JOY B.

JOHNSON
Department of Pharmacology
OUTLINE
 Introduction
 Definition
 Prevalence
 Aetiology
 Risk factors
 Pathophysiology
 Clinical features
 Types of Angina
 Diagnosis
 Objectives
 Therapeutic strategy
 Drug Treatment
 ANGINA PECTORIS
 A Chronic disease of CVS

 Occurs with Intermittent

chest pain spread along the
Chest, Shoulders and Arms.
 Angina pectoris is a term used to describe paroxysms of
chest pain that is caused by myocardial ischemia.
 Myocardial ischemia is a condition in which the amount of
oxygen that is supplied to the heart muscle is insufficient.
 It generally occurs on exertion and it can be relieved by
rest.
 In general, angina is a symptom of coronary artery disease
which occurs in people who have some form of blockade in
the coronary arteries.
 In most severe cases, it occurs with minimal effort or at rest.
PREVALENCE
 The prevalence of angina rises with increasing age, with a mean
age of onset of 62.3 years.

 After five years post-onset, 4.8% of individuals with angina

subsequently die from coronary heart disease.

 Men with angina were found to have an increased risk of

subsequent acute myocardial infarction and coronary heart
disease related death than women.
ETIOLOGY
 Coronary artery spasm
 Atherosclerotic accumulation of plaque buildup causing
critical blockage of the coronary artery.
RISK FACTORS
 Sedentary lifestyle: particularly in case of urban people.
 They generally lead a lifestyle that is characterized by
minimum physical activity.
 The food habits, particularly in case of urban youth are
faulty.
 This puts an additional burden on the heart increasing the
susceptibility of such people to angina pectoris
 High blood pressure or hypertension: People suffering from
high blood pressure are susceptible to a heart attack.
 High cholesterol levels: people whose blood reports show
high cholesterol levels are susceptible to angina pectoris.
 Diabetes: Research studies have proved that diabetes
patients are highly susceptible to angina pectoris.
 Family history of premature ischemic heart disease
Smoking: It is the most common cause of angina pectoris.
Smoking immensely damages the heart muscles.
 Age
 Sex
 Obesity
PATHOPHYSIOLOGY
•It occurs when the Oxygen Supply to the Myocardium is
insufficient for its needs.
 Factors affecting Oxygen Demand Supply Ratio
 Various Chemical Factors released from Ischeamic Muscle
like
1. K+
2. H+
3. Adenosine
are responsible to stimulate the Nociceptors i.e Chest
Pain when the muscles contract with interrupted supply of
blood.

 Also the same mediators that cause Coronary

Vasodilation are responsible for this Pain.
 Also may occur due to accumulation of the waste products
in the heart muscle and stimulate local nerve endings.

 The usual discomfort is regarded as a pressure, heaviness,

tightness, squeezing, burning or choking sensation.

 The angina – coronary occlusion occurs which leads to the

Anginal attack over a period of time.
ANGINA-CORONARY OCCLUSION

CORONARY OCCLUSION
CORONARY CIRCULATION
 Most tissues can increase O2 extraction with demand.
 Heart extracts near maximal amount of O2 at rest.
 Therefore can increase O2 demand by increasing the
Coronary Blood Flow.

Various Coronary
Arteries of Heart
CLINICAL FEATURES
 An uncomfortable pressure, fullness, squeezing, or pain in
the centre of the chest
 Shortness of breath
 Light-headedness'
 Fainting
 Sweating or cold, sweaty skin
 Anxiety or nervousness
 Nausea
 Rapid or irregular heart beat
 Pallor (pale skin)
 Feeling of impending doom
 Types Of Angina Pectoris

1. Stable Angina

2. Unstable Angina

3. Variant Angina (Prinzmetal’s Angina)

4. Anginal Equivalent Syndrome

5. Syndrome- X

6. Silent Ischemia
STABLE ANGINA
 Predictable
 Occurs on exercise, emotion or eating.
 Caused by increase demand of the heart and by a fixed
narrowing of coronary vessels, almost always by atheroma.
 Coronary obstruction is ‘fixed’
 Blood flow fails to increase during increased demand
despite the local factors mediated ‘vasodilation’ and so
ischeamic pain is felt.
 So, the diastolic pressure increases and this causes a
endocrinal ‘crunch’ and thus causing Ischeamatic pain in
this region.
 Thus, a form of acutely developing and rapidly reversible
left ventricular failure results which is relieved by taking rest
and reducing the myocardial workload.
UNSTABLE ANGINA
 This is characterized by Pain that occurs with less exertion ,
cumulating pain at rest.
 The pathology is similar to that involved in Myocardial
Infarction, namely platelet-fibrin thrombus associated with a
ruptured atheromatous plaque, but without complete
occlusion of the vessels.
 The risk of infarction is
substantial, and the main aim of therapy is to reduce this.
VARIANT ANGINA (PRINZMETAL’S ANGINA)
 Uncommon
 Occurs at rest generally during sleep
 Caused by Large Coronary Artery Spasm
 Usually associated with atheromatous disease
 Abnormally reactive and
hypertrophied segments in
the Coronary Artery
 Drugs aimed at preventing &
relieving Coronary Spasm.
ANGINAL EQUIVALENT SYNDROME
 Patient’s with exertional dyspnea rather than exertional
chest pain

 Caused by exercise induced left ventricular dysfunction

ANGINA: SYNDROME X
 Typical , exertional angina with positive exercise stress test
 Anatomically normal coronary arteries
 Reduced capacity of vasodilation in microvasculature
 Calcium channel blockers and Beta blockers are effective.
ANGINA: SILENT ISCHEMIA
 Very Common

 More episodes of Silent than Painful angina in the same

patient.

 Difficult to diagnose

 Generally Exercise testing.

DIAGNOSIS
1. STRESS (EXERCISE) TEST.
2. ECG (ELECTROCARDIOGRAPHY)
3. CARDIAC ANGIOGRAPHY/ CARDIAC
CATHETERIZATION
4. ERGONOVINE TEST
5. BLOOD TEST (BIO-MARKERS)
1. EXERCISE TEST/STRESS TEST
 Used to measure heart’s response to exercise
 Patient asked to walk on a treadmill while the physician
takes the ECG
 So any changes in heart function can be determined
 Alternatively the patient receives an injection of a
radioisotope (generally Thallium) which makes the heart
visible to a special-linked camera
 90% accurate
 But doesn’t identify exactly where and how the coronary
arteries are blocked.
2. ELECTROCARDIOGRAM (ECG)
 Measures electrical activity of the heart
 Provides info about the changes or damages to the heart
muscle
 Doesn’t detect the narrowing of the coronary arteries
 During an Anginal attack the ECG may show
1. S-T phase depression.
2. T- phase inversion and/or
3. Ventricular arrythmia
 ECG- more abnormal with Unstable Angina where the
elevation in S-T segment is found.
 STABLE ANGINA

At Rest

After
Exercise
4. CARDIAC ANGIOGRAPHY/
CARDIAC CATHETERIZATION
 Shows the precise size and location of blockages within the
Coronary arteries
 A catheter is inserted through the blood vessels from the
forearm or groin
 It is snaked through arteries till it reaches the heart
 A fluid is pumped
 So the arteries and the heart are clearly visible
5. ERGONOVINE TEST
 Generally done if the person is assumed to suffer from
Coronary Spasm
 Done along with angiography
 The artery-narrowing drug—Ergonovine or Ach is given to
cause Coronary Spasm
 The persons response to ergonovine is measured
6. BLOOD TEST/BIOMARKERS
 Blood test for amount of Lipids within the blood
 Because lipids major cause of anginal attack
 Lipid profile for :- 1. HDL 2. LDL 3. TRIGLYCERIDES
 Recently the newer biomarkers like the C-reactive protein
and B-type natriuretic protein have been found out and the
tests for each of them is done
 These tests are predictive of the mortality of heart disease
OBJECTIVES
 To relieve the patient from pain
 To increase exercise tolerance
 To identify and treat underlying cause
 To prevent recurrence
 To prevent complications i.e myocardial infarction
THERAPEUTIC STRATEGY
 To decrease the demand for Oxygen
 To increase the supply of Oxygen
TREATMENT
1. ORGANIC NITRATES
2. - ADRENOCEPTOR ANTAGONISTS
3. CALCIUM CHANNEL ANTAGONISTS
4. ANTIPLATELET DRUGS
ORGANIC NITRATES

 Sources of Nitric Oxide

 Oral bioavailability is very low
 (10-20%)
 Excreted via the kidney.
 Metabolised in the liver
 Metabolites are active esp dinitro
 and mononitro forms
 Mechanism Of Action
E.gs of Organic Nitrates

 Nitroglycerin,
 Isosorbide Dinitrate
 Isosorbide-5-Mononitrate
 Amyl Nitrite
PHARMACOLOGICAL ACTIONS
 Dilate both arteries and veins, venous dilation
predominates when these drugs are given at normal
therapeutic doses.
 Venous dilation venous pressure and ventricular
preload ventricular wall stress and oxygen demand by
the heart,thereby the oxygen supply/demand ratio.
 A reduction in preload (reduced diastolic wall stress) also
helps to improve subendocardial blood flow, which is often
compromised in coronary artery disease.
 Mild coronary dilation or reversal of coronary vasospasm
will further enhance the oxygen supply/demand ratio and
diminish the anginal pain.
 Systemic arterial dilation afterload, which can
cardiac output while at the same time ventricular wall
stress and oxygen demand.
 At high concentrations, excessive systemic vasodilation
may lead to hypotension and a baroreceptor reflex that
produces tachycardia.
 When this occurs, the beneficial effects on the oxygen
supply/demand ratio are partially offset.
 Furthermore, tachycardia, by reducing the duration of
diastole, decreases the time available for coronary
perfusion, most of which occurs during diastole
PHARMACO-
LOGICAL
ACTIONS OF
NITRATES
 Nitrates mainly give Vasodilation effect
 The specificity of their action is in dilating the collaterals
 Unlike other vasodilators (dipyridamole) which dilate only
the arteries but not the collaterals
TOXICITY OF NITRATES
 Headache
 Increased mortality
 Recurrence of Myocardial Infarction
 Dizziness
 Flushing
 Rapid heart beat
 Restlessness
 Dry mouth
 Skin rash
 Nausea
CALCIUM CHANNEL ANTAGONISTS
 Disrupt Ca++ through Ca++ channels
 -ve ionotropic effect
 2 types:-
1. Dihydropyridines(amlodipine, nifedipine, nicardipine)
2. Non-Dihydropyridine
1. Phenylalkylamine (verapamil, gallopamil)
2. Benzodiazipenes (diltiazem)
3. Non-selective (bepridil, mibefradil)
MECHANISM OF ACTION
PHARMACOLOGICAL ACTIONS
 They possess vasodilator and cardiodepressant actions.
Systemic vasodilation reduces arterial pressure, which
reduces ventricular afterload (wall stress) thereby
decreasing oxygen demand.
 The more cardioselective CCBs (verapamil and
diltiazem) decrease heart rate and contractility, which
leads to a reduction in myocardial oxygen demand,
which makes them excellent antianginal drugs.
 CCBs can also dilate coronary arteries and prevent or
reverse coronary vasospasm (as occurs in Printzmetal's
variant angina), thereby increasing oxygen supply to
the myocardium.
Pharmaco
-logical
Actions
TOXIC EFFECTS
-ADRENOCEPTOR ANTAGONISTS
 Important in prophylaxis of angina and treating unstable
angina
 Decrease O2 consumption by the heart
 Effects on coronary vessels-not important
 Avoided in variant angina
 As they increase the chances of spasm
E.G’S OF BETA BLOCKERS
 Atenolol
 Propranolol
 Carvedilol
 Labetalol
 Nadolol
 Acebutolol
PHARMACOLOGICAL ACTIONS
MECHANISM OF ACTION
ANTICOAGULANTS
 Anticoagulants are often called "blood thinners," although
they don't really thin blood. They decrease the blood's ability
to clot.
 E.g. Heparin, Dalteparin, Enoxaparin, Warfarin, Aspirin
Summary of drugs used in Angina
IMPROVING OXYGEN DEMAND : SUPPLY RATIO

a. Relaxation of resistance vessels (small arteries and

arterioles) ↓TPR → ↓BP → ↓ Afterload (Nitrates, calcium
channel blockers and beta-blockers)
b. Relaxation of capacitance vessels (veins and venules)
↓Venous return, ↓heart size, ↓Preload (Nitrates and calcium
channel blockers)
c. Blockade or attenuation of sympathetic influence on the
heart ↓Contractility, ↓HR, ↓O2 demand (Beta-blockers)
d. Coronary Dilation, Important mechanism for relieving
vasospastic angina, ↑O2 supply (Nitrates)
COMPARATIVE TOXIC EFFECTS
 COMBINATION THERAPY
1. Nitrates + -blockers :- in stable angina
2. Ca++ channel blockers + -blockers :-in stable
angina when the treatment with nitrates and -
blockers has failed.
3. Ca++ channel blockers + Nitrates :- in unstable
angina
4. All 3 together:- when the combinations of 2 drugs
has failed, where:-
1. Nitrates:- decrease Preload
2. Ca++ channel Blockers:- decrease Afterload
3. -blockers:- decrease heart rate and myocardial
contractions
DRUGS UNDER INVESTIGATION FOR USE IN ANGINA

 RANOLAZINE (P-FOX Inhibitors), a drug that has

been in development for 20 years. It is a Sodium
Channel Blocker.

 NITRIC OXIDE DONORS: L-arginine

 NICORANDIL, a potassium channel activator, and also

has a Nitrogen Donating Moiety.

 IVABRADINE, inhibits the If channel in the sinus node

and thereby causes bradycardia without any negative
inotropic effects.
THANK YOU!!!!