Which of the following posseses highest efficacy to increase HDL cholesterol?

Ans. d (Nicotinic acid) (Ref. KDT 6th/pg. 617, 618; H 17th/pg. Table 350-6)NIACIN (NICOTINIC ACID)# Niacin (but not niacinamide) decreases VLDL and LDL levels--and LP(a) 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 LP(a),# 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 LP(a) 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 (statins)Elevated LDL-C| Cholesterol synthesis, | hepatic LDL receptors, |VLDL productionMyalgias,Arthralgias,Elevated transaminases,Dyspepsia2Cholesterol absorption inhibitors ( Eretimibe)Elevated LDL-Cintestinal cholesterol absorptionElevated transaminases3Bile acid sequestrants (Cholestyramire, Colestipol, Colesevelam)Elevated LDL-C| Bile acid excretion and |LDL receptorsBloating,Constipation,Elevated triglycerides4Nicotinic acidElevated LDL-C,Low HDL-C,Elevated TG|VLDL 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