A 42-year-old woman comes to the office with persistent hyperlipidemia despite 6 months of maintaining a healthy diet and exercising regularly. Although her past medical history is significant for biliary colic secondary to gallstones, the patient has refused elective cholecystectomy. Her father died of a myocardial infarction at age 54, and her mother has diabetes mellitus. The patient's temperature is 36.1 C (97 F), blood pressure is 122/79 mm Hg, pulse is 78/min, and respirations are 14/min. Examination shows no abnormalities. Laboratory studies obtained 1 week ago show elevated serum triglycerides and LDL cholesterol levels. Drug therapy is discussed with the patient. Given this patient's preexisting gallbladder disease, which of the following drugs should be avoided?

Question

A 42-year-old woman comes to the office with persistent hyperlipidemia despite 6 months of maintaining a healthy diet and exercising regularly.  Although her past medical history is significant for biliary colic secondary to gallstones, the patient has refused elective cholecystectomy.  Her father died of a myocardial infarction at age 54, and her mother has diabetes mellitus.  The patient's temperature is 36.1 C (97 F), blood pressure is 122/79 mm Hg, pulse is 78/min, and respirations are 14/min.  Examination shows no abnormalities.  Laboratory studies obtained 1 week ago show elevated serum triglycerides and LDL cholesterol levels.  Drug therapy is discussed with the patient.  Given this patient's preexisting gallbladder disease, which of the following drugs should be avoided?

Quizplus · Accepted Answer

11ec160b_3bce_4d30_9249_71952a6902dc_MD0001_00 In patients with significant hypertriglyceridemia, fibrates are particularly effective due to their ability to upregulate lipoprotein lipase resulting in increased oxidation of fatty acids (liver, muscles). Gemfibrozil and other fibrates inhibit the rate-limiting enzyme in bile acid synthesis, cholesterol 7-alpha-hydroxylase. The reduced bile acid production results in decreased cholesterol solubility and increased microcrystal precipitation, thereby promoting gallstone formation. As a result, fibrates should be used with caution in patients with preexisting gallbladder disease. Patients on fibrate therapy should also be monitored for myopathy, a risk significantly increased when fibrates are used concurrently with statins. (Choice A) Long-term use of statins (eg, atorvastatin) is associated with decreased risk of gallstone disease as inhibition of HMG-CoA reductase reduces cholesterol biosynthesis and bile supersaturation. Side effects of statin therapy include hepatic dysfunction (elevated aminotransferases) and myopathy. (Choice B) Ezetimibe blocks intestinal cholesterol absorption, decreasing liver cholesterol stores and reducing biliary cholesterol content. Adverse effects associated with ezetimibe include elevated transaminases (increased with concurrent use of statins) and diarrhea. (Choice C) Fish oil supplements containing high concentrations of omega-3 fatty acids increase bile acid synthesis, decrease cholesterol saturation in bile, and increase gallbladder motility. The net effect is a decreased risk of gallstone formation. (Choice E) Niacin increases HDL (via reduced catabolism) and lowers triglyceride levels (through inhibition of VLDL secretion). It is associated with lower rates of gallstone disease. Niacin commonly promotes flushing, a temporary prostaglandin-mediated effect often blunted by use of nonsteroidal anti-inflammatory drugs. Educational objective: Gemfibrozil (and other fibrates) can reduce cholesterol solubility and promote gallstone formation by reducing bile acid synthesis. Caution should be used when prescribing fibrate therapy to patients with underlying gallbladder disease. __________ References: Triglycerides and gallstone formation. (http://www.ncbi.nlm.nih.gov/pubmed/20699090)

A 42-Year-Old Woman Comes to the Office with Persistent Hyperlipidemia