A 68-year-old man reports myalgia and fatigue during a follow-up office visit. The patient has been taking high-intensity statin therapy since he had an acute myocardial infarction several weeks ago. His other medical problems include hypertension and type 2 diabetes mellitus. On examination, there is mild generalized muscle tenderness. Serum creatine kinase level is 456 U/L. Vitamin D and TSH levels are within normal range. The patient's statin therapy is discontinued, and he is started on a medication that inhibits cholesterol absorption at the brush border of the small intestine. Which of the following drugs was most likely started in this patient?

Question

A 68-year-old man reports myalgia and fatigue during a follow-up office visit.  The patient has been taking high-intensity statin therapy since he had an acute myocardial infarction several weeks ago.  His other medical problems include hypertension and type 2 diabetes mellitus.  On examination, there is mild generalized muscle tenderness.  Serum creatine kinase level is 456 U/L.  Vitamin D and TSH levels are within normal range.  The patient's statin therapy is discontinued, and he is started on a medication that inhibits cholesterol absorption at the brush border of the small intestine.  Which of the following drugs was most likely started in this patient?

Quizplus · Accepted Answer

11ec160b_3bb6_3227_9249_a919041e43e9_MD0001_00 Cholesterol-lowering agents commonly work in 1 of 3 ways: Ezetimibe decreases intestinal absorption of cholesterol by inhibiting the Niemann-Pick C1-like 1 (NPC1L1) transporter protein, which transports dietary cholesterol from the gastrointestinal lumen into intestinal enterocytes. As a result, the total amount of dietary cholesterol reaching the liver decreases, lowering intrahepatocyte cholesterol levels. To compensate, the liver increases LDL receptor expression, which draws cholesterol out of the circulation. (Choice A) Bile acid sequestrants (eg, colesevelam) bind bile salts in the intestine, decreasing their reabsorption. Subsequent depletion of the bile acid pool causes upregulation of cholesterol 7-α-hydroxylase, which converts cholesterol into bile acids. (Choice C) Fibrates activate peroxisome proliferator-activated receptor-alpha transcription factors, which leads to stimulation of lipoprotein lipase activity and a decrease in triglyceride levels. (Choice D) Nicotinic acid inhibits hepatic triglyceride synthesis, which in turn reduces the liver's availability to synthesize VLDL particles that are subsequently metabolized into LDL in the circulation. (Choice E) Proprotein convertase subtilisin kexin 9 (PCSK9) increases degradation of hepatic LDL receptors. Alirocumab is a monoclonal antibody against PCSK9 that blocks this effect, resulting in increased availability of LDL receptors on hepatocyte membranes and subsequently increased clearance of LDL from the blood. Educational objective: Ezetimibe reduces intestinal absorption of cholesterol. As a result, the amount of dietary cholesterol reaching the liver decreases. To compensate, the liver increases LDL receptor expression, which draws cholesterol out of the circulation. __________ References: Ezetimibe--a new approach in hypercholesterolemia management. (http://www.ncbi.nlm.nih.gov/pubmed/22358082) Inactivating mutations in NPC1L1 and protection from coronary heart disease. (http://www.ncbi.nlm.nih.gov/pubmed/25390462)

A 68-Year-Old Man Reports Myalgia and Fatigue During a Follow-Up