Statins individual drugs

Rhabdomyolysis is a problem with several lipid-lowering drugs (SEDA-13, 1325 SEDA-13, 1328 SEDA-13, 1330 SEDA-19, 409), especially when they are used in combination (37). In individuals with pre-existing renal insufficiency this can lead to an earlier need for chronic dialysis (38). All statins can cause myopathy and rhabdomyolysis, but not all statins are alike. For example, the evidence to date, based on almost 2 decades of experience, points to an extremely low risk of myopathy and rhabdomyolysis with lovastatin, and lovastatin 20 mg tablets are being considered for non-prescription availability in several countries (39). Furthermore, muscle adverse effects do not necessarily occur after a change from one statin to another (40). Interactions between various hypolipidemic drugs and other drugs also sometimes cause rhabdomyolysis (SEDA-18, 426). For instance, itraconazole markedly increases plasma concentrations of lovastatin, and in one subject plasma creatine kinase was increased 10-fold within 24 hours of administration of this combination (41). 

Physicians should check for lipid-lowering drugs before treating elderly individuals with itraconazole (73). Susceptibility to this interaction varies from statin to statin, in that simvastatin is more affected than pravastatin (74). Concomitant use of simvastatin with itraconazole should be avoided, and the same holds true for atorvastatin (75). In another study, the blood concentration of fluvastatin was not significantly increased, whereas that of lovastatin was (76). 

Statins are helpful in decreasing morbidity and mortality in people with high cholesterol, as well as individuals who have normal cholesterol but other risk factors for cardiovascular disease.66 It is estimated that these drugs decrease the risk of a major cardiac event by approximately 30 to 35 percent, although the benefits depend on the extent that cholesterol is reduced and the influence of other risk factors.91,95,126 Nonetheless, statins are now regarded as a mainstay in treating cardiovascular disease, and efforts are underway to expand the use of these medications and to explore the... 

Certain adverse reactions can also be associated with individuals who are carriers of rare disease genes, patients with compromised immune systems, and patients with certain chronic diseases. Peripheral neuropathy from anticancer drugs such as vincristine can be accelerated in specific patients with Charcot-Marie tooth syndrome [38], Park et al. [39] has discussed potential mechanisms that make HIV-positive patients more susceptible to enhanced drug toxicity, and Graham et al. [40] showed that the risk of developing rhab-domyolysis from statin-fibrin combinations increased significantly in older patients with diabetes mellitus. 

Despite inhibition of HMG-CoA reductase by statins, cells compensate by increasing enzyme expression several fold. However, the total body cholesterol is reduced by 20-40% due to increased expression of LDL-receptors after statin administration this enhances LDL (the major cholesterol carrying lipoprotein) clearance from serum with a net reduction of serum cholesterol (Chapter 20). Individuals who lack functional LDL-receptors (homozygous familial hypercholesterolemia. Chapter 20) do not benefit from statin therapy. However, statin therapy is useful in the treatment of heterozygous familial hypercholesterolemia. Since HMG-CoA reductase plays a pivotal role in the synthesis of many products vital for cellular metabolism, inhibitors of the enzyme may have toxic effects. Monitoring of liver and muscle function may be necessary to detect any toxicity of statin drug therapy. A decreased risk of bone fractures with statin therapy has been observed in subjects age 50 years or older, who are being treated for hypercholesterolemia. The mechanism of action of statins in bone metabolism may involve inhibition of prenylation... 

A meta-analysis has examined data from four recent trials of intensive versus conventional statin therapy in patients with acute coronary syndromes or with stable coronary disease involving 27,584 patients [49]. Intensive statin therapy (higher dose or more potent drug) was associated with a further 16% reduction in coronary death and MI (HR 0.84 955 Cl 0.77-0.91 p < 0.0001). This large data base supports the findings from individual trials of the benefits from more intensive therapy and given the high risk in the diabetic population should be translated into routine chnical care for the diabetic patient with established disease. 

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