Myopathy and

StmcturaHy related to nitrofurantoias are Dantrolene [7261-97-4] (38), a peripherally acting muscle relaxant, and its analogues (39), which can be used as an antidote against succiaylcholine-iaduced myopathy and ia autoimmune myasthenia gravis therapy (136,137). 

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. 

Glycogenosis type VIII (phosphorylase b kinase deficiency) gives rise to myopathy and liver disease, either singly or in combination. Phosphorylase b kinase (PBK) converts the inactive b form of both muscle and liver phosphorylases to the active a forms of the enzymes. The ischemic lactate test sometimes shows a flat result as in McArdle s disease, but is more likely to be normal. Histochemical demonstration of myophosphorylase activity in tissue sections shows a near-normal reaction due to the presence of phosphorylase a. Accumulation of glycogen is modest and found mainly in type 2 (fast-twitch glycolytic) muscle fibers. 

The condition known as fatal infantile mitochondrial myopathy and renal dysfunction involves severe diminution or absence of most oxidoreductases of the respiratory chain. MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke) is an inherited condition due to NADHiubiquinone oxidoreductase (complex I) or cytochrome oxidase deficiency. It is caused by a muta-... 

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). 

Myopathy and rhabdomyolysis associated with lovastatin-gemfibrozil combination therapy. JAMA 1990 264 71. 

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. 

Deficiency of the muscle-specific myoadenylate deaminase (MADA) is a frequent cause of exercise-related myopathy and is thought to be the most common cause of metabolic myopathy. MADA catalyzes the deamination of AMP to IMP in skeletal muscle and is critical in the purine nucleotide cycle. It is estimated that about 1-2% of all muscle biopsies submitted to medical centers for pathologic examination are deficient in AMP deaminase enzyme activity. MADA is 10 times higher in skeletal muscle than in any other tissue. Increase in plasma ammonia (relative to lactate) after ischemic exercise of the forearm may be low in this disorder, which is a useful clinical diagnostic test in patients with exercise-induced myalgia... 

Defects of complex IV. These disorders, also termed COX deficiency, have clinical phenotypes that fall into two main groups one in which myopathy is the predominant or exclusive manifestation and another in which brain dysfunction predominates (Fig. 42-3). In the first group, the most common disorder is fatal infantile myopathy, causing generalized weakness, respiratory insufficiency and death before age 1 year. There is lactic acidosis and renal dysfunction, with glycosuria, phosphaturia and aminoaciduria, also termed DeToni-Fanconi-Debre syndrome. The association of myopathy and cardiopathy in the same patient and myopathy and liver disease in the same family has also been described [14]. 

Constipation occurs in fewer than 10% of patients taking statins. Other adverse effects include elevated serum aminotransferase levels (primarily alanine aminotransferase), elevated creatine kinase levels, myopathy, and rarely rhabdomyolysis. 

The C-terminal NCI domain, called type XV endostatin or restin, has antiangiogenic activity similar to endostatin, the NCI domain of type XVIII collagen (see below). ° ° The NCI domain has a trimerization domain, a hinge region that is more sensitive to proteolysis in type XVIII collagen, and the endostatin domain. Lack of type XV collagen in mice causes a skeletal myopathy and cardiovascular defects. ... 

Col6al-deficient mice display an early onset of myopathy, and dysfunction of mitochondria. Details of the relation between the 0 l(VI) chain and pathogenesis of mitochondria are still unknown. 

Pain, muscular weakness, cramps and ease of fatigue are the most usual symptoms of muscular disease. In most cases, it is diseases of the vascular or nervous system or problems with the processes providing energy within the muscle that are responsible for clinical problems with muscles. Other clinical problems include the muscular dystrophies, myotonic disorders, inflammatory myopathies and disorders of neuromuscular transmission (see Walton, 1996). The best known is Duchenne muscular dystrophy. 

HMG-CoA reductase inhibitors Coadministration of niacin and HMG-CoA reductase inhibitors (eg, lovastatin) may result in myopathy and rhabdomyolysis. 

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. 

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. 

Myopathy Myopathy and myositis with pathological changes, similar to that produced by HIV disease, have been associated with prolonged use of zidovudine. Lactic acidosis/severe hepatomegaly with steatosis Rare occurrences of lactic acidosis in the absence of hypoxemia, and severe hepatomegaly with steatosis have been reported with the use of antiretroviral nucleoside analogs, including zidovudine and zalcitabine, and are potentially fatal. 

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... 

Hepatitis, hypersensitivity reactions, myopathy, and rhabdomyolysis occur rarely. 

Colchicine often causes diarrhea and may occasionally cause nausea, vomiting, and abdominal pain. Hepatic necrosis, acute renal failure, disseminated intravascular coagulation, and seizures have also been observed. Colchicine may rarely cause hair loss and bone marrow depression as well as peripheral neuritis, myopathy, and in some cases death. The more severe adverse events have been associated with the intravenous administration of colchicine. 

Simvastatin [NE] Myopathy and rhabdomyolysis noted in patients taking sim-vastatin and cyclosporine. 

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