Fibrate

Source: Wikipedia, the free encyclopedia.
Fibrates
PPAR
Clinical data
WebMDMedicineNet 
External links
MeSHD058607
Legal status
In Wikidata

In

hypolipidemic agents
.

Medical uses

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. Fibrates may be compared to statin drugs, which reduce LDL-cholesterol (LDL-C) and have only limited effects on other lipid parameters. Clinical trials have shown that the combination of statins and fibrates results in a significantly greater reduction in LDL-C and triglyceride levels and greater increases in high-density lipoprotein cholesterol (HDL-C) compared with monotherapy with either drug.[1] Fibrates are used in accessory therapy in many forms of hypercholesterolemia, but the combination of some fibrates (e.g., gemfibrozil) with statins is contraindicated due to an increased risk of rhabdomyolysis.[2]

Fibrates stimulate peroxisome proliferator activated receptor (PPAR) alpha, which controls the expression of gene products that mediate the metabolism of

triglycerides (TG) and high-density lipoprotein
(HDL). As a result, synthesis of fatty acids, TG and VLDL is reduced, whilst that of lipoprotein lipase, which catabolises TG, is enhanced. In addition, production of Apo A1 and ATP binding cassette A1 is up-regulated, leading to increased reverse cholesterol transport via HDL. Consequently, fibrates reduce TG by up to 50% and increase HDL-C by up to 20%, but LDL-C changes are variable. Fewer large-scale trials have been conducted with fibrates than with statins and the results are less conclusive, but reduced rates of cardiovascular disease have been reported with fibrate therapy in the subgroup of patients with low HDL-C levels and elevated TG (e.g. TG > 2.3 mmol/L (200 mg/dL)). Fibrates are usually well tolerated but share a similar side-effect profile to statins. In addition, they may increase the risk of cholelithiasis and prolong the action of anticoagulants. Accumulating evidence suggests that they may also have a protective effect against diabetic microvascular complications.

Clinical trials do support their use as monotherapy agents. Fibrates reduce the number of non-fatal heart attacks, but do not improve all-cause mortality and are therefore indicated only in those not tolerant to statins.[3][4][5]

Although less effective in lowering

hyperlipidemias. Due to a rare paradoxical decrease in HDL-C seen in some patients on fenofibrate, as per US FDA label change, it is recommended that the HDL-C levels be checked within the first few months after initiation of fibrate therapy. If a severely depressed HDL-C level is detected, fibrate therapy should be withdrawn, and the HDL-C level monitored until it has returned to baseline.[citation needed
]

Side effects

Most fibrates can cause mild stomach upset and

sterol 27-hydroxylase expression, therefore making it easier for cholesterol to precipitate and increasing the risk for gallstones
.

In combination with

lipophilic statins
are less prone to cause this reaction, and are probably safer to be combined with fibrates than the more lipophilic statins are.

Drug toxicity includes acute kidney injury.[7]

Pharmacology

PPAR

Although used clinically since at least 1962, the mechanism of action of fibrates remained unelucidated until the 1990s, when it was discovered that fibrates activate

receptors that modulate carbohydrate and fat metabolism and adipose tissue differentiation
.

Activating PPARs induces the transcription of a number of genes that facilitate lipid metabolism.

Fibrates are pharmacologically related to the

PPARγ)[citation needed
]

Fibrates are a substrate of (metabolized by) CYP3A4.[8]

Fibrates have been shown to extend lifespan in the roundworm C. elegans.[9]

Members

See also

References

  1. PMID 15695129
    .
  2. S2CID 31624928
    .
  3. PMID 19698935
    .
  4. S2CID 15570639
    .
  5. PMID 27849333
    .
  6. PMID 15124979
    .
  7. S2CID 207536477
    .
  8. ^ a b Lee, T.K. "Fibrates in Perspective: Answering an Age-Old Question" (PDF). Perspectives in Cardiology. 20 (6): 34–39.
  9. PMID 23603800
    .
Retrieved from "https://en.wikipedia.org/w/index.php?title=Fibrate&oldid=1172701479"