Nitrates Flashcards
Name the 2 types of Nitrate which might be used to treat angina or to cause off-loading in heart failure?
Isosorbide Mononitrate or Glyceryl trinitrate.
Give the 3 common clinical indications for the use of Nitrates and state why.
1) Acute angina/ chest pain associated with ACS - use short acting nitrates (GTN).
2) Prophylaxis of angina - use long acting nitrates (ISMN) if beta blockers and/or calcium channel blockers are not tolerated or insufficient.
3) Pulmonary oedema - use IV nitrates in combination with furosemide and Oxygen.
State the mechanism of action of Nitrates that leads to an overall effect of a reduced preload.
Nitrates converted to NO > NO increases cGMP synthesis > NO also reduces intracellular Calcium in vascular smooth muscle > these cause smooth muscle relaxation, venous and arterial vasodilation > relaxation of venous capacitance vessels reduces cardiac preload and LV filling.
What does a reduced preload cause that is beneficial?
Reduced cardiac work and reduced myocardial oxygen demand. Thus relieving angina and cardiac failure.
State 2 other additional actions of nitrates and the effects of these.
1) Relieve coronary vasospasm and dilate collateral vessels = improves coronary perfusion.
2) Relax systemic arteries = reduce peripheral resistance and afterload.
NOTE: most anti-angina, effects are due to a reduced preload.
1) Name 3 adverse effects of Nitrates.
2) What can sustained use of a Nitrate cause?
1) Flushing, headaches, light-headedness and hypotension.
2) Tolerance - causes reduced symptom relief despite continued use.
How can tolerance (tachyphylaxis) of Nitrates be reduced?
Tolerance can be minimised by careful timing of doses to avoid nitrate exposure overnight. This will provide a >12 hour Nitrate free period during each 24 hour period.
1) Give conditions that use of Nitrates a are contraindicated in.
1) severe aortic stenosis (may cause cardiovascular collapse), patients with haemodynamic instability and patients with hypotension.
How might Nitrates cause cardiovascular collapse in patients with severe aortic stenosis?
Because the heart would be unable to increase cardiac output sufficiently through the narrowed valve area to maintain pressure in the now dilated vasculature.
State 2 important drug interactions of Nitrates.
1) Nitrates are contraindicated with the use of phosphodiesterase inhibitors, for example, sildenafil. This is because these would prolong the hypotensive effect of Nitrates.
2) Nitrates should be used with caution in patients taking antihypertensive medication, as they can precipitate hypotension.
Describe how GTN can be prescribed.
1) in patients with stable angina: GTN prescribed to be taken sublingually as tablets or spray for immediate relief of chest pain. Plasma half life is <5 minutes so there is quick onset and offset.
2) in patients with ACS or heart failure: GTN prescribed as a continuous IV infusion.
1) Describe how Isosorbide mononitrate can be prescribed.
2) When prescribing modified release preparations of ISMN, what is it important to do?
1) Prophylaxis of recurrent angina: ISMN prescribed to be taken BD or TDS as immediate release tablets (plasma half life 4-5 hours). Can also be prescribed as modified release tablets OD or transdermal patches OD.
2) Prescribe by brand name, as there are important differences between preparations.
What advice might you give to somebody if you are prescribing them with GTN?
1) You can develop a headache when starting Nitrates but this is usually short lived.
2) Advise patients to take GTN before activities that usually bring on chest pain, as they are probably make effective when use preventatively.
3) Risk of postural hypotension, so advise patients to sit down to rest before and for 5 minutes after taking sublingual GTN.
When administering Nitrates by IV infusion, what should be monitored?
Blood pressure should be monitored frequently, and the infusion rate adjusted to ensure SBP does not drop below 90mmHg.
