Fibrates

stimulate the beta-oxidative degradation of fatty acids
- liberate free fatty acids for storage in fat or for metabolism in
striated muscle

- increase the activity of lipoprotein lipase,
hence increasing hydrolysis of triglyceride in chylomicrons
and VLDL particles

reduce hepatic VLDL production and increase hepatic LDL
uptake
The fibrates act through paroxysome proliferator activated receptor (PPAR-alpha) which is gene transcription regulating receptor
PPAR-alpha are present in liver, adipocytes & muscle cells.
Activation of PPAR alpha enhances lipoprotein lipase synthesis & fatty acid oxidation
PPAR alpha also mediate enhanced LDL receptor expression in liver
Compare from PPAR gamma agonist glitazones, on which insulin sensitizer act
LDL ↓5-20 %, may ↑ LDL when TG is high
HDL ↑ 10-20 %
TG ↓ 20-50 %
With clofibrate there is risk of gall stones, so not used now a days
Gemfibrozil + statin ↑the risk of myopathy
Fenofibrate is most suitable fibrate for combining with statins
O t h e r e f f e c t s :
improve glucose tolerance
inhibit vascular smooth muscle inflammation
A d v e r s e e f f e c t s:
In patients with renal impairment myositis (rhabdomyolysis) myoglobulinuria, acute renal failure
Fibrates should be avoided in such patients and also in alcoholics)
Mild GI upset
Uses: Mixed dyslipidemia
Diabetic dyslipidemia
Patients with low HDL & high risk of atheromatous disease