Triglycerides fibric acid derivatives

While the fibric acid derivatives have antihyperlipidemic effects, their use varies depending on the drug. For example, Clofibrate (Atromid-S) and gemfibrozil (Lopid) are used to treat individuals with very high serum triglyceride levels who present a risk of abdominal pain and pancreatitis and who do not experience a response to diet modifications. Clofibrate is not used for the treatment of other types of hyperlipidemia and is not thought to be effective for prevention of coronary heart disease. Fenofibrate (Tricor) is used as adjunctive treatment for the reduction of LDL, total cholesterol, and triglycerides in patients with hyperlipidemia. 

Fibric acid derivatives (aryloxyisobutyric acids) include the prototypic drug gemfibrozil. These types of drugs are used mainly to lower triglycerides and to increase HDL. A large placebo-controlled primary prevention trial in hypercholesterolemic men showed that patients treated with gemfibrozil had a statistically lower number of myocardial infarctions, but not of deaths from all causes. 

Although bilberry s effect on triglycerides is similar to that of the fibric acid derivatives (e.g., gemfibrozil, fenofibrate) used therapeutically to treat hypertriglyceridemia, bilberry did not affect thrombus size or composition, suggesting that it does not possess antithrombotic activity, as has been demonstrated with some fibric acid derivatives (1). 

Triglycerides <150 mg/dL Lifestyle glycemic control fibric acid derivatives high-dose statins (in those with high LDL)... 

Bile acid-binding resins may be used to lower cholesterol in transplant patients, but adequate doses are difficult to achieve without the development of GI adverse effects. Because the absorption of CSA is dependent on the presence of bile in the GI tract, patients should be instructed to separate dosing of bile acid-binding resins and CSA by at least 2 hours. Bile acid-binding resins also should be separated from other immunosuppressants by at least 2 hours to avoid physical adsorption in the GI tract. For transplant patients who have hypertriglyceridemia refractory to dietary intervention, fish oil and fibric acid derivatives are well-tolerated, effective alternatives (see Chap. 21). Fibric acid derivatives are most effective in lowering serum triglyceride concentrations. 

Gemfibrozil is a fibric-acid derivative that decreases blood levels of triglycerides and VLDL by decreasing their production. It also decreases cholesterol and increases HDL. 

The fibric acid derivatives (e.g., gemfibrozil and clofibrate) are most effective in lowering triglyceride levels. 

A. Mechanism and Effects Fibric acid derivatives (eg, gemfibrozil, fenofibrate, clofibrate) are ligands for the peroxisome proliferator-activated receptor-alpha (PPAR-a) protein, a receptor that regulates transcription of genes involved in lipid metabolism. Tbis interaction with PPAR-a results in increased activity of lipoprotein lipase and enhanced clearance of triglyceride-rich lipoproteins (Figure 35-2). Cholesterol biosynthesis in the liver is seeondarily reduced. The fibrates reduce serum triglyceride concentrations (Table 35-3). There may be a small reduction in LDL cholesterol and a small increase in HDL levels. 

Fenofibrate (propan-2-yl 2-[4-(4-chlorobenzoyl)phenoxy]-2-methylpropanoate), a fibric acid derivative (Fig. 7.6), mainly exerts its effect via the activation of speciflc nuclear receptor called peroxisome proliferator-activated receptor alpha (PPARa). This PPARa agonist is primarily used to decrease the cholesterol levels in cardiovascular diseases patients. Like statins, fenofibrate also reduces triglycerides and low- and very low density protein levels. It also increases high-density lipoprotein levels in the body. Fenofibrate also has nonlipid (i.e., pleiotropic) effects (reduction in fibrinogen, C-reactive protein, and uric acid levels and improvement in the flow-mediated dilatation). 

Fibric acid derivatives have been used in a variety of clinical trials in an effort to demonstrate their efficacy in reducing both cardiovascular morbidity and mortality and the progression of atherosclerotic disease. These trials also demonstrate the importance of increasing serum HDL and reducing triglycerides when attempting to decrease risk for acute... 

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