1033-44.

American Academy of Pediatrics, Committee on Quality Improvement and Subcommittee on Attention-Deficit/Hyperactivity Disorder. Diagnosis and evaluation of the child with attention-deficit/hyperactivity disorder. Pediatrics. 2000; 105:1158-70.

American Academy of Pediatrics, Subcommittee on Management of Acute Otitis Media. Diagnosis and management of acute otitis media. Pediatrics. 2004;113:1451-65.

American Pharmaceutical Association. Special Report: Medication Administration Problem-Solving in Ambulatory Care. Washington, D.C.: American Pharmaceutical Association; 1994:9.

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), 4th ed. Washington, D.C.: American Psychiatric Association; 1994:78-85.

Beringer P. Cystic fibrosis. In: Herfindal ET, Gourley DR, eds. Textbook of Therapeutics: Drug and Disease Management. 7th ed. Baltimore: Lippincott Williams & Wilkins; 2000:781-94.

Clinical Practice Guidelines for Cystic Fibrosis Committee. Clinical Practice Guidelines for Cystic Fibrosis. Bethesda, Md.: Cystic Fibrosis Foundation; 1997.

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