Nitrates Flashcards
Example of a nitrate
Isosorbide Mononitrate & GTN
How do nitrates work?
Nitrates are converted to nitric oxide (NO). NO increases cyclic guanosine monophosphate (cGMP) synthesis and reduces intracellular Ca2+ in vascular smooth muscle cells, causing them to relax. This results in venous and, to a lesser extent, arterial vasodilatation. Relaxation of the venous capacitance vessels reduces cardiac preload and left ventricular filling. These effects reduce cardiac work and myocardial oxygen demand, relieving angina and cardiac failure. Nitrates can relieve coronary vasospasm and dilate collateral vessels, improving coronary perfusion. They also relax the systemic arteries, reducing peripheral resistance and afterload. However, most of the anti-anginal effects are mediated by reduction of preload.
Indications of nitrates
Short-acting nitrates (glyceryl trinitrate) are used in the treatment of acute angina and chest pain associated with acute coronary syndrome.
Long-acting nitrates (e.g. isosorbide mononitrate) are used for prophylaxis of angina where a β-blocker and/or a calcium channel blocker are insufficient or not tolerated.
Intravenous nitrates are used in the treatment of pulmonary oedema, usually in combination with furosemide and oxygen.
Contraindications of nitrates
Nitrates are contraindicated in patients with severe aortic stenosis, in whom they may cause cardiovascular collapse. This is because the heart is unable to increase cardiac output sufficiently through the narrowed valve area to maintain pressure in the now dilated vasculature.
Nitrates should also be avoided in patients with haemodynamic instability, particularly hypotension.
Side effects of nitrates
As vasodilators, nitrates commonly cause flushing, headaches, light-headedness and hypotension.
Sustained use of nitrates can lead to tolerance, with reduced symptom relief despite continued use. This can be minimised by careful timing of doses to avoid significant nitrate exposure overnight, when it tends not to be needed.
Interactions of nitrates
Nitrates must not be used with phosphodiesterase inhibitors (e.g. sildenafil) because these enhance and prolong the hypotensive effect of nitrates.
Nitrates should also be used with caution in patients taking antihypertensive medication, in whom they may precipitate hypotension.
Elimination of nitrates
Renal
Patient information on nitrates
ISMN is also available as modified-release tablets or transdermal patches, which are prescribed once daily.
Where nitrates are taken regularly, there is a risk of tolerance (tachyphylaxis), which can reduce efficacy. Patients should be advised to take twice daily isosorbide mononitrate morning and mid-afternoon (rather than evening) to ensure >12 hours between pm and am doses
Explain that you are prescribing a nitrate to relieve chest pain and/or breathlessness. Advise your patient that they may develop a headache when starting nitrates, but that this is normally short-lived.
