книга / 2016_Kaplan_USMLE_Step_1_Lecture_Notes_Pharmacology

Learning Objectives

Use knowledge of bisphosphonates and teriparatide to solve problems

BISPHOSPHONATES: ALENDRONATE AND OTHER

DRONATES

λMechanisms: stabilize hydroxyapatite bone structure and also induce osteoblasts to secrete inhibitors of osteoclasts →↓ bone resorption →↓ progression of osteoporosis

λClinical uses:

–Established use in Paget disease

–Efficacy in postmenopausal osteoporosis depends on individual drug, but alendronate is effective and with HRT causes ↑ bone mineral density (BMD).

–Alendronate is drug of choice for glucocorticoid-induced osteoporosis

λSide effects:

–Etidronate and pamidronate → bone mineralization defects

–Gastrointestinal distress, including esophageal ulcers (alendronate)

TERIPARATIDE

λMechanism: recombinant DNA PTH analog

λClinical use: once daily to stimulate osteoblasts and new bone formation

λContinuous infusion would stimulate osteoclast activity

λUsed for less than 2 years; may ↑ risk of osteosarcoma

Chapter Summary

λThe bisphosphonates decrease bone resorption and slow the progress of osteoporosis. Alendronate is effective for treatment of postmenopausal and steroid-induced osteoporosis. The principal potential side effects are gastrointestinal distress and esophageal ulcers.

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Section VIII λ Endocrine Pharmacology

1.A 70-year-old man is diagnosed with benign prostatic hyperplasia (BPH), and his physician is considering drug treatment of the condition. It was decided that the drug finasteride will be used. The effects of finasteride will result in a decrease in the synthesis of what substance?

A.Epinephrine

B.Norepinephrine

C.Dihydrotestosterone

D.Testosterone

E.GnRH

2.Which of the following statements is accurate regarding drug management of hyperthyroidism?

A.The actions of thyroid peroxidase are inhibited by I131

B.Propylthiouracil inhibits the conversion of thyroxine to triiodothyronine

C.Methimazole is unable to cross the placental barrier

D.Iodide salts can be used for long-term management

E.The iodination of tyrosyl residues to form MIT and DIT are inhibited by beta blockers

3.What drug is useful to distinguish neurogenic from nephrogenic diabetes insipidus?

A.Amiloride

B.Demeclocycline

C.Desmopressin

D.Hydrochlorothiazide

E.Lithium

4.The release of insulin from pancreatic beta cells would most likely be stimulated by which of the following?

A.Clonidine

B.Norepinephrine

C.Diazoxide

D.Glipizide

E.Hypoglycemia

5.When used at higher doses than commonly employed for other purposes, what drug can effectively inhibit steroidogenesis in a variety of tissues?

A.Flutamide

B.Misoprostol

C.Clomiphene

D.Tamoxifen

E.Ketoconazole

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Chapter 6 λ Endocrine List and Practice Questions

6.In a patient with type 2 diabetes, which drug mimics the action of incretins to augment glucose-dependent insulin secretion?

A.Acarbose

B.Glucagon

C.Exenatide

D.Metformin

E.Rosiglitazone

7.To supplement other oral type 2 diabetes medication, a patient is prescribed a drug to inhibit the intestinal absorption of carbohydrates. What would be an appropriate drug?

A.Metformin

B.Acarbose

C.Repaglinide

D.Insulin lispro

E.Pioglitazone

8.What is the drug of choice for management of adrenal glucocorticoidinduced osteoporosis?

A.Alendronate

B.Calcitonin

C.Estrogen

D.Ketoconazole

E.Vitamin D

9.Which drug has utility in inhibiting the severe secretory diarrhea of hormone-secreting tumors of the pancreas and GI tract, as well as in the treatment of acromegaly?

A.Octreotide

B.Leuprolide

C.Bromocriptine

D.Sertraline

E.Anastrazole

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Section VIII λ Endocrine Pharmacology

Answers

1.Answer: C. The drug finasteride inhibits the enzyme 5-α reductase, the enzyme that converts testosterone to dihydrotestosterone (DHT). DHT is responsible for prostate enlargement in BPH. The other commonly used drugs in BPH are alpha- 1 antagonists such as prazosin and tamsulosin.

2.Answer: B. Thioamides used at conventional doses in Graves disease are slow to act; they inhibit iodination and the coupling reactions in hormone synthesis

and do not affect the release of stored thyroxine. At high doses, propylthiouracil may act more rapidly because of its inhibition of 5′-deiodinase, preventing the

conversion of T4 to T3. Thioamides are not teratogenic, and they do not decrease glandular size or vascularity; KI plus iodine (Lugol’s solution) is used preoperatively to this end. Use of iodide in hyperthyroidism is only temporary because the thyroid gland “escapes” from its actions within a week or two.

3.Answer: C. Neurogenic diabetes insipidus is treated with desmopressin, a drug

that is similar to vasopressin (ADH), yet is a selective activator of V2 receptors in the kidney. Remember that V1 receptors are present in smooth muscle, and their activation leads to vasoconstriction and bronchoconstriction. Nephrogenic diabetes insipidus (decreased response of vasopressin receptors) is treated with thiazides, except in the case of that induced by lithium, when amiloride is preferred (because thiazides increase blood levels of lithium). In cases where it is necessary to distinguish between neurogenic and nephrogenic, desmopressin is used. Desmopressin would alleviate the symptoms of neurogenic but have no effect in nephrogenic diabetes Insipidus.

4.Answer: D. The release of insulin from the pancreas is stimulated by insulinogens (glucose), sulfonylurea hypoglycemics (glipizide), activators of beta-2 adrenoceptors (e.g., albuterol), and activators of muscarinic receptors (e.g., pilocarpine). Activation of alpha-2 receptors inhibits insulin release (clonidine and norepinpehrine). Hypokalemia, and diazoxide, keep potassium channels on beta cells open resulting in decreased insulin release

5.Answer: E. Ketoconazole is an antifungal drug that decreases the synthesis of various steroids including cortisol and testosterone by inhibiting cytochrome P450 enzymes. Flutamide is an androgen-receptor antagonist, and tamoxifen is a partial agonist (or mixed agonist-antagonist) at estrogen receptors. Misoprostol is a prostanglandin analog used in NSAID-induced ulcers. Clomiphene is used to induce ovulation.

6.Answer: C. Exenatide is a glucagon-like peptide-1 (GLP-1) analog. GLP-1 is an incretin released from the small intestine that enhances glucose-dependent insulin secretion. Metformin is “euglycemic,” lowering elevated glucose levels to the normal range, and acarbose simply prevents postprandial hyperglycemia. Glucagon causes hyperglycemia, an effect that is sometimes employed in management of hypoglycemia. Rosiglitazone increases the sensitivity to insulin by increasing insulin receptor numbers.

7.Answer: B. Acarbose inhibits the enzyme α-glucosidase in the brush borders of the small intestine. This decreases the formation of absorbable carboydrate and thereby decreases glucose absorption. The net effect is that glucose levels after a meal don’t rise as significantly and therefore the insulin demand Is reduced.

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Chapter 6 λ Endocrine List and Practice Questions

8.Answer: A. Alendronate is currently the drug of choice to prevent osteoporosis in patients who must be maintained on steroids for their antiinflammatory and immunosuppressive effects. The drug also decreases bone resorption during menopause and is sometimes favored in patients who are at risk for neoplasias if treated with sex hormones. Care must be taken with

alendronate to avoid esophageal ulceration. Estrogen hormone replacement therapy ± vitamin D also has proven valuable for slowing bone resorption in menopause, and increases in bone mass have been reported for combinations of estrogens with alendronate.

9.Answer: A. Octreotide is a somatostatin analog that is effective for carcinoid and other secretory GI tumors. It has been used to varying degrees in other forms of secretory diarrhea such as chemotherapy-induced and the diarrhea of HIV and diabetes. Octreotide has proven to be of major importance in the management of acromegaly and can significantly decrease the levels of growth hormone.

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SECTION IX

Anticancer Drugs