Fibrate

From Academic Kids

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.

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Fibrates prescribed commonly are:

Uses

Fibrates are used as accessory therapy in many forms of hypercholesterolemia, usually in combination with statins.

Although less effective in lowering LDL, fibrates improve HDL and 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).

Side-effects

Most fibrates can cause mild stomach upset and myopathy (muscle pain with CPK elevations).

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 A powerful statin drug, cerivastatin (Lipobay®), was withdrawn because of this complication.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 the early 1970s, 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 pharmocologically related to the thiazolidinediones, a novel class of anti-diabetic drugs that also act on PPARs (more specifically PPARγ)

See also

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