Nitrates

Common indications

1. Short-acting nitrates (glyceryl trinitrate) are used in the treatment of acute angina and chest pain associated with acute coronary syndrome.
2. 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.
3. Intravenous nitrates are used in the treatment of pulmonary oedema, usually in combination with furosemide and oxygen.

 

Mechanisms of action

• 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.

 

Important adverse effects

• As vasodilators, nitrates commonly cause flushing, headaches, light-headedness, hypotension and reflex tachycardia. 
• 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.

 

Warnings

• 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.

 

Important interactions

• 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.