PRESENTED BY

SUMAYYA SAMREEN
M. PHARMACY FIRST YEAR (PHARMACOLOGY)

Atherosclerosis is a disease which affects large and medium sized arteries.

The lesion characteristics of atherosclerosis is a localized plaque and is composed of
o Cholesterol esters, o Prolification of smooth muscle, o Deposition of fibrous proteins and o Calcification
Such Plaques:

o narrow the arterial lumen causing distal ischemia o weaken the arterial wall leading to formation of aneorysms. the coronary and the cerebral circulations are common sites of atherosclerosis .

The cause of atherosclerosis is not known although several factors have been blamed in the pathogenesis of atherosclerosis. Experimental and epidemiological evidence suggests a relationship between atherosclerosis and elevated levels of plasma lipids (cholesterol and triglycerides). Although there is no diagnostic abnormal pattern of the plasma lipids in subjects with atherosclerosis, an increase in plasma LDL cholesterol and triglycerides has been observed in such patients.

The risk of ischemic heart disease (IHD) in individuals with hypercholesterolaemia is about thrice as great as in those with normal plasma cholesterol. Hence, a reduction of plasma lipid levels either by dietetic restriction or by drugs may prevent the development of atherosclerosis (or) arrest its progress. A reduction in plasma cholesterol infact reduce the risk of Myocandial Infarction.

CLASSIFICATION OF ANTIATHEROSCLEROTIC DRUGS :

These drugs act predominantly on :
Elevated Cholesterol : eg: cholestyramine resli, HMG COA reductase in hibitors (statins) Ezetimibe probocol Elevated triglycerides : eg: Fibric acid derivatives (fibrates), fish oil, Both eg: Nicotinic acid (Niacin).

Mechanism of action of Antiatherosclerotic drugs is by : Inhibition of cholesterol absorption, Interruption of bile acid recirculation, Inhibition of lipid oxidation, Inhibition of cholesterol biosynthesis, Influence on lipid metabolism.

Cholesterol diet induced atherosclerosis in Rabbits. Induction of intimal reactions after endothelial injury. Hypolipidemic activity in rats. Inhibition of the isolated enzyme HMG COA redoctase invitro. Inhibition of the incorporation of Csodium acetate into cholesterol in isolated liver cells. Effect of HMG COA redoctase Inhibitors invivo.

CHOLESTEROL DIET INDUCED ATHEROSCLEROSIS IN Animal model : Rabbit  Test animals RABBITS :are given with diet containing 0.3-2% cholesterol.
 Chemical used formaldehyde.  Apparatus used computerized planimeter.

Procedure :
White New Zealand Male Rabbits

Blood is collected (Marginal ear vein)

Cholesterol & triglycerides are determined

20 Rabbits

10 ( Test )

10 (Control)

Diet with 0.3-2% Cholesterol

Normal Diet

Blood is again withdraw (Cholesterol & triglycerides increased)

Animals Sacrificed

Thoracic aorta

Formaldehyde

Percentage of lesions calculated by Computerised planimeter

Evaluation :
Normal diet rabbits Cholesterol fed rabbits No Staining in Aorta Severe lesions.

COMPUTERISED PLANIMETER

ATHEROGENIC LESIONS

HYPOLIPIDEMIC ACTIVITY IN RATS:

Purpose :
Hyperlipoproteinemia

Cause of arteriosclerosisi (Cholesterol & triglycerides) Classification of lipoproteins :  Chylomicrons  Chylomicrons remnants  VLDL  LDL  HDL Antiarteriosclerotic drugs should reduce VLDL and LDL or elevate HDL.

Procedure :
 Animal modd Male albino wistar rats.  Test drug nicotinic acid (Niacin)  Instrument used HPLC (for determining cholesterol).  Enzymatic assay for determining triglycerides.

20 Rats

Group I ( Test ) 10

Group II (Control) 10

20 hrs before, food is withdrawn but not water

Weighed

Nicotinic acid 1-100 mg/kg dissolved in PEG-400 (5 ml/kg)

only PEG - 400

Blood samples (Retro Orbital Puncture)

Continued for 8 days Animals sacrificed Liver removed (frozen in liq N2 at -25o C)

Blood sample is centrifuged

Cholesterol is determined by Boehringer manhein test by HPLC method

Triglycerides by Enzymatic assay

To estimate Serum lipoproteins serum is collected  VLDL  LDL  VLDL density 1.006 [16 h at 40,000 rpm] density 1.006 to 1.04 [18 h at 40,000 rpm] density 1.04 to 1.21 [18 h at 40,000 rpm]

Frozen samples of liver are extracted with chloroform methanol 2:1 in a teflon homogenizer.

Evaluation :

Average values of body wt, cholesterol and Triglycerides are expressed. Statistical differences between control and treatment groups evaluated.

REFERENCES
1. H. Gerhard Vogel Drug discovery and Evaluation. p. no: 1095 1125. R.S. Satoskar PHARMACOLOGY AND PHARMACOTHERAPEUTICS p. no: 575- 583. K. D. Tripathi Essentials of medical pharmacology. p. no.: 612 620.

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