Anti-Anginal Drugs
B.Pharm Pharmacology II, BP503T — Unit I
Anti-anginal drugs. → jump to section
This page covers syllabus item (d) only. The other five items in this unit — Unit I(a): Introduction to haemodynamics and electrophysiology of heart. Unit I(b): Drugs used in congestive heart failure. Unit I(c): Anti-hypertensive drugs. Unit I(e): Anti-arrhythmic drugs. Unit I(f): Anti-hyperlipidemic drugs. — are published as separate pages.
Anti-Anginal Drugs
The oxygen supply/demand balance behind angina, and how nitrates, beta-blockers, calcium channel blockers and newer agents restore it.
What angina is, and the supply/demand balance
Angina is chest pain from myocardial ischaemia — the heart muscle’s oxygen demand outstrips its oxygen supply, usually because narrowed coronary arteries (atherosclerosis, sometimes spasm) limit supply. Anti-anginal drugs work by lowering demand, raising supply, or both.
| Type | Trigger | Mechanism | Typical drugs |
|---|---|---|---|
| Stable (classic/effort) angina | Exertion | Fixed atherosclerotic narrowing limits supply; demand rises with exercise | Nitrates, beta-blockers, CCBs |
| Unstable angina | Can occur at rest | Plaque rupture with partial thrombosis — a medical emergency, on the spectrum toward myocardial infarction | Urgent treatment, not covered further here |
| Variant (Prinzmetal) angina | Often at rest, cyclical | Coronary artery spasm reduces supply, often with normal or near-normal coronaries | Calcium channel blockers (nitrates also used); beta-blockers can worsen it (unopposed α vasoconstriction) and are avoided |
Oxygen demand rises with heart rate, contractility, and wall tension (related to preload and afterload) — so anti-anginals typically reduce one or more of these.
Nitrates
Organic nitrates (glyceryl trinitrate/nitroglycerin, isosorbide dinitrate, isosorbide mononitrate) are metabolised to release nitric oxide (NO), which activates guanylyl cyclase in vascular smooth muscle, raising cGMP and causing relaxation.
- Main action
- Venodilation at low dose (reduces preload, so reduces wall tension and O₂ demand); arteriolar dilation at higher dose (reduces afterload); also dilates coronary arteries, improving supply, including to ischaemic areas.
- Use in stable angina
- Sublingual GTN for rapid relief of an acute attack; longer-acting oral/transdermal nitrates for prevention.
- Tolerance
- Continuous nitrate exposure causes rapid tachyphylaxis; a daily nitrate-free interval (e.g. overnight) is used to preserve effectiveness.
- Adverse effects
- Headache (from cerebral vasodilation), flushing, postural hypotension, reflex tachycardia.
- Key interaction
- Must not be combined with PDE-5 inhibitors (e.g. sildenafil) — both raise cGMP, and the combination can cause severe, even fatal, hypotension.
Beta-blockers and calcium channel blockers in angina
Beta-blockers
Reduce heart rate and contractility, lowering O₂ demand, and the longer diastole (from a slower heart rate) improves coronary filling time. First-line for chronic stable angina. Avoided in variant/Prinzmetal angina (see above).
Calcium channel blockers
Dihydropyridines (amlodipine, nifedipine) relieve coronary spasm and reduce afterload — useful in variant angina. Non-dihydropyridines (verapamil, diltiazem) also slow the heart and reduce contractility, like beta-blockers, so are useful alternatives when beta-blockers are contraindicated — but the two classes are not usually combined (risk of excessive bradycardia/heart block).
Other anti-anginal agents
- Ranolazine
- Inhibits the late inward sodium current in ischaemic myocytes, indirectly reducing intracellular calcium overload; reduces angina without major effects on heart rate or blood pressure. Add-on therapy.
- Nicorandil
- A potassium-channel opener with an additional nitrate-like (NO donor) action — combines arteriolar and venous dilation.
- Ivabradine
- Selectively inhibits the Iₐ (“funny”) current in the SA node, slowing heart rate without affecting contractility or blood pressure; used when beta-blockers are not tolerated.
- Revascularisation
- Percutaneous coronary intervention (angioplasty ± stent) or coronary artery bypass grafting — a mechanical, not pharmacological, option for severe disease.