M. R. is a 74-year-old man with a history of hypercholesterolemia treated with simvastatin. Two months ago he had a permanent pacemaker placed for sick sinus syndrome. He now presents with a 1-month history of fever, chills, and unexplained weight loss. On physical examination he has a new tricuspid regurgitation murmur. A transesophageal echocardiogram confirms your suspicion of endocarditis. Which of the following antibiotics increases the risk of rhabdomyolysis when given with simvastatin?
c. Daptomycin. Daptomycin may cause elevations in creatine phosphokinase (CPK) levels. The product literature for daptomycin recommends temporary discontinuation of medications that can raise CPK levels when a patient is receiving this antibiotic. Even though this adverse reaction is rare, CPK levels should be monitored weekly in patients receiving daptomycin alone and more frequently if statin therapy is continued.
Put the following regimens in order according to their low-density lipoprotein (LDL)-lowering ability.
Atorvastatin, 10 mg daily (A)
Cholestyramine, 8 g daily (C)
Pravastatin, 20 mg daily (P)
Gemfibrozil, 600 mg twice daily (G)
a. A > P > C > G. HMG-CoA reductase inhibitors decrease LDL by 18% to 55%. Atorvastatin is the most potent agent statin of the group. Bile-acid sequestrants decreased LDL by 15% to 30%. Fibrates decrease LDL by 5% to 20%.
D. L. is a 76-year-old white man with a past medical history significant for DM type 2 and HTN. Chronic AFib was recently diagnosed with coronary artery disease (CAD) and hypercholesterolemia and he was initiated on gemfibrozil 600 mg twice daily and atorvastatin 40 mg daily. His other medications include glyburide, metoprolol, furosemide, levothyroxine, insulin, and aspirin. Two weeks later, he began to experience pain in his right calf, with pain and stiffness throughout his back, buttocks, and thigh. After another week, he was admitted to the hospital with similar heightened symptoms. On admission, his blood urea nitrogen was elevated, and the urinalysis showed orange, cloudy urine; protein, greater than 300; glucose, greater than 1,000; ketones, 2+; hemoglobin, 3+; red blood cell count, 6 to 10; and myoglobin, 1,367. Which of the following statements is true?
b. Forced diuresis with urine alkalinization and discontinuation of gemfibrozil and atorvastatin are indicated for this patient. Rhabdomyolysis secondary to the interaction of atorvastatin and gemfibrozil is responsible for this clinical picture. Rhabdomyolysis is defined as the disintegration of muscle, associated with the excretion of myoglobin in the urine. Clinical signs and symptoms include myalgias, elevated creatine kinase, elevated urine and serum myoglobin, and dark urine. Complications of rhabdomyolysis are numerous and may include renal failure, disseminated intravascular coagulation, metabolic acidosis, and cardiomyopathy. HMGCoA (3-hydroxy-3-methyl-glutaryl-CoA) reductase inhibitors (statins) can be considered direct myotoxins and may induce rhabdomyolysis when used alone. However, the risk of toxicity increases when statins are used in combination with fibric acid derivatives (gemfibrozil or fenofibrate), nicotinic acid, cyclosporine, itraconazole, or erythromycin, to name a few. Treatment of the underlying cause, in this case discontinuation of the offending agents, is necessary. In addition, renal failure caused by products of tissue degradation must be combated with urinary alkalinization and maintenance of a high urine volume.
N. H. is a 57-year-old man status post MI with a BP of 150/88 mmHg and a heart rate of 87 bpm. He is currently on aspirin, clopidogrel, atorvastatin, and lisinopril. Which agent would be the most appropriate addition for treatment of his HTN?
b. Metoprolol. The American College of Cardiology (ACC) and American Heart Association (AHA) recommend the use of β-blockers in patients after surviving an MI to decrease mortality, sudden death, and reinfarction. Therefore, if this patient is not already on a β-blocker, one would be indicated, not only for HTN but also for secondary prevention.
B. T. is a 56-year-old woman with long-standing HTN that is difficult to control. She is currently being treated with amlodipine 10 mg daily, lisinopril 40 mg daily, hydrochlorothiazide 25 mg daily, and clonidine 0.4 mg three times daily. She presented to the emergency room, and her initial BP was 200/110 mmHg. She states she had run out of one of her medications. Which one of her medications would most likely be implicated in causing hypertensive urgency?
d. Clonidine. Abrupt withdrawal of an α2-agonist is the most likely cause of severe rebound HTN. Typically, this is seen within 24 to 48 hours of discontinuation of clonidine and typically occurs in patients taking large doses for longer than 3 months. The best treatment for this is to restart clonidine. β-Blockers could make the situation worse by causing unopposed α1-stimulation.
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