CV - Nitrates: isosorbide mononitrate, glyceryl trinitrate

Question 1

Nitrates: isosorbide mononitrate, glyceryl trinitrate

Common indications

Answer 1

• 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.

Question 2

Nitrates: isosorbide mononitrate, glyceryl trinitrate

Mechanisms of action?

Answer 2

• 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.

Question 3

Nitrates: isosorbide mononitrate, glyceryl trinitrate

Important Side Effects?

Answer 3

• 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.

Question 4

Nitrates: isosorbide mononitrate, glyceryl trinitrate

Warnings?

Answer 4

• 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.

Question 5

Nitrates: isosorbide mononitrate, glyceryl trinitrate

Important Reactions?

Answer 5

• 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.

Question 6

Nitrates: isosorbide mononitrate, glyceryl trinitrate

Px and Administration

Answer 6

• In patients with stable angina, glyceryl trinitrate (GTN) is prescribed to be taken sublingually as tablets or spray for immediate relief of chest pain. GTN has a plasma half-life of <5 minutes, so has a very quick onset and offset of action.
• In patients with acute coronary syndrome or heart failure, GTN is prescribed as a continuous intravenous infusion. Isosorbide mononitrate (ISMN) has a plasma half-life of 4–5 hours and is prescribed two to three times daily as immediate-release tablets for the prevention of recurrent angina.
• ISMN is also available as modified-release tablets or transdermal patches, which are prescribed once daily.
• When prescribing modified-release preparations, prescribe by the brand name, since there are important differences between preparations.