Hyperlipidemias treatment

As described in the previous section, bile acids have evolved over the last years from regulators of bile acid homeostasis to general metabolic integrators. It is therefore not too surprizing that a number of bile acid-activated signaling pathways have become attractive targets for the treatment of gallstones and other metabolic diseases, such as obesity, type 2 diabetes, hyperlipidemia, and atherosclerosis. 

Nicotinic acid is used in the treatment of hyperlipidemia. It causes various changes in lipid and lipoprotein metabolism when administered in high doses (up to 5 g/d) ... 

In general, the higher the LDL level and the more risk factors involved, the greater the risk for heart disease. The main goal of treatment in patients with hyperlipidemia is to lower the LDL to a level that will reduce the risk of heart disease ... 

These drugs, alongwith a diet restricted in saturated fat and cholesterol, are used to treat hyperlipidemia when diet and other nonpharmacologic treatments alone have not resulted in lowered cholesterol levels. 

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. 

Because hyperlipidemia is often treated on an outpatient basis, die nurse explains die drug regimen and possible adverse reactions. If printed dietary guidelines are given to die patient, die nurse emphasizes the importance of following these recommendations. Drug dierapy usually is discontinued if the antihyperlipidemic drug is not effective after 3 months of treatment. 

Hyperlipidemia plays a role in the development of cardiovascular disease (CVD) in patients with CKD. The primary goal of treatment of dyslipidemras is to decrease the risk of atherosclerotic cardiovascular disease. A secondary goal in patients with CKD is to reduce proteinuria and decline in kidney function. Treatment of hyperlipidemia in patients with CKD has been demonstrated to slow the decline in GFRby 1.9 mL/minute per year of treatment with antihyper Epidemic agents.21... 

Koh KK, Quon MJ, Han SH, et al. Additive beneficial effects of fenofibrate combined with atorvastatin in the treatment of combined hyperlipidemia. J Am Coll Cardiol 2005 45(10) 1649-1653. 

The principal use of niacin is for mixed hyperlipidemia or as a second-line agent in combination therapy for hypercholesterolemia. It is a first-line agent or alternative for the treatment of hypertriglyceridemia and diabetic dyslipidemia. 

Nicotinamide should not be used in the treatment of hyperlipidemia because it does not effectively lower cholesterol or triglyceride levels. 

Short-term evaluation of therapy for hyperlipidemia is based on response to diet and drug treatment as measured in the clinical laboratory by total cholesterol, LDL-C, HDL cholesterol, and triglycerides. 

Unlike the previously discussed compounds, which inhibit MTP in both liver and intestine, an intestine-selective orally-active MTP inhibitor JTT-130 (structure not yet disclosed) has been reported to decrease plasma cholesterol and TG in guinea pigs with no hepatic lipid accumulation [16]. Although further studies in human are needed, inhibitors that selectively target intestinal MTP might be a safer alternative as a treatment for hyperlipidemia than the liver-targeting MTP inhibitors. 

The increased degradation of fat that occurs in insulin deficiency also has serious effects. Some of the fatty acids that accumulate in large quantities are taken up by the liver and used for lipoprotein synthesis (hyperlipidemia), and the rest are broken down into acetyl CoA. As the tricarboxylic acid cycle is not capable of taking up such large quantities of acetyl CoA, the excess is used to form ketone bodies (acetoacetate and p-hydroxy-butyrate see p. 312). As H"" ions are released in this process, diabetics not receiving adequate treatment can suffer severe metabolic acidosis (diabetic coma). The acetone that is also formed gives these patients breath a characteristic odor. In addition, large amounts of ketone body anions appear in the urine (ketonuria). 

Treatment of hyperlipidemia is based on the assumption that lowering serum lipids decreases morbidity and mortality of atherosclerotic cardiovascular disease. 

The cornerstone of treatment in primary hyperlipidemia is diet restriction and weight reduction. Limit or eliminate alcohol intake. Use drug therapy in conjunction with diet, and after maximal efforts to control serum lipids by diet alone prove unsatisfactory, when tolerance to or compliance with diet is poor or when hyperlipidemia is severe and risk of complications is high. Treat contributory diseases such as hypothyroidism or diabetes mellitus. 

Hypertriglyceridemia A6 unct /e therapy to diet for treatment of adult patients with hypertriglyceridemia (Fredrickson types IV and V hyperlipidemia). 

Older patients have predominantly Type 2 diabetes mellitus, which shares with Type 1 the risk for retinopathy, nephropathy and neuropathy, but carries a greater risk for macrovascular complications such as coronary artery disease, stroke and peripheral vascular disease. Many such patients have associated obesity, hypertension and hyperlipidemia, compounding the risk of cardiovascular disease. The goals of treatment of DM in the elderly are to decrease symptoms related to hyperglycaemia and to prevent long-term complications. Treatment of type 2 DM can improve prognosis. In the UKPDS trial, sulphonylureas, insulin, and metformin were all associated with a reduction in diabetes-related... 

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