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Chapter 20: Drug Therapy of Dyslipidemias

A patient is prescribed fenofibrate as part of his therapy to raise his/her HDL-C levels. Fenofibrate most likely acts by

a. inhibiting HMG-CoA reductase.

b. binding cell membrane receptors that leads to lowering of adipocyte hormone–sensitive lipase activity.

c. sequestering bile acids in the small intestine.

d. binding PPARα receptors in liver and brown adipose tissue.

e. inhibiting cholesterol uptake from the small intestine.

Answer is d. The effects of fenofibrate and other fibrates on blood lipids are mediated by their interaction with the peroxisome proliferator–activated receptors (PPARs). Fibrates bind to PPARα, which is expressed primarily in the liver and brown adipose tissue and to a lesser extent in the kidney, heart, and skeletal muscle. Fibrates reduce triglycerides through PPARα-mediated stimulation of fatty acid oxidation, increased LPL synthesis, and reduced expression of apoC-III. An increase in LPL would enhance the clearance of triglyceride-rich lipoproteins. A reduction in hepatic production of apoC-III, which serves as an inhibitor of lipolytic processing and receptor-mediated clearance, would enhance the clearance of VLDL. Fibrate-mediated increases in HDL-C are due to PPARα stimulation of apoA-I and apoA-II expression, which increases HDL levels. Most fibric acid agents have potential antithrombotic effects, including inhibition of coagulation and enhancement of fibrinolysis. These salutary effects also could alter cardiovascular outcomes by mechanisms unrelated to any hypolipidemic activity.

A patient is prescribed niacin to reduce his/her triglyceride and LDL-C levels. The side effect(s) of niacin that most commonly limits patient compliance include

a. bloating.

b. flushing and dyspepsia.

c. tinnitus.

d. dry cough.

e. chills.

Answer is b. Two of niacin’s side effects, flushing and dyspepsia, limit patient compliance. The cutaneous effects include flushing and pruritus of the face and upper trunk, skin rashes, and acanthosis nigricans. Flushing and associated pruritus are prostaglandin-mediated. Flushing is worse when therapy is initiated or the dosage is increased but ceases in most patients after 1 to 2 weeks of a stable dose. Taking an aspirin each day alleviates the flushing in many patients. Flushing recurs if only 1 or 2 doses are missed, and the flushing is more likely to occur when niacin is consumed with hot beverages (coffee, tea) or with ethanol-containing beverages. Flushing is minimized if therapy is initiated with low doses (100-250 mg twice daily) and if the drug is taken after breakfast or supper. Dry skin, a frequent complaint, can be dealt with by using skin ...

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