<prompt> Drug possessing highest efficacy to increase plasma HDL is?EzetimibeNicotinic acidGemfibrosilRosuvastatin  <response>: Ans. b Nicotinic acid Ref. Harrisons medicine 17th ed., Table 350-6Statins, fibrates, and bile acid sequestrants have modest effects 5-10, and there is no effect on HDL cholesterol with ezetimibe or omega-3 fatty acids. Nicotinic acid is the only currently available drug with predictableHDL cholesterol-raising properties. Nicotinic acid effectively raises HDL and can be used in patients with diabetes,but high doses 2 gd may worsen glycemic control and increase insulin resistance.MANAGEMENT OF LOW HDL-C Severely reduced plasma levels of HDL-C 20 mgdL accompanied by triglycerides 400 mgdL usually indicate the presence of a genetic disorder, such as a mutation in apoA-I, LCAT deficiency, or Tangier disease. HDL-C levels 20 mgdL are common in the setting of severe hypertriglyceridemia, in which case the primary focus should be on the management of the triglycerides. HDL-C levels 20 mgdL also occur in individuals using anabolic steroids. The presence of an isolated low plasma level of HDL-C in a patient with a borderline plasma level of LDL-C should prompt consideration of LDL-lowering drug therapy in high-risk individuals. Statins increase plasma levels of HDL-C only modestly 5-10. Fibrates also have only a modest effect on plasma HDL-C levels increasing levels 5-15, except in patients with coexisting hypertriglyceridemia, where they can be more effective. Niacin is the most effective available HDL-C-raising therapeutic agent and can be associated with increases in plasma HDL-C by up to -30.Lipid-lowering agentsDrugEffect on LDL Bad cholesterolEffect on HDL Good cholesterolEffect on triglyceridesMechanisms of actionSide effects problemsHMG-CoA reductase inhibitors lovastain, pravastatin, simvastain, atorvastain, rosuvastainInhibit conversion of HMG-CoA to mevalonate, a cholesterol precursorHepatotoxicity LFTs, rhabdomyolysis esp. when used with fibrates and niacinNiacin vitamin B3Inhibits lipolysis in adipose tissue; reduces hepatic VLDL synthesisRed, flushed face, which is by aspirin or long-term use Hyperglycemia acanthosis nigricans Hyperuricemia exacerbates goutBile acid resins cholestyramine, dostipol, colesevelamSlightly Slightly Prevent intestinal reabsorption of bile acids; liver must use cholesterol to make morePatients hate it - tastes bad and causes GI discomfort, absorption of fat-soluble vitamins Cholesterol gallstonesCholesterol absorption blockers ezetimibe---Prevent cholesterol absorption at small intestine brush borderRare - LFTs, diarrheaFibrates gemfibrozil, clofibrate, bezafibrate, fenofibrateUpregulate LPL - TG clearance Activates PPAR-a to induce HDL synthesisMyositis risk with concurrent statins, hepatotoxicity LFTs, cholesterol gallstones esp. with cone current bile acid resinsEducational point:NICOTINIC ACID NIACIN Recently a receptor for nicotinic acid called GPR109A was discovered; it is expressed in adipocytes and, when activated, suppresses the release of NEFA by adipose. Niacin reduces plasma triglyceride and LDL-C levels and raises the plasma concentration of HDL-C. Niacin is also the only currently available lipid-lowering drug that significantly reduces plasma levels of Lpa. Niacin is a safe and effective lipid-lowering agent.Side-effects The most frequent side effect of niacin is cutaneous flushing. Mild elevations in transaminases occur in up to 15 of patients treated. Niacin potentiates the effect of warfarin. Acanthosis nigricans, a dark-colored coarse skin lesion, and maculopathy are infrequent side effects of niacin.Contraindications Peptic ulcer disease Precipitate gouty attacks. Can raise fasting plasma glucose levels. 