Nitrates

Question 1

Give examples of nitrates

Answer 1

GTN and Isosorbide Mononitrate

Question 2

What is the trade name for Isosorbide Mononitrate

Answer 2

Imdur

Question 3

How does Isosorbide Mononitrate work?

Answer 3

Nitrates are pro drugs
They are metabolised into Nitric Oxide
NO increases the level of cGMP synthesis which reduces the level of intracellular calcium in vascular Smooth muscle cells
The reduction in intracellular calcium causes vasodilation in result causing a decrease in pre load and after load and therefore a decreased oxygen demand on the heart

Question 4

What are the main uses for Isosorbide Mononitrate?

Answer 4

1. Angina: prophylactic use where a beta blocker and CCB is inneffective/insuficient
2. Left ventricular heart failure: where diuretics may not work because of renal failure and to treat pulmonary oedema along with furosemide and oxygen
3. Congestive heart failure: As an adjunct

Question 5

What are the contra-indications of Isosorbide Mononitrate?

Answer 5

Severe aortic stenosis: the heart is unable to increase cardiac output sufficiently through the narrowed valve area to maintain pressure in the now dilated vasculature.
Haemodynamic instability, particularly hypotension and hypovalaemia
Closed angle glaucoma
Marked aneamia
Bleeding/Haemorrhage

Question 6

What are common interactions with Isosorbide Mononitrate?

Answer 6

Antihypertensives – potentiates effect
Heparin – increases excreteion of heparain therefore reduces effect
PDE5 Inhibitors – these block deactivation of cGMP whilst nitrates increase cGMP levels; leads to extensive venous pooling and potentially life-threatning hypotension
Example of this is: Sildenafil (Viagra) – risk of severe hypotension

Question 7

What are the side effects of Isosorbide Mononitrate?

Answer 7

Flushing
Headaches 
Light-headedness
Hypotension
Tolerance 
Tachycardia

Question 8

How is Isosorbide Mononitrate eliminated?

Answer 8

Hepatic Metabolism

Excreted in urine and faeces

Question 9

How do you overcome tolerance in Isosorbide Mononitrate?

Answer 9

Many patients on long-acting nitrates rapidly develop tolerance = reduced beneficial effect (therefore have a nitrate-free period of at least 4-8hrs/day), tolerance reversed within 18 hours of stopping nitrates