Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abnormal interaction between low density lipoprotein receptors (LDLR) and their ligands, apolipoprotein E and B, causes decreased catabolism of lipoproteins which carry these apolipoproteins (VLDL, IDL and/or LDL) and thereby increased plasma concentrations of these. In familial hypercholesterolemia (FH), abnormal interaction is due to mutations in the LDLR gene, and in type III hyperlipidemia due to mutations in the apo E gene. A few mutations in the apolipoprotein B (apo B) gene have been described, of which the apo B-3,500Arg-Gln seems by far the most frequent, that causes defective binding to normal LDLR. The metabolic disorder associated with these mutations has been named familial defective apolipoprotein B-100 (FDB). The frequency of the apo B-3,500Arg-Gln mutation is particularly high in Central Europe (Switzerland) with lower frequencies south of the Alpes, in Russia and in Scandinavia. We found an incidence of 1/1250 of the mutation in Denmark (III), employing a DNA based assay optimized to allow detection of the mutation in very small amounts of DNA (I). Since other mutations in the receptor binding domain of the apo B-100 have been described, we developed another DNA based assay, employing DGGE technique, to screen for other mutations in the region of amino acid 3,456 to 3,553 (II). However, no other mutations but the apo B-3,500Arg-Gln have so far been detected in Danish hypercholesterolemic patients. In a study of 5 Danish families with FDB (46 heterozygous FDB patients and 57 unaffected relatives) we found that FDB patients had significantly increased mean cholesterol and LDL cholesterol concentrations, but with a wide range of variation and with approximately 30% having cholesterol concentrations below the 95th percentile for the general population (IV). This was confirmed in a compilation of data on 205 FDB patients from the Netherlands, Germany and Denmark (V). In this study we also compared the biochemical and clinical features of FDB with those of 101 Danish FH patients in whome FDB had been ruled out. Our data support, that the LDL cholesterol elevation is less pronounced in FDB than in FH and that the age-specific prevalence of atherosclerotic cardiovascular disease (CVD) is lower in FDB than in FH. In the compiled study of 205 FDB heterozygotes (V), we found that age, gender and genetic variation in the LDLR gene explained a considerable part of the between-individual variation in total and LDL cholesterol. We conducted a prospective study of the lipid lowering effect of pravastatin and gemfibrozil in 30 Danish FDB patients (VI). Together with other, retrospective, studies, we conclude that the cholesterol lowering effect of HMG-coA-reductase inhibitors, anion binding resins and nicotinic acid is fully comparable to that observed when treating FH patients and type IIa hypercholesterolemic patients, without clinical signs of FH.
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PMID:Familial defective apolipoprotein B-100. 977 89

The effect of different routes and modes of administration of niacin (nicotinic acid) on its hypolipidaemic activity has been evaluated. Our working hypothesis was that the major sites of niacin action are located presystemically (i.e. in the gut wall or the liver, or both) which would make niacin a gastrointestinal drug. For such drugs continuous administration to the gastrointestinal tract is expected to augment their efficacy compared with bolus oral administration or parenteral administration. The hypothesis was examined in two rat models of experimentally induced hyperlipidaemia-Model A, based on a cholesterol-enriched diet, and Model B, in which acute hyperlipidaemia is induced by intraperitoneal administration of triton (225 mg kg(-1)). Continuous administration of niacin into the duodenum at 1.66 mg h(-1) (total dose 40 mg kg(-1) day(-1)) for up to 7 days (Model A) or at 2.22 mg h(-1) over 18 h (Model B) had significantly greater lipid-reducing effects both on total cholesterol and on triglyceride levels (15-25%) and elevation of high-density lipoprotein (HDL) cholesterol levels than did bolus oral administration of the same dose. Continuous duodenal infusion of niacin also had an even greater lipid-reducing effect than continuous intravenous infusion of the drug at the same rate and dose. The results indicate that the site(s) of action are located presystemically and that continuous duodenal administration of a low dose of niacin (40 mg kg(-1)) has a greater lipid-lowering effect than a higher dose (200 mg kg(-1)) administered by peroral bolus administration. These conclusions were validated by administration of a specially designed niacin sustained-release matrix tablet formulation that was non-invasively administered to hyperlipidaemic rats. The hypolipidaemic activity of the sustained-release tablet was of similar magnitude to that resulting from continuous duodenal administration, thus providing a pharmacodynamic rationale for this mode of administration.
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PMID:The effect of the mode of administration on the hypolipidaemic activity of niacin: continuous gastrointestinal administration of low-dose niacin improves lipid-lowering efficacy in experimentally-induced hyperlipidaemic rats. 987 8

Cardiovascular disease related to hyperlipidemia is a significant cause of morbidity and mortality in the United States. The benefit of lowering lipid levels in patients with and without cardiovascular disease has been demonstrated in numerous clinical trials. The results of these trials prompted the National Heart, Blood, and Lung Institute to form the Nation Cholesterol Education Panel (NCEP). This panel developed guidelines for identifying and treating lipid disorders. Before starting antilipemic therapy, patients should be evaluated for secondary causes of hyperlipidemia, including disease states and medications. Risk factors for cardiovascular disease should be identified and used to determine the patient's goal low-density lipoprotein level. Regardless of the drug therapy used, the cornerstone treatment for hyperlipidemia is dietary changes. The NCEP recommendation for dietary modification follows a two-step plan to reduce intake of cholesterol and dietary fats. Other nonpharmacologic treatments for hyperlipidemia include exercise, weight reduction for obese patients, reduction of excessive alcohol use, and smoking cessation . Drug therapy should be considered in patients who do not respond to an adequate trial of dietary modifications and lifestyle changes. The principal lipid-lowering agents currently used are the bile acid sequestrants, nicotinic acid, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, and fibric acid derivatives. Estrogen, fish oil, and alcohol also can decrease the risk of developing heart disease. In pharmacoeconomic studies, lipid-lowering drug therapy has been shown to decrease the number of procedures, hospitalizations, and other medical interventions required by patients with cardiovascular disease.
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PMID:Identifying and managing patients with hyperlipidemia. 1017 Mar 3

Drug treatment of hyperlipidemia was reviewed. In the first part, mode of action, efficacy and safety of lipid-lowering agents were described and in the second part, strategies for treatment of hyperlipidemia was described. Treatment of hypercholesterolemia should be started with statin and if the reduction is not enough, cholestimide or nicotinic acid or probucol can be added. Mild hypertriglyceridemia can be treated with dextran sulfate sodium, but usually low dose of fenofibrate or bezafibrate will be necessary. For severe cases, combination therapy with fibrate and nicotinic acid or ethyl icosapentate is required. Treatment of combined hyperlipidemia should be started with fibrate, but when the increment of cholesterol is superior to triglyceride, statin can be chosen. If these drugs are not fully effective, combination therapy with statin and ethyl icosapentate is recommended.
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PMID:[Anti-hyperlipidemic drug]. 1042 59

Calcium-induced alginate gel beads containing chitosan salt (Alg-CS) was prepared using nicotinic acid (NA), a drug for hyperlipidemia, and investigated its two functions in gastrointestinal tract, (a) NA release from Alg-CS, (b) uptake of bile acids into Alg-CS. The amount of NA incorporated in Alg-CS increased according to increment of CS content. NA was rapidly released from Alg-CS in diluted HCl solution (pH 1.2) or physiological saline without disintegration of the beads. When Alg-CS was placed in bile acid solution it took bile acid into itself. About 80% of taurocholic acid dissolved in the medium was taken into Alg-CS. According to increment of bile acid concentration, the uptake amount increased and an approximately linear relationship existed among them.
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PMID:Preparation of alginate gel beads containing chitosan nicotinic acid salt and the functions. 1047 28

32 patients with hypertriglyceridemia, excessive hypertriglyceridemia, and combined hyperlipidemia, were treated with the nicotinic acid derivative acipimox (Olbetam). First line treatment with bezafibrate, or statins in some with combined hyperlipidemia, had failed. In 10 acipimox was discontinued due to side effects or absence of clinical response. The other 22 completed 6 months of treatment with no side effects. Acipimox caused a significant 54% decrease in triglyceride levels, a 23% decrease in total cholesterol, and a 12% increase in HDL-cholesterol. LDL-cholesterol was difficult to calculate because of the high triglyceride levels, so no results are presented. Although acipimox was much better tolerated than nicotinic acid, it also had side effects, but fewer. Acipimox can therefore be used as a second-line drug, mainly in those with combined hyperlipidemia and hypertriglyceridemia.
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PMID:[Acipimox (Olbetam) as a secondary hypolipemic agent in combined hypertriglyceridemia and hyperlipidemia]. 1088 6

Vanadium, a trace element in human cells and regarded as an essential nutrient, plays an active role in all tissues. It is known that peroxovanadate-nicotinic acid (POV), a complex compound of vanadium, can decrease hyperglycemia; however, its biochemical mechanism remains unclear. The object of the present study is to explore the hypoglycemia mechanism of POV at gene molecular levels. Rats rendered diabetic with streptozotocin were treated with POV. Total RNA was isolated from rat liver, and phenylalanine hydroxylase (PAH) mRNA abundance was determined by reverse transcriptase-polymerase chain reaction. PAH activity, blood glucose, and lipid levels were measured. Significantly increased hepatic PAH activity and corresponding mRNA with concomitant hyperglycemia and hyperlipemia were found in diabetic rats. These levels returned to normal after POV treatment and accompanied by negative glucosuria, normoglycemia, and normolipemia. The results from the current study indicates one of the mechanisms of POV action is to inhibit PAH gene expression and PAH activity, thus decreasing gluconeogenesis and hyperglycemia. At the same time, POV is able to promote diabetic recovery by lowering hyperlipemia.
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PMID:Effect of peroxovanadate compound on phenylalanine hydroxylase gene expression. 1105 10

Drug induced myopathy has been reported with the use of fibric acid derivatives, hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and nicotinic acid. Over the last three decades, hypolipemiants like fibric acid derivatives and statins have been increasingly recognised as causes of rhabdomyolysis and acute renal failure especially during combination therapy and in the presence of underlying renal impairment. We report two cases of bezafibrate-induced rhabdomyolysis in patients with underlying coronary artery disease and pre-existing renal impairment. Both patients developed rhabdomyolysis leading to acute renal failure soon after their hyperlipidaemia treatment was changed from gemfibrozil to bezafibrate. There were no intercurrent illnesses or co-administration of other lipid lowering drugs in both patients. Even though both drugs belong to the same fibric acid derivatives group, these patients developed the complication only after a switchover of therapy.
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PMID:Rhabdomyolysis and acute renal failure following a switchover of therapy between two fibric acid derivatives. 1176 54

Accumulating evidences in recent major clinical studies have shown the importance of anti-hyperlipidemic treatment in preventing atherosclerotic cardiovascular diseases. Lipid-lowering drugs can be divided into HMG-CoA reductase inhibitors (statins), bile-acid sequestrants (resins), nicotinic acid, fibrates and probucol. Among them, statins had revolutionary impact on the treatment of hyperlipidemia since pravastatin, which was developed in Japan, was launched in 1989. Several lipid-lowering drugs are now under development in Japan, including pitavastatin, rosuvastatin, F-1394 (ACAT inhibitor), CS-505 (ACAT inhibitor) and NO-1886 (LPL activator). In this review, characteristics of these new lipid-lowering drugs will be discussed.
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PMID:[Lipid-lowering drugs]. 1177 57

In the present study, we evaluated the effects of combination therapy with niceritrol and pravastatin in patients with hyperlipidaemia. A total of 62 patients with hyperlipidaemia, defined as total cholesterol levels above 220 mg/dl or triglyceride levels above 150 mg/dl, were recruited. Patients were divided into two groups: Group N received initial therapy with niceritrol 750-1500 mg/day, and those in Group P, pravastatin 10 mg/day. After 8 weeks, pravastatin 10 mg/day was added to the Group N treatment regimen for a further 8 weeks, while patients in Group P were given niceritrol 750-1500 mg/day in addition to pravastatin for 8 weeks. After the 8-week combination therapy study period, total cholesterol levels were 209.6 mg/dl in Group N and 220.7 mg/dl in Group P. Decreased triglyceride and lipoprotein(a) levels and increased high-density lipoprotein cholesterol levels, neither of which were achieved by pravastatin administration alone, were achieved with the combination of pravastatin and niceritrol. We conclude that when a single lipid-lowering drug fails to show therapeutic value, attempting combination therapy with a nicotinic acid preparation and a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) is worthwhile.
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PMID:The effects of combination therapy with niceritrol and pravastatin on hyperlipidaemia. 1216 44


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