Nitrates

Nitrates indications

short acting GTN for acute angina in ACS

long acting Isosorbide mononitrate for prophylaxis of Angina where a-blocker and ccb not tolerated or sufficient

IV nitrate infusion used in treatment of ACS (if there is ongoing ischaemia), pulmonary oedema (usually in combination with furosemide and oxygen), and hypertensive emergencies (although other agents, such as labetalol or sodium nitroprusside, are preferred).

Nitrates MOA

Nitrates are quickly converted to nitric oxide (NO) after absorption.

NO increases cyclic guanosine monophosphate (cGMP) synthesis and decreases intracellular calcium in vascular smooth muscle cells, leading to venous and arterial vasodilation.

This reduces cardiac preload and left ventricular filling, decreasing cardiac work and oxygen demand, thus alleviating angina and cardiac failure.

Nitrates also relieve coronary vasospasm, dilate collateral vessels, and reduce peripheral resistance and afterload. However, their main antianginal effects stem from preload reduction.

Nitrates adverse effects

commonly cause flushing, headaches, light-headedness, and hypotension. (also visual effects)

Regular 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

Nitrates warnings and interactions

contraindicated in severe aortic stenosis (need vasoconstriction), avoided in hypotension

not taken with PDE inhibitors (sildenafil) they enhance hypotensive effects.

caution with other antihypertensives

Nitrates glyceryl trinitrate, isosorbide mononitrate practical prescribing prescription and admin

GTN spray and buccal tablets administered sublingually short half life 5 minutes quick on and off

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 (MR) tablets or transdermal patches, which are prescribed once daily. When prescribing MR preparations, include the brand name, since there are important differences between preparations.

headaches may occur but usually short lived. take before tasks that normally bring on angina as they are better preventers. due to risk of hypotension take while sitting down and rest before and for 5 minutes after taking GTN.

when pain occurs take GTN under tongue wait 5 minutes, if pain still occurs take 2nd dose wait 5 minutes. if after 15 minutes still not work or after 2 doses call ambulance and take 3rd dose. (RULE OF 3)

Nitrates glyceryl trinitrate, isosorbide mononitrate practical prescribing monitoring and extra

Resolution of symptoms is the best indicator of efficacy.

When administering by IV infusion, monitor blood pressure frequently (e.g. every 15 minutes initially).

the infusion rate should be adjusted to relieve symptoms while avoiding hypotension (e.g. ‘Increase GTN infusion rate by 0.5 mL/hr every 15–30 minutes until chest pain/breathlessness relieved, provided systolic BP is >90 mmHg’).

Owing to the development of tolerance, continuous IV infusions of nitrates are usually stopped after 24–48 hours, in favour of oral agents. It may be possible to stop chronic nitrate treatment following successful percutaneous intervention or bypass surgery.

tablets discarded after 8 weeks may be better for those with infrequent symptoms to take spray

allow nitrate free time (at night most likely) to avoid tolerance

additional notes

If using GTN more than twice a week then long term prophylaxis

Mononitrate MR take OD

Dinitrate MR take BD because 12 hour duration

GTN tablets prescription and dispensing

available in 300, 500 and 600 mcg

supplied in glass container <100 tabs only

closed with foil line cap

no cotton wool wadding

discard after 8 weeks

rectal ointment discard 8 weeks after opening