atherosclerosis by jitendra bhangale

© 2010 Delmar, Cengage Learning1

atherosclerosisBy- Jitendra Bhangale

Assistant Professor & Head,Department of Pharmacology,Smt N. M. Padalia Pharmacy

College,Ahmedabad


Introduction

Signs and Symptoms

Causes

Mechanism Of Atherosclerosis

Risk Factors

Screening and Diagnosis

Management and Prevention

Recent Research

ReferencesBy Jitendra Bhangale

Asst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad

Contents


Atherosclerosis is a process in which patchy deposits of fatty material develop in walls of medium-sized and large arteries leading to blocked blood flow.

It is commonly referred to as hardening of the arteries. It is caused by formation of multiple plaques within the arteries.

The atheromatous plaque is divided into three components:

1. Atheroma

2. Underlying areas of cholesterol crystals.

3.Calcification at outer base of older lesions.By Jitendra Bhangale


Introduction


Atherosclerosis becomes seriously symptomatic when interfering with coronary circulation supplying the heart, leading to Heart Attack.

If it blocks blood vessels in brain, then it causes Stroke.

If blood supply to arms and legs is reduced, it can cause Peripheral Vascular Diseases [PVD].

By Jitendra Bhangale Asst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy

College, Ahmedabad

Signs & Symptoms



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Signs & Symptoms


Atherosclerosis is Chronic Inflammatory Response starting with damage or injury to inner layer of artery.

Damage may be caused by factors:

High BP

High Cholesterol

Irritant: nicotine

Certain diseases


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Causes



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Mechanism


Raised low density

lipoprotein

Reduced high density

lipoprotein

Hypertension

Diabetes Mellitus

Cigarette Smoking


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Obesity

Physical Inactivity

Raised C-reactive protein

Raised coagulation factors(e.g. Factor VII, Fibrinogen.)

Family history and early heart diseases

Risk factors



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Screening and diagnosis

StressTest

measures

blo

od

supply

to h

eart

CoronaryAngiography

spec

ific

shows

coro

nari

es

Narrowing in

Site

s of

Electro-cardiogram

measures

ele

ctr

ical

impulse

s


Blood tests: used to evaluate kidney and thyroid function as well as to check cholesterol levels and the presence of anemia.

Chest X-ray: shows the size of your heart and whether there is fluid build up around the heart and lungs.

Echocardiogram: shows a graphic outline of the heart’s movement

Ejection fraction (EF): determines how well your heart pumps with each beat.


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Screening and diagnosis


Many people are able to manage coronary artery disease with lifestyle changes and medications.

Other people with severe coronary artery disease may need angioplasty or surgery.


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Management



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Management


Stenting a stent is introduced into a blood vessel on a balloon catheter and advanced into the blocked area of the artery the balloon is then inflated and causes the stent to expand until it fits the inner wall of the vessel, conforming to contours as needed the balloon is then deflated and drawn backThe stent stays in place permanently, holding the vessel open and improving the flow of blood.


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Management


Angioplasty:-a balloon catheter is passed through the guiding catheter to the area near the narrowing. A guide wire inside the balloon catheter is then advanced through the artery until the tip is beyond the narrowing. the angioplasty catheter is moved over the guide wire until the balloon is within the narrowed segment. balloon is inflated, compressing the plaque against the artery wall once plaque has been compressed and the artery has been sufficiently opened, the balloon catheter will be deflated and removed.


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Management


Bypass surgery

healthy blood vessel is removed from leg, arm or chest

blood vessel is used to create new blood flow path in your heart

the “bypass graft” enables blood to reach your heart


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by flowing around (bypassing) the blocked portion of the diseased artery. The increased blood flow reduces angina and the risk of heart attack.

Management


Cholesterol medications [Lipid Lowering drugs]:Statins: HMG-COA Reductase InhibitorsFibratesBile Acid Binding ResinsOthers: Nicotinic Acid, Probucol, Fish Oil.

Antiplatelet Medications-AspirinAnti Coagulants- Heparin, WarfarinBP Medications- ACE inhibitors, Beta blockers, Ca+ channel blockersOther Medications


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Hypocholesterolemic agents


E.g. Simvastatin, Pravastatin, Lovostatin,

Atorvastatin

The statins are all potent competitive inhibitors of

the enzyme 3-hydroxy-3-methylglutaryl coenzyme A

reductase (HMG CoA reductase), the rate-limiting

enzyme in cholesterol biosynthesis.

The liver is their target organ, and decreased hepatic

cholesterol synthesis ultimately leads to increased

removal of LDL particles from the circulation.By Jitendra Bhangale


Statins


Adverse effect of statins:-

Myositis inflammation of skeletal muscle

accompanied by pain, weakness, and high

levels of serum creatine kinase.

Rhabdomyolysis, i.e., disintegration of

muscle with urinary excretion of myoglobin

and kidney damage.


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Statins


E.g. Gemfibrozil, Fenofibrate, Clofibrate

The fibrates typically lower VLDL triglyceride and elevate plasma HDL cholesterol.

The reduction of plasma triglycerides in humans appears due to increased lipoprotein lipase (LPL) activity.

The fibrates activate a nuclear receptor (transcription factor) termed peroxisomal proliferation activated receptor (PPAR) that is a member of the steroid hormone receptor superfamily.

PPAR increases transcription of the LPL gene and decreases transcription of the apolipoprotein CIII gene (apo CIII).

Since LPL is responsible for catabolism of VLDL triglyceride and apo CIII is an inhibitor of LPL activity, the combined consequences of these changes are increased LPL activity and enhanced removal of triglyceride from the circulation.


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Fibrates


Adverse effect of fibrates:-

GI distress

Myositis and erectile dysfunction, particularly

with clofibrate


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Fibrates


e.g. Colestyramine & Colesipol

These drugs are basically anion exchange resins that remain in the gut, bind intestinal bile acids, and greatly increase their fecal excretion.

The lowered concentration of bile acids returning to the liver by the enterohepatic circulation results in derepression of 7- α hydroxylase, the rate-limiting enzyme for conversion of cholesterol to bile acids.

This results in increased use of cholesterol to replace the excreted bile acids and lowering of hepatic cholesterol.

Thus, similar to the statins, the ultimate actions of the bile acid–sequestering resins are upregulation of transcription of the LDL receptor gene, increased hepatic receptor activity, and lowering of plasma LDL cholesterol


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Resins


Nicotinic acid decreases formation and secretion of VLDL by the

liver.

This action appears secondary to its ability to inhibit fatty acid

mobilization from adipose tissue.

Circulating free fatty acids provide the main source of fatty

acids for hepatictriglyceride synthesis, and lowering triglyceride

synthesis lowers VLDL formation and secretion by the liver.

Since plasma VLDL is the source of LDL, lowering VLDL can

ultimately lower LDL. In addition, nicotinic acid shifts LDL particles

to larger sizes.


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Nicotinic acid


Adverse effect of nicotinic acid

Intense cutaneous flush

Gastrointestinal (GI) distress

liver dysfunction (especially at high doses),

Decreased glucose tolerance,

hyperglycemia

hyperuricemia


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Nicotinic acid



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Prevention

Exercise for at least 30 mins a day 5 days a week

Eat Healthy Foods

Manage Depression, Stress & Anxiety


1. Rang, H. P., Dale, M. N., Pharmacology, Churchill Livingston, UK, 306-309.

2. Dipiro, Joseph L, Pharmacotherapy:A Pathophysiological Approach, Elsevier, 405.

3. Roger and Walker, Clinical Pharmacy and Therapeutics,Churchill, 353

4. Katzung, B. G., Basic and Clinical Pharmacology, Lange Medical Publisher, USA, 316,317,184.

5. Barar, F. S. K., Essentials of Pharmacotherapeutics; Delhi, 341

6. Tripathi; K. D., Medical Pharmacology, 500-501


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References



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THANK YOU

atherosclerosis by jitendra bhangale

Documents

learning pharmacy

apo ciii

blood vessel

nicotinic

adverse effect

heart attack

balloon catheter

cholesterol