This MedLibrary.org supplementary page on Fibrate is provided directly from the open source Wikipedia as a service to our readers. Please see the note below on authorship of this content, as well as the Wikipedia usage guidelines. To search for other content from our encyclopedia supplement, please use the form below:
Related Sponsors
In pharmacology, the fibrates are a class of amphipathic carboxylic acids. They are used for a range of metabolic disorders, mainly hypercholesterolemia (high cholesterol), and are therefore hypolipidemic agents.
Contents |
Members
Fibrates prescribed commonly are:
- Bezafibrate (e.g. Bezalip)
- Ciprofibrate (e.g. Modalim)
- Clofibrate (largely obsolete due to side-effect profile, e.g. gallstones)
- Gemfibrozil (e.g. Lopid)
- Fenofibrate (e.g. TriCor)
Indications
Fibrates are used as accessory therapy in many forms of hypercholesterolemia, usually in combination with statins. Clinical trials do support its use as a monotherapy agent.
Although less effective in lowering LDL, fibrates improve HDL and triglyceride levels (i.e. increase HDL levels and decrease triglyceride levels), and seem to improve insulin resistance when the dyslipidemia is associated with other features of Syndrome X (hypertension and diabetes mellitus type 2).
Mechanism
Fibrates are agonists of the PPAR-α receptor in muscle, liver, and other tissues. Activation of PPAR-α signaling results in:
- Increased β-oxidation in the liver
- Decreased hepatic triglyceride secretion
- Increased lipoprotein lipase activity, and thus increased VLDL clearance
- Increased HDL
- Increased clearance of remnant particles
and many more...
Side effects
Most fibrates can cause mild stomach upset and myopathy (muscle pain with CPK elevations). Since fibrates increase the cholesterol content of bile, they increase the risk for gallstones.
In combination with statin drugs, fibrates cause an increased risk of rhabdomyolysis (idiosyncratic destruction of muscle tissue, leading to renal failure). A powerful statin drug, cerivastatin (Lipobay), was withdrawn because of this complication. The less lipophilic statins are less prone to cause this reaction, and are probably safer when combined with fibrates.
Pharmacology
Although used clinically since at least the 1930s[1], the mechanism of action of fibrates remained unelucidated until, in the 1990s, it was discovered that fibrates activate PPAR (peroxisome proliferator-activated receptors), especially PPARα. The PPARs are a class of intracellular receptors that modulate carbohydrate, fat metabolism and adipose tissue differentiation.
Activation of PPARs causes transcription of a number of genes on the DNA that facilitate lipid metabolism.
Fibrates are structurally and pharmacologically related to the thiazolidinediones, a novel class of anti-diabetic drugs that also act on PPARs (more specifically PPARγ)
Fibrates are a substrate of (metabolized by) CYP3A4.[1]
See also
|
|||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||
References
Wikipedia content modification information:
- This page was last modified on 5 October 2008, at 17:46.
Wikipedia Authorship and Review
Wikipedia content provided here is not reviewed directly by MedLibrary.org. Wikipedia content is authored by an open community of volunteers and is not produced by or in any way affiliated with MedLibrary.org.
Wikipedia Usage Guidelines
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article on "Fibrate".
The URL for this specific entry is:
All Wikipedia text is available under the terms of the GNU Free Documentation License. (See Copyrights for details). Wikipedia® is a registered trademark of the Wikimedia Foundation, Inc.