What is the mechanism of action of statin drugs?

What is the mechanism of action of statin drugs?

Mechanism of Action Statins work by competitively blocking the active site of the first and key rate-limiting enzyme in the mevalonate pathway, HMG-CoA reductase. Inhibition of this site prevents substrate access, thereby blocking the conversion of HMG-CoA to mevalonic acid.

What is the difference between statins and fibrates?

Statins lower LDL-cholesterol (LDL-C), with limited effects on other lipid parameters. Fibrates improve atherogenic dyslipidemia characterized by high triglyceride and/or low HDL-C levels and elevated concentrations of small dense LDL particles, with or without high LDL-C levels.

How do fibrate drugs work?

Fibrates stimulate cellular fatty acid uptake, conversion to acyl-CoA derivatives, and catabolism by the β-oxidation pathways, which, combined with a reduction in fatty acid and triglyceride synthesis, results in a decrease in VLDL production.

What is the mechanism of action of cholestyramine?

Cholestyramine binds to bile acids in the intestine. This prevents their absorption, and the cholestyramine/bile acid complexes are eliminated in the stool. As a result, the body loses bile acids. To compensate for this loss, the liver increases the conversion of cholesterol to bile acids.

Do all statins have the same mechanism of action?

Despite having the same mechanism of action and comparative effects on cholesterol profiles, statins can still be subdivided into one of two categories: type I, fungal-derived statins (lovastatin, pravastatin, simvastatin); or type II, synthetically-derived statins (fluvastatin, cerivastatin, atorvastatin, rosuvastatin …

What is the mechanism of action of gemfibrozil?

The mechanism of action of gemfibrozil is not entirely understood. It increases VLDL clearance by stimulating vascular endothelial cell lipoprotein lipase activity. Gemfibrozil binds to PPAR-alpha which, in turn, increases fatty acid oxidation and reduces triglycerides levels.

How do fibrates work to lower triglycerides?

Fibrates lower blood triglyceride levels by reducing the liver’s production of VLDL (the triglyceride-carrying particle that circulates in the blood) and by speeding up the removal of triglycerides from the blood.

Why are statins and fibrates not used together?

The major concern when using a statin-fibrate combination is the potential increased risk for myopathy and rhabdomyolysis.

How do fibrates lower triglycerides?

Fibrates reduce plasma triglycerides by inhibiting their hepatic synthesis and increasing their catabolism. They reduce the synthesis of triglyceride–very low density lipoprotein (VLDL) by increasing the beta-oxidation of fatty acids in the liver.

Is cholestyramine and statin?

Cholestyramine was approved for use in the United States in 1973 and is one of the oldest and safest cholesterol lowering agents, but it is currently used largely as an adjunctive therapy when statins or other lipid lowering agents result in an inadequate decrease in cholesterol levels.

What is the mechanism of action of ursodeoxycholic acid?

Multiple mechanisms of action of UDCA have been described aiming at one or more of the pathogenetic processes of cholestatic liver diseases: (1) protection of injured cholangiocytes against toxic effects of bile acids, (2) stimulation of impaired biliary secretion, (3) stimulation of detoxification of hydrophobic bile …

What is the mechanism of action of fibrates and statins?

These bio-molecular effects of fibrates are entirely due to their capacity to activate PPAR alpha and to induce the over expression of genes containing a PPRE in their promoter. Therefore, the mechanism of action of the statins and fibrates depends on their capacity to modulate the expression of genes controlling the lipoprotein metabolism.

What are fibrates and how do they work?

Fibrates activate specific transcription factors belonging to the nuclear hormone receptor superfamily, termed peroxisome proliferator-activated receptors (PPARs). The PPAR-α form mediates fibrate action on HDL cholesterol levels via transcriptional induction of synthesis of the major HDL apolipoproteins, apoA-I and apoA-II.

How do fibrates work in hypertriglyceridaemia?

Mechanism of action of fibrates Fibrates are effective in hypertriglyceridaemia and hypercholesterolaemia. They affect both triglyceride-rich and cholesterol-rich particles and have at least four separate modes of action. These include limitation of substrate availability for triglyceride synthesis in the liver; promotion of the a …

What is the role of PPAR in fibrate action?

The PPAR-α form mediates fibrate action on HDL cholesterol levels via transcriptional induction of synthesis of the major HDL apolipoproteins, apoA-I and apoA-II. Fibrates lower hepatic apoC-III production and increase lipoprotein lipase—mediated lipolysis via PPAR.