Currently available hypolipidaemic drugs and future therapeutic developments.

Article Details

Citation

Farmer JA, Gotto AM Jr

Currently available hypolipidaemic drugs and future therapeutic developments.

Baillieres Clin Endocrinol Metab. 1995 Oct;9(4):825-47.

PubMed ID
8593127 [ View in PubMed
]
Abstract

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.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
ColestipolBile acidsGroupHumans
Yes
Binder
Details
Pharmaco-metabolomics
DrugDrug GroupsMetaboliteChangeDescription
FluvastatinApprovedLDL cholesterol
decreased
Fluvastatin decreases the level of LDL cholesterol in the blood
NiacinApproved Investigational NutraceuticalLDL cholesterol
decreased
Niacin decreases the level of LDL cholesterol in the blood
NiacinApproved Investigational NutraceuticalGlucose
increased
Niacin increases the level of Glucose in the blood
NiacinApproved Investigational NutraceuticalTriglycerides
decreased
Niacin decreases the level of Triglycerides in the blood
ClofibrateApproved InvestigationalTriglycerides
decreased
Clofibrate decreases the level of Triglycerides in the blood
LovastatinApproved InvestigationalLDL cholesterol
decreased
Lovastatin decreases the level of LDL cholesterol in the blood
CholestyramineApproved InvestigationalLDL cholesterol
decreased
Cholestyramine decreases the level of LDL cholesterol in the blood
GemfibrozilApprovedTriglycerides
decreased
Gemfibrozil decreases the level of Triglycerides in the blood
CiprofibrateApproved InvestigationalTriglycerides
decreased
Ciprofibrate decreases the level of Triglycerides in the blood
ColestipolApprovedLDL cholesterol
decreased
Colestipol decreases the level of LDL cholesterol in the blood
NiacinApproved Investigational NutraceuticalTriglycerides
decreased
Niacin decreases the level of Triglycerides in the blood
BezafibrateApproved InvestigationalTriglycerides
decreased
Bezafibrate decreases the level of Triglycerides in the blood
FenofibrateApprovedTriglycerides
decreased
Fenofibrate decreases the level of Triglycerides in the blood
NiacinApproved Investigational NutraceuticalLDL cholesterol
decreased
Niacin decreases the level of LDL cholesterol in the blood
SimvastatinApprovedLDL cholesterol
decreased
Simvastatin decreases the level of LDL cholesterol in the blood