Fibrate: Difference between revisions
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==Overview== | ==Overview== | ||
In [[pharmacology]], the '''fibrates''' are a class of amphipathic [[carboxylic acid]]s. They are used for a range of [[metabolism|metabolic]] disorders, mainly [[hypercholesterolemia]] (high [[cholesterol]]), and are therefore [[hypolipidemic agent]]s. | In [[pharmacology]], the '''fibrates''' are a class of amphipathic [[carboxylic acid]]s. They are used for a range of [[metabolism|metabolic]] disorders, mainly [[hypercholesterolemia]] (high [[cholesterol]]), and are therefore [[hypolipidemic agent]]s. | ||
== Members == | == Members == | ||
Fibrates prescribed commonly are: | Fibrates prescribed commonly are: | ||
* [[Bezafibrate]] (e.g. Bezalip®, available in Europe not approved in USA) | * [[Bezafibrate]] (e.g. Bezalip®, available in Europe not approved in USA) | ||
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* [[Gemfibrozil]] (e.g. Lopid®, available in USA) | * [[Gemfibrozil]] (e.g. Lopid®, available in USA) | ||
* [[Fenofibrate]] (e.g. TriCor®, available in USA) | * [[Fenofibrate]] (e.g. TriCor®, available in USA) | ||
Fenofibric acid (Trilipix) is | Fenofibric acid (Trilipix) is FDA approved for combination use with [[statin]], in patients with mixed [[dyslipidemia]]. | ||
==Indications== | ==Indications== | ||
Fibrates are used as accessory therapy in many forms of [[hypercholesterolemia]], usually in combination with [[statin]]s. Trials do support its use as monotherapy. | Fibrates are used as accessory therapy in many forms of [[hypercholesterolemia]], usually in combination with [[statin]]s. Trials do support its use as monotherapy. | ||
Although less effective in lowering [[Low-density lipoprotein|LDL]], fibrates improve [[High-density lipoprotein|HDL]] and [[triglyceride]] levels, and seem to improve [[insulin resistance]] when the [[dyslipidemia]] is associated with other features of [[syndrome X (metabolic)|Syndrome X]] ([[hypertension]] and [[diabetes mellitus]] type 2). | Although less effective in lowering [[Low-density lipoprotein|LDL]], fibrates improve [[High-density lipoprotein|HDL]] and [[triglyceride]] levels, and seem to improve [[insulin resistance]] when the [[dyslipidemia]] is associated with other features of [[syndrome X (metabolic)|Syndrome X]] ([[hypertension]] and [[diabetes mellitus]] type 2). | ||
==Doses== | |||
Different doses of fenofibrate are available in the markets. The standard adult dose is usually >100 mg/day. However, dose lowering is required for patients with renal insufficiency ([[creatinine clearance]] < 80). Clinical trials are required to prove the relative efficacy of the different doses of [[fibrates]]. | |||
==Side effects== | ==Side effects== | ||
* Mild stomach upset | |||
* [[Myopathy]] (muscle pain with [[creatine kinase|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]] [[statin]]s are less prone to cause this reaction, and are probably safer when combined with fibrates. | * 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]] [[statin]]s are less prone to cause this reaction, and are probably safer when combined with fibrates. | ||
* Clofibrate are no longer used because they were found to increase morbidity and mortality rates. Also, increased rates of malignancy in rodents have been found. | |||
* Fibrates are excreted via kidney. It can cause reversible increases in serum creatinine levels. Thus, reduction in doses are indicated in cases with increased serum [[creatinine]] levels. [[Gemfibrozil]]'s excretion is independent of [[renal function]], and can be used in patients with [[chronic kidney disease]]. | |||
==Pharmacology== | ==Pharmacology== | ||
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* [[statin]] | * [[statin]] | ||
{{Lipid modifying agents}} | |||
[[Category:Fibrates]] | [[Category:Fibrates]] | ||
[[Category:Drugs]] | [[Category:Drugs]] | ||
Latest revision as of 15:24, 27 September 2011
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
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.
Members
Fibrates prescribed commonly are:
- Bezafibrate (e.g. Bezalip®, available in Europe not approved in USA)
- Ciprofibrate (e.g. Modalim®, available in Europe not approved in USA)
- Clofibrate (largely obsolete due to side-effect profile, e.g. gallstones)
- Gemfibrozil (e.g. Lopid®, available in USA)
- Fenofibrate (e.g. TriCor®, available in USA)
Fenofibric acid (Trilipix) is FDA approved for combination use with statin, in patients with mixed dyslipidemia.
Indications
Fibrates are used as accessory therapy in many forms of hypercholesterolemia, usually in combination with statins. Trials do support its use as monotherapy.
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).
Doses
Different doses of fenofibrate are available in the markets. The standard adult dose is usually >100 mg/day. However, dose lowering is required for patients with renal insufficiency (creatinine clearance < 80). Clinical trials are required to prove the relative efficacy of the different doses of fibrates.
Side effects
- Mild stomach upset
- 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.
- Clofibrate are no longer used because they were found to increase morbidity and mortality rates. Also, increased rates of malignancy in rodents have been found.
- Fibrates are excreted via kidney. It can cause reversible increases in serum creatinine levels. Thus, reduction in doses are indicated in cases with increased serum creatinine levels. Gemfibrozil's excretion is independent of renal function, and can be used in patients with chronic kidney disease.
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 pharmacologically related to the thiazolidinediones, a novel class of anti-diabetic drugs that also act on PPARs (more specifically PPARγ)