Lipids disorder

Niacin (vitamin B3) has broad applications in the treatment of lipid disorders when used at higher doses than those used as a nutritional supplement. Niacin inhibits fatty acid release from adipose tissue and inhibits fatty acid and triglyceride production in liver cells. This results in an increased intracellular degradation of apolipoprotein B, and in turn, a reduction in the number of VLDL particles secreted (Fig. 9-4). The lower VLDL levels and the lower triglyceride content in these particles leads to an overall reduction in LDL cholesterol as well as a decrease in the number of small, dense LDL particles. Niacin also reduces the uptake of HDL-apolipoprotein A1 particles and increases uptake of cholesterol esters by the liver, thus improving the efficiency of reverse cholesterol transport between HDL particles and vascular tissue (Fig. 9-4). Niacin is indicated for patients with elevated triglycerides, low HDL cholesterol, and elevated LDL cholesterol.3... 

Niacin should be instituted at the lowest dose and gradually titrated to a maximum dose of 2 grams daily for ER and SR products and no more than 5 grams daily for IR products. FDA-approved niacin products are preferred because of product consistency. Moreover, niacin products labeled as no flush don t contain nicotinic acid and therefore have no therapeutic role in the treatment of lipid disorders.28 The time until maximum effect on lipids for niacins is generally 3 to 5 weeks. 

A complete history and physical examination should assess (1) presence or absence of cardiovascular risk factors or definite cardiovascular disease in the individual (2) family history of premature cardiovascular disease or lipid disorders (3) presence or absence of secondary causes of hyperlipidemia, including concurrent medications and (4) presence or absence of xanthomas, abdominal pain, or history of pancreatitis, renal or liver disease, peripheral vascular disease, abdominal aortic aneurysm, or cerebral vascular disease (carotid bruits, stroke, or transient ischemic attack). 

Many patients treated for primary hyperlipidemia have no symptoms or clinical manifestations of a genetic lipid disorder (e.g., xanthomas), so monitoring is solely laboratory based. 

A detailed family history should be obtained that includes information about premature CHD, hypertension, familial lipid disorders, and diabetes mellitus. 

The clinical effects of chloroform toxicity on the central nervous system are well documented. However, the molecular mechanism of action is not well understood. It has been postulated that anesthetics induce their action at a cell-membrane level due to lipid solubility. The lipid-disordering effect of chloroform and other anesthetics on membrane lipids was increased by gangliosides (Harris and Groh 1985), which may explain why the outer leaflet of the lipid bilayer of neuronal membranes, which has a large ganglioside content, is unusually sensitive to anesthetic agents. Anesthetics may affect calcium-dependent potassium conductance in the central nervous system (Caldwell and Harris 1985). The blockage of potassium conductance by chloroform and other anesthetics resulted in depolarization of squid axon (Haydon et al. 1988). 

Monitoring Pretreatment and annual exams should include blood pressure, breasts, abdomen and pelvic organs, including Papanicolaou smear. Perform preventative measures and screening, which should include total and HDL cholesterol within 5-year intervals. Advise the pathologist of OC therapy when relevant specimens are submitted. Do not prescribe for more than 1 year without another physical exam. Lipid disorders Closely follow women taking OCs who are being treated for hyperlipidemias. 

Lipid disorders Treatment with ritonavir alone or in combination with saquinavir has resulted in substantial increases in the concentration of total triglycerides and cholesterol. 

Perform triglyceride and cholesterol testing prior to initiating tipranavir/ritonavir therapy and at periodic intervals during therapy. Manage lipid disorders as clinically appropriate. 

A 38-year-old man with a family history of cardiovascular and cerebrovascular disease makes an appointment for a routine physical examination with a physician he has not seen before. He explains that his father died young of a heart attack and that two paternal uncles have suffered strokes in their late 40s. Physical examination reveals yellowish lumps on his eyelids (xanthelasmas, which are often associated with a lipid disorder) and a resting blood pressure of 186/95 mm Hg. There is some excess visceral fat, and his body mass index calculates to 26.5. Total serum cholesterol (476 mg/dL) and triglycerides (288 mg/dL) are elevated and subsequent angiography reveals atherosclerotic restrictions of at least two coronary arteries. 

Contemporary management of lipid disorders The evolving importance of statin therapy. Clin Courier 1998 28(No.35) l-7. 

Protease inhibitors may increase the risk of bleeding in hemophiliacs. These drugs should be used with caution in patients with diabetes, lipid disorders, and hepatic disease. Dosage adjustment may be necessary. 

Mixed hyperlipidemia is one of the most common lipid disorders, but only a minor fraction of the affected patients has a monogenic inherited disease. Most patients with mixed hyperlipidemia have a familial combined hyperlipidemia, a multifactorial disease for which the causative factors are not known. Patients have elevated remnant lipoproteins with elevated triglycerides > 3.0 mmol/1 and total cholesterol > 5.0 mmol/1. Two rare monogenic disorders lead to such a lipoprotein pattern,... 

Knopp, R.H. (1999) Drug therapy drug treatment of lipid disorders. New Engl J. Med. 341, 498-511. 

Golio. A.M, and HJ, Puwnull Mammi of Lipid Disorders Rednuni> the Risk for Coronan Heart />iw[Pg.932]

Most clinical work with raloxifene 60 mg/day for the treatment of osteoporosis and lipid disorders in the menopause has been performed in Western populations. A multinational multicenter study in 483 Asian women (and a similar placebo control group) treated for 1 year has now confirmed that the efficacy and the adverse effects of the treatment are very similar to those in western populations (32). 

Aldesleukin can cause lipid disorders. Recurrent and marked hypocholesterolemia with reduced high- and low-density lipoproteins, and slight increases in plasma triglycerides have been observed after high-dose aldesleukin... 

In contrast to its effects on glucose metabolism, tacrolimus offers potential advantages over ciclosporin for lipid disorders (1101). Compared with ciclosporin-based immunosuppressive regimens, total cholesterol and LDL cholesterol serum concentrations were lower in patients taking tacrolimus for 1 year (1102). Both findings were considered to result from a significant glucocorticoidsparing effect of tacrolimus. 

Although it is not exactly clear how much these agents can reduce the risk of a major cardiac event (e.g., infarction, stroke), these drugs will probably remain the first choice for people with certain hyper-lipidemias (e.g., increased triglycerides). These drugs are likewise advocated for mixed hyperlipidemias that are common in metabolic disorders such as type 2 diabetes mellitus (see Chapter 32).32,141 Certain fibrates can be used with other drugs, such as statins, to provide more comprehensive pharmacologic control of certain lipid disorders.30,147... 

Adverse Effects. Sirolimus may cause blood lipid disorders, including hypercholesterolemia and hypertriglyceridemia.42 Other side effects include blood disorders (anemia, leukopenia, thrombocytopenia),... 

The patient should be asked about existing personal risk factors for coronary heart disease (CHD) including smoking, hypertension, and diabetes meUitus. A detailed family history should be obtained that includes information about premature CHD, hypertension, familial lipid disorders, and diabetes meUitus. 

Brown WV (1995) Niacin for lipid disorders. Indications, effectiveness, and safety. Postgraduate Medicine 98, 185-89, and 192-3. 

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