A 63-year-old man comes to the office for a follow-up visit. Two months ago, he was hospitalized for chest pain and was found to have a blockage in the left anterior descending artery. He had percutaneous coronary intervention with placement of a drug-eluting stent, and was discharged on appropriate medical therapy. His other medical problems include hypertension, type 2 diabetes mellitus, and degenerative joint disease. The patient has been taking all his medications as prescribed. He has no chest pain but does have diffuse muscle aches and cramps, especially after exercise. Physical examination is unremarkable. Laboratory testing reveals elevated serum creatine kinase. The medication most likely responsible for this patient's current findings also causes which of the following effects?

Question

A 63-year-old man comes to the office for a follow-up visit.  Two months ago, he was hospitalized for chest pain and was found to have a blockage in the left anterior descending artery.  He had percutaneous coronary intervention with placement of a drug-eluting stent, and was discharged on appropriate medical therapy.  His other medical problems include hypertension, type 2 diabetes mellitus, and degenerative joint disease.  The patient has been taking all his medications as prescribed.  He has no chest pain but does have diffuse muscle aches and cramps, especially after exercise.  Physical examination is unremarkable.  Laboratory testing reveals elevated serum creatine kinase.  The medication most likely responsible for this patient's current findings also causes which of the following effects?

Quizplus · Accepted Answer

This patient's symptoms are most likely due to statin-induced myopathy. Statins are an effective treatment for hypercholesteremia and are now routinely prescribed for all patients with symptomatic coronary artery disease, regardless of baseline cholesterol levels. Myopathy is the most common complication of statin use, and symptoms can range from myalgia or myopathy, with or without myonecrosis (elevated serum creatine kinase), to frank rhabdomyolysis. Statins act through competitive inhibition of HMG-CoA reductase, preventing conversion of HMG-CoA to mevalonic acid (the rate-limiting step in cholesterol biosynthesis). Decreased liver cholesterol synthesis leads to increased hepatic clearance of LDL from the circulation by LDL receptors. After mediating endocytosis of LDL particles, the LDL receptors are returned to the cell surface for reuse (receptor recycling); LDL is digested and used for metabolic purposes. This increase in LDL receptor recycling allows intrahepatic cholesterol levels to remain at normal levels while blood levels are kept low. (Choice A) Nonsteroidal anti-inflammatory drugs inhibit cyclooxygenase (prostaglandin synthase), leading to decreased synthesis of gastric mucosal prostaglandin. (Choice B) Angiotensin-converting enzyme (ACE) inhibitors inhibit the conversion of angiotensin I to angiotensin II. ACE also acts as a kininase, and ACE inhibition also leads to increased plasma bradykinin levels. (Choice C) Stimulation of beta-2 receptors by catecholamines increases extracellular potassium movement into cells. This effect is blocked by beta-blockers (primarily non-selective agents such as propranolol or labetalol), which impair potassium entry into cells and cause minor elevations in plasma potassium. (Choice E) Thiazide diuretics increase calcium reabsorption in the distal tubule of the nephron and can lead to hypercalcemia. In contrast, decreased calcium excretion is useful in patients with renal stones due to hypercalciuria. (Choice F) Metformin inhibits hepatic gluconeogenesis via inhibition of the mitochondrial isoform of glycerophosphate dehydrogenase in the liver. Typical side effects of metformin include gastrointestinal upset and diarrhea. Myopathy is not a common effect. Educational objective: Statins inhibit the intracellular rate-limiting step of cholesterol biosynthesis via competitive inhibition of HMG-CoA reductase. This leads to enhanced hepatic LDL receptor recycling and increased LDL clearance from the circulation. Statin-induced myopathy (eg, myalgia, elevated creatine kinase) is the most common complication of statin use. __________ References: Inhibitors of cholesterol biosynthesis increase hepatic low-density lipoprotein receptor protein degradation. (http://www.ncbi.nlm.nih.gov/pubmed/8561503) The LDL receptor. (http://www.ncbi.nlm.nih.gov/pubmed/19299327)

A 63-Year-Old Man Comes to the Office for a Follow-Up