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)

 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

 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