PRESENTED BY

SUMAYYA SAMREENM. 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 ando Calcification

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

Such Plaques:

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.

Elevated Cholesterol : eg: cholestyramine resli,

HMG COA reductase in hibitors (statins)

Ezetimibe probocol

These drugs act predominantly on :

Elevated triglycerides : eg: Fibric acid

derivatives (fibrates), fish oil,

Both eg: Nicotinic acid (Niacin).

Mechanism of action of Antiatherosclerotic drugs is by :

Animal model : Rabbit Test animals are given with diet containing 0.3-2% cholesterol.

Chemical used – formaldehyde.

Apparatus used – computerized planimeter.

Blood is collected (Marginal ear vein)

White New Zealand Male Rabbits

Cholesterol & triglycerides are determined

20 Rabbits

10 10 ( Test ) (Control)

Blood is again withdraw(Cholesterol & triglycerides increased)

Diet with Normal 0.3-2% Cholesterol Diet

Animals Sacrificed

Thoracic aorta

Formaldehyde

Percentage of lesions calculated byComputerised planimeter

Normal diet rabbits No Staining in AortaCholesterol fed rabbits Severe lesions.

COMPUTERISED PLANIMETER

ATHEROGENIC LESIONS

Hyperlipoproteinemia

Cause of arteriosclerosisi (Cholesterol & triglycerides)

Classification of lipoproteins :

Chylomicrons

Chylomicrons remnants

VLDL

LDL

“ Antiarteriosclerotic drugs should reduce VLDL and LDL or elevate HDL.

HDL

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 Group II ( Test ) 10 (Control) 10

20 hrs before, food is withdrawn but not water

Weighed

Nicotinic acid only PEG - 4001-100 mg/kg dissolved in PEG-400 (5 ml/kg)

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 byEnzymatic assay

To estimate “Serum lipoproteins” serum is collected

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

VLDL density – 1.006 [16 h at 40,000 rpm]

LDL density – 1.006 to 1.04 [18 h at 40,000 rpm]

VLDL density – 1.04 to 1.21 [18 h at 40,000 rpm]

Average values of body wt, cholesterol andTriglycerides are expressed.

Statistical differences between control and treatment groups evaluated.

1. H. Gerhard Vogel “Drug discovery and Evaluation”. p. no: 1095 – 1125.

2. R.S. Satoskar “PHARMACOLOGY AND PHARMACOTHERAPEUTICS” p. no: 575- 583.

3. K. D. Tripathi “Essentials of medical pharmacology”. p. no.: 612 620.