Muscle, skeletal rhabdomyolysis

It is essential that a Synacthen test is performed in this patient to exclude or confirm the diagnosis of adrenal failure. As the patient has severe skeletal muscle pain the creatine kinase should be measured as the hyperkalaemia may be due to potassium released from damaged muscle. If rhabdomyolysis were detected, it would be important to monitor renal function and calcium status carefully. 

HMG-CoA REDUCTASE INHIBITORS AND FlBRIC ACID DERIVATIVES. The antihyperlipidemic drugp, particularly die HMG-CoA reductase inhibitors, have been associated with skeletal muscle effects leading to rhab-domyolysis. Rhabdomyolysis is a very rare condition in which muscle damage results in die release of muscle cell contents into die bloodstream. Rhabdomyolysis may precipitate renal dysfunction or acute renal failure The nurse is alert for unexplained muscle pain, muscle tenderness, or weakness, especially if tiiey are accompanied by malaise or fever. These symptoms should be reported to die primary health care provider because the drug may be discontinued. 

Skeletal muscle dysfunction can cause myalgia, bone pain, weakness, and potentially fatal rhabdomyolysis. Respiratory muscle weakness and diaphragmatic contractile dysfunction can cause acute respiratory failure. 

Musculoskeletal Effects. Muscular rigidity was observed in humans after acute cyanide poisoning (Grandas et al. 1989) and rhabdomyolysis, a clinical syndrome characterized by skeletal muscle injury, was observed in a man who ingested 0.57 mg CNVkg in a suicide attempt (Saincher et al. 1994). 

Rhabdomyolysis is the destruction of skeletal muscle tissues and may be associated with lipid-regulating drugs such as the fibrates and the statins. The risk of this side-effect is increased in patients with renal impairment and with hypothyroidism. Rhabdomyolysis may also occur with nicotinic acid, the antipsychotic aripiprazole, and the anaesthetic propofol. 

Skeletal muscle effects All statins have been associated with myalgia, myopathy (ie, muscle pain, tenderness, or weakness with creatine phosphokinase [CPK] values above 10 times the ULN), and rhabdomyolysis. Factors that may predispose patients... 

Skeletal muscle effects The use of fibrates alone, including fenofibrate, may occasionally be associated with myopathy. Treatment with drugs of the fibrate class has been associated on rare occasions with rhabdomyolysis, usually in patients with impaired renal function. Consider myopathy in any patient with diffuse myalgias, muscle tenderness or weakness, or marked elevations of creatine phosphokinase levels. 

Skeletal muscle effects In clinical trials, there was no excess of myopathy or rhabdomyolysis associated with ezetimibe compared with the relevant control arm (placebo or HMG-CoA reductase inhibitor alone). However, myopathy and rhabdomyolysis are known adverse reactions to HMG-CoA reductase inhibitors and other lipid-lowering drugs. 

Skeletal muscle myopathy often leads to release of CK of the MM type. Rhabdomyolysis Is one of the major side effects of treatment with the cholesterol-lowering drugs the statins. 

In skeletal muscle fibers whose motor nerve has been severed, ACh receptors spread over the entire cell membrane after a few days. In this case, succinylcholine would evoke a persistent depolarization with contracture and hyperkalemia. These effects are likely to occur in polytraumatized patients undergoing follow-up surgery. The use of succinylcholine is waning because of its marked adverse effects (rhabdomyolysis hyperkalemia cardiac arrest)... 

After an extensive literature search, the authors reported that the main pathophysiological mechanism underlying cocaine associated rhabdomyolysis is unknown. They suggested that cocaine blocks the reuptake of noradrenaline and dopamine, resulting in increased sympathetic activity. This, coupled with potent vasoconstriction by the cocaine metabolite benzoylecgo-nine, can lead to skeletal muscle ischemia and injury and result in rhabdomyolysis. 

Two young patients with phencyclidine toxicity developed acute rhabdomyolysis and myoglobinuria, probably secondary to skeletal muscle injury due to an acute dys-tonic motor reaction (18) and 30 reported cases of rhabdomyolysis associated with acute renal insufficiency have been reviewed (19). 

Myoglobinuria is the presence of myoglobin in the urine, often associated with rhabdomy-olysis. Rhabdomyolysis is the rapid breakdown of skeletal muscle tissue. The destruction of the muscle leads to the release of the breakdown products of damaged muscle cells into the blood stream some of these, such as myoglobulin, are harmful to the kidney and may lead to acute kidney failure. 

For instance/ the interaction between cerivastatin and gemfibrozil/ which has resulted in cases of severe rhabdomyolysiS/ is likely due to the inhibition of cerivastatin metabolism by gemfibrozil (i.e./ pharmacokinetic interaction)/ in addition to the propensity of both drugs to cause skeletal muscle toxicity (i.e./ pharmacodynamic interaction) (13-15). 

Rhabdomyolysis occurred in subjects with isoniazid poisoning in a retrospective analysis of 270 patients seen over a 5-year period at the PhUlipine General Hospital in Manilla (42). Skeletal muscle creatine kinase activity was raised in 31 of the 52 evaluable subjects who had taken more than 2.4 g/day of isoniazid. Creatine kinase activity peaked on days 5-6 and fell thereafter. Two patients developed acute renal insufficiency and required dialysis. Seizures occurred in all patients, and their duration, but not their frequency, correlated with raised creatine kinase activity. However, it is likely that factors other than seizures contribute to rhabdomyolysis in patients with isoniazid poisoning. 

Studies in rats demonstrate that subcutaneous administration of 3 mg of the PPD hydrochloride induces skeletal muscle lesions in the form of rhabdomyolysis with infiltration of inflammatory cells, necrosis and accumulation of neutral hpids and dilatation of sacro-plasmic reticulum [17]. 

In animal studies it was proved that PPD has a toxic effect on the parasympathetic nerves [14]. In humans, neurotoxicity consist of mental status alterations ranging from drowsiness to coma were reported. Also flaccid paraparesis has been published [6] [25]. Foot drop, palatopharyngeal and laryngeal paralysis were also reported (25). Rhabdomyolysis following intoxication with PPD has been reported [28-30]. Skeletal muscle biopsy of patients showed scattered coagulation necrosis and inflammatory cellular infiltration [30]. 

Pathological syndromes may result in muscular spasm, as seen in the exertional myopathies, or weakness, as seen in hyperkalemic periodic paralysis (HYPP). Similarly, infectious diseases may result in muscular rigidity (C. tetani infection (tetanus)) or paralysis (C. botulinum intoxication (botulism)). Overt rhabdomyolysis may result from the ingestion of the coccidiostats monensin, rumensin and lasalocid, or one of a number of plant mycotoxins. Dietary deficiencies of selenium or vitamin E have also been described as having severe deleterious effects on skeletal muscle health. 

Epidemiologic analysis of factors influencing exertional rhabdomyolysis in thoroughbreds. American Journal of Veterinary Research 60 1562-1566 Miller R D 1995 Skeletal muscle relaxants. In Katzung B G (ed) Basic and clinical pharmacology. Appleton Lange, Norwalk, NJ, pp. 404-418... 

Ward T L, Valberg S J, Gallant E M et al 2000 Calcium regulation by skeletal muscle membranes of horses with recurrent exertional rhabdomyolysis. American Journal of Veterinary Research 61 242-247... 

Skeletal muscle Cases of rhabdomyolysis (muscle fiber breakdown), leading to acute renal failure secondary to myoglobinuria, have been reported with cerivastatin and other drugs in this class. Myopathy, defined as muscle aching or muscle weakness, associated with increases in plasma creatine kinase values to greater than 10 times the upper limit of normal, was seen in 0.4% of patients in US cerivastatin clini cal trials. 

Rhabdomyolysis is the breakdown of muscle fibers, the result of skeletal muscle injury, which leads to the release of potentially toxic intracellular contents into the plasma. The causes are diverse muscle trauma from vigorous exercise, electrolyte imbalance, extensive thermal burns, crush injuries, infections, various toxins and drugs, and a host of other factors. 

Among the adverse effects of statins, rhabdomyolysis is considered to be a rare but significant one [30]. Global gene expression analysis of two skeletal muscle cell lines (differentiated rat L6 myo-tubes and a human skeletal muscle cell line) treated with statins... 

Any disorder that results in necrosis of skeletal muscle cells (i.e., rhabdomyolysis) can result in the release of large amounts of intracellular phosphorus into the systemic circulation. This condition is frequently associated with acute renal failure and thus severe hyperphosphatemia may develop due to increased endogenous phosphorus release coupled with decreased renal phosphorus excretion. Bowel infarction, malignant hyperthermia, and severe hemolysis are also conditions that may increase endogenous release of phosphorus. 

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