This document discusses hypolipidemic drugs, which lower lipid and lipoprotein levels in the blood. It covers the classification of lipoproteins and causes of hyperlipoproteinemia. The main classes of hypolipidemic drugs discussed are statins, fibrates, bile acid sequestrants, nicotinic acid, ezetimibe, and gugulipid. Each drug class is explained in terms of its mechanism of action, effects on lipids, and common adverse effects.

1. Hypolipidemic Drugs

2. • These are the drugs which lower the level of lipids
and lipoproteins in blood.
• Lipids are carried in plasma in lipoproteins.
• The core of lipoprotein globules: triglycerides (TGs)
or cholesteryl esters (CHEs)
• Outer layer has phospholipids, free cholesterol and
apoproteins.

3. •Lipoproteins
1) Chy.
2) Chy. Rem.
3) VLDL
4) IDL
5) LDL
6) HDL

4. •Hyperlipoproteinemias
1) Secondary: Diabetes, myxoedema, nephrotic
syndrome, chronic alcoholism, drugs
(coticosteroids, oral contraceptives, beta-blockers)
2) Primary:
a) A single gene defect (Monogenic)
b) Multiple genetic (Polygenic or multifactorial)

5. LIPID TRANSPORT

7. CLASSIFICATION
• Lovastatin, Simvastatin, Pravastatin
• Atorvastatin, Rosuvastatin
HMG-CoA reductase inhibitors
(Statins)
• Cholestyramine
• Colestipol
Bile acid sequestrants (Resins):
• Clofibrate, Gemfibrozil
• Bezafibrate,
• Fenofibrate.
Activate lipoprotein lipase
(Fibric acid derivatives):
• Nicotinic acid
Inhibit lipolysis and triglyceride
synthesis
• Ezetimibe, Gugulipid
Others

8.  Decreased hepatic cholesterol
synthesis upregulates LDL
receptor synthesis, increasing
LDL clearance from plasma into
liver cells.
 The main biochemical effect of
statins is therefore to reduce
plasma LDL. There is also some
reduction in plasma triglyceride
and increase in HDL

9. Adverse effects
All statins are remarkably well tolerated
Notable side effects are:
• Headache, nausea, bowel upset, rashes.
• Sleep disturbances (probably more with lipophilic drugs).
• Rise in serum transaminase can occur, but liver damage is rare.
• Muscle tenderness
• Myopathy is the only serious reaction, but is rare

12.  They are agonists at PPARα nuclear receptors4 in humans
 The main effects are to increase transcription of the genes for lipoprotein
lipase, apoA1 and apoA5.
 They increase hepatic LDL uptake.
 In addition to effects on lipoproteins, fibrates reduce plasma C-reactive
protein and fibrinogen, improve glucose tolerance and inhibit vascular smooth
muscle inflammation by inhibiting the expression of the transcription factor
nuclear factor κB

13. Adverse effects
 Rhabdomyolysis is unusual but can be severe, giving rise to acute renal failure associated with
excretion of muscle proteins, especially myoglobin, by the kidney.
 Fibrates should be avoided in such patients and also in alcoholics, who are predisposed to
hypertriglyceridaemia but are at risk of severe muscle inflammation and injury.
 Rhabdomyolysis can also be caused (rarely) by statins and the combined use of fibrates with
this class of drugs is therefore generally inadvisable.
 Gastrointestinal symptoms, pruritus and rash are more common than with statins

16. Taken by mouth, they sequester bile
acids in the intestine and prevent
their reabsorption and enterohepatic
recirculation

17. Resins have been shown to retard atherosclerosis, but are
not popular clinically because they are unpalatable
inconvenient, have to be taken in large doses, cause
flatulence and other g.i. symptoms, interfere with
absorption of many drugs and have poor patience
acceptability.

18. NICOTINIC ACID (NIACIN)
•Niacin, like fibrates, is also well suited for lowering
triglycerides by 20–50%. It may also lower LDL by 5–25%
and increase HDL by 15–35%. Niacin may
cause hyperglycemia and may also cause liver damage.
The niacin derivative acipimox is also associated with a
modest decrease in LDL.

19. Adverse effects
 The large doses needed for hypolipidaemic action are poorly tolerated.
 Nicotinic acid is a cutaneous vasodilator: marked flushing, heat and itching.
 Dyspepsia is very common; vomiting and diarrhoea occur when full doses are
given. Peptic ulcer may be activated.
 Dryness and hyperpigmentation of skin can be troublesome.

20. EZETIMIBE
Ezetimibe is one of a group of azetidinone cholesterol absorption inhibitors,
and is used as an adjunct to diet and statins in hypercholesterolaemia. It
inhibits absorption of cholesterol (and of plant stanols) from the duodenum by
blocking a transport protein (NPC1L1) in the brush border of enterocytes,
without affecting the absorption of fat-soluble vitamins, triglycerides or bile
acids

23. Gugulipid
• It is mixture of sterones obtained from “gum guggul” which has been used in
Ayurveda.
• Modest lowering of plasma cholesterol and triglycerides occurs after continued use
of gugulipid.
• It is well tolerated.
Side effects:
• Loose stool