MEDICINAL CHEMISTRY

(iii) Intermediate density lipoproteins (IDL): These are the lipoproteins obtained
when the triglyceride content of VLDL are partially digested in capillaries by the action
of extrahepatic lipoprotein lipase. They have a diameter of 20 - 35 nm.
(iv) Low Density Lipoproteins (LDL): Due to further action of lipoprotein lipase on
IDL in the circulation, most of the remaining triglyceride content of IDL is digested
resulting into the loss of apoproteins C and E from their structure. The density of particle
is increased and diameter is brought down to 18 - 28 nm. These particles are now termed
as LDL which consist of cholesterol, phospholipids and apoprotein B - 100. LDL also
contains B - 74 and B - 26. They have longest plasma half-life of about 1.5 days amongst
the lipoproteins.
LDL Particles are finally delivered to hepatic and certain extrahepatic tissues for further
lysosomal degradation to release the cholesterol, which can be utilised in cell membrane
formation.
(v) Chylomicros: These are the largest species of triglyceride rich lipoproteins,
which are involved in the, transportation of dietary fat from gut. These are secreted into
the lymph and contain apoprotein A and B-48.
Lipid Lowering Agents act either by reducing the production of lipoprotein or by
increasing their removal from blood. The main aim is to decrease plasma cholesterol.
The risk of atherosclerosis is associated with an increased plasma cholesterol, and a high
LDL:HDL ratio.
There are several mechanisms by which pharmacological agents can affect the
metabolism of cholesterol and the relative levels of various cholesterol carrying
lipoproteins in the plasma.
(i) Inhibit synthesis of cholesterol (e.g. HMG - CoA reductase inhibition;
Lovastatin).
ii) Alter the relative levels of different plasma lipoproteins e.g. clofibrate,
gemfibrozil, nicotinic acid and possibly probucol, thyroid hormone, androgens.
(iii) Sequester bile acids in the intestine, e.g. cholestyramine and colestipol.
(iv) Inhibit cholesterol absorption in the intestine, e.g. neomycin and plant steroids,
such as β-sitosterol.
Classification of antihyperlipidemic agents
(i) HMG-CoA-reductase Inhibitor: e.g. Lovastatin, Simvastatin, Pravastatin
(ii)Fibric acid derivatives: e.g. Clofibrate, Fenofibrate, Ciprofibrate, Bezafibrate,
Gemfibrozil
(iii) Bile-acid sequestrants: e.g. Cholestyramine, colestipol
(iv) Inhibition of LDL oxidation: e.g. Probucol
(v) Miscellaneous Agents: e.g. Nicotinic acid, Neomycin, β-Sitosterol, Acipimox,
Metformin, Dextrothyroxine