When the supply of oxygen and nutrients

in the blood is insufficient to meet the

demands of the heart, the heart muscle

aches.

The heart demands a large supply of

oxygen to meet the demands placed on it.

Oxygen demand

Oxygen supply=

>

Coronary blood flow

Regional myocardial distribution

Ventricular volume

LV pressure

Wall tension

Heart rate

Contractile state

Aortic pressure

Coronary vascular resistance

Chronic stable angina (also called classic or effort angina)

Unstable angina(also called preinfarction or crescendo angina)

Vasospastic angina(also called Prinzmetal’s or variant angina)

The goal of therapy with antianginal

agents is to restore the balance

between oxygen supply and demand in

the ischemic region of the myocardium.

CLASSIFICATION1.Nitrates Short acting: Glyceryl trinitrate (GTN, Nitro glycerine) Long acting: Isosorbide dinitrate (short acting by S.L

route), Isosorbide mononitrate, Erythrityl tetranitrate, Pentaerythritol tetranitrate

2.β-Blockers

Propranolol, Metoprolol, Atenolol and others.

3.Calcium channel blockers Phenyl alkylamine : Verapamil Benzothiazepine : Diltiazem Dihydropyridines : Nifedipine, Felodipine, Amlodipine,

Nitrendipine, Nimodipine, Lacidipine, Benidipine  

4.Potassium channel opener

Nicorandil, Pinacidil

5.Others Dipyridamole, Trimetazidine,

Oxyphedrine

Clinical Classification

(A)Used to abort or terminate attack GTN,

Isosorbide dinitrate (sublingually).

(B)Used for chronic prophylaxis All other drugs.

Therapeutic Objectives Increase blood flow to ischemic heart muscle and/or

Decrease myocardial oxygen demand

Minimize the frequency of attacks and decrease the

duration and intensity of anginal pain

Improve the patient’s functional capacity with as few side

effects as possible

Prevent or delay the worst possible outcome, MI

Available forms:

Sublingual Ointments

Buccal Transdermal patches

Chewable tablets Inhalable sprays

Capsules Intravenous solutions

Dila of coronary vessels

Dila of coronary vessels

Arterial dilatation Arterial dilatation

Mainly vasodilatation Mainly vasodilatation

Relaxation of vascular smooth muscle fibres

Relaxation of vascular smooth muscle fibres

Increased cGMP Increased cGMP

Dephosphorylation of myosin light chain (reduced ca+ conc in the cytosol)

Dephosphorylation of myosin light chain (reduced ca+ conc in the cytosol)

Nitrates Nitrates

Stimulate Guanylyl cyclase

Stimulate Guanylyl cyclase

Release nitric oxide Release nitric oxide

Denitrated in the smooth muscle cell

Cause vasodilation due to relaxation of smooth muscles

Potent dilating effect on coronary arteries

Used for prophylaxis and treatment of angina

Nitroglycerin Prototypical nitrate

Large first-pass effect with PO forms

Used for symptomatic treatment of ischemic heart

conditions (angina)

I.V form used for BP control in perioperative

hypertension, treatment of CHF, ischemic pain, and

pulmonary edema associated with acute MI

isosorbide dinitrate

(Isordil, Sorbitrate, Dilatrate SR)

isosorbide mononitrate

(Imdur, Monoket, ISMO)

Used for: Acute relief of angina

Prophylaxis in situations that may provoke angina

Long-term prophylaxis of angina

Side Effects Headache

Usually diminish in intensity and frequency

with continued use

Tachycardia, postural hypotension

Tolerance may develop (Monday disease)

Isosorbide dinitrate

Isosorbide dinitrate has active initial

metabolites.

This drug is administered orally or sublingually;

it has better oral BA and a longer half-life (up to

1 h) than nitroglycerin.

Timed-release oral preparations are available

with durations of action up to 12 hours.

Therapeutic uses

1. Sublingual nitroglycerin is most often used for

severe, recurrent Prinzmetal's angina.

2. Continuous infusion or slowly absorbed

preparations of nitroglycerin (including the

transdermal patch) or derivatives with longer half-

lives have been used for unstable angina and

for CHF in the presence of MI.

Adverse effects

Nitrates and nitrites produce vasodilation,

which can lead to orthostatic hypotension, reflex

tachycardia, throbbing headache (may be dose

limiting), blushing, and a burning sensation.

Tolerance.

Large doses produce methemoglobinemia and

cyanosis.

Atenolol (Tenormin)

Metoprolol (Lopressor)

Propranolol (Inderal)

Nadolol (Corgard)

Mechanism of Action Decrease the HR, resulting in decreased myocardial

oxygen demand and increased oxygen delivery to

the heart

Decrease myocardial contractility, helping to

conserve energy or decrease demand

Therapeutic Uses Antianginal

Antihypertensive

Cardioprotective effects, especially after MI

Side Effects

Body System Effects

Cardiovascular bradycardia, hypotension

second- or third-degree heart block

heart failure

Metabolic Altered glucose and lipid

metabolism

Side Effects

Body System Effects

CNS dizziness, fatigue,

mental depression, lethargy,

drowsiness, unusual dreams

Other impotence

wheezing, dyspnea

Phenyl alkylamine:

Verapamil Benzothiazepine:

Diltiazem Dihydropyridines:

Nifedipine,Felodipine,Amlodipine, Nitrendipine,Nimodipine,Lacidipine 

Mechanism: Calcium channel-blocking agents produce a

blockade of L-type (slow) calcium channels, which decreases contractile force and oxygen requirements.

Agents cause coronary vasodilation and relief of spasm

they also dilate peripheral vasculature and decrease cardiac afterload.

Preload refers to total volume of blood in the left ventricle of the heart and the pressure it exerts before the left ventricle contracts. Afterload then is the amount of pressure exerted by the left ventricle when it does contract.

Pharmacologic properties

C C blocking agents can be admi orally.

When admi intravenously, they are effective within minutes.

The therapeutic use of these drugs in angina is generally reserved for instances in which nitrates are ineffective or when β-Blks C/I.

Serum lipids are not increased.

These drugs produce hypotension.

Verapamil Verapamil produces slowed

conduction through the AV node (predominant effect); this may be an unwanted effect in some situations (especially in the treatment of hypertension).

Verapamil may produce AV block when used in combination with β-blks.

The toxic effects of verapamil include myocardial depression, heart failure, and edema.

Verapamil also has peripheral vasodilating effects that can reduce afterload and BP

The peripheral effects of verapamil can produce headache, reflex tachycardia, and fluid retention.

These dihydropyridine CCBls have predominant actions in the peripheral vasculature; they decrease afterload and to a lesser extent preload and lower blood pressure.

These drugs have significantly less direct effect on the heart than verapamil.

Diltiazem Diltiazem, a benzothiazepine, is

intermediate in properties between verapamil and the dihydropyridines.

Diltiazem is used to treat variant (Prinzmetal's) angina, either naturally occurring or drug-induced and stable angina.

Bepridil Bepridil blocks both slow and fast sodium

channels and both voltage-dependent and receptor-mediated calcium channels.

Bepridil is used only when other agents have failed or have elicited intolerable A/E.

Bepridil may cause ventricular arrhythmias.

Therapeutic Uses First-line agents for treatment of angina,

hypertension, and supraventricular tachycardia

Short-term management of atrial fibrillation and

flutter

Several other uses

Their efficacy is similar to nitrates, beta

blockers, CCBs

Main advantages of Nicorandil, it has

longer DOA and does not cause

tolerance

Administered orally

Arterial dilators Arterial dilators

↓Preload↓Preload

VenodilatorsVenodilators

Hyperpolarization of the membrane

Hyperpolarization of the membrane

K+ efflux

K+ efflux

Open ATP-dependent K+ channels

Open ATP-dependent K+ channels

Nicorandil & Pinacidil

Nicorandil & Pinacidil

↓ Afterload ↓ Afterload

Headache Hypotension Palpitation Flushing N,V