THE APhA COMPLETE REVIEW FOR PHARMACY, 7th Ed

14. Thyroid, Adrenal, and Miscellaneous Endocrine Drugs - Jeremy Thomas, PharmD, CDE

14-1. Thyroid

Hypothyroidism

Disease overview

Definition and epidemiology

• Hypothyroidism is a syndrome resulting from deficient thyroid hormone production that results in a slowing down of all bodily functions.

• Retardation of growth occurs in infants and children.

• Its prevalence is greater in women and increases with age; it affects 1.5% to 2.0% of women and 0.2% of men.

Types

• Most cases are caused by thyroid gland failure (primary hypothyroidism).

• Hashimoto's disease (chronic lymphocytic thyroiditis) is the cause of 90% of primary hypothyroidism.

• Pituitary failure causes secondary hypothyroidism.

• Hypothalamic failure causes tertiary hypothyroidism.

• Iatrogenic hypothyroidism follows exposure to radiation with radioiodine or external radiation.

• Other causes may include thyroidectomy, iodine deficiency, enzymatic defects, iodine, lithium, and interferon-alfa.

Clinical presentation

• Symptoms include cold intolerance, fatigue, somnolence, constipation, menorrhagia, myalgia, and hoarseness.

• Signs include thyroid gland enlargement or atrophy, bradycardia, edema, dry skin, and weight gain.

• Myxedema coma is an end stage of hypothyroidism characterized by weakness, confusion, hypothermia, hypoventilation, hypoglycemia, hyponatremia, coma, and shock.

Pathophysiology

• Thyroxine (T4) is the major hormone secreted by the thyroid; T4 is converted to the more potent triiodothyronine (T3) in tissues.

• Thyroxine secretion is stimulated by thyroid-stimulating hormone (TSH).

• TSH secretion is inhibited by T4, forming a negative feedback loop.

• Hashimoto's disease is an autoimmune-mediated disease resulting from cell- and antibody-mediated thyroid injury.

• Antimicrosomal antibodies are directed against thyroidal antigens.

Diagnosis

• Plasma TSH assay is the initial test of choice if hypothyroidism is suspected clinically.

• TSH levels are elevated in primary hypothyroidism.

• Low plasma-free T4 (or T4 index) confirms the diagnosis of hypothyroidism.

Treatment principles

• Synthetic thyroxine (levothyroxine) is the drug of choice for hypothyroidism because it is chemically stable, inexpensive, and free of antigenicity and because it has uniform potency.

• The typical dose is 100-125 mcg po once daily; the dose is reduced to 50 mcg in the elderly and to 25 mcg in patients with coronary artery disease to decrease the risk of precipitating angina.

• The goal of therapy is to maintain plasma TSH in the normal range.

• Dose changes are made at 6- to 8-week intervals until the TSH is normal.

• Overtreatment is detected by subnormal TSH and is associated with osteoporosis and atrial fibrillation.

• Failure to respond to appropriate doses is most often due to poor compliance.

• Do not use thyroid hormones to facilitate weight loss in euthyroid patients.

• Thyroid hormones have a narrow therapeutic index; careful monitoring of clinical condition and thyroid function is required.

Drug therapy for hypothyroidism

Thyroid preparations for the treatment of hypothyroidism are described in

Table 14-1.

Mechanism of action

Thyroid hormones enhance oxygen consumption by most tissues and increase basal metabolic rate and metabolism of carbohydrates, lipids, and proteins.

Patient counseling

• Take once daily, 30 minutes before breakfast, because food may decrease absorption.

• Replacement therapy is usually for life; do not discontinue without advice of the prescriber.

• Notify the prescriber if you experience rapid or irregular heartbeat, chest pain, shortness of breath, nervousness, irritability, tremors, heat intolerance, or weight loss.

• Do not take antacids, calcium, or iron supplements within 4 hours of levothyroxine.

Adverse effects

• Cardiovascular: Tachycardia, arrhythmia, angina, myocardial infarction

• Central nervous system (CNS): Tremor, headache, nervousness, insomnia, irritability, hyperactivity

• Gastrointestinal (GI): Diarrhea, vomiting, cramps

• Miscellaneous: Weight loss, fatigue, menstrual irregularities, excessive sweating, heat intolerance, fever, muscle weakness, hair loss, decreased bone mineral density, hypersensitivity

Drug interactions

• Amiodarone may cause hypothyroidism or hyperthyroidism.

• Antacids decrease absorption of levothyroxine. Separate administration by at least 4 hours.

• Antidiabetic agents may be less effective with levothyroxine. An increase in the insulin or oral hypoglycemic dose may be needed.

• Bile acid sequestrants reduce absorption of levothyroxine. Separate administration by at least 4 hours.

• Enzyme-inducing antiepileptic agents increase hepatic degradation of levothyroxine. The thyroxine dosage may need to be increased.

• Estrogens may decrease response to levothyroxine. The levothyroxine dosage may need to be increased.

• Lithium commonly causes hypothyroidism.

• Levothyroxine may enhance warfarin's effect. The warfarin dosage may need to be decreased.

• Levothyroxine supplementation may reduce digoxin levels.

• Sucralfate may decrease levothyroxine absorption. Separate administration by at least 4 hours.

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

• Soybean formula decreases levothyroxine absorption.

• Sympathomimetic drugs may potentiate the effects of levothyroxine.

• Levothyroxine may enhance theophylline clearance.

Monitoring parameters

• Plasma TSH should be done every 6-8 weeks until normalization.

• Signs and symptoms of hypothyroidism should improve within a few weeks.

• Once the optimum replacement dose is attained, a physical examination should be made and TSH level should be monitored every 6-12 months.

• Patients at risk for coronary artery disease should be monitored for angina.

Pharmacokinetics

• The U.S. Food and Drug Administration states that all levothyroxine products should be considered therapeutically inequivalent unless equivalence (AB rating) has been established and noted in the "Orange Book."

• Levoxyl, Levothroid, Synthroid, Unithroid, and some generics are bioequivalent.

• Because of the narrow therapeutic index of levothyroxine, many experts recommend rechecking TSH concentrations 6-8 weeks after any change in formulation, even when bioequivalent.

• Oral absorption is improved by fasting but decreased by dietary fiber, drugs, and foods.

• A half-life of 7 days allows once-daily dosing.

• Average bioavailability of levothyroxine products ranges from 40% to 80%. When a switch is made from oral to intravenous levothyroxine, the dosage should be reduced by 25% to 50%.

Other

• Use of natural thyroid hormones such as desiccated thyroid USP is discouraged because their potency and stability are less predictable than synthetic levothyroxine.

• Synthetic T3 (liothyronine) has a shorter half-life than levothyroxine, has a higher incidence of cardiac side effects, and is more difficult to monitor.

Hyperthyroidism

Disease overview

Definition and epidemiology

• Hyperthyroidism (thyrotoxicosis) is the clinical syndrome that results when tissues are exposed to high levels of thyroid hormone.

• Thyrotoxicosis is more common in women than men, occurring in 3 per 1,000 women.

Types

• Graves' disease is the most common cause of hyperthyroidism.

• Toxic multinodular goiter (MNG), toxic adenoma, and exogenous thyroid hormone ingestion may also cause hyperthyroidism.

• Thyroid storm is a life-threatening, sudden exacerbation of all the symptoms of thyrotoxicosis, characterized by fever, tachycardia, delirium, and coma.

• Hyperthyroidism may be caused by drugs such as amiodarone and iodine.

Clinical presentation

• Symptoms include heat intolerance, weight loss, weakness, palpitations, and anxiety.

• Signs include tremor, tachycardia, weakness and eyelid lag, and warm, moist skin.

• Other manifestations include atrial fibrillation and congestive heart failure.

Pathophysiology

• Graves' disease is an autoimmune disease in which thyroid-stimulating antibodies are produced. These antibodies mimic the action of TSH on thyroid tissue.

• Toxic adenomas and MNGs are masses of thyroid tissue that secrete thyroid hormones independent of pituitary control.

Diagnosis

Elevated T4 or T3 in the presence of a decreased TSH confirms the diagnosis of hyperthyroidism.

Treatment principles

• There are three primary methods for controlling hyperthyroidism: surgery, radioactive iodine (RAI), and antithyroid (thioamide) drugs.

• The goal is to minimize symptoms and eliminate excess thyroid hormone.

• RAI is often considered the treatment of choice in Graves' disease, toxic adenomas, and MNGs.

• Propylthiouracil is preferred in pregnancy; RAI is contraindicated.

• Thioamide drugs (propylthiouracil and methimazole) have no permanent effect on thyroid function.

• Adjunctive treatments for hyperthyroidism include β-adrenergic receptor blockers or calcium channel blockers to control tachycardia associated with hyperthyroidism.

Drug therapy of hyperthyroidism

Antithyroid medications are summarized in

Table 14-2.

Thioamides

Mechanism of action

• Propylthiouracil and methimazole inhibit the synthesis of thyroid hormones by preventing the incorporation of iodine into iodotyrosines and by inhibiting the coupling of monoiodotyrosine and diiodotyrosine to form T4 and T3.

• Propylthiouracil inhibits the peripheral conversion of T4 to T3.

Patient counseling

• This medication prevents excessive thyroid hormone production.

• It must be taken regularly to be effective.

• Do not discontinue use without first consulting your physician.

• Notify your physician if fever, sore throat, unusual bleeding, rash, abdominal pain, or yellowing of the skin occurs.

Adverse effects

• CNS: Fever, headache, paresthesias

• General: Rash, arthralgia, urticaria

• GI: Jaundice, hepatitis

• Hematologic: Agranulocytosis, leukopenia, bleeding

Drug interactions

Potentiation of warfarin's effect may occur.

Monitoring parameters

• Monitor for improvement in signs and symptoms of hyperthyroidism.

• Perform thyroid function tests; watch for signs and symptoms of agranulocytosis (fever, malaise, sore throat).

Pharmacokinetics

Propylthiouracil has a short half-life, requiring more frequent dosing than methimazole.

Iodides

Mechanism of action

• Medication blocks hormone release and inhibits thyroid hormone synthesis.

• Medication may be used when rapid reduction in thyroid hormone secretion is desired, such as in thyroid storm, or to decrease glandular vascularity prior to thyroidectomy.

Patient instructions

• Dilute with water or fruit juice to improve taste.

• Notify physician if fever, skin rash, metallic taste, swelling of the throat, or burning of the mouth occurs.

Adverse effects

Adverse effects include rash, swelling of salivary glands, metallic taste, burning of the mouth, GI distress, hypersensitivity, and goiter.

Drug interactions

Lithium potentiates antithyroid effect of iodides.

Monitoring parameters

Monitor for improvement in signs and symptoms of hyperthyroidism and for adverse effects.

14-2. Adrenals

Cushing's Syndrome

Disease overview

Definition and epidemiology

• Cushing's syndrome results from chronic glucocorticoid excess.

[Table 14-2. Antithyroid Medications]

• The incidence rate is 2-4 persons per million population cases each year.

Types

• Cushing's syndrome is usually iatrogenic, caused by therapy with glucocorticoid drugs.

• Endogenous Cushing's syndrome is usually caused by overproduction of adrenocorticotropic hormone (ACTH) by pituitary gland adenomas (Cushing's disease).

Clinical presentation

Patients may present with obesity involving the face, neck, trunk, and abdomen; hypertension; hirsutism; acne; amenorrhea; depression; thin skin; easy bruising; diabetes; and osteopenia.

Pathophysiology

The hypothalamus produces corticotropin-releasing hormone, which stimulates the anterior pituitary gland to release ACTH. Circulating ACTH stimulates the adrenal cortex to produce cortisol.

Diagnosis

• Diagnosis is usually based on signs and symptoms of hypercortisolism.

• Dexamethasone suppression test or 24-hour urine cortisol measurement may be used.

Treatment principles

• If the syndrome is iatrogenic, minimization of corticosteroid exposure is essential.

• Pharmacotherapy of Cushing's syndrome is aimed at reducing cortisol production or activity with drugs, radiation, or surgery.

Drug therapy of Cushing's syndrome

Drugs for Cushing's syndrome are described in

Table 14-3.

Mechanism of action

• Drugs used to treat Cushing's disease suppress synthesis of cortisol.

• Ketoconazole inhibits cytochrome P-450 (CYP450)-dependent enzymes and cortisol synthesis.

• Aminoglutethimide inhibits conversion of cholesterol to pregnenolone.

• Mitotane is a cytotoxic drug that suppresses ACTH secretion and reduces synthesis of cortisol.

• Metyrapone decreases cortisol synthesis by inhibition of 11-hydroxylase activity.

Patient counseling

Ketoconazole should be taken with food. Separate from antacids by at least 2 hours. Notify the physician if abdominal pain, yellow skin, or pale stool occurs.

Adverse effects

• Ketoconazole causes nausea, vomiting, headache, impotence, and hepatotoxicity.

• Aminoglutethimide causes drowsiness, rash, weakness, hypotension, nausea, loss of appetite, hypothyroidism, and blood dyscrasias.

• Metyrapone causes nausea, vomiting, dizziness, and sedation.

• Mitotane may cause nausea, vomiting, diarrhea, and tiredness.

Drug interactions

• Ketoconazole is a CYP450 3A4 enzyme inhibitor and may increase serum concentrations of cyclosporine, warfarin, cisapride, and triazolam. Drugs that lower gastric acidity will decrease ketoconazole absorption. Rifampin decreases ketoconazole levels.

• Aminoglutethimide may induce metabolism of warfarin.

Monitoring parameters

Cortisol monitoring is required with mitotane.

Adrenal Insufficiency

Disease overview

Definition and epidemiology

• Primary adrenocortical deficiency (Addison's disease) is caused by autoimmune-mediated

[Table 14-3. Drugs for Cushing's Syndrome]

   destruction of the adrenal cortex and results in glucocorticoid and mineralocorticoid deficiency.

• Addison's disease occurs in 5-6 persons per million population per year.

Types

• Primary adrenal insufficiency (Addison's disease) involves autoimmune destruction of the adrenal cortex.

• Secondary insufficiency occurs after cessation of chronic exogenous corticosteroid use.

• Acute adrenal insufficiency, or Addisonian crisis, is an endocrine emergency precipitated by severe stress.

Clinical presentation

• Glucocorticoid deficiency (weight loss, malaise, abdominal pain, and depression)

• Mineralocorticoid deficiency (dehydration, hypotension, hyperkalemia, and salt craving)

Pathophysiology

• Cortisol is synthesized in the adrenal cortex when cholesterol is converted to pregnenolone by ACTH.

• The adrenal cortex secretes aldosterone, cortisol, and androgenic hormones.

• Mineralocorticoids (e.g., aldosterone) enhance reabsorption of sodium and water from the distal tubule of the kidney and increase urinary potassium excretion.

• Glucocorticoids affect glucose, carbohydrate, and fat metabolism; produce anti-inflammatory and immunosuppressive effects; and affect other physiologic processes.

• Chronic administration of corticosteroids produces inhibition of pituitary ACTH secretion and reduced cortisol production (hypothalamic-pituitary-adrenocortical [HPA] axis suppression).

• Abrupt cessation of steroids may precipitate adrenal insufficiency.

Diagnosis

A cosyntropin (ACTH) stimulation test may be used to assess hypocortisolism.

Treatment principles

• Addison's disease requires lifelong glucocorticoid and mineralocorticoid replacement.

• Hydrocortisone 100 mg intravenous (IV) q8h is the drug of choice for acute adrenal crisis.

• "Stress doses" of corticosteroids are given for minor illness, injury, or surgery. If stress is severe, hydrocortisone 100 mg IV q8h is used.

• Gradual tapering of corticosteroids reduces the risk of adrenal insufficiency in patients with HPA axis suppression.

• Nonadrenal uses for corticosteroids are numerous, including allergic reactions; inflammatory conditions; hematologic disorders; rheumatic disorders; neurologic diseases; cancer; immunosuppression; pulmonary, renal, skin and thyroid diseases; and hypercalcemia.

• Fludrocortisone has minimal anti-inflammatory activity and is used only when mineralocorticoid activity is needed, such as when increased blood pressure is desired.

Drug therapy of adrenal insufficiency

Information about corticosteroids is provided in

Table 14-4.

Mechanism of action

• Glucocorticoids increase blood glucose by stimulating gluconeogenesis and glycogenolysis; fat deposition is increased.

• Catabolic effects occur in lymphoid, connective tissue, bone, muscle, fat, and skin.

• Inhibition of inflammation and immunosuppression, vasoconstriction, reduction in prostaglandin and leukotriene synthesis, decreased neutrophils at sites of inflammation, and inhibition of macrophage function result.

Patient counseling

• These drugs may cause stomach upset, so take them with food.

• It is preferable to take the dose before 9:00 am.

• Wear or carry identification if on chronic steroid therapy.

• Therapy may mask signs of infection.

• Drugs may increase insulin or oral hypoglycemic requirements if patient is diabetic.

• Notify the physician if weight gain, muscle weakness, sore throat, or infection occurs.

• Report tiredness, stomach pain, weakness, and high or low blood sugar to the physician.

• Do not discontinue abruptly if taking long term.

Adverse effects

• Cardiac: Hypertension, sodium and fluid retention, atherosclerosis

• CNS: Insomnia, anxiety, depression, psychosis

• Metabolic: Obesity, hyperglycemia, hypokalemia, amenorrhea, impotence

• Ophthalmic: Cataracts, glaucoma

[Table 14-4. Corticosteroids and Dose Equivalents]

• Immune: Infections, impaired wound healing, leukocytosis

• Musculoskeletal: Myopathy, osteoporosis

Drug interactions

• Rifampin and other enzyme-inducing drugs increase metabolism of corticosteroids and decrease their effectiveness.

• Concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids increases risk of peptic ulcer disease.

• Corticosteroids may impair immunologic response to vaccines.

• Estrogens may increase corticosteroid clearance.

• Ketoconazole, macrolides, and other CYP450 3A4 enzyme-inhibiting drugs may decrease clearance of corticosteroids.

• Corticosteroids increase insulin and oral hypoglycemic drug requirements.

Monitoring parameters

Patients should be monitored for weight gain, edema, increased blood pressure, electrolytes, blood glucose, and infection.

Pharmacokinetics

Many dosage forms, doses, and schedules are used, including tablets, topicals, enemas, oral liquids, injections, and depot injection forms for intra-articular or intramuscular use.

14-3. Miscellaneous Endocrine Drugs

ACTH and Cosyntropin

Table 14-5 provides information about ACTH and cosyntropin.

[Table 14-5. ACTH and Cosyntropin]

Therapeutic uses

ACTH and cosyntropin are used for diagnosis of adrenal insufficiency. Occasionally, ACTH is used as an alternative to corticosteroids.

Mechanism of action

• ACTH stimulates the adrenal cortex to secrete adrenal hormones.

• If ACTH fails to elicit an appropriate cortisol response, adrenal insufficiency is present.

• Cosyntropin is a synthetic peptide that is similar to human ACTH, but less allergenic.

Patient counseling and adverse effects

Patients should receive the same counseling as for corticosteroids. Adverse effects are the same.

Drug interactions

Enzyme-inducing drugs will decrease effects.

Monitoring parameters

Monitoring parameters are the same as for corticosteroids.

Vasopressin and Desmopressin

Table 14-6 describes the dosages for vasopressin and desmopressin.

Therapeutic uses

• Vasopressin: Diabetes insipidus, variceal hemorrhage, shock, ventricular fibrillation

• Desmopressin: Nocturnal enuresis, diabetes insipidus, hemophilia A, von Willebrand's disease

Mechanism of action

• Vasopressin is also known as antidiuretic hormone (ADH); it increases water resorption.

• Vasopressin causes vasoconstriction in portal and splanchnic vessels (GI tract).

• Desmopressin is a synthetic derivative of vasopressin with ADH activity and only minimal vasoconstrictive properties; it increases clotting factor VIII levels.

Patient counseling

For intranasal desmopressin, the patient should be instructed on proper intranasal use. The following instructions should also be given:

• Discard the bottle after 25 or 50 doses.

• Do not transfer the solution to another bottle.

• The drug may cause nasal irritation.

• Notify the physician if bleeding is not controlled or if headache, shortness of breath, or severe abdominal cramps occur.

Adverse effects

• Vasopressin: Angina, myocardial infarction, vasoconstriction, hyponatremia, gangrene, abdominal cramps, tissue necrosis if extravasation occurs, hypersensitivity

• Desmopressin: Abdominal pain, headache, flushing, nausea, nasal irritation, vulvar pain, nosebleed, rhinitis, hypersensitivity

Drug interactions

• Drugs may enhance effects of other pressors.

• Carbamazepine and chlorpropamide potentiate the effect of desmopressin on ADH.

[Table 14-6. Vasopressin and Desmopressin]

Monitoring parameters

• With diabetes insipidus, monitor urine volume and plasma osmolality.

• With von Willebrand's disease, monitor factor VIII levels and bleeding time.

• When intravenous vasopressin is used, monitor blood pressure and pulses.

Androgens and Anabolic Steroids

Table 14-7 provides information about androgens and anabolic steroids.

Therapeutic uses

• Androgens and anabolic steroids are used to treat hypogonadism, delayed puberty, metastatic breast cancer, anemia, AIDS wasting in HIV-infected men, corticosteroid-induced hypogonadism and osteoporosis, and moderate to severe vasomotor symptoms associated with menopause (when combined with estrogen).

• They are schedule C-III controlled substances because they are intentionally misused for performance-enhancing effects and enhanced muscular development and endurance.

Mechanism of action

• Androgens promote growth and development of male sex organs and maintenance of secondary sex characteristics.

• Androgens also cause retention of nitrogen, sodium, potassium, and phosphorus; increase protein anabolism; and decrease protein catabolism.

• Androgens are responsible for the growth spurt of adolescence and termination of linear growth by fusion of epiphyseal growth centers.

• Exogenous androgens stimulate production of red blood cells and suppress endogenous testosterone release through feedback inhibition of luteinizing hormone and suppress spermatogenesis through feedback inhibition of follicle-stimulating hormone.

Patient counseling

• Medication may cause stomach upset.

• Notify a physician if swelling of the ankles or persistent erections occur.

[Table 14-7. Androgens and Anabolic Steroids]

• This product is a controlled substance; do not misuse or abuse it.

• For females, notify physician if deepening of the voice, increased facial hair, or menstrual irregularities occur.

• Patients receiving transdermal testosterone should be provided with the manufacturer's patient instructions and carefully counseled on use and disposal of the system.

Adverse effects

• General: Jaundice, hepatitis, edema, high abuse potential in an effort to enhance athletic performance, hypercholesterolemia and atherosclerosis, increased aggression and libido

• Women: Hirsutism, voice deepening, acne, decreased menses, clitoral enlargement

• Men: Acne, sleep apnea, gynecomastia, azoospermia, prostate enlargement, decreased testicular size

14-4. Key Points

• Levothyroxine is the drug of choice for hypothyroidism.

• Lower doses of levothyroxine are used in elderly and cardiac patients.

• Overtreatment with thyroid hormones causes osteoporosis and atrial fibrillation.

• Antacids, bile acid sequestrants, sucralfate, calcium, and iron supplements decrease absorption of levothyroxine and must be separated by at least 4 hours.

• Propylthiouracil and methimazole are thioamide derivatives used to treat hyperthyroidism.

• Thioamides may cause life-threatening agranulocytosis or hepatitis, so patients must report to their physician if they experience fever, sore throat, abdominal pain, or jaundice.

• Drugs used to treat Cushing's disease inhibit synthesis of cortisol.

• Corticosteroid should be used at the lowest dose for the shortest time to reduce the risk of HPA axis suppression and adrenal insufficiency.

• Patients with adrenal insufficiency must receive supplemental corticosteroids in times of physiologic stress.

• Vasopressin and desmopressin are antidiuretic hormones.

• Androgens and anabolic steroids are abused by athletes seeking to enhance performance.

14-5. Questions

Use Patient Profile 1 to answer questions 1 and 2.

 

Patient name: Jasmine Ricardo

Address: 189 Jonesborough Road

Age: 78

Height: 48 inches

Sex: Female

Weight: 103 lbs

Race: Hispanic

Allergies: Cats

Diagnosis:

Pharmacist notes

Primary

1. Hypercholesterolemia

Date

Comment

 

2. Anemia

2/23

Patient reminded to continue taking aspirin 325 mg for CAD

 

3. Coronary artery disease

2/23

Patient to take OTC ferrous sulfate 325 mg daily for 3 months for anemia.

Advised patient to begin docusate 100 mg qd if constipation occurs.

Secondary

1. Hypertension

       



Medication orders:

Date

Rx no.

Physician

Drug and strength

Quantity

Sig

Refills

3/21

89995

Stubie

Synthroid 0.025 mg

30

1 po qd

0

2/23

88768

Hooper

Zocor 40 mg

30

1 po qhs

5

2/23

88769

Hooper

Questran 4 g

60

1 packet bid, mix with juice

5

2/23

88770

Hooper

Tenormin 50 mg

30

1 po qd

5

2/23

88771

Hooper

Enalapril 5 mg

60

1 po bid

5

1.

The Synthroid prescription dispensed to Mrs. Ricardo on 3/21 requires advising her to

A. take 4 hours before or 4 hours after Questran.

B. take with food.

C. watch for signs of infection.

D. take as needed to keep her desired level of energy.

E. discontinue if she experiences nausea.

 

2.

Which of the following of Mrs. Ricardo's conditions could the Synthroid exacerbate?

A. Hypercholesterolemia

B. Anemia

C. Coronary artery disease

D. Hypertension

E. Constipation

 

3.

Excessive doses of levothyroxine may cause

A. weight gain.

B. osteoporosis.

C. cold intolerance.

D. bradycardia.

E. sedation.

 

4.

Which of the following drugs may produce hypothyroidism?

I. Amitriptyline

II. Lithium

III. Amiodarone

A. I only

B. III only

C. I and II only

D. II and III only

E. I, II, and III

 

5.

All of the following may decrease the effect of thyroid hormone supplementation except

A. antacids.

B. bile acid sequestrants.

C. estrogens.

D. sucralfate.

E. theophylline.

 

6.

A patient who is suffering from heat intolerance, weight loss, tachycardia, tremor, and anxiety may be treated with

A. acetaminophen.

B. mitotane.

C. cyproheptadine.

D. propylthiouracil.

E. diazepam.

 

7.

A patient with atrial fibrillation may require a decreased warfarin dosage when which of the following drugs is initiated?

A. Liothyronine

B. Rifampin

C. Methimazole

D. Phenytoin

E. Diphenhydramine

 

8.

Which of the following drugs is used to treat Cushing's disease?

I. Ketoconazole

II. Aminoglutethimide

III. Mitotane

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 drugs works by decreasing cortisol synthesis?

A. Cortrosyn

B. ACTH

C. Oxandrolone

D. Prednisone

E. Metyrapone

 

10.

Decreased ketoconazole absorption may occur if it is administered concomitantly with which of the following?

A. Antacids

B. Food

C. Warfarin

D. Cyclosporine

E. CYP450 3A4 inhibitors

 

11.

Close monitoring of adrenal hormone secretion may be required when administering which of the following?

A. Methyltestosterone

B. Mitotane

C. Desmopressin

D. Iodides

E. Propylthiouracil

 

12.

Which of the following is used to treat adrenal crisis?

A. Cosyntropin

B. Aminoglutethimide

C. Fluoxymesterone

D. Vasopressin

E. Hydrocortisone

 

13.

Which of the following is not an effect of glucocorticoids?

A. Immunosuppression

B. Decreased prostaglandin synthesis

C. Inhibition of glycogenolysis

D. Decreased neutrophils at sites of infection

E. Inhibition of macrophages

 

Use Patient Profile 2 to answer questions 14 and 15.

 

Patient name: Stuart Big

Date of admission: 4/21 at 15:26

Address: 440 Mountain Lane

     

Age: 28

Height: 5´8″

Sex: Male

Weight: 178 lbs

Race: White

Allergies: Aspirin

Diagnosis:

     

Admit diagnosis

1. Anaphylactic reaction to aspirin

Secondary

1. Type 2 diabetes mellitus

   

2. Hypertension



Laboratory:

Date

Time

Lab

Result

(Normal range)

4/21

15:29

Glucose

144

(60-110 mg/dL)

4/21

19:20

Glucose

181

(60-110 mg/dL)

4/22

06:00

Glucose

240

(60-110 mg/dL)

4/22

12:21

Glucose

289

(60-110 mg/dL)

4/22

19:15

Glucose

352

(60-110 mg/dL)

4/23

06:20

Glucose

391

(60-110 mg/dL)

4/23

12:32

Glucose

443

(60-110 mg/dL)



Active medication orders:

Date

Time

Name and strength

Route

Frequency or schedule

4/21

15:30

Solu-Medrol 125 mg

IV

q6h

4/21

15:30

Dextrose 5%/NaCl 0.9%

IV

200 mL/h

4/21

15:30

Diphenhydramine 50 mg

IV

q6h

4/21

17:03

Glipizide 5 mg

po

bid

4/21

17:03

Glucophage 850 mg

po

bid

4/21

17:03

Captopril 50 mg

po

tid



Discontinued medication orders:

Date

Time

Name and strength

Route

Frequency or schedule

4/21

15:30

Epinephrine 0.1 mg

Subcutaneous

Stat

4/21

15:30

Diphenhydramine 50 mg

IV

Stat



Dietary:

Date

       

4/21

1,800 kcal American Diabetes Association diet

14.

Which of the following is least likely to contribute to the increased blood glucose seen in this patient?

A. Dextrose 5%/NaCl 0.9% solution

B. Captopril

C. Epinephrine

D. Methylprednisolone

E. Anaphylaxis

 

15.

Mr. Big is discharged on a new prescription for Deltasone 40 mg qd for 7 days. He should be instructed to

A. check feet closely for wounds.

B. take ibuprofen for musculoskeletal pain.

C. take on an empty stomach.

D. take at bedtime.

E. wear identification for steroid therapy.

 

16.

Chronic administration of glucocorticoids predisposes patients to which of the following?

A. Arthritis

B. Obesity

C. Alzheimer's disease

D. Osteoporosis

E. Hepatitis

 

17.

A patient is taking prednisone 40 mg daily for 6 months. On abrupt cessation, which of the following may occur?

A. Myopathy

B. Diabetes

C. Infection

D. Adrenal crisis

E. Psychosis

 

18.

An increased risk of peptic ulcer disease occurs when NSAIDs are combined with which of the following?

A. Ranitidine

B. Ferrous sulfate

C. Dexamethasone

D. Carbamazepine

E. Acetaminophen

 

19.

Which of the following drugs may be used to diagnose adrenal insufficiency?

A. Desmopressin

B. Clemastine

C. Captopril

D. Cosyntropin

E. Aminoglutethimide

 

20.

Decreased urine production is an effect of

A. carmustine.

B. propylthiouracil.

C. ACTH.

D. desmopressin.

E. SSKI.

 

21.

Which of the following hormones is secreted by the pituitary gland?

A. Adrenocorticotropic hormone

B. Testosterone

C. Cortisol

D. Thyroxine

E. Corticotropin-releasing hormone

 

22.

Chronic administration of Winstrol may produce all of the following complications except

A. prostate enlargement.

B. increased testicular size.

C. gynecomastia in men.

D. accelerated atherosclerosis.

E. decreased menses in women.

 

23.

Androderm is administered

A. once daily.

B. three times per week.

C. once weekly.

D. every 2 weeks.

E. monthly.

 

24.

Which of the following is not an acceptable indication for testosterone?

A. Anemia

B. Hypogonadism

C. Delayed puberty

D. Body building

E. Metastatic breast cancer

 

14-6. Answers

1.

A. Bile acid sequestrants reduce levothyroxine absorption and must be separated from levothyroxine administration by at least 4 hours. Levothyroxine should be administered before a meal on an empty stomach to maximize absorption.

 

2.

C. Thyroid hormones enhance oxygen consumption and increase the oxygen demand. Mrs. Ricardo has a past medical history of coronary artery disease (CAD) and is elderly. Thyroid supplementation would actually lower her cholesterol in the long run but may precipitate angina acutely.

 

3.

B. Levothyroxine decreases bone mineral density and when given in supratherapeutic doses may cause osteoporosis. For this reason, the lowest possible replacement dose should be administered.

 

4.

D. Lithium and amiodarone have both been associated with hypothyroidism. Amiodarone contains iodine and may cause hypo- or hyperthyroidism.

 

5.

E. Numerous drugs are known to decrease thyroid hormone absorption, including antacids that contain divalent and trivalent cations, calcium salts, magnesium, sucralfate, and bile-acid sequestrants. Estrogens and enzyme-inducing drugs may decrease circulating thyroid hormone levels and necessitate a dose increase of thyroxine.

 

6.

D. Heat intolerance, weight loss, tachycardia, tremor, and anxiety are cardinal features of hyperthyroidism. Propylthiouracil is effective at reducing the excessive thyroxine level.

 

7.

A. Liothyronine (Cytomel) is T3, a potent thyroid hormone. In states of hypothyroidism, metabolism is decreased. However, if thyroid hormone is supplemented, blood clotting factors will be metabolized more quickly, leading to decreased warfarin requirements.

 

8.

E. Ketoconazole, aminoglutethimide, and mitotane are all used to treat Cushing's disease. Ketoconazole is most commonly known as an antifungal agent, but it inhibits cortisol synthesis at high doses (800-1,200 mg daily).

 

9.

E. Metyrapone (Metopirone) inhibits 11 hydroxylase activity and thus decreases cortisol synthesis.

 

10.

A. Ketoconazole requires the presence of stomach acid to be absorbed. Any drug that decreases gastric acidity will decrease the extent of ketoconazole absorption. Food increases ketoconazole absorption because food stimulates release of gastric acid.

 

11.

B. Mitotane is cytotoxic to adrenal cells and thus reduces cortisol synthesis and release. ACTH increases cortisol release. Close monitoring of cortisol levels is important when this drug is used.

 

12.

E. Hydrocortisone is the drug of choice for adrenal crisis because it possesses both mineralocorticoid and glucocorticoid properties. Although cosyntropin increases cortisol release, patients with adrenal crisis may not have enough adrenal reserve to meet their increased demand.

 

13.

C. Glucocorticoids have potent effects on glucose and carbohydrate metabolism. They promote glycogen breakdown, rather than inhibit it.

 

14.

B. Captopril increases insulin sensitivity and would not be expected to contribute to increased blood glucose. This patient's blood glucose began rising shortly after admission. His IV fluids contain glucose; epinephrine increases blood glucose by increasing glycogen breakdown, methylprednisolone (Solu-Medrol) promotes glycogenolysis, and anaphylaxis would be expected to increase stress response, thereby leading to increased epinephrine release and increased blood glucose.

 

15.

A. The patient has a history of diabetes and will be given prednisone (Deltasone), which would be expected to increase blood glucose. When diabetes is poorly controlled, infections are more likely to occur. For this reason, he should monitor more closely for wounds that may become infected. He will not be taking prednisone long enough to develop adrenal insufficiency, so there is no need for him to wear identification for steroid therapy.

 

16.

D. Glucocorticoids have catabolic effects on a number of tissues, including muscle, fat, skin, and bone. Chronic administration leads to osteopenia and osteoporosis.

 

17.

D. Chronic administration of glucocorticoids such as prednisone will lead to feedback inhibition of pituitary ACTH release and atrophy of the adrenal cortex. When prednisone is abruptly stopped, the adrenals will not be able to meet the body's demand for cortisol during severe stress, and adrenal crisis may occur.

 

18.

C. Corticosteroids such as dexamethasone (Decadron) are known to increase the risk of peptic ulcers when used in combination with NSAIDs.

 

19.

D. Cosyntropin (Cortrosyn) is a synthetic analogue of ACTH that is used to diagnose adrenal insufficiency. It works by stimulating the adrenal cortex to secrete cortisol. If cosyntropin administration does not result in an appropriate increase in cortisol release, adrenal insufficiency is present.

 

20.

D. Desmopressin (DDAVP) is a synthetic analogue of vasopressin, or antidiuretic hormone. Thus, it decreases urine production by increasing water resorption.

 

21.

A. Adrenocorticotropic hormone, or ACTH, is released by the pituitary and acts on the adrenal glands to increase cortisol release. Corticotropin-releasing hormone is released by the hypothalamus and acts on the pituitary to stimulate ACTH release.

 

22.

B. Stanozolol (Winstrol) is an androgen that would be expected to promote growth and development of male sex organs. However, chronic administration leads to feedback inhibition of testosterone secretion, which leads to testicular atrophy.

 

23.

A. Testosterone transdermal systems (Androderm, Testoderm) are applied once daily for 24 hours. Longer-acting androgens are available, such as nandrolone decanoate (Deca-Durabolin), for once-weekly administration.

 

24.

D. Anabolic steroids may be abused by those who are seeking enhanced muscular development and endurance, such as athletes. For this reason, all of these agents are subject to the Controlled Substances Act.

 

14-7. References

Baskin HJ, Cobin RH, Duick DS. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the evaluation and treatment of hyperthyroidism and hypothyroidism (AACE Thyroid Task Force). Endocr Pract. 2002; 8:457-69.

Chrousos GP. Adrenocorticosteroids and adrenocortical antagonists. In: Katzung BG, ed. Basic and Clinical Pharmacology. 11th ed. New York: McGraw-Hill; 2009.

Chrousos GP. The gonadal hormones and inhibitors. In: Katzung BG, ed. Basic and Clinical Pharmacology. 11th ed. New York: McGraw-Hill; 2009.

Dayan CM, Daniels GH. Chronic autoimmune thyroiditis. N Engl J Med. 1996;335:99-106.

Dong BJ. Thyroid disorders. In: Herfindal ET, Gourley DR, eds. Textbook of Therapeutics: Drug and Disease Management. Philadelphia: Lippincott Williams & Wilkins; 2006.

Dong BJ, Greenspan FG. Thyroid and antithyroid drugs. In: Katzung BG, ed. Basic and Clinical Pharmacology. 11th ed. New York: McGraw-Hill; 2009.

Dong, BJ, Hauck WW, Gambertoglio JG, et al. Bioequivalence of generic and brand name levothyroxine products in the treatment of hypothyroidism. JAMA. 1997;277:1205-13.

Hoffmeister AM, Tietze KJ. Adrenocortical dysfunction and clinical use of steroids. In: Herfindal ET, Gourley DR, eds. Textbook of Therapeutics: Drug and Disease Management. Philadelphia: Lippincott Williams & Wilkins; 2006.

Master SB. Hypothalamic and pituitary hormones. In: Katzung BG, ed. Basic and Clinical Pharmacology. 11th ed. New York: McGraw-Hill; 2009.

McEvoy GK, ed. AHFS Drug Information 2009. Bethesda, Md.: American Society of Health-System Pharmacists; 2009.

U.S. Food and Drug Administration. Orange book: Approved drug products with therapeutic equivalence evaluations. Accessed at: http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm.