Nitrates

Question 1

Mechanism of action (derivés nitrés)?

Answer 1

Nitrates increase cGMP synthesis, which reduces intracellular Ca in vascular smooth muscle cells, causing them to relax. This results in venous, &to a lesser extent, arterial vasodilation.
Relaxation of venous capacitance resistance reduces the preload &left ventricular filling. These effects reduce cardiac work &myocardial oxygen demand, relieving angina &cardiac failure.

Question 2

Name some nitrates? short-acting &long-acting, separately

Answer 2

short-acting : nitroglycerine (=trinitrite, which in its pure state, is a potent explosive) : plasma half-life : mns.
long-acting : isosorbide dinitrate, isosorbide mononitrate (plasma half-life : 4-5 hrs).
apparentés : nitroprussiate de Na, molsidomine, nicorandil.

Question 3

Indications?

Answer 3

• short-acting nitrates : acute angina &ACS
• long-acting nitrates : prophylaxis of angina, where b-blockers &/or Ca channel blockers are insufficient or not tolerated.
• IV nitrates : pulmonary oedema in combination with Fursemide &oxygen.

Question 4

How are nitrates taken?

Answer 4

Nitrates are prbbly more effective at preventing than terminating angina, patients are advised to take trinitrite before tasks that bring about their angina, sit before/after taking the sublingual medication to avoid postural hypotension.
Nitrates induce tachyphylaxis, &are therefore taken in a way to ensure a ‘nitrate-free period’ everyday, usually during night, to prevent this. Ex : isosorbide mononitrate twice daily; one the morning, second the mid-afternoon instead of evening (ensure 12hrs intervals between am &pm doses). Patches, applied the morning &removed at bedtime.

Question 5

Important AE?

Answer 5

Dizziness, flushing, light-headedness, hypotension. Tachyphylaxis (ensure free-nitrate periods of time when its effect isn’t needed)

Question 6

Important interactions?

Answer 6

Do not associate with phosphodiesterase inhibitors, &be wary of the co-admin of anti-hypertensive drugs.