ANGINA PECTORIS

ANGINA PECTORIS

By:- PARTH SHAH M.Pharm(Pharmacology)

ANGINA PECTORISA Chronic disease of CVS

Occurs with Interminent chest pain spread along the Chest, Shoulders and Arms.

•Angina pectoris, or angina, as it is commonly referred to, and coronary artery disease or arteriosclerosis are closely related.

•Angina occurs in people who have some form of blockage in the coronary arteries. In other words, it occurs in people with coronary heart disease.

•Angina pectoris: a heart condition marked by paroxysms of chest pain due to reduced oxygen to the heart

• 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 CIRCULATIONMost 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

Types Of Angina Pectoris1. Stable Angina

2. Unstable Angina

3. Variant Angina (Prinzmetal’s

Angina)

4. Anginal Equivalent Syndrome

5. Syndrome- X

6. Silent Ischemia

STABLE ANGINAPredictableOccurs 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 ANGINAThis is characterized by Pain that occurs with

less excertion , cumulating pain at rest.The pathology is similar to that involved in

Myocardial Infraction, namely platelet-fibrin thrombus associated with a ruptured atheromatous plaque, but without complete occulation of the vessels.

The risk of infraction is subtanial, and the main aim of therapy is to reduce this.

VARIANT ANGINA (PRINZMETAL’S ANGINA)UncommonOccurs at rest generally during sleepCaused by Large Coronary Artery SpasmUsually associated with atheromatous

diseaseAbnormally reactive and

hypertrophied segments in the Coronary Artery

Drugs aimed at preventing & relieving Coronary Spasm.

ANGINAL EQUIVALENT SYNDROMEPatient’s with exertional dyspnea rather

than exertional chest pain

Caused by exercise induced left ventricular dysfunction

ANGINA: SYNDROME XTypical , exertional angina with positive

exercise stress testAnatomically normal coronary arteriesReduced capacity of vasodilation in

microvasculatureCalcium channel blockers and Beta blockers

are effective.

ANGINA: SILENT ISCHEMIAVery Common

More episodes of Silent than Painful angina

in the same patient.

Difficult to diagnose

Gnerally Exercise testing.

DIAGNOSIS1. STRESS (EXERCISE) TEST.2. ECG (ELECTROCARDIOGRAPHY)3. CHEST X-RAY4. CARDIAC ANGIOGRAPHY/ CARDIAC

CATHETERIZATION5. ERGONOVINE TEST6. BLOOD TEST (BIO-MARKERS)

1. EXERCISE TEST/STRESS TESTUsed to measure heart’s response to exercisePatient asked to walk on a treadmill while the

physician takes the ECG So any changes in heart function can be

determinedAlternatively the patient recieves an injection

of a radioisotope (generally Thallium) which makes the heart visible to a special-linked camera

90% accurateBut doesn’t identify the exactly where and

how the coronary arteries are blocked.

2. ELECTROCARDIOGRAM (ECG)Measures electrical activity of the heartProvides info about the changes or damages

to the heart muscleDoesn’t detect the narrowing of the coronary

arteriesDuring an Anginal attack the ECG may show 1. S-T phase depression.2. T- phase inversion and/or3. Ventricular arrythmia ECG- more abnormal with Unstable Angina

where the elevation in S-T segment is found.

STABLE ANGINA

At Rest

After Excercise

3. CHEST X-RAYPerformed to rule out any lung disease or

heart damage that may be causing the pain.Also may reveal enlargement of heart

4. CARDIAC ANGIOGRAPHY/ CARDIAC CATHETERIZATIONShows the precise size and location of

blockages within the Coronary arteriesA cathereter is inserted through the blood

vessels from the forearm or groinIt is snaked through arteries till it reaches

the heartA fluid is pumpedSo the arteries and the heart are clearly

visible

5. ERGONOVINE TESTGenerally done if the person is assumed to

suffer from Coronary SpasmDone along with angiographyThe artery-narrowing drug—Ergonovine or

Ach is given to cause Coronary SpasmThe persons response to ergonovanine is

measured

6. BLOOD TEST/BIOMARKERSBlood test for amount of Lipids within the

bloodBecause lipids major cause of anginal attackLipid 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 moratality of heart disease

TREATMENT3 Classes of drugs used according their mode

of action

1. NITRATES2. - ADRENOCEPTOR ANTAGONISTS3. CALCIUM CHANNEL ANTAGONISTS4. ANTIPLATELET DRUGS

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 ↓Contactility, ↓HR, ↓O2 demand (Beta-blockers)

d. Coronary Dilation, Important mechanism for relieving vasospastic angina, ↑O2 supply (Nitrates)

NITRATESProdrugsSources of Nitric OxideEg:- Nitroglycerin, Isosorbide Dinitrate Isosorbide-5-Mononitrate

Mechanism Of Action

PHARMACO-LOGICAL ACTIONS OF NITRATES

Nitrates mainly give Vasoldilation effectThe specificity of their action is in dilating the

collateralsUnlike other vasodilators (dipyridamole) which

dilate only the arteries but not the collaterals

TOXICITY OF NITRATESHeadacheIncreased mortalityRecurrence of Myocardial InfractionDizzinessFlushingRapid heart beatRestlessnessDry mouthSkin rashNausea

MARKETED FORMULATIONSGTN Sorbitrate (PIRAMAL)Vasovin (TORRENT)

ISMO retard (PIRAMAL)Angicor (NOVARTIS)

Nitroglyceride

Isosorbide-5-monophosphate

CALCIUM CHANNEL ANTAGONISTSDisrupt Ca++ through Ca++ channels-ve ionotrpic effect2 types:-1. Dihydropyridine (amlodipine, nifedipine,

nicardipine)2. Non-Dihydropyridine

1. Phenylalkylamine (verapamil, gallopamil)2. Benzodiazapenes (diltiazem)3. Non-selective (bepridil, mibefradil)

MECHANISM OF ACTION

Pharmacological Actions

TOXIC EFFECTS

MARKETED PREPARATIONSCalaptin (PIRAMAL)Vasopten (TORRENT)Coriem XL (RANBAXY)Dicard (INTAS)Amtas (INTAS)Cadeut (PFIZER)

Verapamil

Diltiazem

Amplodipine

-ADRENOCEPTOR ANTAGONOSTSImportant in prophylaxis of angina and

treating unstable anginaDecrease O2 consumption by the heartEffects on coronary vessels-not importantAvoided in variant anginaAs they increase the chances of spasmEg:-

Atenolol Propranolol

PHARMACOLOGICAL ACTIONS

MECHANISM OF ACTION

MARKETED PREPARATIONSBetacard ( TORRENT)

Aten (ZYDUS CADILA)

Betacap (SUN PHARMA)

Cardilax (INTAS)

ANTICOAGULANTS Anticoagulants are often called "blood

thinners," although they don't really thin blood. They decrease the blood's ability to clot.Eg Heparin, Dalteparin, Enoxaparin, Warfarin,

Aspirin

COMPARITIVE TOXIC EFFECTS

COMBINATION THERAPY1. Nitrates + -blockers :- in stable angina2. 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 Preload2. Ca++ channel Blockers:- decrease Afterload3. -blockers:- decrease heart rate and

myocardial contractions

Recommended Drug therapy for Angina with other medications

NEWER DRUGSRANOLAZINE (Ranexa™; CV Therapeutics,

Inc.), a drug that has been in development for 20 years. It is a Sodium Channel Blocker.

NICORANDIL, a potassium channel activator, and also has a Nitrogen Donating Moeity.

IVABRADINE, inhibits the If channel in the sinus node and thereby causes bradycardia without any negative inotropic effects.

THANK YOU!!!!