Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 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

Simvastatin, a chemical derivative of lovastatin, is an antihyperlipidemic medication that inhibits hydroxymethylglutaryl coenzyme A reductase. Animal and clinical data suggest simvastatin is twice as potent as lovastatin. It lowers serum cholesterol by inhibiting hepatic synthesis of cholesterol and, more importantly, by increasing the number of low-density lipoprotein (LDL) receptors present on hepatic cellular membranes. Simvastatin, when used at doses of 40 mg/d in patients with heterozygous familial hypercholesterolemia, significantly reduces total cholesterol (greater than 30 percent) and LDL cholesterol (35-45 percent) and tends to reduce triglycerides and raise high-density lipoprotein (HDL) cholesterol. The agent is also effective in patients with polygenic hypercholesterolemia, familial dysbetalipoproteinemia, and nephrotic syndrome. Addition of cholestyramine to simvastatin enhances the LDL cholesterol-lowering effect to approximately 55 percent. Common clinical adverse effects reported with simvastatin use include headaches and gastrointestinal complaints. Transient elevations in serum transaminases and creatine phosphokinase have also been seen. Based on data currently available, the drug's clinical activity and adverse-effect profile are similar to those of lovastatin. Therefore, there is no need for formularies to contain both medications. To choose between the two, one needs to consider the incidence of adverse effects and the daily cost of each product when used at equally effective doses. That information is now now available and, until it is, a clear recommendation cannot be made. Simvastatin, presently marketed in several countries, is investigational in the U.S. but is expected to be available soon.
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PMID:Simvastatin: a review of its pharmacology and clinical use. 202 34

Mortality from coronary artery disease is a common problem in treated hypertensive patients, and these people have a high prevalence of elevated cholesterol levels. A study was undertaken to determine whether cholesterol could be lowered effectively without major side effects in patients with treated hypertension. Forty-nine patients (mean age 67.6 years) with cholesterol greater than 5.5 mmol/l were placed on a reduced-fat (less than 30% of calories from fat with a ratio of polyunsaturated to saturated fats of less than 1) diet for 3 months. If the cholesterol was between 5.5 and 7.5 mmol/l and total cholesterol divided by high-density lipoprotein cholesterol was greater than 4.5, the patients were randomly allocated either to the simvastatin (24 patients) or the placebo group (25 patients). Diet and placebo caused minor and insignificant falls in cholesterol and no change in triglycerides or lipids. Treatment with simvastatin reduced cholesterol levels from 6.85 to 4.75 mmol/l (P less than 0.001), triglycerides from 2.7 to 2.1 mmol/l (P less than 0.01), low-density lipoproteins from 4.6 to 2.6 mmol/l (P less than 0.001) and high-density lipoproteins rose from 1.09 to 1.18 mmol/l (P less than 0.01). Total cholesterol divided by high-density lipoprotein cholesterol fell from 6.3 to 4.0 (P less than 0.001). The drug was well tolerated and the side-effect profile did not differ from the placebo in clinical or biochemical events. The active drug was stopped in one patient (abdominal pain, dizziness, headache, tiredness) and in two patients taking the placebo (elevated creatine phosphokinase, cardiovascular collapse). Simvastatin effectively lowered total cholesterol and improved the lipoprotein profile. The dose required in most patients was 40 mg/day. Simvastatin may be an acceptable drug to improve the lipoprotein profile in order to determine whether this improves the prognosis in patients treated for hypertension.
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PMID:Simvastatin in the treatment of hypercholesterolaemia in patients with essential hypertension. 233 14

Simvastatin is the second in the class of compounds known as hydroxy-methylglutaryl-coenzyme A reductase inhibitors to be extensively studied in humans. The drug has now been given to over 1,800 patients with primary hypercholesterolemia for periods of up to two years. In the range of dosage from 10 to 40 mg once daily, therapy is associated with reductions of up to 30 percent in total cholesterol and 40 percent in low-density lipoprotein cholesterol levels, as well as with increases of approximately 10 percent in high-density lipoprotein cholesterol levels. The most common clinical adverse experiences are mild gastrointestinal effects and headache, which seldom require discontinuation of therapy. Elevations of creatine kinase (skeletal muscle isoenzyme) levels to more than three times the upper limit of the normal range have been seen in about 3 percent of patients, but also have seldom required discontinuation of therapy. Conversely, elevations of hepatic transaminase levels to more than three times the upper limit of the laboratory normal range have been seen in about 1.5 percent of patients and have caused discontinuation of therapy in 0.6 percent of patients treated. Simvastatin appears to be an effective and well-tolerated agent for the treatment of primary hypercholesterolemia and, as further study confirms long-term safety and efficacy, it should become a useful addition to the therapeutic armamentarium.
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PMID:Simvastatin: the clinical profile. 280 50

Familial hypercholesterolaemia is a frequent, inherited, monogenic disorder, associated with accelerated development of atherosclerotic disease leading to coronary artery disease. Life expectancy of patients with familial hypercholesterolaemia is reduced by 15-30 years unless they are adequately treated with lipid-lowering therapy. Given the chronic nature of this disease, the selection of a therapeutic approach should be strongly based on its long-term safety and tolerability. The introduction of HMG-CoA reductase inhibitors has revolutionised the treatment of familial hypercholesterolaemia. Simvastatin 40-80 mg/day effectively reduces serum low density lipoprotein (LDL)-cholesterol levels. Furthermore, simvastatin reduces triglycerides and mildly raises high density lipoprotein-cholesterol levels. In addition to the hypolipidaemic effect, other potentially important effects, such as improvement of endothelial function and reduction of LDL oxidation and vascular inflammation, have been associated with HMG-CoA reductase inhibitor therapy. Simvastatin has also been shown to abolish the progression, and even facilitate the regression, of existing human atherosclerotic lesions. The good safety and tolerability profile of simvastatin is clearly highlighted by the low rate of therapy discontinuation observed in several population-based clinical trials. The most common adverse events leading to the discontinuation of therapy are gastrointestinal upset and headache. Asymptomatic elevations in liver transaminase levels and myopathy are uncommon. The overwhelming clinical evidence regarding the long-term use of HMG-CoA reductase inhibitor therapy in patients with familial hypercholesterolaemia together with the long-term safety data (particularly relating to simvastatin) provide support for the use of this drug as a first-line agent when pharmacological treatment is indicated. Early intervention with simvastatin treatment can be successfully implemented with favourable economic benefits.
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PMID:Benefits and risks of simvastatin in patients with familial hypercholesterolaemia. 1290 47