This document describes different types of antihyperlipidemic drugs used to treat various types of hyperlipidemias. It discusses the mechanisms and side effects of niacin, fibrates like gemfibrozil and clofibrate, bile acid sequestrants like cholestyramine, statins which inhibit HMG CoA reductase, and ezetimibe which inhibits cholesterol absorption. The types of hyperlipidemia and appropriate drug therapies are outlined.

1. ANTIHYPERLIPIDEMIC DRUGS

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

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

7. 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.

8. 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.

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

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

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

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

13.  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.

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

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

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

17. GEMFIBROZIL & CLOFIBRATE
 ORAL- WELL ABSORBED
 EXCRETION - RENAL

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

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

20. 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

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

22. HMG Co A REDUCTASE INHIBITORS
 LOVASTATIN
 PRAVASTATIN
 FLUVASTATIN
 SIMVASTATIN

23.  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

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

25. 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.

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

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

28. 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.

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