ANTIANGINAL DRUGS

Presentation by- ANURAG CHANDAB.Pharm 6th semesterRoll no- 14Gurunanak institute of pharmaceutical science and technology.

Angina pectoris-

The primary cause of angina is an imbalance between myocardial oxygen demand and oxygen supplied by coronary vessels

This imbalance may be due to:

•a decrease in myocardial oxygen delivery•an increase in myocardial oxygen demand•or both

The discomfort abates when supply becomes adequate for demand. Typically angina lasts for seconds to minutes, up to 15 minutes

Classically angina is not associated with ischemic cell death

Types of Angina Pectoris

Stable Angina Variant Angina Unstable Angina

Effort , Typical. Atherosclerosis

Exercise, Emotion, Heavy meal. ↓ Pain

Prinzmetal. ↓ α- receptor mediated Vasoconstriction With or without atherosclerosis.

↓ Pain even at rest

Accelrated Severe typeDue to rupture of an atheromatous plaque attracting platelet deposition and progressive occlusion of the coronary artery

Antianginal AgentsThree major classes of agents are used

individually or in combination to treat angina:1. Organic nitrates:

Vasodilate coronary arteriesReduce preload and aferload

2. Beta-adrenergic blockers:Decrease heart rate and contractility - decrease

in cardiac work and O2 consumptionImprove myocardial perfusion due to decrease in

heart rate – decreased in ventricular wall tensionExercise tolerance

3. Calcium channel blockers:Vasodilate coronary arteriesReduce afterloadThe non-dihydropyridines (verapamil and

diltiazem) also decrease heart rate and contractility

Mechanism of Action of Nitrovasodilators

Nitric Oxide

activates

converts

Guanylate Cyclase*

GTPcGMP

activates

cGMP-dependent protein kinase

Activation of PKG results in phosphorylation of several proteins that reduce intracellular calcium

causing smooth muscle relaxation

Nitrates become denitrated by glutathione S-transferase

to release

Actions of Nitrates - GTN1. Preload reduction:

Dilatation of veins more than arteries – peripheral pooling of Blood – decrease venous return

Will lead to reduction in preload – decreased end diastolic size – decrease in fibre length

Less wall tension to develop for ejection (Laplace`s law) – less oxygen consumption and reduction in ventricular wall pressure (crunch abolished)

2. Afterload reduction: Some amount of arteriolar dilatation – Decrease in peripheral Resistance

(afterload reduction) – reduction in Cardiac work (also fall in BP) Standing posture – pooling of Blood in legs – reflex tachycardia

(prevented by lying down and foot end raising) However in large doses opposite happens – marked fall in BP – reflex

tachycardia – increased cardiac work – precipitation of angina

Actions of Nitrates - contd.

3.Mechanism of angina relief: Variant angina – coronary vasodilatation Classical angina – reduction in Cardiac load Increased exercise tolerance

4. Other actions: Cutaneous vasodilatation (flushing occurs), meningeal vessels dilatation (headache) and decreased renal blood flow

β-Adrenoceptor Blockers

β-Bs → Suppress the activation of the heart (β1). Reduce the work of the heart by ↓ heart rate& cardiac contractility → ↓ C.O.& slight ↓ B.P.

↓

Propranolol

.It is not a vasodilator , so it may worsen variant angina..

.It is used prophylactically to severity& frequency of typical anginal attacks.

.It cardiac O2 demand through: .-ve chronotropic & inotropic actions. .Slight of B.P.

Propranolol can be combined with Nitrates

for typical angina. ( to side effects of both drugs).

Ca++ channel blockers

Nifedipine, Verapamil, Diltiazem Mechanism of action on vascular tissue :

Blocking of Ca++ transmembrane channels in vascular smooth muscle fibers.

→ interference with inward of movement of Ca++

→ affects depolarization & contraction processes

→with relaxant effects mainly on arteriole smooth muscle.

Nifedipine: Prominent vasodilator actions, used in all types of angina with reflex tachycardia & leg œdema.

Verapamil: .Slows conduction & ↓ Heart rate. .Greater –ve inotropic effect with little Vasodialation effects. Diltiazem: .CVS effects similar to verapamil.

.It is used in angina by ↓ coronary spasm (variant angina).

Selection of antianginal drugs

For patients with concomitant diseases:

Concomitant disease Most preferred drugs

Less preferred drugs

Bronchial asthma.

Heart failure

Hypertension.

Diabetes Mellitus.

C.C.Bs, Nitrites& Nitrates.

Nitites & Nitrates.

β-Bs , C.C.Bs.

C.C,Bs ,Nitrites & Nitrates.

β-Bs.

β-Bs ,verapamil,Diltiazem.Nitrites & Nitrates.

β-Bs.

THANK

YOU

Reference-1) Tripathi K.D,Essentials of medical pharmacology. Sixth edition.2)Introduction to pharmacology by S.K kulkarni updated seventh edition.