• Nitrates should be used with caution in people with:
• Left ventricular outflow obstruction (significant aortic stenosis or obstructive hypertrophic cardiomyopathy).
• Closed-angle glaucoma.
• The combination of a nitrate and a phosphodiesterase inhibitor (sildenafil, tadalafil, or vardenafil) is contraindicated.

In depth

• Short-acting, sublingual glyceryl trinitrate should be used for immediate relief of an episode of angina, or before activities that are likely to precipitate angina.
• Long-acting oral nitrates should be used regularly to decrease the frequency and severity of anginal symptoms.
• Isosorbide mononitrate is generally preferred to isosorbide dinitrate.

In depth

• Standard-release nitrate preparations: use an asymmetric dosing interval to minimize nitrate tolerance.
• For mononitrate preparations, this can be achieved with twice-daily dosing, for example at 8 a.m. and 3 p.m., or 2 p.m. and 10 p.m.
• For dinitrate preparations, dosing may be more complicated because dinitrate requires more frequent administration than mononitrate.
• Modified-release nitrate preparations: use a once-daily dose to maintain a nitrate-low period and thus minimize tolerance.
• Modified-release preparations are significantly more expensive than standard-release preparations, but they may be useful for people who find it difficult to comply with an asymmetric dosing regimen.

In depth

• Transient hypotension that manifests as dizziness, weakness, and palpitations has been reported with isosorbide mononitrate. Hypotension often presents as postural hypotension occurring shortly after drug administration.
• Headache occurs in more than 60% of people receiving glyceryl trinitrate (GTN) and 25–40% of people receiving isosorbide dinitrate or mononitrate. In addition, GTN may precipitate a migraine headache in people with a history of migraine.
• Tolerance to headache usually occurs over 1–2 weeks, although 10–20% of people cannot tolerate nitrates because of headache.
• To minimize the risk of headache, start at a low dose (for example 10 mg twice a day) and titrate up.
• Burning, stinging, or tingling of the mouth is experienced by some people taking sublingual GTN tablets.
• If this is bothersome, consider using a lower dose of GTN tablets, or a GTN sublingual spray.

In depth

• The concurrent use of phosphodiesterase inhibitors (sildenafil, tadalafil, and vardenafil) with nitrates is contraindicated.
• A nitrate should not be given for at least 24 hours after the last dose of sildenafil or vardenafil, and for at least 48 hours after the last dose of tadalafil.
• Sildenafil and vardenafil should not be used for at least 24 hours after the last dose of a nitrate, and tadalafil should not be used for at least 48 hours after the last dose of a nitrate.
• Advise people with angina who are taking a phosphodiesterase inhibitor that they must not use glyceryl trinitrate if they have an angina attack during sexual intercourse. Advise them to stop sexual activity and, if their pain does not resolve, they should call for an ambulance.

In depth

• Instruct the person in the correct use of their sublingual glyceryl trinitrate (GTN), and what to do if their angina attack does not respond to sublingual GTN.
• Key points for discussion include:
• Why GTN has been prescribed (it helps the heart work better, but it is not a painkiller).
• How to use the spray or tablets.
• When to use GTN to treat chest pain and to prevent pain if it can be precipitated.
• Likely adverse effects.
• What to do if pain persists after two doses or beyond 15 minutes.
• The short shelf-life of GTN tablets once opened (8 weeks), and how to obtain further supplies.

In depth