Hypolipidemic Drugs

HYPOLIPIDEMIC DRUGS LIPID TRANSPORT  Transported as lipo proteins Central core-TG and CE Outer coat-Phospholipid, FC, Apolipoproteins 6 Classes of lipoproteins: chylomicrons, rem, VLDL, LDL ,IDL, HDL

CLASSIFICATION     

HMG-CoA reductase inhibitors:statins Bile acid sequestrants: resins Fibric acid derivatives:clofibrate Nicotinic acid: Others:probucol

STATINS  Lovastatin,simvastatin,atorvastatin,rosuva  M.O.A:inhibits cholesterol synthesis  ACTIONS:1.increase in LDL receptor

2. Decrease in LDL, IDL 3. Increase in HDL  Statins differ in potency and max efficacy  Dose dependent effect  Max effect at mid night  ADR:headache,GI upset,rashes,sleep dis,

Increase in liver enzymes Muscle damage and increase in CPK  DI:CYP 3A4 dependent  CI:pregnancy,lactation,trauma, illness, surgery8  USES: Primary and secondary hyperlipidemias

IHD: decrease in MI risk and mortality  OTHER EFFECTS: increased CA compliance

plaquestabilization,endothelialfunction, ReducedLDL oxidation, anti inflammatory action BILE ACID SEQUESTRANTS  Cholestyramine,colestipol,colesevelam  M.O.A:large polymeric cationic exchange resins which bind bile acids and

prevent their absorbtion  ACTIONS:Cholesterol to bile acids

Clearence of LDL,IDL, LDL receptor up regulation  USES: primary hypercholesterolemia

used in combination pruritus digitalis toxicity  ADR:constipation, bloating ,diarrhea

gallstones,dry skin  DI: Interferes with absorption

FIBRIC ACID DERIVATIVES  Gemfibrozil,fenofibrate  M.O.A:Activate lipoprotein lipase  Actions:peroxisome proliferator activated receptor alpha(PPARα)

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enhances LPL synthesis fattyacid oxidation LDL receptor expression

decrease hepatic TG synthesis degradation of VLDL and circulating TG increase in HDL,decrease in VLDL secretion

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 USES:Hypertriglyceridemia

dysbetalipoproteinemias  ADR:GI symptoms,rashes,myopathy, arrythmias ,hypokalemia ,increase in liver

enzymes NIACIN  Nicotinic acid  MOA : inhibits TG synthesis in liver

Inhibits lipolysis in adipose tissue Increases activityof LPlipase  ACTIONS :Decrease in VLDL ,IDL,LDL

Increase in HDL Increase in Tpa Decrease in fibrinogen  USES: wide spectrum hypolipidemic

Adjunctive to statins and fibrates  ADR: Cutaneous vasodilator

GI upset dryness and pigmentation liver dysfunction,hyperglycemia hyperuricemia  DI: postural hypotension, myopathy

NEWER DRUGS  INHIBITORS OF INTESTINAL STEROL ABSORPTION: ezetimibe

 MTP INHIBITORS  ACAT INHIBITORS