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 RENAL DISEASE LIVER DISEASE 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.