• Goal of therapy. The goal of therapy with
antianginal agents is to restore the
balance between oxygen supply and
demand in the ischemic region of the
Types of angina
1. Classic angina (angina of exercise).
Ø occurs when oxygen demand exceeds oxygen
supply, usually because of diminished coronary flow.
2. Vasospastic (Prinzmetal's, or variant) angina.
Ø results from reversible coronary vasospasm that
decreases oxygen supply and occurs at rest.
Ø Some individuals have mixed angina, in which both
exercise-induced and resting attacks may occur.
Low oxygen supply High oxygen demand
Anti anginal drugs
Nitrates and nitrites
• Structure and mechanism
• Nitrates and nitrites are polyol esters of nitric acid
(nitrates) or nitrous acid (nitrites) that relax
vascular smooth muscle.
• Nitrates and nitrites activate guanylate cyclase and
increase cyclic guanine nucleotides.
• This activates cGMP-dependent kinases that
ultimately lead to dephosphorylation of myosin light
– These drugs dilate all vessels:
A. Peripheral venodilation decreases cardiac
preload and myocardial wall tension
B. arterial dilation reduces afterload.
– Both of these actions lower oxygen demand by
decreasing the work of the heart.
– Coronary vessels may also be dilated, and coronary
blood flow to ischemic regions is increased.
• Nitrates and nitrites ameliorate the symptoms of
classic angina predominantly through the
improvement of hemodynamics.
• Variant angina is relieved through effects on
• Nitrates and nitrites form nitrosothiol in smooth
muscle by reaction with glutathione.
• Tolerance occurs upon glutathione depletion.
– Bioavailability and selected drugs.
– These drugs have a large first-pass effect due
to the presence of high-capacity organic
nitrate reductase in the liver, which inactivates
– Nitrates have a t1/2 of less than 10 minutes.
• Nitroglycerin is preferably administered
sublingually for rapid delivery and short duration.
• Sustained-delivery systems [Transderm-Nitro,
Nitrodisc] are available and are used to maintain
• Aerosol, topical, intravenous, and oral preparations
are also available.
• Amyl nitrite
– is a volatile liquid that is inhaled.
– An unpleasant odor
– extensive cutaneous vasodilation render it less
desirable than nitroglycerin.
• Isosorbide dinitrate
• Isosorbide dinitrate has active initial metabolites.
• This drug is administered orally or sublingually;
• it has better oral bioavailability 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.
Continuous exposure may lead to tolerance.
• Large doses produce methemoglobinemia and
– β-Adrenoceptor antagonists decrease:
• heart rate
• blood pressure
– resulting in decreased myocardial oxygen
– Combined therapy with nitrates is often preferred in
the treatment of angina pectoris because of the
decreased adverse effects of both agents.
– β-Adrenoceptor antagonists are contraindicated in the
presence of bradycardia, AV block and asthma.
Calcium channel-blocking agents
– Calcium channel-blocking agents produce a
blockade of L-type (slow) calcium channels,
which decreases contractile force and oxygen
ØAgents cause coronary vasodilation and relief of
Øthey also dilate peripheral vasculature and
decrease cardiac afterload.
– Pharmacologic properties
• Calcium channel-blocking agents can be administered orally.
• When administered intravenously, they are effective within
• The therapeutic use of these drugs in angina is generally
reserved for instances in which nitrates are ineffective or
when β-adrenoceptor antagonists are contraindicated.
• Serum lipids are not increased.
• These drugs produce hypotension.
Selected CCB drugs
– 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-adrenoceptor antagonists.
– The toxic effects of verapamil include
myocardial depression, heart failure, and
– Verapamil also has peripheral vasodilating
effects that can reduce afterload and blood
– The peripheral effects of verapamil can
produce headaches, reflex tachycardia, and
Nifedipine, isradipine, nisoldipine,
• These dihydropyridine calcium-channel
blockers 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, a benzothiazepine, is intermediate in
properties between verapamil and the
– Diltiazem is used to treat variant (Prinzmetal's)
angina, either naturally occurring or drug-
induced and stable angina.
– 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 adverse
– Bepridil may cause ventricular arrhythmias.
• Dipyridamole is a nonnitrate coronary vasodilator that
interferes with uptake of the vasodilator adenosine.
• It potentiates the effect of PGI2 (prostacyclin,
epoprostenol) and dilates resistance vessels and inhibits
• Dipyridamole may be used for prophylaxis of angina
pectoris, but the efficacy of this drug is not proved.
• Dipyridamole produces adverse effects that include the
worsening of angina, dizziness, and headache.
K CHANNEL OPENERS :
• The most prominent action of K+ channel
• Causes Smooth muscle relaxation of Vascular
and Visceral tissues.
• Used for angina pectoris.
• Trimetazidine is an anti-ischemic (anti-anginal)
agent, that improves myocardial glucose
utilization through inhibition of fatty acid