книга / 2016_Kaplan_USMLE_Step_1_Lecture_Notes_Pharmacology

Chapter 4 λ Blood Disorder Drug List and Practice Questions

Answers

1.Answer: A. Platelet aggregation is stimulated by many compounds, including

ADP, thromboxane A2, fibrin, and serotonin. Clopidogrel, along with ticlopidine, blocks ADP receptors and prevent platelet activation. Prostacyclin (PGI2) from endothelial cells is a naturally occurring compound that inhibits platelet

aggregation by stimulating PGI2 receptors. Aspiring inhibits the synthesis of thromboxane A2. Abciximab is a monoclonal antibody targeted to the glycoprotein IIb/IIIa receptor which inhibits aggregation. Montelukast blocks leukotriene receptors and is used in asthma.

2.Answer: D. Discontinuing warfarin is appropriate during pregnancy because it is a known teratogen that causes bone dysmorphogenesis. The patient will need continued protection against thrombus formation, and heparin (or a related low molecular weight compound) is usually advised, despite the fact that the drug will require parenteral administration and can cause thrombocytopenia.

3.Answer: E. Enoxaparin is a low-molecular weight heparin. As such, it is smaller and will have a longer half-life compared to heparin. It still has a risk of causing bleeding and thrombocytopenia, but is not more rapid in onset. Heparins do not affect the synthesis of clotting factors, but rather rapidly inactivate existing factors.

4.Answer: C. Warfarin inhibits the hepatic synthesis of factors II (prothrombin), VII, IX, and X. Its onset of anticoagulation activity is slow, and its impact on individual coagulation factors depends on their half-lives. Factor VII and protein C have much shorter half-lives than prothrombin, and so the extrinsic pathway and protein C system are the first to be affected by warfarin. The intrinsic pathway continues to function for 2 to 3 days, causing a state of hypercoagulability and possible vascular thrombosis.

5.Answer: D. Alteplase is thrombolytic (or “fibrinolytic”) because it activates plasminogen, resulting in the increased formation of plasmin. Its efficacy is equivalent to that of streptokinase, but alteplase has the advantage of only activating plasminogen bound to fibrin (clot specific) but not free plasminogen. All thrombolytics can cause bleeding, which may be counteracted to some extent by administration of antifibrinolysins, such as aminocaproic acid.

6.Answer: C. Warfarin binds extensively (98%) but weakly to plasma proteins and can be displaced by other drugs (e.g., ASA, chloral hydrate, phenytoin, sulfinpyrazone, and sulfonamides), resulting in an increase in its anticoagulant

effects. Bile acid sequestrants bind acidic drugs such as warfarin, preventing their gastrointestinal absorption (↓ prothrombin time [PT]), and cimetidine, which inhibits the metabolism of warfarin, causing an increase in PT. Vitamin K restores levels of prothrombin and several other coagulation factors, but the action is slow (24 to 48 hours). Due to antiplatelet effects, even low doses of ASA may enhance bleeding in patients on warfarin.

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SECTION VIII

Endocrine

Pharmacology

Chapter 1 λ Drugs Used in Diabetes

–Drug interactions mainly with first-generation drugs →↑ hypoglycemia with cimetidine, insulin, salicylates, sulfonamides

METFORMIN

λ“Euglycemic,” ↓ postprandial glucose levels, but does not cause hypoglycemia or weight gain

λMechanisms: may involve ↑ tissue sensitivity to insulin and/or ↓ hepatic gluconeogenesis (Figure VIII-1-2)

λUse: monotherapy or combinations (synergistic with sulfonylureas)

λSide effects: possible lactic acidosis; gastrointestinal distress is common

ACARBOSE

λNo hypoglycemia

λMechanisms: inhibits α-glucosidase in brush borders of small intestine →↓ formation of absorbable carbohydrate →↓ postprandial glucose →↓ demand for insulin (Figure VIII-1-2).

λSide effects: gastrointestinal discomfort, flatulence, and diarrhea—recent concern over potential hepatotoxicity

THIAZOLIDINEDIONES: PIOGLITAZONE AND

ROSIGLITAZONE

λMechanisms: bind to nuclear peroxisome proliferator-activating receptors (PPARγ) involved in transcription of insulin-responsive genes → sensitization of tissues to insulin, plus ↓ hepatic gluconeogenesis and triglycerides and ↑ insulin receptor numbers (Figure VIII-1-2).

λSide effects: less hypoglycemia than sulfonylureas, but weight gain and edema reported

Figure VIII-1-2. Modes of Action of Drugs Used to Treat Diabetes

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Chapter 1 λ Drugs Used in Diabetes

Chapter Summary

λType 1 (IDDM) and type 2 (NIDDM) diabetes mellitus are defined at the beginning of the chapter.

λThe times of activity onset, peak activity, and duration of activity for lispro, regular, lente, and ultralente insulins are summarized in Table VIII-1-1.

λThe oral antidiabetic drugs are the sulfonylureas, metformin, acarbose, thiazolidinediones, and repaglinide.

λBy blocking K+ channels in the pancreatic cells, the sulfonylureas stimulate insulin release. The extra insulin in turn inhibits glucagon release from the cells and increases peripheral tissue sensitivity to insulin (Figure VIII-1-1).

The firstand second-generation drugs are listed. The adverse effects include weight gain and potential hypoglycemia.

λMetformin enhances tissue sensitivity to insulin and inhibits liver gluconeogenesis. The potential side effect is lactic acidosis.

λAcarbose inhibits intestinal-glucosidase, thereby slowing glucose absorption and decreasing insulin demand. The side effect is gastrointestinal distress.

λThe thiazolidinediones (glitazones) act via peroxisome proliferation activating receptors that control insulin-responsive genes. They are less hypoglycemic than the sulfonylureas, but they still induce weight gain and edema and have potential liver toxicity.

λRepaglinide, like the sulfonylureas, stimulates-cell secretion of insulin. Figure VIII-1-2 summarizes the modes of action of these drugs.

λBoth exenatide and sitagliptin increase glucose-dependent insulin secretion.

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