Drug possessing highest efficacy to increase plasma HDL is?
Ans. b (Nicotinic acid) (Ref. Harrison's medicine 17th ed., Table 350-6)Statins, 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 g/d) may worsen glycemic control and increase insulin resistance.MANAGEMENT OF LOW HDL-C# Severely reduced plasma levels of HDL-C (<20 mg/dL) accompanied by triglycerides <400 mg/dL usually indicate the presence of a genetic disorder, such as a mutation in apoA-I, LCAT deficiency, or Tangier disease.# HDL-C levels <20 mg/dL 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 mg/dL 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 cholesterol"Effect on HDL "Good cholesterol"Effect on triglyceridesMechanisms of actionSide effects/ problemsHMG-CoA reductase inhibitors (lovastain, pravastatin, simvastain, atorvastain, rosuvastain)|||||Inhibit conversion of HMG-CoA to mevalonate, a cholesterol precursorHepatotoxicity (| LFTs), rhabdomyolysis (esp. when used with fibrates and niacin)Niacin (vitamin B3)|||||Inhibits lipolysis in adipose tissue; reduces hepatic VLDL synthesisRed, flushed face, which is | by aspirin or long-term use Hyperglycemia (acanthosis nigricans) Hyperuricemia (exacerbates gout)Bile acid resins (cholestyramine, dostipol, colesevelam)||Slightly |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, fenofibrate)||||||Upregulate LPL - | TG clearance Activates PPAR-a to induce HDL synthesisMyositis (| risk with concurrent statins), hepatotoxicity (| LFTs), cholesterol gallstones (esp. with cone current bile acid resins)Educational 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 Lp(a).# 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.
Ezetimibe
Nicotinic acid
Gemfibrosil
Rosuvastatin
Hypolipidemic