Myopathy prevention

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... 

Clinical Use. Azathioprine (Imuran) is a cytotoxic agent that is structurally and functionally similar to certain anticancer drugs, such as mercaptopurine.22,30 Azathioprine is primarily used to prevent the rejection of transplanted organs, especially in patients with kidney transplants. Azathioprine may also be used to suppress immune responses in a wide range of other conditions, such as systemic lupus erythematosus, dermatomyositis, inflammatory myopathy, hepatic disease, myasthenia gravis, and ulcerative colitis. As presented in Chapter 16, azathioprine is also used as an antiarthritic disease-modifying agent. 

Clinton, M.E., Dettbam, W-D. (1987). Prevention of phospholine-induced myopathy with d-tubocurarine, atropine sulfate, diazepam, and creatine phosphate. J. Toxicol. Environ. Health 21 435-44. 

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. 

Sket, D., Dettham, W-D., Clinton, M.E., Sketelj, J., Cucek, D., Brzin, M. (1991a). Prevention of diisopropylphosphoro-fluoridate-induced myopathy hy hotulinum toxin type A blockage of quantal release of acetylcholine. Acta Neuro-pathol. 82 134 2. 

Musculoskeletal. Proximal myopathy and tendon rupture may occur. Osteoporosis develops insidiously leading to fractures of vertebrae, ribs, femora and feet. Pain and restriction of movement may occur months in advance of radiographic changes. A biphosphonate, with or without vitamin D, is useful for prevention and treatment. Growth in children is impaired. A vascular necrosis of bone (femoral heads) is a serious complication (at higher doses) it appears to be due to restriction of blood flow through bone capillaries. 

A cluster of 25 cases of transient or permanent diplopia occurred after 13 retrobulbar blocks, 10 peribulbar blocks, and two unknown techniques, possibly related to the non-availability of hyaluronidase, highhghting the likely importance of hyaluronidase in preventing anesthetic-related myopathy in the extraocular muscles (290). Other reports of 21 cases of persistent postoperative diplopia following the peribulbar technique (291) and 4 cases foUowing the retrobulbar technique during the period of non-availabihty of hyaluronidase support this theory (292). Bupivacaine and lidocaine may be contraindicated for peribulbar or retrobulbar injections without hyaluronidase. 

Propofol infusion syndrome mimics the mitochondrial myopathies, in which there are specific defects in the mitochondrial respiratory chain. The clinical features of mitochondrial myopathy result from a disturbance in lipid metabolism in cardiac and skeletal muscle. These patients generally remain well until stressed by infection or starvation, although subclinical biochemical abnormalities of mitochondrial transport can be demonstrated. It has been suggested that early management of critically iU children may not include adequate calorific intake to balance the increase in metabolic demands, and that in susceptible children the diversion of metabolism to fat substrates may cause the propofol infusion sjmdrome. It is unclear if the dose or duration of propofol infusion alters this effect. As adults have larger carbohydrate stores and require lower doses of propofol for sedation, this may account for the relative rarity of the sjmdrome in adults. The authors suggested that adequate early carbohydrate intake may prevent the propofol infusion syndrome (71). 

Ezetimibe is used for secondary prevention against established atherosclerotic CVD to achieve an optimal atherogenic cholesterol level in patients with intolerance to high-doses of statins. It can further be used in combination with statins to achieve lower LDL-C levels in very-high-risk patients [59]. Ezetimibe inhibits the Niemann-Pick Cl-Like 1 (NPClLl)-dependent intestinal cholesterol absorption in the apical brush border membrane of jejuna enterocytes [14], and thus it only moderately lowers LDL-C (12-25 %) [60]. Meanwhile, common adverse effects associated with ezetimibe therapy include gastrointestinal disturbances, while infrequent adverse effects such as rash, angioedema, anaphylaxis, hepatitis, cholelithiasis, cholecystitis, thrombocytopenia, raised creatine kinase, myopathy, and rhabdomyolysis may occur [46]. 

Characteristic lesions of vitamin E deficiency in animals include necrotizing myopathy (inaccurately referred to as nutritional muscular dystrophy), exudative diathesis, nutritional encephalomalacia, irreversible degeneration of testicular tissue, fetal death and resorption, hepatic necrosis, and anemia. Several of these conditions are directly related to peroxidation of unsaturated lipids in the absence of vitamin E, and others can be prevented by synthetic antioxidants or vitamin E. 

Local adverse effects from ICSs include oropharyngeal candidiasis and dysphonia that are dose-dependent. The dysphonia appears to be due to a local corticosteroid-induced myopathy of the vocal cords. The use of a spacer device can decrease oropharyngeal deposition and thus decrease the incidence and severity of local side effects. In infants who require delivery through a facemask, the parent should clean the nasal-perioral area with a damp cloth following each treatment to prevent topical candidal infections. 

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