What causes myopathy in statins?
Regarding pharmacodynamics, certain genetic factors can increase the risk of statin-induced myopathy. Some examples are those associated with plasma membrane calcium transporting ATPase or with mitochondrial energy production regulated by the CoQ2 gene.
Does simvastatin cause myopathy?
The most severe adverse effect of statins is myotoxicity, in the form of myopathy, myalgia, myositis or rhabdomyolysis.
What is HMGCR myopathy?
A subset of immune-mediated necrotizing myositis, anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) myopathy is a rare disease that occurs in 0.9 to 1.4 cases per 100,000 people. It causes significant muscle weakness that does not resolve with discontinuation of the statin.
What is HMG CoA myositis?
Anti-hydroxymethylglutaryl CoA reductase (HMGCR) myopathy is a subtype of myositis characterized by proximal muscle weakness, elevated serum creatine kinase (CK) levels, and autoantibodies recognizing HMGCR1.
What causes myopathy?
Myopathy develops as the result of either inherited (congenital or genetic) disorders or acquired conditions of the muscles. Most commonly, people develop acquired myopathy from muscle fatigue, electrolyte imbalance, or dehydration, resulting in stiffness or cramping.
What does HMG-CoA reductase do?
The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase catalyzes the conversion of HMG-CoA to mevalonate, a four-electron oxidoreduction that is the rate-limiting step in the synthesis of cholesterol and other isoprenoids.
What are the symptoms of inflammatory myopathy?
General symptoms of chronic inflammatory myopathy include slow but progressive muscle weakness that starts in the proximal muscles—those muscles closest to the trunk of the body. Other symptoms include fatigue after walking or standing, tripping or falling, and difficulty swallowing or breathing.
Who gets myopathy?
Anyone can get a myopathy. Some develop at an early age, while other types develop later in life.
What causes Nemaline myopathy?
This disease is caused by a variety of genetic defects, each one affecting one of the filament proteins required for muscle tone and contraction. It can be inherited in an autosomal recessive or autosomal dominant pattern, meaning it can be produced by defective genes contributed by either one or both parents.
What controls HMG-CoA reductase?
HMG CoA reductase has been long recognized as the rate-limiting enzyme in synthesis of cholesterol and as such is a primary focus of regulation. This is underscored by a multivalent system mediated by sterol and nonsterol isoprenoids that exerts stringent feedback control on reductase through multiple mechanisms 2.
What happens if HMG-CoA reductase activity is inhibited?
Inhibition of HMG-CoA reductase reduces cholesterol biosynthesis in the liver. Synthetic drugs, statins, are commonly used for the treatment of hypercholesterolemia.