Nitrates offer coronary arteriolar and venous vasodilatation, which are the basis of symptomatic relief of effort angina.
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Table 2: Optimal use of nitrates in stable coronary artery disease (SCAD) [adapted from ESC guidelines]1
| Short-acting nitrates for acute effort angina |
- Standard initial therapy: Sublingual nitroglycerin (0.3-0.6 mg) every 5 min until the pain goes or a maximum of 1.2mg within 15min.
- Nitroglycerin spray acts more rapidly.
- Nitroglycerin can be used prophylactically when angina can be expected (e.g.) activity after a meal, emotional stress, sexual activity and in colder weather.
- Isosorbide dinitrate (5mg sublingually) helps to abort anginal attacks for about 1 h. The dinitrate onset of anti-anginal action (within 3-4 min) is slower than with nitroglycerin but its effects persist for several hours, conferring longer protection.
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| Long-acting nitrates for angina prophylaxis |
- Long-acting nitrates are not continuously effective if regularly taken over a prolonged period without a nitrate-free or nitrate-low interval of about 8-10 hours (tolerance).
- Worsening of endothelial dysfunction is a potential complication.
- Routine use of long-acting nitrates as first line therapy for patients with effort angina needs re-evaluation.
- Isosorbide dinitrate (oral preparation) is frequently given for the prophylaxis of angina. However, current evidence does not support its prolonged therapy.
- Mononitrates have similar dosage and effects to those of isosorbide dinitrate.
- Nitrate tolerance is also a potential problem, which can be prevented by changes in dosing and timing of administration, as well as by using slow-release preparations.
- Thus only twice daily rapid-release preparations or very high doses of slow-release mononitrate – also twice daily – give sustained anti-anginal benefit.
- Transdermal nitroglycerin patches fail to cover 24 h during prolonged use.
- A discontinuous administration at 12 h intervals allows on and off effects to start within mins and last 3-5 h.
- There are no efficacy data for second or third doses during chronic administration.
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| Nitrate side-effects |
| Hypotension is the most serious, and headache the most common side-effect of nitrates. |
| Nitrate drug interactions |
- Many are pharmacodynamic, including potentiation of vasodilator effects with calcium channel blockers (CCBs).
- Serious hypotension can occur with the selective PDE5 inhibitors (sildenafil and others) for erectile dysfunction or for the treatment of pulmonary hypertension. Sildenafil decreases BP by about 8.4/5.5mmHg and by much more with nitrates.
- Nitrates should not be given with alpha-adrenergic blockers.
- In men with prostatic problems taking tamsulosin (alpha1A and alpha1D blocker), nitrates can be given.
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Apart from non-compliance, treatment failure includes nitric oxide resistance and nitrate tolerance.
Table 1 indicates the main side-effects, contra-indications and major drug-drug interactions for each class of anti-ischaemic drugs.
Also see Algorithm on the medical management of patients with stable coronary artery disease.
Reference: 1- [Adapted from] 2013 ESC guidelines on the management of stable coronary artery disease. Eur Heart J. 2013 Oct ;34(38):2949-3003. MIMS Ireland Copyright®