Why do statin drugs cause rhabdomyolysis?

Rhabdomyolysis is a well-documented side effect of statin therapy. This risk is increased with concurrent use of medications that inhibit cytochrome p450-3A4 (CYP3A4), such as macrolide antibiotics.

Does statins cause rhabdomyolysis?

However, the risk of developing rhabdomyolysis from statin therapy is very low, around 1.5 for each 100,000 people taking statins. Rhabdomyolysis or milder forms of muscle inflammation from statins can be diagnosed with a blood test measuring levels of the enzyme creatinine kinase.

Does simvastatin cause rhabdomyolysis?

Simvastatin was the most common statin medication reported in association with rhabdomyolysis (55 cases), most commonly taken at a dose of 40 mg/day.

What is the mechanism of action of HMG-CoA reductase inhibitors?

HMG-CoA reductase inhibitors (also known as statins) lower LDL cholesterol in the blood by blocking hepatic HMG Co-A reductase, the rate-limiting enzyme in cholesterol biosynthesis. This action depletes the intracellular cholesterol pool, leading to an up-regulation of LDL receptors and a decrease in serum cholesterol.

Which medications may cause rhabdomyolysis?

Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors)
Antihistamines (particularly in children)
Salicylates.
Caffeine.
Fibric acid derivatives (eg, bezafibrate, clofibrate, fenofibrate, and gemfibrozil)
Neuroleptics/antipsychotics.

What is the function of HMG reductase?

HMG-CoA Reductase (or 3-hydroxy-3-methyl-glutaryl-CoA reductase or HMGR) is the rate-controlling enzyme of the mevalonate pathway, responsible for cholesterol and other isoprenoid biosynthesis. HMGR is a transmembrane protein, containing 8 domains, that is anchored in the membrane of the endoplasmic reticulum.

Where does HMG CoA reductase work?

Introduction. Also known as statins, HMG-CoA reductase inhibitors work by inhibiting the synthesis of cholesterol in the liver by the enzyme HMG-CoA reductase.

How is HMG-CoA reductase activated?

Regulation of HMG-CoA reductase occurs at 4 different levels of feedback regulation. First by regulation of transcription of the reductase gene, which is activated by sterol regulatory element binding protein, a protein that binds to the promoter of the HMGR gene when cholesterol levels fall.

What is drug induced rhabdomyolysis?

Rhabdomyolysis can result from direct muscle injury by myotoxic drugs, such as cocaine and alcohol. This mechanism must be distinguished from rhabdomyolysis that develops secondarily from muscle ischemia due to prolonged seizures or local muscle compression in comatose states following drug overdosage.

What is the most common cause of rhabdomyolysis?

Rhabdomyolysis is a potentially life-threatening syndrome resulting from the breakdown of skeletal muscle fibers with leakage of muscle contents into the circulation. The most common causes are crush injury, overexertion, alcohol abuse and certain medicines and toxic substances.