Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027121 (myositis)
 4,538 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 25 patients with primary dyslipoproteinemias and severe premature atherosclerosis, during an average combined Lopid-Mevacor treatment span of 12.5 months per patient, our specific aim was to assess safety and efficacy of open-label therapy with diet, gemfibrozil (Lopid), and lovastatin (Mevacor). Because targeted lipid values were not reached on diet alone (low-density lipoprotein cholesterol [LDLC] less than 120 mg/dl, high-density lipoprotein cholesterol [HDLC] greater than 35 mg/dl or total cholesterol [TC]/HDLC less than 4.5), the patients received Lopid, 1.2 gm/day as their initial lipid-lowering drug. Because targeted lipid levels were not reached with Lopid treatment alone after 3 or more months, Mevacor was added, with 17 subjects receiving 20 mg/day, five receiving 40 mg, two receiving 60 mg, and one receiving 80 mg. Outpatient visits were repeated during combined therapy every 6 to 8 weeks, with an average of 6.4 visits per subject, 162 measurements of fasting lipids and liver function tests, and 127 measurements of creatine phosphokinase (CPK). By selection, all patients had normal liver function (gamma-glutamyltransferase, serum glutamic-oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) levels) and normal CPK levels at baseline. No gamma-glutamyltransferase levels were high during combined therapy. Of the 162 liver function test measurements, five (3.1%) SGOT levels and three (1.9%) SGPT levels were high. Of 127 CPK measurements, three (2.4%) were high; one subject had a high CPK measurement, and one subject had two high measurements for CPK. No symptomatic myositis or myalgias developed in the subjects; none had palpable skeletal muscle tenderness.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Safety and efficacy of combined gemfibrozil-lovastatin therapy for primary dyslipoproteinemias. 234 62

Prior studies of cardiac transplant recipients have shown that pravastatin reduces 12-month rejection and mortality after cardiac transplantation and simvastatin reduces 4-year mortality, low-density lipoprotein (LDL) cholesterol levels, and intimal thickening. In a 12-month observational study, cardiac transplant recipients received open-label pravastatin 40 mg (n = 42) or simvastatin 20 mg daily (n = 45) on an alternating basis from the time of transplantation. Lipid levels, safety, and post-transplant outcomes were compared. We found no significant differences in total LDL or high-density lipoprotein cholesterol, triglycerides, linearized infection or rejection rates, liver function tests, or immunosuppressant dosages between groups at 1, 3, 6, or 12 months. Rhabdomyolysis or myositis occurred only in patients on simvastatin (n = 6, 13.3%) with no episodes for patients on pravastatin (p = 0. 032). Survival at 12 months on an actual treatment basis was 97.6% for patients on pravastatin and 83.7% for those on simvastatin (p = 0.078). Immunosuppression-related deaths occurred in only 2.4% (1 patient) on pravastatin vs 15.6% (n = 7) on simvastatin (p = 0.06). Pravastatin and simvastatin resulted in comparable lipid profiles. Pravastatin use was however free from the high rates of rhabdomyolysis and myositis seen with simvastatin use. Pravastatin was additionally associated with a trend toward superior survival, attributable to fewer immunosuppression-related deaths. For safety and pharmacokinetic reasons, pravastatin should be considered the statin of choice after heart transplantation.
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PMID:Efficacy and safety of pravastatin vs simvastatin after cardiac transplantation. 1086 32

Hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors have pleiotropic actions that affect many systems other than lowering blood cholesterol concentrations. Hypercholesterolaemia is an adverse effect of immunosuppressive drug therapy and hence it is a common finding after organ transplantation. HMG-CoA reductase inhibitors lower cholesterol concentrations in transplant recipients but they also offer additional benefits. Since they impair the production of mevalonate, they reduce the concentrations of downstream products including farnesyl and geranyl phosphate. These isoprenoid moieties are required for protein prenylation and HMG-CoA reductase inhibitors impair this function in some cells. This action affects the immune system, especially in patients taking cyclosporin, and has been proposed as the mechanism whereby these drugs increase the half-life of transplanted organs. Other mechanisms have also been proposed including an increase in the free fraction of cyclosporin and a reduction in the time that low density lipoprotein (LDL) spends in blood. The latter effect reduces the extent of oxidation of LDL and hence reduces the damage caused by oxidised LDL. Chronic rejection is poorly understood but appears to involve both immune and non-immune processes. HMG-CoA reductase inhibitors affect both processes. At present, the evidence of benefit from statin prescription is confined to heart and kidney transplant recipients but it is likely that recipients of other organ transplants would also benefit. Drug interactions between cyclosporin and HMG-CoA reductase inhibitors are a limiting factor to their use. Pravastatin appears to be the best HMG-CoA reductase inhibitor for organ transplant recipients because of its lesser potential to interact with cyclosporin and hence cause myositis, which may thus allow higher doses to be used. Other, non-immunosuppressive drugs (including diltiazem and ketoconazole) have been shown to reduce transplant organ damage by unknown mechanisms and are widely prescribed in some transplant centres. More specific inhibitors of protein prenylation may afford useful immunosuppression, thereby prolonging transplant organ half-lives and also reducing the risk of cancer.
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PMID:The effect of HMG-CoA reductase inhibitors on chronic allograft rejection. 1598 99