Plasma niacin

Correct answer = D. Clofibrate and gemfibrozil Increase the activity of lipoprotein lipase, thereby increasing the removal of VLDL from plasma. Niacin inhibits lipolysis in adipose tissue and thus eliminates the building blocks needed by the liver to produce triacylglycerol and there-... 

Niacin reduces plasma LDL cholesterol, lipoprotein (a), triglycerides and raises HDL cholesterol in all types of hyperlipoproteinemia [26]. Although available on the market for more than 40 years, the mechanisms of action of niacin are poorly understood. Putative mechanisms are the activation of adipose tissue LPL, diminished HTGL activity, a reduced hepatic production and release of VLDL, and composi-... 

Gemfibrozil reduces the synthesis of VLDL and, to a lesser extent, apolipoprotein B with a concurrent increase in the rate of removal of triglyceride-rich lipoproteins from plasma. Clofibrate is less effective than gemfibrozil or niacin in reducing VLDL production. 

Pharmacokinetics Niacin is rapidly absorbed from the Gl tract peak serum concentrations usually occur within 45 minutes. The plasma elimination half-life is approximately 45 minutes. Approximately one third of an oral dose is excreted unchanged in the urine. 

Plasma levels of cholesterol in hyperlipidemic patients during treatment with niacin. 

Therapeutic uses Niacin lowers plasma levels of both cholesterol and triacylglycerol. Therefore, it is particularly useful in the treatment of Type lib and IV hyperlipoproteinemia, in which both VLDL and LDL are elevated. Niacin is also used to treat other severe hypercholesterolemias, often in combination with other antihyperlipidemic agents (see p. 215). In addition, it is the most potent antihyperlipidemic agent for raising plasma HDL levels. 

Pharmacokinetics Niacin is administered orally. It is converted in the body to nicotinamide, which is incorporated into the cofactor nicotinamide adenine dinucleotide (NAD+). Niacin, its nicotinamide derivative and other metabolites are excreted in the urine. [Note Nicotinamide alone does not decrease plasma lipid levels.]... 

Therapeutic uses The bile acid binding resins are the drugs of choice (often in combination with diet or niacin) in treating Type lla and lib hyperlipidemias. [Note In those rare individuals who are homozygous for Type lla, that is, for whom functional LDL receptors are totally lacking, these drugs have little effect on plasma LDL levels.] Cholestyramine can also relieve pruritus caused by accumulation of bile acids in patients with biliary obstruction. 

Fu CS, Swendseid ME, Jacob RA, and McKee RW (1989) Biochemical markers for assessment of niacin nutritional status in young men levels of erythrocyte niacin coenzymes and plasma tryptophan./owraa/o/JVMtrifton 119,1945-9. 

Garg R, MalinowM, Pettinger M, Upson B, and Hunninghake D (1999) Niacin treatment increases plasma homocyst(e)ine levels. American Heart Journal 138, 1082-7. 

Niacin is readily absorbed from the gastrointestinal tract. The peak serum concentration for an immediate release oral dosage form is usually seen within 45 min of niacin ingestion 4-5 h for an extended release tablet. Niacin is hepatically metabolized and widely distributed into body tissues. Niacin is renally excreted. Excess amounts of niacin, beyond daily needs, are excreted largely unchanged in the urine. The plasma half-life is 45 min. 

At present, no blood markers are commonly used as indicators of niacin status. Most assessments of niacin nutriture have been based on measurement of the 2 urinary metabolites, N -methylnicotinamide and N -methyl-2-pyridone-5-carboxamide. Normally, adults excrete 20% to 30% of their niacin in the form of methylnicotinamide and 40% to 60% as the pyridone. An excretion ratio of pyridone to methylnicotinamide of 1.3 to 4.0 is thus normal, but latent niacin deficiency is indicated by a value below 1.0. As depletion occurs, the pyridone is absent for weeks before clinical signs are noted, and the methylnicotinamide excretion falls to a minimum at about the time that clinical signs are evident.f HPLC methods are currently the methods of choice, though some capillary electrophoresis methods have been developed. However, the measurement of 2-pyridone and N -methylnicotinamide concentrations in plasma may provide a more reliable metabolite ratio than urine measurements. A newer approach that may prove valuable is the ratio of NAD/NADP in erythrocytes and plasma tryptophan. A ratio of NAD/NADP below 1.0 would be indicative of a risk of developing niacin deficiency. ... 

JV -Methyl-2-pyridone-5-carboxamide plasma levels provide an indication of low niacin intake by dropping below detection limits. 

Because total cholesterol is comprised of cholesterol derived from LDL, VLDL, and HDL, determination of HDL is useful when total plasma cholesterol is elevated. HDL may be elevated by moderate alcohol ingestion (less than two drinks per day), physical exercise, smoking cessation, weight loss, oral contraceptives, phenytoin, and terbutaline. Smoking, obesity, a sedentary lifestyle, and drugs such as )3-blockers lower HDL. Only exercise and smoking cessation could be recommended as interventions for low HDL concentrations. Niacin and gemfibrozil also increase HDL concentrations. 

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