ANTIHYPERLIPIDEMIC DRUGS. TYPE I Familial hyperchylomicronemia More chylomicrons Lipoprotein...

ANTIHYPERLIPIDEMIC DRUGSANTIHYPERLIPIDEMIC DRUGS

TYPE ITYPE I

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

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

TYPE II ATYPE II A

Familial hypercholesterolemia ↑LDL, normal VLDL ↑ IHD Rx – low cholesterol & low saturated fat

diet, drugs such as colestipol or cholestyramine or statins.

Familial hypercholesterolemia ↑LDL, normal VLDL ↑ IHD Rx – low cholesterol & low saturated fat

diet, drugs such as colestipol or cholestyramine or statins.

TYPE II BTYPE 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.

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 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.

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 TYPE IV

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

or Statins.

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

or Statins.

TYPE VTYPE V

Familial mixed hypertriglyceridemia ↑ VLDL ↑ chylomicrons ↑ Cholesterol ↑↑ TAG Obese , diabetic Rx– Wt. reduction ,diet control, Niacin,

Clofibrate or Gemfibrozil or Statins.

Familial mixed hypertriglyceridemia ↑ VLDL ↑ chylomicrons ↑ Cholesterol ↑↑ TAG Obese , diabetic Rx– Wt. reduction ,diet control, Niacin,

Clofibrate or Gemfibrozil or Statins.

Pharmacological Management of Hyperlipidemia

Pharmacological Management of Hyperlipidemia

DIET : ADJUNCT TO DRUGS

AVOID DRUGS : PREGNANT, LACTATING

DIET : ADJUNCT TO DRUGS

AVOID DRUGS : PREGNANT, LACTATING

NIACINNIACIN

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

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.

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 USESTHERAPEUTIC USES

Oral - route Urinary excretion FAMILIAL HYPERTRIGLYCERIDEMIA

MIXED HYPERLIPIDEMIA

HYPERCHOLESTEROLEMIAS

Oral - route Urinary excretion FAMILIAL HYPERTRIGLYCERIDEMIA

MIXED HYPERLIPIDEMIA

HYPERCHOLESTEROLEMIAS

SIDE EFFECTSSIDE EFFECTS

CUTANEOUS FLUSH , PRURITUS RX : ASPIRIN

NAUSEA , VOMITING

HYPER - URECEMIA & GOUT.

CUTANEOUS FLUSH , PRURITUS RX : ASPIRIN

NAUSEA , VOMITING

HYPER - URECEMIA & GOUT.

GEMFIBROZIL , CLOFIBRATEGEMFIBROZIL , CLOFIBRATE

LIPO PROTEIN LIPASE – STIMULATED TRIACYLGLYCEROLS – BROKEN VLDL , CHYLOMICRONS – REDUCED

CHOLESTEROL IN BILE - INCREASED

LIPO PROTEIN LIPASE – STIMULATED TRIACYLGLYCEROLS – BROKEN VLDL , CHYLOMICRONS – REDUCED

CHOLESTEROL IN BILE - INCREASED

GEMFIBROZIL & CLOFIBRATEGEMFIBROZIL & CLOFIBRATE

ORAL- WELL ABSORBED

EXCRETION - RENAL

ORAL- WELL ABSORBED

EXCRETION - RENAL

USESUSES

MAINLY FOR TRIACYLGLYCEROLS i.e TYPE IV

DYSBETALIPOPROTEINEMIA i.e TYPE III

MAINLY FOR TRIACYLGLYCEROLS i.e TYPE IV

DYSBETALIPOPROTEINEMIA i.e TYPE III

SIDE EFFECTSSIDE EFFECTS

GIT DISTURBANCES MYOPATHY , MALIGNANCY (Clofibrate) GALL STONE FORMATION CI : GB DISEASE,

–RENAL DISEASE

–LIVER DISEASE

GIT DISTURBANCES MYOPATHY , MALIGNANCY (Clofibrate) GALL STONE FORMATION CI : GB DISEASE,

–RENAL DISEASE

–LIVER DISEASE

BILE ACID BINDING RESINSBILE 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

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 , COLESTIPOLCHOLESTYRAMINE , COLESTIPOL

USE - HYPERLIPIDEMIAS Mainly for TYPE II A & II B

SIDE EFFECTS – CONSTIPATION , BLOATING FAT SOL. VITAMIN DEFICIENCY.

USE - HYPERLIPIDEMIAS Mainly for TYPE II A & II B

SIDE EFFECTS – CONSTIPATION , BLOATING FAT SOL. VITAMIN DEFICIENCY.

HMG Co A REDUCTASE INHIBITORSHMG Co A REDUCTASE INHIBITORS

LOVASTATIN

PRAVASTATIN

FLUVASTATIN

SIMVASTATIN

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

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

USES – HYPERLIPIDEMIAS FAMILIAL HYPERCHOLESTEROLEMIA – lack

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

PROBUCOLPROBUCOL

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 increases the rate of LDL metabolism

block the intestinal transport of cholesterol.

The net result is a significant reduction in plasma cholesterol levels.

PROBUCOLPROBUCOL

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

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

INTERACTIONSINTERACTIONS

MAINLY SEEN WITH WARFARIN

GEMFIBROZIL , CLOFIBRATE CHOLESTYRAMINE , COLESTIPOL HMG Co A INHIBITORS

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.

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.

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