Nitrates

Nitrates

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Nitrates have been used for many years to treat stable angina but more recently have found a place in treating unstable angina and heart failure. They act as a source of nitric oxide. Venodilation is their most prominent effect but certain arteriolar beds (eg coronary) are also dilated.

Glyceryl trinitrate is the most commonly used nitrate. It has a half-life of only a few minutes. Extensive removal by the liver makes oral administration ineffective. It is therefore given sublingually, intravenously or, for prolonged action due to continued absorption, transdermally. Glyceryl trinitrate is also used transdermally in the treatment of Raynaud’s phenomenon.

Isosorbide mononitrate is nearly 100% bioavailable after oral administration and has a half-life of about five hours. Sustained-release formulations permit once-daily dosing.

Isosorbide dinitrate has low bioavailability of about 25% when given orally, but sublingual absorption is satisfactory. It has a half-life of about 45 minutes after sublingual administration. Many of isosorbide dinitrate's effects are due to the presence of isosorbide mononitrate, one of its active metabolites.

Adverse effects: Tolerance to nitrates occurs with frequent or continuous exposure, and can develop within 24 hours. Whatever the drug or route of administration, it is important to ensure a nitrate-free interval of 10 to 12 hours each day. Patients should be advised to apply or take their nitrate at the time of the day when angina is most frequent (eg at night for nocturnal angina or in the morning for diurnal angina). Major dose-related adverse effects of nitrates include headache and hypotension.

Precautions: Glyceryl trinitrate tablets deteriorate on storage and it is recommended that tablets should be kept in their original bottle and kept for no more than three months after opening. This problem does not occur with the isosorbide nitrates or the glyceryl trinitrate sublingual spray. Gyceryl trinitrate can be adsorbed onto some plastics (eg PVC). Ensure that an appropriate giving set is used (eg glass infusion bottle and polyethylene administration set).

Interactions: Phosphodiesterase type 5 inhibitors—sildenafil, tadalafil and vardenafil—must not be used concomitantly with nitrates, because they potentiate the vasodilatory effect of circulating nitric oxide, resulting in significant hypotension. Nitrates should not be administered within 3 to 5 days of tadalafil, or within 24 hours of sildenafil or vardenafil.