Muscle damage

HYDANTOINS Fhenytoin is the most commonly prescribed anticonvulsant because of its effectiveness and relatively low toxicity. However, a genetically linked inability to metabolize phenytoin has been identified. For this reason, it is important to monitor serum concentrations of the drug on a regular basis to detect signs of toxicity Fhenytoin is administered orally and parenterally. If the drug is administered parenterally, the IV route is preferred over the intramuscular route because erratic absorption of phenytoin causes pain and muscle damage at the injection site... 

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. 

Lieber, R.L. Friden, J. (1993). Muscle damage is not a function of muscle force but active strain. J. Appl. Physiol. 74,520-526. 

Diseases affecting skeletal muscle are not always primary diseases of muscle, and it is necessary first to determine whether a particular disorder is a primary disease of muscle, is neurogenic in origin, is an inflammatory disorder, or results from vascular insufficiency. A primary disease of muscle is one in which the skeletal muscle fibers are the primary target of the disease. Neurogenic disorders are those in which weakness, atrophy, or abnormal activity arises as a result of pathological processes in the peripheral or central nervous system. Inflammatory disorders may result in T-cell mediated muscle damage and are often associated with viral infections. Vascular insufficiency as a result of occlusion in any part of the muscle vasculature can cause severe disorders of muscle, especially in terms of pain, metabolic insufficiency, and weakness. 

Primary hyperkalemic periodic paralysis is usually first manifest in childhood. Attacks may last for a period of a few hours to several days, and the degree of muscle damage associated with the condition appears to increase with age and frequency of attacks. Vacuolation and dilatation of the SR is the most obvious form of damage, and it increases with age. 

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. 

Systemic muscle damage, often associated with pain and discomfort, is a well known problem associated with specific drugs such as epsilon amino caproic acid (EACA), clofibrate, emetine, vincristine, chloroquine, D-penicillamine, and anabolic steroids. Notes on each of these drugs follow, but for a detailed discussion of drug-induced muscle damage refer to Argov and Mastaglia (1988) and Harris and Blain (1990). 

EACA muscle damage is sudden in onset and though rare is well recognized. It is uncommon when treatment involves the use of low doses below 18 g day. It usually occurs several weeks after the commencement of treatment. The drug can cause a severe necrotizing myopathy. Capillary occlusion and fibrin deposition in... 

Clofibrate causes a necrotizing myopathy, particularly in patients with renal failure, nephrotic syndrome or hypothyroidism. The myopathy is painful and myokymia of unknown origin is sometimes present. The mechanism of damage is not known, but p-chlorophenol is a major metabolite of clofibrate and p-chlorophe-nol is a particularly potent uncoupler of cellular oxidative phosphorylation and disrupts the fluidity of lipid membranes. Muscle damage is repaired rapidly on the cessation of treatment. 

Emetine emetine is still used at high doses for the treatment of patients with severe amebiasis. Muscle damage is uncommon but when it does occur can be a severe generalized necrotizing myopathy. The outcome is, at times, fatal, especially when an emetine-induced cardiomyopathy is also present. Despite the suggestion that there may be neuritic changes, there is no evidence that emetine damages peripheral nerve. The myopathy is usually painful but reversible. The mechanism of action of emetine is unknown. 

A second group of myotoxic toxins, found almost exclusively in the venoms of cobras, are the cytotoxins (often called cobratoxins, cytolysins, cardiotoxins, or direct lytic factors). These, rather than phospholipases, are almost certainly the primary cause of muscle damage following bites by cobras. Their mechanism of action is not properly known, but it is certainly the case that their action is potentiated by the presence of phospholipases in the venom, even if the phospholipases concerned are not, themselves, myotoxic. The cytotoxins of cobra venom possess no hydrolytic activity of any kind. 

A third group of myotoxic factors are very short polypeptides, devoid of hydrolytic activity. These toxins, found in the venom of a few species of North American rattlesnakes, cause a dilatation of sarcoplasmic reticulum and can cause severe muscle damage. 

Although it is possible to identify a group of particularly toxic components in venom, it should be noted that the venoms are complex mixtures of components, many of which are synergistic. Muscle damage is particularly severe if myotoxic activity is combined with hemorrhagic activity. In this case, muscle regeneration is impaired, because the regenerating tissue is rendered anoxic at a time of intense metabolic activity. 

Free Radicals and Exercise-induced Muscle Damage 178 7. References 180... 

Free-radical species have been implicated in the pathogenesis of both muscle fatigue and muscle damage, and the evidence for these will be discussed separately. 

Amelink, G.J. (1990). Exercise induced muscle damage. Ph.D. thesis, University of Utrecht. 

Foxley, A., Edwards, R.H.T. and Jackson, M.J. (1991). Enhanced lipid peroxidation in Duchenne muscular dystrophy may be secondary to muscle damage. Biochem. Soc. Trans. 19, 1805. 

Jackson, M.J. and Edwards, RH.T. (1988). Free radicals, muscle damage and muscular dystrophy. In Reactive Oxygen Species in Chemistry, Biology and Medicine (ed. A. Quintanilha) pp. 197-210, Plenum, New York. 

Jackson, M.J., Jones, D.A. and Edwards, RH.T. (1984). Experimental skeletal muscle damage the nature of the calcium-activated degenerative processes. Eur. J. Clin. Invest. 14, 369-374. 

Thompson, R.H. and J.R. Todd. 1974. Muscle damage in chronic copper poisoning of sheep. Res. Veterin. Sci. 16 97-99. 

The number of satellite cells in skeletal muscle declines with age so that recovery after injury is slower in the elderly. Moreover, no satellite cells are present in cardiac muscle, and damage (e.g. after a heart attack) is not repaired but is replaced by scar tissue. These are no reports of severe muscle damage in top sports personalities berg treated with embryonic stem cells. Rapid recovery from such damage, may be financially rewarding to both the athlete and the club, so that such treatment may be considered in the future. 

Cao P, Hanai J, Tanksale P, Imamura S, Sukhatme VP, Lecker SH (2009) Statin-induced muscle damage and atrogin-1 induction is the result of a geranylgeranylation defect. FASEB J 23 2844-2854... 

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