Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013395 (dyspepsia)
 4,879 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Clinical experience with fluvastatin in > 1,800 North American patients treated for an average of 61 weeks has shown it to be safe and well tolerated. Frequencies of transaminase and creatine kinase elevations compare favorably with those observed during long-term administration of other 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors. Further, whereas frank rhabdomyolysis has been encountered with treatment with all other HMG-CoA reductase inhibitors, this syndrome has not been observed to date with fluvastatin in studies here or abroad; a single case of myopathy, which was probably related to physical exertion, was reported in a patient receiving fluvastatin. Although dyspepsia was observed more commonly in fluvastatin patients the incidence, along with that of other adverse events (e.g., headache), and the number of treatment discontinuations proved statistically indistinguishable from those of placebo controls. Whether the favorable safety profile of fluvastatin is related to this synthetic agent's unique biopharmaceutical profile is a matter of ongoing long-term inquiry.
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PMID:Updated clinical safety experience with fluvastatin. 819 19

Dyslipidaemia may be treated with a number of safe and effective pharmacological agents that target specific lipid disorders through a variety of mechanisms. The bile-acid sequestrants--cholestyramine and colestipol--primarily decrease LDL cholesterol by binding bile acids, thereby decreasing intrahepatic cholesterol, and by increasing the activity of LDL receptors. Nicotinic acid lowers LDL cholesterol and triglyceride by decreasing VLDL synthesis and by decreasing free fatty acid mobilization from peripheral adipocytes. The HMG-CoA reductase inhibitors--fluvastatin, lovastatin, pravastatin and simvastatin--lower LDL cholesterol by partially inhibiting HMG-CoA reductase (the rate-limiting enzyme of cholesterol biosynthesis) and by increasing the activity of LDL receptors. The fibric-acid derivatives--bezafibrate, ciprofibrate, clofibrate, fenofibrate and gemfibrozil--primarily decrease triglyceride by increasing lipoprotein lipase activity and by decreasing the release of free fatty acids from peripheral adipose tissue. Probucol decreases LDL cholesterol by increasing non-receptor-mediated LDL clearance; as an anti-oxidant, probucol also decreases LDL oxidation; oxidized LDL which is thought to lead to atherogenesis. Although these agents have been proven safe in clinical trials, like any drug, they carry the risk for adverse effects. The bile-acid sequestrants may cause constipation, reflux oesophagitis, and dyspepsia, and may bind coadministered medications such as digitalis glycosides, beta blockers, warfarin, and exogenous thyroid hormone. Nicotinic acid use is commonly associated with flushing and pruritus and may also cause non-specific gastrointestinal complaints, hepatotoxicity (hepatic necrosis, hepatitis, or elevated liver enzymes), gout, myolysis, decreased glucose tolerance and increased fasting glucose levels, and ophthalmological complications including decreased visual acuity, toxic amblyopia, and cystic maculopathy. The HMG-CoA reductase inhibitors may produce liver enzyme elevations, creatine kinase elevations and rhabdomyolysis. The combination of a reductase inhibitor and a fibrate increases the risk for rhabdomyolysis. Possible adverse effects of the fibric-acid derivatives include abdominal discomfort, nausea, flatulence, increased lithogenicity of bile, liver enzyme elevations and creatine kinase elevations. Probucol may increase the QTc interval and may cause non-specific gastrointestinal complaints.
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PMID:Currently available hypolipidaemic drugs and future therapeutic developments. 859 27

The pharmacokinetics, safety, and tolerability of cerivastatin, a synthetic HMG-CoA reductase inhibitor were studied in 49 healthy volunteers. In this double-blind, parallel group, multiple-dose study, volunteers were randomized as age-matched, male-female pairs and stratified into younger (18-65 years, premenopausal females) or older (65-85 years, postmenopausal females) groups. Thirty-two (16 female, 16 male) subjects received 0.2 mg cerivastatin daily for 7 days; 17 received placebo. Between all males and females, no differences in cerivastatin pharmacokinetics were observed. The AUCnorm in older females was 21% higher than in older males, while the AUCnorm in younger females was 26% lower than in younger males. The Cmax in older females was 30% higher than in age-matched males or younger males and females. All other pharmacokinetic parameters, including half-life, tmax, accumulation ratios, and steady state plasma levels were similar in all treatment groups. The most common adverse events, including headache (4), dyspepsia (4), and rash (4), were equally distributed between groups. Treatment-emergent elevations (< 2 x ULN) in creatine kinase occurred in one subject. Transaminase elevations occurred in nine subjects, most were less than 3 x ULN, and were equally distributed between groups. In conclusion, cerivastatin was well tolerated. The minor differences in the pharmacokinetics of cerivastatin 0.2 mg between genders does not require modification of dosage.
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PMID:Influence of gender on the pharmacokinetics, safety, and tolerability of cerivastatin in healthy adults. 1131 78

Premna integrifolia Linn. is a medicinal plant used in "Dhasamula" drug preparation of Ayurvedic systems of medicine in the treatment of various ailments like bronchitis, dyspepsia, liver disorders, piles, constipation, hyperlipidemia and fever. The anti-atherosclerotic activity of hydroalcoholic extract (HAE) of root bark of P. integrifolia was evaluated in high fat diet induced atherosclerosis rats. Sixty Wistar rats were divided into six groups: the first group served as control, the second group was fed with high fat diet and the other three groups were fed with high fat diet along with various concentrations of HAE and the last group was treated with atorvastatin for 30 days. Lipid and lipoprotein profile, atherogenic index, and cardiac markers and histopathological evaluation of aorta were determined in high fat diet induced atherosclerosis rats. HAE of P. integrifolia produced a significant and dose-dependent anti-atherosclerotic activity in terms of reduction in lipids and lipoprotein profile, atherogenic index, HMG-CoA reductase activity, marker enzymes such as lactate dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP), alteration in collagen and calcium contents, mild mineralization and focal rupture of intima and media of aorta was noticed in treated groups as compared to the control. The results suggested that anti-atherosclerotic activity of HAE of P. integrifolia Linn. was due to its modulatory activity on metabolic pathway of lipid. The results contribute to the validation of the traditional use of Agnimantha in high fat diet induced atherosclerosis rats.
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PMID:Anti-atherosclerotic activity of root bark of Premna integrifolia Linn. in high fat diet induced atherosclerosis model rats. 2940 27

Wuwei Qingzuo San (WWQZS), as a renowned traditional Mongolian patent medicine approved by Chinese State Food and Drug Administration, is used to treat hyperlipidemia, indigestion, and other ailments related to disorder of production of essence and phlegm, a typical abnormal metabolism of blood in traditional Mongolian medicine. A combination of network pharmacology and validation experiments in hyperlipidemia hamster is used to understand the potential mechanism of WWQZS for hypolipidemic effects, further for an integrated concept of traditional theory, bioactive constituents, and molecular mechanism for TMM. Through network pharmacology, we obtained 212 components, 219 predicted targets, and 349 known hyperlipidemia-related targets form public database and used Metascape to carry out enrichment analysis of 43 potential and 45 candidate targets to imply numerous BP concerned with metabolism of lipid, regulation of kinases and MF related to lipid binding, phosphatase binding, and receptor ligand activity that are involved in anti-hyperlipidemia. In addition, KEGG pathways that explicated hypolipidemic effect were involved in pathways including metabolism associated with kinase function according to MAPK signaling pathway, AMPK signaling pathway, and PI3K-Akt signaling pathway. Meanwhile, in HFD-induced hamster model, WWQZS could significantly reduce TC and ALT and help decrease TG, LDL-C as well; liver pathological section implied that WWQZS could relieve liver damage and lipid accumulation. Western blot indicated that WWQZS may upregulate CYP7A1 and activate AMPK to suppress the expression of HMGCR in livers. In conclusion, our results suggest that WWQSZS plays important dual hypolipidemic and liver-protective role in livers in HFD-induced hamster model. Through this research, a new reference is also provided to other researches in the study of ethnopharmacology.
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PMID:The Potential Mechanism of Wuwei Qingzhuo San against Hyperlipidemia Based on TCM Network Pharmacology and Validation Experiments in Hyperlipidemia Hamster. 3245 62