ANTIANGINAL DRUGS

CLASSES THERAPEUTIC USES MOA ADVERSE EFFECTS

Organic nitrates Vascular smooth muscle Nitrates denitrated by glutathione S-  Venodilatation : postural
 Nitroglycerin  Veins >> arteries transferase hypotension, syncope, reflex
 Isosorbide  Venodilatation ↓ tachycardia, dizziness
dinitrate Peripheral pooling of blood→ ↓VR → ↓ LV Nitric oxide  Arterial dilatation : headache,
 Isosorbide preload→ ↓V wall tension → ↓ myocardial ↓ flushing
mononitrate oxygen demand Guanylate cyclase  methaemoglobin
 Arterial dilatation
↓ afterload → ↓ myocardial oxygen demand
 Coronary artery dilatation GTP cGMP
↑ blood supply to for redistribution to ↓
ischemic area cGMP-dependent protein kinase
↓
Erectile tissue Activation of PKG results in phosphorylation of
Relaxation → permits inflow of blood into several proteins
corpora cavernosa → enhance erection ↓
Reduce i/cellular Ca2+
Bronchi, GIT, GUT
No clinical value d/t brief action

Platelets
↑ cGMP → ↓ platelet aggregation

Haemoglobin
Nitrite ion + Hb (methaemoglobin) → low
affinity for oxygen → pseudocyanosis, tissue
hypoxia → death

**at LARGE doses, resistance arteries &

arterioles dilate, cause ↓ arterial pressure
Calcium channel Vascular smooth muscle Act on α 1 subunit of L-type Ca2+ channel  Cardiac depression : cardiac
blockers  Arteries >> veins ↓ arrest, bradycardia, AV block,
 Verapamil Do not cause postural hypotension Bind at Ca2+ channel failure
 Diltiazem  Arterial dilatation ↓  Flushing, dizziness, nausea,
 Amlodipine ↓ PVR & ↓ BP (stable angina) ↓ Ca2+ channel opening constipation (verapamil),
 Dihydropyridines  Coronary vasodilatation ↓ peripheral edema
(nifedipine, Improve oxygen delivery (variant angina) Block Ca2+ influx (dihydropyridines)
nicardipine)  Dihydropyridines & diltiazem (less effect) ↓  Reduce cardiac rhythm
Relaxation
Cardiac muscle
 Verapamil & diltiazem (less effect) **block more effectively
Reduce/block impulse generation in SA node & Active channel
conduction in AV node → ↓ cardiac Depolarized
contractility & ↓ CO → ↓ oxygen demand
**mainly affect SMOOTH MUSCLE & CARDIAC
Cerebral vasospasm & infarct following MUSCLE
subarachnoid haemorrhage
 Nimodipine & nicardipine
- High affinity for cerebral BV, reduce
morbidity ass. haemorrhagic shock
β−¿ adrenoceptor  Treatment of stable & unstable angina ↓ heart rate and ↓ blood pressure  Bronchoconstriction (non-
blockers (tolol’s family)  Prophylaxis of angina ↓ selective blocker) – asthmatic &
 Propranolol  Non-selective blockers are avoided in ↓ myocardial oxygen consumption chronic pulmonary dz
 Atenolol variant angina - ↑coronary spasm  Cardiac depression
 Metoprolol  Bradycardia
 Fatigue - ↓ CO & ↓ muscle
perfusion in exercise
 CNS effect (propranolol)
- insomnia, unpleasant
dreams
K+ channel openers  combines activation of K+ channel & ↑ membrane K+ permeability with K+ efflux  Headache
 nicorandil nitrovasodilator (NO donor) from cell  Flushing
 dilates arteries & veins ↓  Dizziness
 use for symptomatic patients Hyperpolarization
↓ ↓
Closure of L-type Inhibition of
i/cellular Ca2+ channel Ca2+
release
↓
 Reduced free i/cellular Ca2+
↓ ↓
Hypoxia Vasodilation

Clinical Pharmacology Of Antianginal Therapy

STABLE ANGINA UNSTABLE ANGINA VARIANT ANGINA

 Therapy for atherosclerosis – modification of  Antiplatelet therapy (aspirin, clopidogrel)  Nitrates & CCB
risk factor, antilipid  Nitroglycerin & β blockers
 Nitrates / CCB / β blockers
 Hypertensive ptn : CCB and/or β blockers
 Normotensive ptn : nitrates (single/2 drugs)
 Surgical revascularization