Fibrates

The hypotriglyceridemic action of fibrates involves combined effects on LPL and apolipoproteinCIII (apoCIII). LPL is up-regulated [11], whereas apoCIII, an inhibitor of LPL, is down-regulated [12], leading to enhanced hydrolysis of triglyceride- 

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Asphalt aluminum roof coating (nonfibrated). Asphalt aluminum roof coating (fibrated)... 

Type II, fibrated lap cement (asbestos) Type III, fibrated lap cement (nonasbestos) Type I, nonfibrated... 

PPARa NR1C1 Fatty acids, leukotriene B4, fibrates... 

Insight from the PPARa Knockout Mouse. PPARa-deficient adult mice are viable, fertile, and healthy, indicating that PPARa is not essential for embryonic development. When adult PPARa-7- mice are treated with fibrates, the characteristic response to PP is abolished, with no liver weight increase, no increase in... 

PPARa Liver, heart, skeletal muscle, atherosclerotic lesions TG- and LDL-C-lowering and HDL-C-raising re-directs excess cholesterol from the peripheral tissues to the liver for excretion into the bile via HDL-C slowed progression of atherosclerosis Fatty acids, eico-sanoids (fatty acids derived from FAS ) Fibrates fenofibrate (Tricor ), genfibrozil (Lopid ) Dyslipidemia... 

Consider niacin or a fibrate for additional pharmacotherapy if high density lipoprotein (HDL) is <40 mg/dL... 

A fibrate derivative or niacin should be considered in select patients with a low high-density lipoprotein (HDL) cholesterol less than 40 mg/dL (1.04 mmol/L) and/or a high triglyceride level greater than 200 mg/dL (2.26 mmol/L). In a large randomized trial in men with established CAD and low levels of HDL cholesterol, the use of gemfibrozil (600 mg twice daily) significantly decreased the risk of non-fatal myocardial infarction or death from coronary causes.78... 

Combination drug therapy is an effective means to achieve greater reductions in LDL cholesterol (statin + ezetimibe or bile acid resin, bile acid resin + ezetimibe, or three-drug combinations) as well as raising HDL cholesterol and lowering serum triglycerides (statin + niacin or fibrate). 

Specific concomitant medications or consumptions (check specific statin package insert for warnings) fibrates (especially gemfibrozil, but other fibrates too), nicotinic acid (rarely), cyclosporine, azole antifungals such as itraconazole and ketoconazole, macrolide antibiotics such as erythromycin and clarithromycin, protease inhibitors used to treat Acquired Immune Deficiency Syndrome, nefazodone (antidepressant), verapamil, amiodarone, large quantities of grapefruit juice (usually more than 1 quart per day), and alcohol abuse (independently predisposes to myopathy)... 

The predominant effects of fibrates are a decrease in triglyceride levels by 20% to 50% and an increase in HDL cholesterol levels by 9% to 30% (Table 9-8). The effect on LDL cholesterol is less predictable. In patients with high triglycerides, however, LDL cholesterol may increase. Fibrates increase the size and reduce the density of LDL particles much like niacin. 

Fibrates are the most effective triglyceride-lowering drugs and are used primarily in patients with elevated triglycerides and low HDL cholesterol. 

Fibrates work by reducing apolipoproteins B, C-III (an inhibitor of LPL), and E, and increasing apolipoproteins A-I and A-II through activation of peroxisome proliferator-activated receptors-alpha (PPAR-a), a nuclear receptor involved in cellular function. The changes in these apolipoproteins result in a reduction in triglyceride-rich lipoproteins (VLDL and IDL) and an increase in HDL. 

Omega-3 fatty acids (eicosapentaenoic acid and docosa-hexaenoic acid), the predominant fatty acids in the oil of cold-water fish, lower triglycerides by as much as 35% when taken in large amounts. Fish oil supplements may be useful for patients with high triglycerides despite diet, alcohol restriction, and fibrate therapy. This effect may be modulated thru PPAR-a and a reduction in apolipoprotein B-100 secretion. Omega-3 fatty acids reduce platelet aggregation and have... 

Fibrates are the most effective triglyceride-lowering agents and also raise HDL cholesterol levels. Combination therapy with a fibrate, particularly gemfibrozil, and a statin has been found to increase the risk for myopathy. Of the 31 rhabdomyolysis deaths reported with cerivastatin use, 12 involved concomitant gemfibrozil.25 Therefore, more frequent monitoring, thorough patient education, and consideration of factors that increase the risk as reviewed previously should be considered. 

Niacin can be combined with a fibrate in patients with high elevations in serum triglycerides. The combination may increase the risk of myopathy compared to either agent alone. 

Once the LDL cholesterol goal is achieved, assess non-HDL cholesterol in those with metabolic syndrome and intensify LDL-lowering therapy further or consider adding niacin or fibrate. 

From the preceding sections, it is clear that chemokines are important players in atherosclerotic disease and, as such, are being considered as possible targets in the treatment of this prevalent inflammatory condition. Under consideration at this time are both traditional nonspecific therapies [e.g., 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, fibrates, etc.], as well as chemokine specific approaches (142). 

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