💊 Nitrates

Nitrates are a class of vasodilators used primarily for the treatment and prevention of angina pectoris, a symptom of coronary artery disease.

Nitrates are metabolised to nitric oxide (NO) in vascular smooth muscle cells. NO activates guanylate cyclase, leading to increased cyclic guanosine monophosphate (cGMP). This results in dephosphorylation of myosin light chains and subsequent smooth muscle relaxation, causing vasodilation.

They are indicated for the acute relief of angina pectoris (e.g., sublingual glyceryl trinitrate). Long-acting nitrates are used for the prophylaxis of angina. They may also be used in the management of acute heart failure, particularly with pulmonary oedema, due to their preload-reducing effects.

Absolute contraindications include severe anaemia, closed-angle glaucoma, and hypertrophic obstructive cardiomyopathy. Concomitant use with phosphodiesterase-5 (PDE5) inhibitors (e.g., sildenafil) is an absolute contraindication due to the risk of profound hypotension. Severe hypotension or hypovolaemia are also contraindications.

Common side effects include headache (due to cerebral vasodilation), flushing, and dizziness. Postural hypotension is common, especially with initial doses. Reflex tachycardia can occur. Tolerance to the effects of nitrates can develop with continuous use.

Blood pressure should be monitored, especially during initiation of treatment or dose titration, to assess for hypotension. Patients should be advised to sit or lie down when taking sublingual preparations to minimise the risk of syncope. Efficacy in reducing angina symptoms should be assessed.

Always ask about concomitant medications, specifically PDE5 inhibitors, as this is a critical interaction. Counsel patients on the correct use of sublingual preparations for acute angina and the importance of sitting down. Explain common side effects like headache and dizziness.

Nitrates work by releasing nitric oxide, causing vasodilation. Remember the 'first-pass' effect for oral nitrates and the need for a nitrate-free interval to prevent tolerance. The severe interaction with PDE5 inhibitors is a high-yield fact. Headaches are a very common side effect.

SBA questions frequently test the absolute contraindication with PDE5 inhibitors, leading to severe hypotension. Expect scenarios involving a patient presenting with angina and questions about acute management. The concept of nitrate tolerance and how to manage it (nitrate-free interval) is also a common theme.