ANTIHYPERLIPIDEMIC DRUGS

TYPE I Familial hyperchylomicronemia More chylomicrons Lipoprotein lipase deficiency No Risk of CAD Rx – low fat diet

TYPE II A Familial hypercholesterolemia ↑LDL, normal VLDL ↑ IHD Rx – low cholesterol & low saturated fat diet, drugs such as colestipol or cholestyramine or statins.

TYPE II B Familial Mixed Hyperlipidemia TYPE II A + ↑ VLDL – over production of VLDL by liver Rx -- low cholesterol & low saturated fat diet, drugs such as colestipol or cholestyramine or statins or Niacin.

TYPE III Familial Dysbetalipoproteinemia ↑IDL caused by over production or underutilization, due to mutant apoE ↑ TAG , ↑ Cholesterol levels Xanthomas & CAD risk increased Rx – Wt reduction, Exercise & diet control, Niacin or Clofibrate or statins.

TYPE IV Familial hypertriglyceridemia ↑VLDL - ↑ Circulating TAG, Normal LDL levels Obese , diabetic. Rx – wt. reduction, diet , Niacin or Gemfibrozil or Statins.

TYPE V Familial mixed hypertriglyceridemia ↑ VLDL ↑ chylomicrons ↑ Cholesterol ↑↑ TAG Obese , diabetic Rx– Wt. reduction ,diet control, Niacin, Clofibrate or Gemfibrozil or Statins.

Pharmacological Management of Hyperlipidemia DIET : ADJUNCT TO DRUGS AVOID DRUGS : PREGNANT, LACTATING

NIACIN water-soluble vitamin Lipolysis - inhibited Free fatty acids – decreased Triglycerides – decreased VLDL , LDL - REDUCED CHOLESTEROL - REDUCED HDL - INCREASED

Nicotinic acid: Nicotinic acid reduces the plasma levels of both VLDLs and LDLs by inhibiting hepatic VLDL secretion, as well as suppressing the flux of FFA release from adipose tissue by inhibiting lipolysis. Because of its ability to cause large reductions in circulating levels of cholesterol, nicotinic acid is used to treat Type II, III, IV and V hyperlipoproteinemias.

THERAPEUTIC USES Oral - route Urinary excretion FAMILIAL HYPERTRIGLYCERIDEMIA MIXED HYPERLIPIDEMIA HYPERCHOLESTEROLEMIAS

SIDE EFFECTS CUTANEOUS FLUSH , PRURITUS RX : ASPIRIN NAUSEA , VOMITING HYPER - URECEMIA & GOUT.

GEMFIBROZIL , CLOFIBRATE LIPO PROTEIN LIPASE – STIMULATED TRIACYLGLYCEROLS – BROKEN VLDL , CHYLOMICRONS – REDUCED CHOLESTEROL IN BILE - INCREASED

GEMFIBROZIL & CLOFIBRATE ORAL- WELL ABSORBED EXCRETION - RENAL

USES MAINLY FOR TRIACYLGLYCEROLS i.e TYPE IV DYSBETALIPOPROTEINEMIA i.e TYPE III

SIDE EFFECTS RENAL DISEASE LIVER DISEASE GIT DISTURBANCES MYOPATHY , MALIGNANCY (Clofibrate) GALL STONE FORMATION CI : GB DISEASE, RENAL DISEASE LIVER DISEASE

BILE ACID BINDING RESINS WATER INSOLUBLE BIND WITH BILE ACID AND BILE SALTS COMPLEX -NOT ABSORBED ENTEROHEPATIC RECIRCULATION –REDUCED CHOLESTEROL USE – INCREASED LDL LEVELS – FALL CHOLESTEROL LEVEL - FALLS

CHOLESTYRAMINE , COLESTIPOL USE - HYPERLIPIDEMIAS Mainly for TYPE II A & II B SIDE EFFECTS – CONSTIPATION , BLOATING FAT SOL. VITAMIN DEFICIENCY.

HMG Co A REDUCTASE INHIBITORS LOVASTATIN PRAVASTATIN FLUVASTATIN SIMVASTATIN

HMG Co A REDUCTASE – RATE LIMITING STEP FOR CHOLESTEROL SYN. LDL – BROKEN DOWN KINETICS : ORAL ABS. – GOOD FIRST PASS METABOLISM – GOOD SITE OF ACTION - LIVER EXCRETION – MAINLY BILE, STOOL

USES – HYPERLIPIDEMIAS FAMILIAL HYPERCHOLESTEROLEMIA – lack LDL receptors --LESS EFFECT SIDE EFFECTS : LIVER FUNCTION – RENAL DYSFUNCTION MYOPATHY, RHABDOMYOLYSIS – RARE CI : CHILD, PREGNANT, LACTATING

PROBUCOL Probucol increases the rate of LDL metabolism block the intestinal transport of cholesterol. The net result is a significant reduction in plasma cholesterol levels.

PROBUCOL LDL – REDUCED NOT VERY USEFUL USED SOMETIMES FOR II A & II B SIDE EFFECTS – GIT QT INTERVAL PROLONGED CI : PREGNANCY

INTERACTIONS MAINLY SEEN WITH WARFARIN GEMFIBROZIL , CLOFIBRATE CHOLESTYRAMINE , COLESTIPOL HMG Co A INHIBITORS

Cholesterol absorption inhibitors Ezetimibe Selectively inhibits intestinal absorption of dietary and biliary cholesterol in small intestine leading to a decrease in the delivery of intestinal cholesterol to the liver. This leads to a depletion in the hepatic cholesterol stores.

Metabolized in the small intestine and liver CI – hepatic insufficiency.