Anti-anginal drugs

ANTI-ANGINAL DRUGS
Anginal pain occurs when the coronary
blood flow is insufficient to meet the
hearts metabolic requirements:
- spasm of coronary artery
- fixed narrowing of coronary artery
due to an atheromatous plaque,some
times complicated by platelet-fibrin
thrombus.

DRUGS THAT ARE USED IN

ANGINA

Organic nitrates
Calcium antagonists
- adrenoceptor antagonists

Organic nitrates
Powerful vasodilators,acting mainly on
capacitance vessels to reduce preload.
Act by intracellular production of NO,
which stimulates cGMP formation,
affecting both contractile proteins and
Calcium regulation.
Tolerance occurs experimentally,but
not thought to be important clinically.

 Effectiveness in angina is due partly to

reduced cardiac load,partly to dilatation
of collateral coronary vessels,causing
more effective distribution of coronary
flow.
In variant angina,dilatation of constricted coronary vessels is beneficial.
Important compound are:
Glyceryl trinitrate,used sublingually
for rapid anti-anginal effect;

-Isosorbide dinitrate,used sublingualy

or orally for prophylaxis and more
sustained effect
Nitroprusside,used for rapid lowering
of blood pressure,acts in the same
way.
No serious unwnted effects; headache
postural hypotension may occur initially,but tolerance develops.
In overdose,may cause
methaemoglobinaemia.

CALCIUM ANTAGONISTS
Three main types,typified by Verapamil,
Diltiazem ,Dihydropyridines (e.g. nifedipine) respectively.
Act by preventing opening of voltagegated Ca channels (L-type).
Mainly affect heart and smooth muscle,
causing inhibition of Ca2+ entry associated
with depolarisation.

 Selectivity between heart and smooth

muscle varies:
Verapamil is relatively cardioselective.
Nifedipine is relatively smooth-musleselective and Diltiazem is intermediate
Vasodilator effect (mainly Dihydropyridine ) is mainly on resistance vessels,
causing reduced afterload.
Calcium antagonists also dilate
coronary vessels,but this is not clinically important except in Variant angina.

 Clinical uses include:

Antidysrhythmic therapy (mainly
verapamil,diltiazem,especilly atrial tachycardias),heart failure (dihydropyridines), Angina (by reducing cardiac
work) and Hypertension.
Unwanted effects
(headache,constipation) are generally
minor.There is a risk of causing cardiac
failure or heart block with verapamil
and diltiazem.

Dari Medical Pharmacology at a Glance , M.J. NEAL ,second ed. 1995

Anti-anginal therapy
Unstable angina is caused by plateletfibrin thrombus on coronary artery
atheroma.The most important drug is
aspirin,because it reduces the
incidence of myocardial infarction.
Glyceryl trinitrate as an intravenous
infusion is very effective in relieving in
this setting.

 Stable angina is caused by fixed coro

nary artery narrowing due to atheroma.
Drugs and other measures to prevent
progression of atheroma and cause it
regression are important long-term measures.
Duration of pain in stable angina is
usually only a few minutes on stopping
exercise; this can be reduced by sublingual glyceryl trinitrate.

 The frequency of anginal attacts can be

reduced by regular use of:
-organic nitrates (e.g. isosorbide mono
nitrate given regularly by mouth or
glyceryl trinitrate administered trans
dermally via a patch,or sublingually
immediately before exertion).
- - adrenoceptor antagonists (e.g.
atenolol,metoprolol).
- calcium antagonists (diltiazem,amlo
dipine)

Clinical uses of organic nitrates

Stable angina
- Prevention (e.g. regular isosorbide
mono-nitrate; or glyceryltrinitrate sublingually immediately before exertion)
- Treatment ( sublingual glyceryltrini
trate).
1

 Unstable angina: Intravenous glyceryl

trinitrate (as supplement to aspirin)
To reduce cardiac pre-load in patients
with heart failure,especially those un
able to take ACE inhibitors.
Uses related to relaxation of other
smooth muscles (e.g. uterine,billiary)
are being investigated).