Myopathies toxic

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. 

NRTls are structural analogues of the natural nucleotides that form the building blocks of RNA and DNA in human cells. Their use as part of HAART has dramatically modified the natural history of HIV infection. They, however, cause a range of drag- or tissue-specific toxicides zidovudine (AZT) causes myopathy zalcitabine (ddC), didanosine (ddl), and lamivudine (3TC) cause neuropathy stavudine (d4T) causes neuropathy or myopathy and lactic acidosis (Dalakas 2001). During phase 1 and 11 trials, the dose-limiting toxicity of didanosine, zalcitabine, and stavudine was identified as peripheral neuropathy (Dalakas 2001). 

The myopathy associated with chronic alcohol abuse has also been associated with increased free-radical activity (Martin and Peters, 1985) as have various other toxicity syndromes affecting muscle, such as cocaine toxity (Kloss et al., 1983). Little work appears to have been undertaken on the possible role of free radicals in the inflammatory myopathies, although, by analogy with other inflammatory disorders, this is likely to be an area worthy of further study. 

The answer is a. (Hardman, pp 885-8870 Lovastatin should not be used in patients with severe liver disease. With routine use of lovastatin, serum transaminase values may rise, and in such patients the drug may be continued only with great caution. Lovastatin has also been associated with lenticular opacities, and slit-lamp studies should be done before and one year after the start of therapy There is no effect on the otic nerve. The drug is not toxic to the renal system, and reports of bone marrow depression are very rare There is a small incidence of myopathy, and levels of creatinine kinase should be measured when unexplained muscle pain occurs. Combination with cyclosporine or clofibrate has led to myopathy There is no danger in use with bile acid sequestrants. 

It is unclear whether the myopathy was a direct toxic effect of chlordecone on the muscle or whether the myopathy was a consequence of neuronal dysfunction. In addition, arthralgia in the proximal joints was reported by 4 of 23 workers with active symptoms of chlordecone intoxication (Taylor 1982, 1985). No cause for the joint pain could be determined. 

Significant adverse reactions include fatigue headache drowsiness paresthesias difficulty in micturition diarrhea reversible increases in serum transaminases dyspnea bronchospasm asthenia muscle cramps nausea vomiting fever with aching and sore throat toxic myopathy rashes systemic lupus erythematosus vision abnormality hypoesthesia ventricular arrhythmias intensification of AV block mental depression scalp tingling. 

Zidovudine has been associated with hematologic toxicity, including neutropenia and severe anemia, particularly in patients with advanced human immunodeficiency (HIV) disease (see Warnings). Prolonged use of zidovudine has been associated with symptomatic myopathy. 

Daptomycin can give quite a few adverse reactions. The primary toxicities associated with daptomycin use are myopathies. Significant rates of cardiovascular, central nervous system, dermatological, gastrointestinal and hematological side effects have also been reported. 

Its adverse effects are dose dependent. Hematological effects include anaemia and leucopenia. Other effects are nausea, headache, myalgia, insomnia, and rarely, myopathy and hepatotoxicity. CNS toxicity can manifest itself as seizures, confusion... 

Atorvastatin, simvastatin, rosuvastatin Inhibit HMG-CoA reductase Reduce cholesterol synthesis and up-regulate low-density lipoprotein (LDL) receptors on hepatocytes modest reduction in triglycerides Atherosclerotic vascular disease (primary and secondary prevention) t acute coronary syndromes Oral duration 12-24 h Toxicity Myopathy, hepatic dysfunction Interactions CYP-dependent metabolism (3A4, 2C9) interacts with CYP inhibitors... 

Daptomycin Binds to cell membrane, causing depolarization and rapid cell death Bactericidal activity against susceptible bacteria more rapidly bactericidal than vancomycin Infections caused by grampositive bacteria including sepsis and endocarditis IV administration renal clearance (half-life 8 h) dosed once daily inactivated by pulmonary surfactant so cannot be used to treat pneumonia Toxicity Myopathy monitoring of weekly creatine phosphokinase levels recommended... 

In a placebo-controlled study of 1142 hypercholestero-lemic patients treated with pravastatin for 8-16 weeks, the numbers of adverse drug experiences were similar in the treated and untreated individuals (1). Rash was the only adverse clinical event that was different (4.0 versus 1.1%). However, in the same patients withdrawal of therapy during follow-up was thought to be necessary in 3.2% of those given pravastatin alone. Myopathy was observed in one instance only, and increases in creatine kinase activity in those taking pravastatin did not differ significantly from controls. There were marked persistent increases in transaminases in 1.1%, with no cases of symptomatic hepatitis. Pravastatin is believed to have a particularly low potential for nervous system-related adverse effects, as it has not been shown to enter the cerebrospinal fluid, and clinical experience suggests that muscle toxicity occurs less often with pravastatin than with lovastatin (2). 

The major population at risk for aluminum loading and toxicity consists of individuals with renal failure. In a study by Alfrey (1980), 82% of nondialyzed uremic patients and 100% of dialyzed uremic patients had an increased body burden of aluminum. The decreased renal function and loss of the ability to excrete aluminum, ingestion of aluminum compounds to lessen gastrointestinal absorption of phosphate, the aluminum present in the water used for dialysate, and the possible increase in gastrointestinal absorption of aluminum in uremic patients can result in elevated aluminum body burdens. The increased body burdens in uremic patients has been associated with dialysis encephalopathy (also referred to as dialysis dementia), skeletal toxicity (osteomalacia, bone pain, pathological fractures, and proximal myopathy), and hematopoietic toxicity (microcytic, hypochromic anemia). Pre-term infants may also be particularly sensitive to the toxicity of aluminum due to reduced renal capacity (Tsou et al. 1991)... 

In the past several clinical patterns have been described. The most important recognized clinical patterns or types of Al toxicity include two types of encephalopathy. Firstly, the classical dialysis dementia sometimes referred to as dialysis encephalopathy syndrome (DES) or dementia dialytica [24, 28, 37, 42, 70-74] and secondly, the acute or subacute Al encephalopathy [41]. There are also two types of bone disease - either osteomalacia with bone fractures and proximal myopathy or aplastic bone disease [41, 75, 76]. There is quite some confusion in the definitions of Al toxicity in the literature. Because there seems to be an obligatory lag phase of at least several days to weeks for symptoms to occur, acute Al encephalopathy, defined as a direct result of a single overdose, probably does not exist. Because of the long lag phase of several months to years necessary to develop the chronic dialysis encephalopathy and also because acute Al encephalopathy has an abrupt, sudden onset of symptoms one can understand why the term acute is used instead of the more descriptive subacute . The descriptions dialysis dementia [37, 42, 46, 73, 74] and dialysis encephalopathy [33-36, 38, 40, 41, 78] are also unfortunate because true dementia is rare in Al encephalopathy [73] and non-dialyzed patients can also develop these symptoms [78]. There are also many dialysis-related encephalopathy syndromes unrelated to Al. As an example,... 

The rate of myopathy with a statin alone in the general population is 0.1-0.5% and 0.2-2.5% with combination therapy. Rhabdomyolysis is very rare at 0.02-0.04%. However, the latter carries a significant morbidity and mortality. In a review of Food and Drug Administration (FDA) reports published in 2002, there were 38 deaths in 631 patients (6.3%) [31]. Pravastatin and fluvastatin have been less frequently implicated in fatal cases of rhabdomyolysis [31]. It is postulated that the more hepatoselective hydrophilic statins, such as pravastatin, are less likely to penetrate muscle cells than are lipophilic statins, and therefore represent a lower risk for myopathy, particularly in the event of an interacting drug increasing their blood levels to within the toxic range [26, 32]. 

Russo and Jacobson [38] conclude that there is little evidence to suggest that statins are more hepatotoxic in patients with pre-existing liver disease, and that they may be used for the usual indications with increased monitoring. However, they go on to advise that their use should be avoided in patients with acute liver disease until the acute episode has passed, presumably to avoid the risk of reduced clearance of the drug causing accumulation and an increased risk of toxicity, such as myopathy or rhabdomyolysis. 

CICLOSPORIN COLCHICINE t colchicine plasma concentrations and t toxic effects (hepatotoxicity, myopathy), t penetration of ciclosporin through blood-brain barrier and t risk of neurotoxicity Competitive inhibition of P-gp with t penetrations of ciclosporin to the tissues. Ciclosporin inhibits the transport of colchicine Avoid co-administration... 

The most serious adverse effect of simvastatin is myopathy, which rarely may progress to rhabdomyolysis. Abnormalities of liver function may also occur. These effects are dose-dependent, and a number of drugs and foods may inhibit the metabolism of simvastatin, thereby increasing its toxicity. Examples of these are grapefruit juice and erythromycin, both of which should be avoided in patients taking simvastatin. 

Gupta, R.C., Dettbam, W-D. (1992). Potential of memantine, d-tubocurarine and atropine in preventing acute toxic myopathy induced by organophosphate nerve agents soman, sarin, tabun and VX. NeuroToxicology 13 500-14. 

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