STAGE
rd
3
Pharmacology
Anti anginal drugs
Pathophysiological definition of angina pectoris ; is imbalance between oxygen demand or
requirement by heart and oxygen supply to it ; due to defect in coronary arteries through
partial block by thrombus or atherosclerosis ; sometimes coronary arteries are normal , but
there is spasm of arteries lead to inadequate blood supply to myocardium .
So, anti anginal drugs act by:-
1) Increase oxygen supply to heart by:-
A-dilating coronary arteries.
b- Slowing the heart rate (because coronary blood flow occur during diastole).
2) Reduction the demand by:-
a- reducing after load (peripheral resistance)
b- Reducing pre load (venous filling pressure)
c- Slowing heart rate
Anti anginal drugs:-
1) Organic nitrates group; include
-
:
(Angesid) R
(Nitroglycerin) (NTG)
trinitrate
Glycerial
A)
Is a drug of choice in treatment acute form of angina pectoris ,it is potent vasodilator ,it
relaxes smooth muscles of blood vessels ( on venous side more than arterial side ), lead to
decrease in preload and after load on the heart lead to reduce myocardial oxygen and
energy demand
On venous side lead to decrease venous return to heart, lead to decrease ventricular volume
and consequently lead decrease left ventricular diastolic pressure
On arterial side lead to decrease arterial blood pressure lead to reduction ejection time by
this decrease heart work and decrease oxygen and energy demand and overcome on the
anginal pectoris
Beside increase oxygen supply to heart by increase coronary vasodilatation
GTN, has very quick onset of action within 5 minutes when taken sublingually , its half life is
5 minutes and duration of action 20-30 minutes ;GTN, not used orally because it has
extensive first effect in the liver ,it is given sublingually 0.5 mg at beginning of anginal
pectoris or when there is anticipated of angina .
-
effects:
Side
1) Headache (throbbing or bursting in nature) occur due to stretching of pain sensitive
tissues around the meningeal arteries.
2) Flushing.
3) Reflex tachycardia.
4) Hypotension.
5) Methaemoglobinaemia occur with heavy dosage (due to nitrite products)
6) GTN ointment or skin patches may cause dermatitis and skin rash
GTN; present as tablet ,lingual spray , ointment or cream for skin on chest ,transdermal
patch or paste (5-10mg ) once or twice per day .
B) Oral preparation of nitrate is called Isosorbide mononitrate and Isosorbide dinitrate
;specific for oral use because it is not destroyed by hepatic enzymes ;it causes relaxation of
blood vessels ,longer half life than GTN (about 20 minutes ) , duration of action 2 hours .
Used in chronic cases of angina pectoris and as prophylaxis to prevent further attack
Tolerance, occur by frequent use of Nitrate group mostly with long-acting preparation as
Isosorbide mononitrate , so either by withdrawal for short time (12 hours) or by using
Nicorandil which is specific for resistant cases
Clinical uses:
1-Treatment acute anginal attack
2-Rapid prophylaxis i.e. before achieving exercise
3-Long term prophylaxis, in chronic angina as skin patches or sustained- release oral tablet
-
adrenoceptor antagonists :
–
β
)
2
Mechanism of action through lowing cardiac oxygen demand by reducing heart rate ,blood
pressure and myocardial contractility ; β1- blockers advisable to use one daily as
cardioselective drugs e.g. Atenolol 50-100 mg , Metoprolol 200mg daily , Bisoprolol (5-10mg
daily ) ; while β2 receptor of heart will be free and mediated vasodilatation and
bronchodilatation .
β- Blockers should not withdrawal abruptly, because this precipitate dangerous arrhythmias,
worsening angina or M.I. (The β –blockers withdrawal syndrome).
Oxprenolol and Pindolol have partial agonist (intrinsic sympathomimetic activity) and
therefore; tend to cause less bradycardia.
Propranolol ; needed high doses because extensive first pass effect ,beside it lipid soluble
can cross the BBB and cause side effects like nightmares ,drowsiness .
Other possible side effects of beta-blockers; exacerbate cardiac failure and peripheral
vascular diseases; provoke bronchospasm in patients with obstructive airway disease.
Contraindication vasospastic (variant angina)
3) Calcium –channel blockers:-
Nifedipine, Amlodipine, Nicardipine
Diltiazem, Verapamil.
Mode of action by inhibiting the slow current of calcium ions to the vascular smooth muscles
(mainly arterioles), so block calcium influx, lead to
1-relaxation of the coronary artery spasm, which improves the myocardial blood supply
2-vasodilation of the peripheral arterioles, decreasing the peripheral resistance and
afterload, thereby reduce the myocardial oxygen demand
Nifedipine, is relatively selective to calcium channels in vascular smooth muscles and it is
mainly an arteriolar vasodilator
Diltiazem and Verapamil show greater effect on calcium channels in the heart, they
decreases the heart rate and myocardial contractility (negative inotropic effect), which
reduces myocardial oxygen requirement
Have anti-arrhythmic effect because they decrease the rate of SA node and slow AV-
conduction which is useful in treatment of supraventricular tachycardia ( SVT) and
decreasing ventricular rate in case of atrial fibrillation and flutter
Their co-administration with beta-blockers potentiates the AV block and can lead to heart
failure
Contraindication in patient with bradycardia and second or third degree heart block (due to
negative effect on myocardial conducting and contracting system
Side effects
1-Hypotension with reflex tachycardia greatest with Nifedipine
2 – Diltiazem and Verapamil can cause bradycardia
3-Headache, flushing, dizziness
4- Gum hypertrophy
5-Ankyle edema
6-Constipation .
4) Potassium –channel activators e.g. Nicorandil; has venous dilatation and arterial
dilatation without tolerance as seen with nitrate.
For treatment of angina; low dose of Aspirin +GTN sublingually + β –blocker; then added
calcium channel blocker or long acting nitrate.