Fibrates

from Wikipedia, the free encyclopedia

Fibrates ( fibric acids and their derivatives) are a group of carboxylic acids that are used as drugs to treat high blood lipid levels . The intake of fibrates is indicated in hypercholesterolemia and hypertriglyceridemia .

Mechanism of action

Fibrates increase the activity of fatty acid degradation in peroxisomes by binding to the intracellular PPAR α . Similar to the mechanism of glucocorticoid receptors , the binding of the fibrates to PPAR α leads to the dimerization of the receptor and subsequent binding to the DNA . Among other things, this leads to an increased breakdown of LDL cholesterol . In addition, the VLDL synthesis is reduced. The result is a decrease in LDL cholesterol by 10–20% and an increase in “good” HDL cholesterol by 5–10%. The triglycerides decrease by 20–40%.

Fibrates lead via a PPAR α -mediated downregulation of cholesterol-7α-hydroxylase and sterol-27-hydroxylase to increased secretion of cholesterol in the bile and thus to an increased risk of cholesterol-containing gallstones.

The use of fibrates is controversial because - in contrast to statins - they have not provided evidence of a prolongation of life. In the treatment of CHD , they are the second choice lipid- lowering agents, especially when statins are not tolerated or hypertriglyceridemia dominates.

Interactions and side effects

When taking other drugs at the same time, there may be interactions. So there may be increased anticoagulation while taking oral anticoagulants as well as to increased blood sugar while taking oral hypoglycemic agents and insulin come. There is also an increased risk of myopathies when taking statins and nicotinic acid derivatives at the same time .

As a side effect, there is often a tendency to form gallstones . Symptoms of the gastrointestinal tract are also observed.

Dismantling

The fibrates are metabolized to clofibric acid in the body . This accumulates in the groundwater due to its high microbial persistence and low sorption capacity.

Representative

literature

  • Pharmacology and Toxicology 2006, Karow / Lang-Roth
  • Medicinal chemistry 2005, Steinhilber / Schubert-Zsilavecz / Roth

Individual evidence

  1. Post SM, Duez H, Gervois PP et al. Fibrates suppress bile acid synthesis via peroxisome proliferator-activated receptor-alpha-mediated downregulation of cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase expression. Arterioscler Thromb Vasc Biol. 2001; 21 (11): 1840-5.
  2. Drugs Commission of the German Medical Association: guidelines for lipid metabolism disorders , May 2012, accessed on January 31, 2014.
  3. Fenofibrate for dyslipidaemia ( Memento of the original from March 4, 2016 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. , Rational Assessment of Drugs and Research, National Medicines Policy, Australia February 2006, accessed January 31, 2014.  @1@ 2Template: Webachiv / IABot / www.nps.org.au
  4. Traugott Scheytt, Susanne Grams, Holger Fell: Occurrence and behavior of a drug (clofibric acid) in groundwater . In: groundwater . tape 3 , no. 2 , June 1, 1998, pp. 67-77 , doi : 10.1007 / s767-1998-8568-1 ( PDF ).