Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0000737 (abdominal pain)
 31,184 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, has been administered to approximately 2,400 patients with primary hypercholesterolemia with a mean follow-up of 1 year in controlled clinical studies and their open extensions. Approximately 10% of this population received simvastatin for a period of greater than or equal to 2 years. The population on whom this safety analysis is based had a mean age of 50 years; 62% were men and approximately 27% had preexisting coronary artery disease. Simvastatin was titrated to the maximal daily dose of 40 mg each evening in 56% of the study population (last recorded dose). The most frequently reported drug-related clinical adverse experiences were constipation (2.5%), abdominal pain (2.2%), flatulence (2.0%) and headaches (1%). Persistent elevations of serum transaminase levels greater than 3 times the upper limit of normal were observed in only 1% of this cohort with only 0.1% of the total population requiring discontinuation of therapy. There were no clinically apparent episodes of hepatitis. Discontinuation of therapy due to myopathy was extremely rare (0.08%). Only minimal increases in the frequency of lens opacities (1%) were observed from baseline to the last lens examination during follow-up, consistent with the expected increase in lens opacity development due to normal aging. Patients who were greater than or equal to 65 years old had a clinical and laboratory safety profile comparable to the nonelderly population.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term safety and efficacy profile of simvastatin. 195 Oct 69

Fibric acid derivatives (FADs) are a class of drugs that have been shown to reduce the production of very low-density lipoprotein (VLDL) while enhancing VLDL clearance due to the stimulation of lipoprotein lipase activity. The drugs can reduce plasma triglyceride levels while raising high-density lipoprotein (HDL) cholesterol levels. Their effects on low-density lipoprotein (LDL) cholesterol levels are less marked and more variable. There is evidence that oral gemfibrozil (Lopid, Parke-Davis, Morris Plains, NJ) can reduce the risk of serious coronary events, specifically in those patients who had elevations of both LDL cholesterol levels and total plasma triglyceride levels with lower HDL cholesterol levels. Newer FADs (bezafibrate, ciprofibrate, fenofibrate) have been shown to have greater efficacy in reducing LDL cholesterol than gemfibrozil but, in general, these drugs are not as effective as the other primary drugs used to lower LDL levels. The FADs are also used to treat adult patients with very high levels of triglycerides who have pancreatitis and whose disease cannot be managed with dietary therapy. The FADs are well tolerated, with dyspepsia and abdominal pain the most common adverse effects. A small risk of cholelithiasis exists with these drugs, and caution should be used when combining these drugs with HMG-CoA reductase inhibitors because the combination increases the incidence of hyperlipidemic myositis and rhabdomyolysis.
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PMID:Effects of gemfibrozil and other fibric acid derivatives on blood lipids and lipoproteins. 204 26

The long term use of lipid-lowering drugs in the treatment of patients with hyperlipoproteinaemia is aimed at reducing plasma concentrations of known atherogenic lipoproteins with a favourable effect on lipid deposition in the arterial wall. A less common aim is to prevent the adverse sequelae of hyperchylomicronaemia in patients with severe hypertriglyceridaemia. The decision to begin drug therapy should be made only after the exclusion of secondary factors and after an adequate trial of diet has failed to produce acceptable concentrations of plasma lipids and lipoproteins. The bile acid sequestrants (cholestyramine and colestipol), nicotinic acid, fenofibrate and inhibitors of hydroxymethylglutaryl coenzyme A (HMG CoA) reductase (e.g. lovastatin or simvastatin) are the most effective drugs for use in patients with primary hypercholesterolaemia; these agents reduce plasma concentrations of total and LDL-cholesterol by 15 to 45%. For those patients with concurrent hypertriglyceridaemia, nicotinic acid, lovastatin or simvastatin, or fenofibrate are the preferred drugs for initial use; bile acid sequestrants frequently exacerbate hypertriglyceridaemia in these patients. Fibric acid derivatives (e.g. clofibrate, gemfibrozil, bezafibrate or fenofibrate) are all effective in the therapy of patients with type III hyperlipoproteinaemia, as is nicotinic acid and I have found lovastatin to be effective also. Gemfibrozil or nicotinic acid are the most effective agents to use in the treatment of patients with severe hypertriglyceridaemia who are at increased risk of abdominal pain and pancreatitis. Combined therapy with drugs which have different mechanisms of action can be effectively used in the treatment of patients with severe hypercholesterolaemia or combined hyperlipidaemia; for the former group, combinations which use bile acid sequestrants, HMG CoA reductase inhibitors and nicotinic acid are the most effective.
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PMID:An overview of lipid-lowering drugs. 307 24

Mevinolin reduces cholesterol synthesis by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. The safety and effectiveness of this agent was evaluated in a double-blind, placebo-controlled study in 59 healthy men (serum cholesterol 3.88--7.76 mmol/liter) in five centers. Subjects maintained their usual diet and activities. Doses of 6.25, 12.5, 25, or 50 mg twice daily for 4 wk produced mean reductions of total serum cholesterol fo 23--27% [vs. placebo (4%), P less than 0.01]. Mean low density lipoprotein cholesterol fell 35--45%, while high density lipoprotein and very low density lipoprotein cholesterol, and triglycerides were not significantly affected. Mean apolipoprotein B fell 27--34%. 50 mg was not significantly more effective than 6.25 mg. Mevinolin was generally well tolerated, and no serious clinical or laboratory abnormalities occurred. One subject (12.5 mg) was withdrawn because of abdominal pain and diarrhea. These results suggest that if long-term safety can be demonstrated, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase are likely to prove useful in the treatment of hypercholesterolemia.
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PMID:Cholesterol-lowering effect of mevinolin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme a reductase, in healthy volunteers. 691 2

Rosuvastatin (Crestor), an HMG-CoA reductase inhibitor (statin), has a favorable pharmacologic profile, including its selective uptake by hepatic cells, hydrophilic nature, and lack of metabolism by cytochrome p450 (CYP) 3A4 isoenzyme. This last property means that the potential for CYP3A4-mediated drug interactions and, as a consequence, adverse events is low in those requiring concomitant therapy with a statin and agents metabolized by CYP3A4. In a broad spectrum of adult patients with dyslipidemias, oral rosuvastatin 5-40 mg once daily effectively and rapidly improved lipid profiles in several large, randomized, mainly double-blind, multicenter trials of up to 52 weeks' duration. After 12 weeks' treatment, rosuvastatin was significantly (all p < 0.05) more effective at milligram equivalent dosages than atorvastatin, pravastatin, and simvastatin in improving the overall lipid profiles of patients with hypercholesterolemia (intent-to-treat analyses). Moreover, overall a significantly (all p < 0.001) higher proportion of patients achieved National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III low-density lipoprotein-cholesterol (LDL-C) goals with rosuvastatin 10 mg/day than with therapeutic starting dosages of these other statins after 12 weeks' treatment in pooled analyses. Rosuvastatin treatment for up to 52 weeks was generally well tolerated in patients with dyslipidemias in clinical trials. The most commonly reported treatment-related adverse events were myalgia, constipation, asthenia, abdominal pain, and nausea; these were mostly transient and mild. The incidence of proteinuria or microscopic hematuria with rosuvastatin 10 or 20 mg/day was <1% versus <1.5% with rosuvastatin 40 mg/day; these events were mostly transient and not associated with acute or progressive deterioration in renal function at recommended dosages. Importantly, very few patients experienced elevations in serum creatine phosphokinase (CPK) levels of over [corrected] 10-fold the upper limit of normal (0.2-0.4% of patients) or treatment-related myopathy (<or=0.1%) [i.e. muscle aches or weakness plus the same elevated serum CPK levels] at dosages of 5-40 mg/day. In conclusion, rosuvastatin treatment effectively and rapidly improves the lipid profile in patients with a broad spectrum of dyslipidemias. In those with hypercholesterolemia (including high-risk patients), rosuvastatin was more efficacious than and generally as well tolerated as atorvastatin, simvastatin, and pravastatin, with significantly more rosuvastatin recipients achieving their NCEP ATP III target LDL-C levels. Thus, rosuvastatin has emerged as a valuable choice for first-line treatment in the management of low- to high-risk patients requiring lipid-lowering drug therapy.
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PMID:Rosuvastatin: a review of its use in the management of dyslipidemia. 1504 23

The administration of statins in patients with liver disease is not an absolute contraindication. Hepatotoxicity is a rare and often dose-related event and in the literature there are only a few described cases of fatal rhabdomyolysis in patients with chronic liver disease after statin administration. During treatment with 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, the factors responsible for myopathy may either be related to the patient, or due to interactions with other medications that are metabolic substrates of the same isozymes and therefore able to increase blood statin concentration. The most important side effects consist of increased transaminase levels, abdominal pain or muscle weakness, increased serum levels of creatine kinase and rhabdomyolysis. In this article we report a case of fatal rhabdomyolysis with acute renal failure after gastric endoscopy, where midazolam was used as a sedation agent in a patient with chronic liver disease treated with a high dose of atorvastatin. Therefore, we suggest paying particular attention to the potential risks of associating atorvastatin and midazolam in patients with chronic liver disease who need to undergo gastric endoscopy.
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PMID:Rhabdomyolysis after midazolam administration in a cirrhotic patient treated with atorvastatin. 2513 49