Question
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- (a) Classify drugs used to treat Angina. Describe the mechanism of action, therapeutic uses and adverse effects of Nitrates. Add a note on Prinzmetal Angina. ( 4 mark(s)
- (b) Describe the management of Acute left ventricular failure. 5 mark(s)
Answer
a) Classification of antianginal drugs
| Class | Examples |
|---|---|
| Nitrates | Glyceryl trinitrate, Isosorbide dinitrate/mononitrate |
| Beta-blockers | Atenolol, Metoprolol |
| Calcium channel blockers | Amlodipine, Verapamil, Diltiazem |
| Newer agents | Ranolazine, Nicorandil (K⁺ channel opener with nitrate-like action) |
Nitrates — mechanism, uses, adverse effects Mechanism: nitrates are enzymatically denitrated within vascular smooth muscle to release nitric oxide, activating soluble guanylyl cyclase → raises cGMP → dephosphorylates myosin light chain kinase → smooth muscle relaxation. They dilate veins more than arteries, pooling blood peripherally and reducing venous return, which lowers end-diastolic ventricular size/pressure and, by the Laplace relationship, reduces the wall tension (and oxygen demand) the ventricle must generate — the dominant benefit in classical angina. They also preferentially dilate larger conducting coronary arteries, redistributing flow toward ischemic zones — the principal benefit in variant angina. Uses: acute and prophylactic relief of angina, acute coronary syndrome, acute left ventricular failure, cyanide poisoning (nitrite-induced methemoglobin binds cyanide). Adverse effects: throbbing headache, flushing, postural hypotension with reflex tachycardia; tolerance with continuous exposure (managed with a daily nitrate-free interval); dangerous potentiation of hypotension with PDE-5 inhibitors (contraindicated within 24 hours of sildenafil).
Note on Prinzmetal angina Unpredictable angina occurring at rest or during sleep, caused by recurrent localized coronary vasospasm (sometimes superimposed on atherosclerosis), rather than the fixed, exertion-provoked narrowing of classical angina. Nitrates and calcium channel blockers (which directly counteract vasospasm) are the mainstay of treatment; beta-blockers are relatively less useful and can theoretically worsen vasospasm through unopposed alpha-mediated vasoconstriction.
b) Management of acute left ventricular failure
- Oxygen — corrects hypoxia.
- IV Furosemide — rapid venodilation and diuresis, relieving pulmonary congestion.
- IV Glyceryl trinitrate — venous pooling reduces preload, improving pulmonary congestion (the emergency preparation of choice).
- Morphine (used cautiously) — reduces anxiety, sympathetic drive, and preload via venodilation.
- Inotropic support (Dobutamine) if hypotensive/in cardiogenic shock.
- Treat the precipitating cause (arrhythmia, ischemia, hypertensive crisis) alongside symptomatic management.