A 50 years old man was recently diagnosed to be having coronary artery disease. There was no added risk factors except for a LDL value of 150-165mgs/dl. The single drug most appropriate for initial therapy is
Answer: d) Statins (any)DYSLIPIDEM1AType of disorderLipo Proteins increasedLipids elevatedRisk of CADtreatmentTri GlyceridesCholesterolICM+++NormalNoNoneIIaLDLNormal+++++StatinsIIbVLDL and LDL+++++++Statins, fibrates, nicotinic acidIIIIDLand CM++++++FibratesIVVLDL++Normal++Fibrates, nicotinic acidVVLDL and CM++NormalNoNone* TG is elevated in all except type lla; Cholesterol is elevated only in type II (lla, lib) and type III.* Type II is treated with statins and III and IV with fibrates.* I and V do not increase the risk of atherosclerosis and require no treatment. DesirableBorderline to highHighTotal cholesterol<200200-239>240LDL cholesterol<130130-159>160HDL cholesterol >60Men>40 Women>50 Triglycerides<150150-199>200CAUSES OF:HypercholesterolemiaHypertriglyceridemia* Hypothyroidism* Early nephrosis* Resolving lipemia* Immunoglobulin- lipoprotein complex disorders* Anorexia nervosa* Cholestasis* Hypopituitarism* Corticosteroid excess* Diabetes mellitus* Alcohol ingestion* Severe nephrosis* Immunoglobulin- lipoprotein complex disorders* Lipodystrophy* Isotretinoin* Protease inhibitors* Estrogens* Uremia* Corticosteroid excess* Myxedema* Glycogen storage disease* Hypopituitarism* AcromegalyANTI - PYSLIPIDEMIC DRUGS* HMG-CoA reductase inhibitors (Statins): Lovastatin, Simvastatin, Pravastatin, Atorvastatin, Rosuvastatin, Pitavastatin* Bile acid sequestrants(Resins): Cholestyramine, Colestipol* Lipoprotein lipase activators (PPARa activators, Fibrates): Clofibrate, Gemfibrozil, Bezafibrate, Fenofibrate.* Lipolysis and triglyceride synthesis inhibitor: Nicotinic acid* Sterol absorption inhibitor: Ezetimibe.* First line drugs - statins, bile acid binding resins and intestinal cholesterol absorption inhibitors.* Second line drug include fibrates and niacin.STATINS: (HMG CoA reductase inhibitor)* Most powerful LDL lowering agents, also lower TG, IDL and VLDL and increases HDL slightly.* No effect on lipoprotein (a).* Have pleotropic effects (antioxidant, anti-inflammatory and anti-proliferative properties).* In response to the reduced free cholesterol content within hepatocytes, synthesis of LDL receptors is increased and their degradation is reduced.* The greater number of LDL receptors on the surface of hepatocytes increases removal of LDL from the blood* Most potent statin is rosuvastatin > atorvastatin >fluvastatin and lovastatin(least potent)* Activity of HMG CoA reductase is maximum at night, so these drugs are administered at night.* Rosuvastatin (ti/2 =14 hours) -long acting drug,* Pravastatin: decreases plasma fibrinogen levels.* Lovastatin and simvastatin are administered as prodrugs.* All drugs except Pravastatin are metabolized extensively by hepatic microsomal enzymes.* Statins have pleiotropic effects (effects unrelated, or indirectly related, to their effect on plasma LDL)o Improved endothelial functiono Reduced vascular inflammationo Reduced platelet aggregabilityo Increased neovascularisation of ischaemic tissueo Increased circulating endothelial progenitor cellso Stabilisation of atherosclerotic plaqueo Antithrombotic actionso Enhanced fibrinolysiso Inhibition of germ cell migration during developmento Immune suppressiono Protection against sepsis.* Major adverse effect - myopathy (high when combined with fibrates or niacin) & hepatotoxicity* These drugs are the first line drugs for type lla, type lib and secondary hyperlipoproteinemia.BILE ACID BINDING RESINS* Bind to bile acids in the intestinal lumen - decrease its reabsorption - depletion of cholesterol pool of liver* Bile acids inhibit TG production in the liver and their deficiency results in elevation of TGs.* Bile acid binding resins are used only for type lla disorder (TGs are normal in this condition). Drugs in this group include cholestyramine, colestipol and colesevelam (better compliance).FIBRATES* Inhibits lipoprotein lipase by activating a nuclear receptor, PPARa (peroxisome proliferators activated receptor alpha).* Major effect of the fibrates is to reduce TG (contained in VLDL) and to increase HDL.* Clofibrate - malignancies, post cholecystectomy complications & did not prevent Ml (banned now).* Gemfibrozil, fenofibrate and bezafibrate are currently available.* Fenofibrate is a prodrug with longest half life. It has maximum LDL cholesterol lowering action.* Risk of myopathy is lower & also reduce plasma fibrinogen level.* DOC in hypertriglyceridemia (type III and IV) and can be used with other drugs in type Mb (fenofibrate, as it has maximum LDL reducing action).* DOC for treating type III hyperlipoproteinemia as well as subjects with severe hypertriglyceridemia (triglycerides >1000 mg/dL) who are at risk for pancreatitis.* Fenofibrate is uricosuric -can be used in hyperuricemia.* Fenofibrate: risk of elevation of creatinine.* Gl distress and elevation of aminotransferases are important adverse effects of fibric acid derivatives.* Risk of myopathy is increased if used with statins (except bezafibrate).NICOTINIC ACID (Niacin, (vitamin B3))* Decreases LDL, VLDL and triglycerides along with increase in HDL cholesterol.* Acts by inhibiting lipolysis in the adipose tissue.* Among all hypolipidemic drugs, niacin has maximum HDL increasing property.* Niacin is the only lipid-lowering drug that reduces Lp(a) levels significantly, by "40%;* It is useful for type lib, III and IV disorders.* Adverse effects: cutaneous flushing, pruritis, Gl toxicity and hyperuricemia. Niacin can also lead to hepatotoxicity which is manifested by fall in both LDL as well HDL cholesterol.INTESTINAL CHOLESTEROL ABSORPTION INHIBITOR* Ezetimibe acts by inhibiting the absorption of cholesterol by the intestine by blocking uptake via the Neimann-Pick C-like 1 protein.* Can be used alone or combined with statins for type lla and lib hyperlipoproteinemia.MISCELLANEOUS DRUGS* Probucol inhibits oxidation of LDL and cause reduction in levels of both HDL and LDL cholesterol.* Gugulipid causes modest decrease in LDL & slight increase in HDL. Diarrhea is the adverse effect.* Saroglitazar: dual PPAR- and PPAR-agonist. Novel therapeutic agent for diabetic dyslipidemia. Decreases serum triglycerides, HbAlC & increases HDL cholesterol. Dosage: 4mg OD* a-tocopherol acetate (vitamin E) has no effect on lipid levels but is a powerful antioxidant.* Niacin is the best agent available for increasing HDL (increments of 30-40%); it also |, triglycerides by 35-45% (as effectively as fibrates & statins) and |, LDL levels by 20-30%* Changes in plasma lipoprotein levels, particularly increases in high-density lipoprotein (HDL), have been associated with the protective effects of ethanol.* Factors associated with elevation of plasma FFA followed by increased output of triacylglycerol and cholesterol into the circulation in VLDL include emotional stress and coffee drinking.* Red wine increases HDL, because of its content of antioxidants.* Regular exercise lowers plasma LDL but raises HDL.NEWER DRUGS* Avasimibe is an inhibitor of enzyme ACAT-1 (acetyl coenzyme A: cholesterol acetyl transferase -1) which forms cholesterol ester from cholesterol.* Torcetrapib, Anacetrapib: increases HDL by inhibiting cholesterol ester triglyceride transport protein.ALCOHOL* Regular alcohol consumption inhibits hepatic oxidation of free fatty acids, thus promoting hepatic TG synthesis and VLDL secretion.* Regular alcohol use also raises plasma levels of HDL-C and should be considered in patients with the unusual combination of elevated TGs and elevated HDL-C.DrugEffect on LDLEffect on TriglyceridesEffect on HDLStatins||||||||Fibrates||||||||Niacin|||||||||Bile acid Winding resins|||Minimal/ slight increase|Cholesterol Absorption In tilts It ors|Minimal EffectMinimal Effect
Gemfibrozil
Nicotinic acid
Bile acid binding resins
Statins (Any)
Hypolipidemic