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)

Few data are available on the relative efficacy and tolerability of lovastatin and pravastatin, two 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, currently available in North America for treatment of hypercholesterolemia. The recommended starting dose is 20 mg QD with the evening meal for lovastatin. The recommended starting dose is 10 mg or 20 mg once daily at bedtime for pravastatin. In a double blind, double placebo, multicenter, randomized study, we compared the changes in plasma lipids and apolipoproteins in 217 patients with primary hypercholesterolemia treated for eight weeks with lovastatin 20 mg QD to pravastatin 10 mg QD or pravastatin 20 mg QD. The reductions in total cholesterol (TC) (21%), low-density lipoprotein cholesterol (LDL-C) (28%), and apolipoprotein B (apo B) (22%) were comparable for the lovastatin 20-mg and pravastatin 20-mg groups. Lovastatin 20 mg QD was significantly more effective than pravastatin 10 mg QD in lowering TC and LDL-C after four weeks of therapy and in the reduction of apo B after four and eight weeks of therapy. At the end of eight weeks of therapy, the mean reductions in TC and LDL-C were numerically greater with lovastatin 20 mg QD compared with pravastatin 10 mg QD, but the differences were not statistically significant. At the end of eight weeks, there was no difference between pravastatin 20 mg and pravastatin 10 mg in lowering TC and LDL-C. The frequency of overall side effects, including central nervous system-related symptoms and headache, was similar and low in all groups.
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PMID:Comparison of the short-term efficacy and tolerability of lovastatin and pravastatin in the management of primary hypercholesterolemia. 161 49

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

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