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 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

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, dosage and administration, and adverse effects of lovastatin are reviewed. Lovastatin is the first agent marketed in a new class of pharmacologic compounds called the 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors. By competitively inhibiting HMG CoA reductase, the drug disrupts the biosynthesis of cholesterol in hepatic and peripheral cells. This increases the synthesis of low-density-lipoprotein (LDL) receptors and thereby increases the uptake of LDL cholesterol from the plasma. In doses of 20 to 80 mg daily, lovastatin decreases total and LDL cholesterol concentrations 25 to 45%. It also substantially reduces concentrations of triglycerides, very-low-density-lipoprotein (VLDL) cholesterol, and apolipoprotein B and slightly increases high-density-lipoprotein (HDL) cholesterol concentrations. Lovastatin is effective in patients with heterozygous familial and nonfamilial (polygenic) hypercholesterolemia but is ineffective in patients with homozygous familial hypercholesterolemia. It is also effective in combination with bile acid sequestrants, nicotinic acid, and gemfibrozil. Administration of lovastatin once daily in the evening (to enhance compliance) or twice daily is recommended to maximize the drug's cholesterol-lowering effects. Headache and gastrointestinal complaints are the most common adverse effects. Treatment has been withdrawn from 1.9% of patients receiving the drug because of elevated aminotransferase concentrations. The relationship of lovastatin to the development of lens opacities requires further evaluation. Lovastatin is highly effective in the treatment of primary hypercholesterolemia and represents an important therapeutic advance. Safety with long-term use and effect on coronary heart disease remain to be established.
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PMID:Lovastatin: a new cholesterol-lowering agent. 327 32

To evaluate the effect of hypercholesterolemic treatment on coronary artery disease in patients known to be susceptible to disease progression, 44 patients with familial hypercholesterolemia and coronary artery disease were started on a lipid-lowering diet and either probucol (1 g/day) or colestipol (30 g/day). After 5 months of monotherapy, all patients went on a regimen of diet and 2-drug therapy. To date, combination therapy has continued for 3.4 to 4.1 years, and has resulted in the following changes from baseline in mean serum lipid levels: -48.5% in total cholesterol, -53.3% in low density lipoprotein cholesterol, -30.0% in high density lipoprotein cholesterol and +14.5% in triglycerides. The reduction in low density lipoprotein cholesterol apparently improved the clinical status of these patients despite the associated drop in high density lipoprotein cholesterol. In the 19 patients who underwent coronary arteriography before admission to the study, follow-up arteriograms showed that combined treatment stabilized the progression of established lesions and prevented the formation of new ones. Side effects occurred mainly with monotherapy and during the early phase of combination therapy. Reactions included diarrhea, constipation, other vague abdominal symptoms, headache and joint stiffness. In all instances, the side effects gradually subsided after the institution of combination therapy. The combination of probucol and colestipol plus diet appears to be effective in treating most patients with familial hypercholesterolemia.
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PMID:Effects of combined probucol-colestipol treatment for familial hypercholesterolemia and coronary artery disease. 352 77

We have evaluated the hypolipidemic effects of mevinolin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme in cholesterol biosynthesis in 13 patients with heterozygous familial hypercholesterolemia (FH). Patients were maintained on a low-cholesterol diet and received sequentially increasing doses of 5, 10, 20, and 40 mg of mevinolin twice daily for a period of 1 mo on each dose. Plasma concentrations of low density lipoprotein cholesterol decreased by 19.8% on the 5 mg twice daily dose (P less than 0.05 vs. base line), 28.4% on 10 mg of mevinolin twice daily (P less than 0.05 vs. 5 mg twice daily), 35% on 20 mg of mevinolin twice daily (P less than 0.05 vs. 10 mg twice daily), and 37.7% on 40 mg of mevinolin twice daily (not statistically different from 20 mg twice daily). Concentrations of high density lipoprotein cholesterol remained stable on all doses of mevinolin whereas plasma triglyceride levels fell significantly on the 20 mg (-30.7%) and 40 mg (-34.3%) twice daily doses of mevinolin. Mevinolin was well tolerated and all patients completed the study period. Side effects during the period of study were limited to transient insomnia and headaches in two patients, transient increases in alkaline phosphatase in three patients, and a modest but sustained increase in alkaline phosphatase in a fourth patient. These results indicate that mevinolin is an effective hypolipidemic agent in patients with heterozygous FH but that the optimal doses in these patients are greater than those previously reported in normal volunteers. If long-term safety can be satisfactorily established, mevinolin offers considerable promise in the therapy of heterozygous FH.
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PMID:Hypocholesterolemic effects of mevinolin in patients with heterozygous familial hypercholesterolemia. 656 64

Childhood dyslipidemia is on the rise and increasingly being recognized as an important risk factor for adult cardiovascular disease. Due to a heightened awareness surrounding this problem, the American Academy of Pediatrics published a clinical report concerning prevention, screening, diagnosis, and treatment of dyslipidemia in children. Of concern among practitioners is when to initiate pharmacologic therapy and which medications are safe and appropriate in children. The report addresses this concern by suggesting that pharmacologic management begin only in pediatric patients with substantially elevated LDL levels. Since statins are the drugs of choice among adult patients with elevated LDL levels, it would be appropriate to evaluate their outcome in pediatric patients. To evaluate the efficacy and safety of statins for the treatment of pediatric dyslipidemia, a comprehensive search was performed of the MEDLINE database and International Pharmaceutical Abstracts as well as references from additional review articles. The manufacturer was contacted for data regarding a newly approved statin. Fourteen trials were identified, eight of which were randomized, controlled trials involving greater than 50 patients with primary or familial hypercholesterolemia. Overall, the studies showed that statins are effective at lowering LDL levels (reduction from baseline: 17% to 50%) and are fairly well tolerated, with headache, gastrointestinal distress, and myalgia being the most common adverse effects. Statins were found to be an efficacious option for the management of familial hypercholesterolemia of childhood. However, concerns regarding long term safety and efficacy have not been established, and data in patients with secondary lipid disorders is lacking.
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PMID:Use of statins for dyslipidemia in the pediatric population. 2247 8