A physician-validated, board-style question from the Active Transport QBank. Try it, then check the reasoning for every option.
A 63-year-old man with high blood pressure, dyslipidemia, and diabetes presents to the clinic for routine follow-up. He has no current complaints and has been compliant with his chronic medications. His blood pressure is 132/87 mm Hg and his pulse is 75/min and regular. On physical examination, you notice that he has xanthelasmas on both of his eyelids. He currently uses a statin to lower his LDL but has not reached the LDL goal you have set for him. You would like to add an additional medication for LDL control. Of the following, which statement regarding fibrates is true?
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A
Fibrates can cause significant skin flushing and pruritusIncorrect. Flushing and pruritus are characteristic of niacin (nicotinic acid), mediated by prostaglandin release - not a feature of fibrates.
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B
Fibrates can potentiate the risk of myositis when given with statinsCorrect. Fibrates (especially gemfibrozil) potentiate statin-induced myopathy and rhabdomyolysis by interfering with statin metabolism - the key safety concern with this combination.
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C
Fibrates can increase the risk of cataractsIncorrect. Cataracts are associated with chronic corticosteroid use, not fibrates.
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D
Fibrates inhibit the rate-limiting step in cholesterol synthesisIncorrect. The rate-limiting step in cholesterol synthesis (HMG-CoA reductase) is inhibited by statins; fibrates act on PPAR-alpha to increase LPL activity.
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E
Fibrates work primarily by inhibiting intestinal cholesterol absorptionIncorrect. Inhibition of intestinal cholesterol absorption is the mechanism of ezetimibe; fibrates act via PPAR-alpha activation to upregulate lipoprotein lipase and lower triglycerides.
↑ Tap an answer to reveal the reasoning
Answer: B. Fibrates (gemfibrozil, fenofibrate) activate PPAR-alpha, increasing lipoprotein lipase activity and decreasing apolipoprotein C-III, which lowers triglycerides dramatically (30-50%) and raises HDL modestly. They have a smaller effect on LDL, and they are mainly used for hypertriglyceridemia rather than LDL reduction.
The most important safety issue is that combining fibrates with statins POTENTIATES THE RISK OF MYOPATHY, including rhabdomyolysis. Gemfibrozil is the worst offender because it inhibits glucuronidation of statins (especially simvastatin), raising statin levels and myotoxicity; fenofibrate has a much lower interaction profile and is preferred when combination is needed. Patients on combination therapy should be monitored for muscle symptoms and CK if symptomatic.
Other fibrate adverse effects: cholesterol gallstones (decreased bile-acid conjugation), transaminitis, and a small reversible creatinine rise. Niacin causes flushing and pruritus (option A). Statins (not fibrates) inhibit the rate-limiting step in cholesterol synthesis (HMG-CoA reductase). Cataracts are associated with corticosteroids, not fibrates.
**Why each option:**
**A.** Flushing and pruritus are characteristic of niacin (nicotinic acid), mediated by prostaglandin release - not a feature of fibrates.
**B.** Correct. Fibrates (especially gemfibrozil) potentiate statin-induced myopathy and rhabdomyolysis by interfering with statin metabolism - the key safety concern with this combination.
**C.** Cataracts are associated with chronic corticosteroid use, not fibrates.
**D.** The rate-limiting step in cholesterol synthesis (HMG-CoA reductase) is inhibited by statins; fibrates act on PPAR-alpha to increase LPL activity.