<prompt> Which of the following posseses highest efficacy to increase HDL cholesterol?GemfibrosilEnofibrateAtorvastatinNicotinic acid  <response>: Ans. d Nicotinic acid Ref. KDT 6thpg. 617, 618; H 17thpg. Table 350-6NIACIN NICOTINIC ACID Niacin but not niacinamide decreases VLDL and LDL levels--and LPa in most patients It often increases HDL levels significantly. Q It should not be used in diabetics.Mechanism of Action Niacin inhibits VLDL secretion, in turn decreasing production of LDL. Increased clearance of VLDL via the LPL pathway contributes to triglyceride reduction. Niacin has no effect on bile acid production. Excretion of neutral sterols in the stool is increased acutely as cholesterol is mobilized from tissue pools and a new steady state is reached. The catabolic rate for HDL is decreased. Fibrinogen levels are reduced, and levels of tissue plasminogen activator appear to increase. Niacin inhibits the intracellular lipase of adipose tissue via receptor-mediated signaling, possibly reducing VLDL production by decreasing the flux of free fatty acids to liver. Nicotinic acid decreases both LDL-C and VLDL-C, while raising plasma HDL1-C, and is frequently effective for this condition when used in combination with HMG-CoA reductase inhibitors. Niacin is the only currently available lipid-lowering drug that significantly reduces plasma levels of LPa, It is the most effective drug currently available for raising HDL-C levels.Therapeutic Uses Dosage 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 hyperlipoproteinemia and in those with familial dysbetalipoproteinemia. Niacin reduces levels of LPa in many subjects. It is clearly the most effective agent for increasing levels of HDL. For treatment of heterozygous familial hypercholesterolemia, most patients require 2-6 g of niacin daily. It is contraindicated in diabetics. It is particularly useful in patients with combined hyperlipidemia and low plasma levels of HDL-C and is effective in combination with statins.Toxidty Qraneous vasodilation and sensation of warmth after each dose Tachyphylaxis Pruntus, rashes, dry skin or mucous membranes, and acanthosis nigricans Niacin should be avoided in patients with severe peptic disease. Rarelj, true hepatotoxicity may occur and is an indication for discontinuing the drug. Niacin may be given to diabetics who are receiving insulin and to some receiving oral agents if insulin resistance is not increased. Hyperuricemia occurs in some patients. Rarely, mein is associated with arrhythmias, mostly atrial, and a reversible toxic amblyopia. Patients should be instructed to report blurring of distance vision. Niacin may potentiate the action of antihypertensive agents, requiring adjustment of their dosages. Dryness cf mucous membranes is occasional.DrugIndicationsMechanismCommon side effects1HMG-CoA reductase inhibitors statinsElevated LDL-C Cholesterol synthesis, hepatic LDL receptors, VLDL productionMyalgias,Arthralgias,Elevated transaminases,Dyspepsia2Cholesterol absorption inhibitors EretimibeElevated LDL-Cintestinal cholesterol absorptionElevated transaminases3Bile acid sequestrants Cholestyramire, Colestipol, ColesevelamElevated LDL-C Bile acid excretion and LDL receptorsBloating,Constipation,Elevated triglycerides4Nicotinic acidElevated LDL-C,Low HDL-C,Elevated TGVLDL hepatic synthesisCutaneous flushing,Gl upset,Elevated glucose, uric acid, and liver function tests5Fibric acid derivativesElevated TG, elevated remnants LPL, VLDL synthesisDyspepsia, Myalgia,Gallstones, Elevated transaminases6Omega-3 fatty acidsElevated TG TG catabolismDyspepsia,Diarrhea,Fishy odor to breath 