4. • There are 4 main classes of lipoprotein, differing in the relative
proportion of the core lipids and in the type of apoprotein.
• They also differ in size and density on which basis they are
classified as;
1. High density lipoproteins (HDL)
2. Low density lipoproteins (LDL)
3. Very low-density lipoproteins (VLDL)
4. Chylomicrons
Various types of hyperlipidemia are found.
a. Primary: the plasma triglycerides and cholesterol concentration
are raised, and particular-lipoprotein classes are increased.
b. Secondary: they occur because of diabetes, alcoholism, liver
disease and by some drugs like chlorthalidone, corticosteroids.
5. Anti Hyperlipidaemic Agents
Hypolipidaemic drugs are those which
lower the levels of lipids and lipoproteins
in blood. The hypolipidemic drugs have
attracted considerable attention because
of their potential to prevent
cardiovascular disease by retarding the
accelerated atherosclerosis in
hyperlipidemic individuals.
The high risk of atherosclerosis is
associated with an increased plasma
cholesterol and a high LDL:HDL ratio.
6. • The current
pharmacotherapy
includes the
following:
1. HMG CoA reductase
(or 3-hydroxy-3-
methyl-glutaryl-CoA
reductase or HMGR)
inhibitors (statins).
2. Bile acid
sequestrants (resins).
3. Drugs that activates
lipoprotein lipase (fibric
acid derivatives).
4. Drugs that inhibit
lipolysis and
triglyceride synthesis
(nicotinic acid).
Combined therapeutic regimen is useful in the
following cases:
• When LDL levels are insignificantly increased
during treatment of hypercholesterolemia with a
resin.
• When LDL and VLDL levels are both elevated
initially.
• When LDL and VLDL levels are normalized with a
single agent.
• When elevated level of lipoprotein or HDL
deficiency coexist with other hyperlipidaemias.
13. Synthesis and drug profile
• I. HMG CoA-Reductase Inhibitors
• Mode of action: These kinds of drugs
competitively inhibit the conversion
of 3-hyroxy-3-methyl glutaryl
coenzyme (HMG CoA) to
mevalonate, which is the rate-limiting
step in cholesterol synthesis and
results in receptor mediated uptake
and catabolism of intermediate density
lipoprotein and very low-density
lipoprotein
14. Lovastatin:
Lovastatin is produced
commercially via a multi-stage
fermentation process which
originates from cultures of a
strain of Aspergillus terreus.
This is the first clinically used
statin, which is lipophilic and
given orally in the precursor
lactone form.
17. Mechanism of action: (statins)
• Statins competitively inhibit conversion of 3-Hydroxy-3-
methyl glutaryl coenzyme A to mevalonate which is the rate
limiting step in the synthesis of cholesterol by the enzyme
HMG-COA reductase
Effect on plasma lipids (%):
1. LDL: ↓ 20-55
2. HDL: ↑ 5-15
3. TG: ↓ 10-35
18. Drug Profile of Fibric acid derivatives
CLOFIBRATE
uses:
• It is a drug of choice in the
treatment of type III, IV, and
V hyperlipoproteinaemias.
20. Gemfibrozil:
• USES:
• Gemfibrozil is the first line drug for
patients with markedly increased TG levels
irrespective of CH levels.
• It is most effective in type III
hyperproteinaemia also beneficial for type
IV and V.
22. Mechanism of action (fibrates)
These drugs activate receptors
called α-peroxisome proliferator-
activated receptors, which enhance
the synthesis of lipoprotein lipase
and increase the degradation of very
low-density lipoprotein.
This also enhances the fatty acid
oxidation.
Effect on plasma lipids (%):
LDL : ↓ 5-15
HDL : ↑ 10-20
TG : ↓ 20-50
23. Bile Acid Sequestrants
1. Cholestyramine resin:
Effect on lipid profile (%)
LDL: ↓ 15-25
HDL: ↑ 3-5
TG: not affected, may increase in some
It is a styrene copolymer with divinyl benzene and quaternary ammonium functional group. The resin is
insoluble in water, remains unchanged in the intestinal tract, unaffected by digestive enzymes, and is not
absorbed. These are basic ion exchange resins, which binds with bile acids, interferes in the
enterohepatic circulation and leads to the excretion of cholesterol in faeces. This also indirectly leads to
the enhanced hepatic metabolism of cholesterol to bile acids, so more LDL receptors are exposed on
liver cells and the plasma intermediate density and very low-density lipoprotein clearance is more.
25. Mechanism
of Action:
Nicotinic acid inhibits the lipolysis of
triglycerides by hormone sensitive lipase, which
reduces transport of the free fatty acids to liver
and decreases hepatic triglycerides synthesis.
Reduction of triglycerides synthesis decreases
the production of hepatic VLDL.
Effect on plasma lipids (%):
1.LDL : ↓ 15-25
2.HDL : ↑ 20-35
3.TG : ↓ 20-50
26. References:
Textbook of Medicinal Chemistry
Vol-I by V. Alagarsamy
Medicinal Chemistry by D.
Sriram. P. Yogeeswari
Essentials of Medical
Pharmacology by K.D. Tripathi 8th
Edition
Foye’s principle of Medicinal
Chemistry
