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Chapter 19: Hematologic and Renal Pharmacology

Compared to unfractionated heparin (UFH), low-molecular-weight heparin (LMWH) has all of the following advantages EXCEPT:

(A) Greater bioavailability when given by subcutaneous injection.

(B) The anticoagulant response is highly correlated to body weight.

(C) Significantly less likely to develop heparin-induced thrombocytopenia.

(D) Duration of action is shorter, permitting easier titration to effect.

(E) Can be safely used in the outpatient setting.

The answer is D. Heparins exert their effect by binding with circulating antithrombin and inducing a conformational change that exposes the active site for binding with clotting factor proteases (thrombin, factor IXa and factor Xa). Normally the inhibition of these proteases by antithrombin is a slow reaction; heparin accelerates the rate 1,000-fold. LMWH have been shown to be as effective as UFH for several indications, such as prevention and treatment of venous thromboembolism. Unfractionated heparin contains heparin molecules of varying sizes, ranging from 5,000 to 30,000 Daltons. Only one third of all molecules in UFH are estimated to be capable of exerting the anticoagulant effect. However, UFH is active on all three coagulation factors. In contrast, LMWHs inactivate factor Xa, with a much more limited effect on thrombin.

Purported advantages to LMWH over UFH include:

  • greater bioavailability than UFH when administered subcutaneously

  • an anticoagulant response that correlates well with body weight; this allows for the prescription of a fixed dose

  • a prolonged duration of effect due to reduced binding to macrophages and endothelial cells, allowing for dosing every 12–24 hours

  • no need for laboratory monitoring, due to stable and predictable pharmacokinetics (as well as the poor correlation between anti-Xa activity and clinical bleeding)

  • fewer side effects such as heparin-induced thrombocytopenia or osteoclast-mediated osteoporosis

  • ease and safety of administration at home

One disadvantage of LMWH is that reversal is incomplete with protamine. Protamine is relatively effective in neutralizing the antithrombin activity, but much less effective at reversing the anti-factor Xa activity. No other reversal agent exists for use with LMWH.

Ref: Katzung BG, Masters SB, Trevor AJ. Basic and Clinical Pharmacology. 12th ed. (LANGE Basic series). New York, NY: McGraw Hill; 2012.

Which of the following is MOST accurate regarding interactions between warfarin and other drugs?

(A) Barbiturate use results in a decreased dose requirement of warfarin.

(B) Metronidazole use results in a significant increase in plasma concentrations of warfarin.

(C) Non-selective NSAIDs are contraindicated during warfarin use.

(D) Amiodarone may ...

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