Probucol

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Probucol (Lorelco) is a hypocholesterolemic drug with few side effects that modestly (15-30%) decreases elevated plasma LDL cholesterol levels. The marginal

TABLE 23.4 Summary of Major Drug Interactions

Drug Interactions and Special Precautions

Statins Inhibition of cytochromal P450 3A4 can greatly increase serum statin levels. Grapefruit juice inhibits intestinal P450 3A4 and raises serum statins.

Fluvastatin may increase warfarin toxicity because both compete with P450 2C9 for metabolism. Cerivastatin can cause fatal rhabdomyolysis;risk with other statins unclear.

Bile acid resins Interferes with absorption of many drugs (give other drugs 1 hr before or 6 hr after the resin). May in terfere with absorption of fat-soluble vitamins.

Nicotinic acid (niacin) Cutaneous flush can limit compliance. Giving niacin after meals and use of aspirin may decrease flushing.

Gradually increase niacin dose to maximum.

Fibrates Potentates coumarin anticoagulants. Therefore, reduce dose of anticoagulant and monitor plasma pro-

thrombin.

Use clofibrate as second-line drug because it increased death rate in an early study.

Avoid use with statins, since the combination may increases risk of myositis and rhabdomyolysis.

LDL-lowering action plus reports that it can lower HDL cholesterol resulted in its discontinuation as a hypocholesterolemic drug. However, it still may reduce the risk of CHD because it is a powerful antioxi-dant.

The oxidation hypothesis of atherosclerosis states that oxidation of lipids in LDL is required for LDL uptake by macrophages and smooth muscle cells in the intima of arteries, leading to their transformation to foam

Use the following information to answer questions 1 through 4:

A 54-year white man (5', 11"; 189 lb) has a plasma total triglyceride of 105 mg/dL and total cholesterol of 431 mg/dL. Plasma HDL is 53 mg/dL. Electrophoresis of his plasma lipoproteins shows an intense p-band; all others are normal. He is taking itraconazole for a persistent fungal infection. He had two older brothers who both died of myocardial infarction at 57 and 63 years of age.

1. What hyperlipoproteinemia does this patient most likely have?

2. What is the most likely biochemical basis of this patient's hyperlipidemia?

(A) Abnormal apolipoprotein E content of serum p-lipoproteins.

(B) Increased transcription of the HMG CoA re-ductase gene in liver.

(C) Overproduction of VLDL particle by the liver.

(D) Reduced hepatic LDL-receptor activity.

(E) Reduced lipoprotein lipase activity.

cells, an early event in atherogenesis. A recent clinical trial reported that use of probucol decreased the rate of restenosis of coronary arteries by 50% in patients who underwent angioplasty. Fluvastatin also has potent an-tioxidant properties that may contribute to its antiath-erosclerotic effects. These findings suggest that reducing high plasma lipids may not be the only approach to retarding the progression of atherosclerosis and decreasing the risk of coronary heart disease.

3. What drugs would be contradicted in this patient if his use of itraconazole was not discontinued?

(A) Cholestyramine

(B) Gemfibrozil

(c) Niacin

(d) Probucol (E) Simvastatin

4. If the patient was treated with cerivastatin, what adverse effects would be of greatest potential concern?

(A) Constipation

(B) Hepatic dysfunction

(C) Hyperglycemia

(D) Intense cutaneous flush

(E) Rhabdomyolysis

Use the following information to answer questions 5 through 8:

A 42-year-old white woman (5', 4"; 207 lb) has a plasma total triglyceride of 1042 mg/dL and total cholesterol of 368 mg/dL. Plasma HDL cholesterol is 72 mg/dL. Electrophoresis of the plasma lipoproteins shows a intense pre-p-band; all others are normal or absent. Blood glucose is normal. She is not taking any medications.

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