Nitrates

Question 1

What effect do these drugs have?

Answer 1

Vasodilating effects

Question 2

Main indications for their use?

Answer 2

Management of angina and the acute treatment of heart failure

Question 3

What common drug is used in patients with ischaemic heart disease to relieve angina attacks?

Answer 3

Sublingual glyceryl trinitrate

Question 4

Mechanism of action?

Answer 4

• nitrates cause the release of nitric oxide in smooth muscle, activating guanylate cyclase which then converts GTP to cGMP, which in turn leads to a fall in intracellular calcium levels
• in angina they both dilate the coronary arteries and also reduce venous return which in turn reduces left ventricular work, reducing myocardial oxygen demand

Question 5

Side effects?

Answer 5

• hypotension
• tachycardia
• headaches
• flushing

Question 6

What is nitrate tolerance?

Answer 6

Many patients who take nitrates develop tolerance and experience reduced efficacy

Question 7

How should a patient with nitrate tolerance be managed?

Answer 7

Patients who develop tolerance should take the second dose of isosorbide mononitrate after 8 hours, rather than after 12 hours. This allows blood-nitrate levels to fall for 4 hours and maintains effectiveness.
This effect is not seen in patients who take modified release isosorbide mononitrate