Nitrates

Question 1

What are common indications?

Answer 1

1. short acting nitrates are used in acute angina and chest pain associated with ACS
2. Long acting nitrates- prophylaxis of angina where BB/CCB is insufficient or not tolerated
3. IV nitrate infusions for ACS (if ongoing ischaemia), pulmonary oedema (usually combination of furosemide and oxygen) , hypertensive emergency

Question 2

What is the mechanism of action?

Answer 2

Nitrates are rapidly converted to NO once absorbed

NO increases cGMP synthesis and reduces intracellular Ca2+ in vascular smooth cells causing them to relax.

Results in arterial and venous vasodilation

Relaxation of vessels reduces cardiac preload and left ventricular filling.

This reduces cardiac work and myocardial oxygen demand

Question 3

What are common side effects?

Answer 3

due to vasodilatory effects:
nitrates cause flushing
headaches
light-headedness
hypotension

Question 4

What can regular use of nitrates lead to and how can this be avoided?

Answer 4

It can lead to tolerance (tachyphylaxis), with reduced symptom relief. This can be minimised by careful timing of doses to avoid significant nitrate exposure over night (provide 18 hour gap). (Nitrate-free period every day during time of inactivity)

Question 5

What is nitrates contraindicated in and should be avoided?

Answer 5

Severe aortic stenosis

avoided in hypotension- abrupt vasodilation due to nitrate administration may can cardiovascular collapse.

Question 6

What are important interactions and why?

Answer 6

Avoid PDE inhibitors. this is because PDE is responsible for metabolisng cGMP, and so PDE inhibitors enhance the hypotensive effects of nitrates.

Nitrates should be used with caution in people taking antihypertensive medication.

Question 7

What are dosages for each indication?

Answer 7

-GTN spray/tablet: 400mcg
has half life of 5 minutes so very quick onset and offset of action.

GTN IV: for ACS/HF starting dose 1mg/hour

-Isosorbide mononitrate;
half life 4-5 hours BD/TDS if immediate release

-ISMN- mr OD

Question 8

When should isosorbide mononitrate be prescribed as brand and why?

Answer 8

For modified release preparations as there are important differences between preparations.

Question 9

What are monitoring requirements for IV infusion?

Answer 9

Monitor blood pressure frequently
Be careful in causing hypotension

IV usually stopped after 24-48 hours, in favour of oral agents.