Hyperlipidemia and

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. 

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. 

Alcoholism leads to fat accumulation in the liver, hyperlipidemia, and ultimately cirrhosis. The exact mechanism of action of ethanol in the long term is stiU uncertain. Ethanol consumption over a long period leads to the accumulation of fatty acids in the liver that are derived from endogenous synthesis rather than from increased mobilization from adipose tissue. There is no impairment of hepatic synthesis of protein after ethanol ingestion. Oxidation of ethanol by alcohol dehydrogenase leads to excess production of NADH. 

RUKMINI c, REDDY SASTRY c, MCPEAKP, LYNCH I (2000) Method for treating hypercholesterolemia, hyperlipidemia, and atherosclerosis. US Patent 6,126,943. 

TOMEO A c, GELLER M (1995) Antioxidant effect of tocotrienols in patients with hyperlipidemia and carotid stenosis. Lipids, 30 1179-83. 

Father died at age 45 from coronary disease, mother alive at age 62 with type 2 diabetes mellitus, hypertension, hyperlipidemia, and gastroesophageal reflux disease... 

Patients are at risk for the cardiovascular complications of hypertension, hyperlipidemia, and hyperglycemia. 

EF is a 45-year-old woman who presents to the dermatologist for evaluation of facial acne. She has a history of a 25 lb (11.36 kg) weight gain, irregular menses, and frequent vaginal yeast infections over the past 2 years. She complains of increased facial hair growth and lower extremity muscle weakness. Physical examination reveals facial acne, facial hirsutism, truncal obesity, thin skin, and purple abdominal striae. Her past medical history is significant for hypertension, type 2 diabetes mellitus, hyperlipidemia, and rheumatoid arthritis. 

Sirolimus, a target of rapamycin inhibitor, works by decreasing the ability of T cells to respond to IL-2. The major adverse events associated with sirolimus are decreased wound healing, hyperlipidemia, and myelosuppression. This agent appears to have promising effects because it may allow calcineurin inhibitor withdrawal in some patients. 

Hyperlipidemia is seen in up to 60% of heart, lung, and renal transplant patients and greater than 30% of liver transplant patients.64 66 As a result of elevated cholesterol levels, transplant recipients are not only at an increased risk of atherosclerotic events, but emerging evidence also shows an association between hyperlipidemia and allograft vasculopathy.66 Hyperlipidemia, along with other types of cardiovascular disease, is now one of the primary causes of morbidity and mortality in long-term transplant survivors.67... 

Massy ZA. Hyperlipidemia and cardiovascular disease after organ transplantation. Transplantation 2001 72(6 suppl) S13-15. 

Describe the etiology and risk factors for substrate intolerance, including hyperglycemia, hypoglycemia, hyperlipidemia, and azotemia, in patients receiving PN. 

Nevertheless, some atypical antipsychotic drugs, such as clozapine and olanzapine, have been linked to substantial weight gain, hyperlipidemia and type II diabetes, a new range of medically serious side-effects. 

Side effects of thiazides include hypokalemia, hypomagnesemia, hypercalcemia, hyperuricemia, hyperglycemia, hyperlipidemia, and sexual dysfunction. Loop diuretics have less effect on serum lipids and glucose, but hypocalcemia may occur. 

B Chronic hyperlipidemia and chronic infection potentiate inflammation and lipid oxidation. An increase of lipid oxidation might inhibit tbe immune system and thus facilitate a chronic infection and a rise in oxLDL-mediated apoptosis. 

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). 

In 1995 the FDA approved saquinavir, the first protease inhibitor, for use in combination with other nucleoside analogue medications. In 1999 a soft gel capsule formulation of saquinavir with considerably improved absorption characteristics was developed. Ritonavir and indinavir have been approved for use alone or in combination with nucleoside analogue medications in people with advanced HIV disease. Nelfinavir is the first protease inhibitor labeled for use in children. Amprenavir is the newest of the protease inhibitors. Amprenavir can be taken with or without food, but it should not be taken with a high-fat meal because the fat content may decrease the absorption of the drug. The most disturbing adverse reactions to protease inhibitors consist of the lipodystrophy syndrome with severe hyperlipidemia and unpredictable fat redistributions over the body... 

The low incidence of ischemic heart disease in the black population of Africa may mitigate the seriousness of the consequence of the metabolic effects of thiazide diuretics, for example hyperlipidemia and hypo-kalemia. 

Atherosclerosis is a progressive vascular fibroproliferative-inflammatory disease. It is triggered, maintained, and driven by risk factors such as hypercholesterolemia, hyperlipidemia, and hypertonus [28]. The characteristic clinical manifestation of atherosclerosis is the atherosclerotic lesion, developing in the vessel wall (atherosclerotic plaque). 

Type VI/Hers hepatomegaly, mild hypoglycemia, hyperlipidemia, and ketosis symptoms improve with age Type IX/phosphorylase kinase deficiency similar to type VI presentation (X-linked)... 

The major steps in the management of patients with chronic heart failure are outlined in Table 13-3. The ACC/AHA 2005 guidelines suggest that treatment of patients at high risk (stages A and B) should be focused on control of hypertension, hyperlipidemia, and diabetes, if present. Once symptoms and signs of failure are present, stage C has been entered, and active treatment of failure must be initiated. 

Alcohol indirectly affects hematopoiesis through metabolic and nutritional effects and may also directly inhibit the proliferation of all cellular elements in bone marrow. The most common hematologic disorder seen in chronic drinkers is mild anemia resulting from alcohol-related folic acid deficiency. Iron deficiency anemia may result from gastrointestinal bleeding. Alcohol has also been implicated as a cause of several hemolytic syndromes, some of which are associated with hyperlipidemia and severe liver disease. 

In combination with a resin or reductase inhibitor, niacin normalizes LDL in most patients with heterozygous familial hypercholesterolemia and other forms of hypercholesterolemia. These combinations are also indicated in some cases of nephrosis. In severe mixed lipemia that is incompletely responsive to diet, niacin often produces marked reduction of triglycerides, an effect enhanced by marine omega-3 fatty acids. It is useful in patients with combined hyperlipidemia and in those with dysbetalipoproteinemia. It is clearly the most effective agent for increasing HDL and the only agent that may reduce Lp(a). 

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