Myopathies drug-induced

Other Inflammatory Muscle Disorders Endocrine Myopathies Thyroid Disorders Adrenal Disorders Pituitary Disorders Parathyroid Disorders Pancreatic Disorders Drug-Induced and Toxic Myopathies Management of Muscle Disease... 

To cover these various disorders in an orderly and comprehensive manner, the following sections are devoted, respectively, to the muscular dystrophies the congenital myopathies the metabolic myopathies the myotonias, periodic paralyses, and malignant hyperpyrexia the neurogenic disorders the inflammatory muscle disorders the endocrine myopathies and the drug-induced and toxic myopathies. 

Drug-induced and toxic myopathies are probably more common than is generally realized, but the distinctive feature of these conditions is that muscle damage is usually resolved rapidly once the causal agent is removed. The specific causes of damage vary considerably as does the presence of pain and discomfort. 

Corticosteroids a chronic painless myopathy associated with the long-term use of corticosteroids is a particularly common example of drug-induced muscle disorder. It is almost certain that mild cases are overlooked because steroids are so frequently used to treat inflammatory myopathies such as polymyositis. Fluorinated steroids are particularly frequently implicated, and the incidence of drug-induced muscle disease is dose and time-related. The presence of muscle weakness can even complicate topical steroid therapy. Corticosteroid-induced myopathy is mediated via intramuscular cytosolic steroid receptors. The steroid-receptor complexes inhibit protein synthesis and interfere with oxidative phosphorylation. The myopathy is associated with vacuolar changes in muscle, and the accumulation of cytoplasmic glycogen and mitochondrial aggregations. 

OwczarekJ, Jasinska M, Orszulak-Michalak D. Drug-induced myopathies. An overview of the possible mechanisms. Pharmacol Rep. 2005 57 23-34. 

Sripathi N, Wortmann RL, Phillips PS (2006) Genetic risk factors associated with lipidlowering drug-induced myopathies. Muscle Nerve 34 153-162... 

Guis, S., J-P. Mattel, and F. Liote. 2003. Drug-induced and toxic myopathies. Best Practice in Research in Clinical Rheumatology 17 877-907. 

Mastaglia, F. L. 2006. Drug-induced myopathies. Practical Neurology 6 4—13. 

Ivy Sharer. In the case of Ivy Sharer, a diffuse myopathic process was ) superimposed on her AIDS and her pulmonary tuberculosis, either of which could have caused progressive weakness. In addition, she could have been suffering from a congenital mtDNA myopathy, symptomatic only as she ages. A systematic diagnostic process, however, finally led her physician to conclude that her myopathy was caused by a disorder of oxidative phosphorylation induced by her treatment with zidovndine (AZT). Fortunately, when AZT was discontinued, Ivy s myopathic symptoms gradually subsided. A repeat skeletal muscle biopsy performed 4 months later showed that her skeletal muscle cell mtDNA had been restored to normal and that she had experienced a reversible drug-induced disorder of oxidative phosphorylation. 

Bannwarth, B. (2002). Drug-induced myopathies. Expert Opin Drug Safl(l) 65-70. 

Myopathy and neuropathy Colchicine myoneuropathy appears to be a common cause of weakness in patients on standard therapy who have elevated plasma levels caused by altered renal function. It is often unrecognized and misdiagnosed as polymyositis or uremic neuropathy. Proximal weakness and elevated serum creatine kinase are generally present, and resolve in 3 to 4 weeks following drug withdrawal. Maiabsorption of vitamin B-f2- Colchicine induces reversible malabsorption of vitamin B-12, apparently by altering the function of ileal mucosa. 

Tipranavir both inhibits and induces the CYP3A4 system. When used in combination with ritonavir, its net effect is inhibition. Tipranavir also induces P-glycoprotein transporter and thus may alter the disposition of many other drugs (Table 49-4). Concurrent administration of tipranavir with fosamprenavir or saquinavir should be avoided owing to decreased blood levels of the latter drugs. Tipranavir/ritonavir may also decrease serum levels of valproic acid and omeprazole. Levels of lovastatin, simvastatin, atorvastatin, and rosuvastatin may be increased, increasing the risk for rhabdomyolysis and myopathy. 

The lactic acidosis seen with these drugs has ranged from mild and chronic to acute, severe, and fatal [95-106]. The acidosis generally develops after several months of therapy. Patients with NRTl-associated lactic acidosis present with symptoms of nausea, vomiting and abdominal pain. Other features often include elevated liver enzymes, hepatic steatosis, pancreatitis and elevated creatinine kinase with evidence of a myopathy, and liver failure. The lactic acidosis may persist for many weeks despite discontinuation of the NRTl [95-106]. NRTl-related mitochondrial toxicity may also present with rhabdomyolysis and acute kidney failure [110]. Mortality related to NRTl-induced acute lactic acidosis is high, in the range of 50% to 100%, despite drug discontinuation. 

Abd TT, Jacobson TA (2011) Statin-induced myopathy a review and update. Expert Opin Drug Saf 10 373-387... 

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