The nitroso group (−N = O−) in sodium nitroprusside reacts with sulphydryl groups (–SH) in vascular smooth muscle, forming nitric oxide and nitrosothiol derivatives.

Both metab stimulate guanylate cyclase, ↑cGMP levels and produce generalized relaxation of vascular smooth muscle (both arterial and venular dilatation)

MoA is same for inorganic nitrates although GTN must first combine with Thio containing compound to produce NO. NO activates guanylyl cyclase in smooth muscles which ↑cGMP leading to a ↓intracellular Ca and vasodilation. Venous > arterial dilation and the benefits in angina are believed to be related to decreased MVO2.

Equal Arterial and venous dilation
Attenuates HPV in lungs
Increases ICP due to increase in CBF
Renal blood flow maintained

Venous > arterial dilation
Can cause bronchodilation
↑ICP due to ↑in CBF
Disrupt renal autoregulation in CCF pts.
relaxation of sphincter of Oddi

Main side effects are from excessive hypotension and include nausea, vomitting, abdominal pain, and postural hypotension.

Abrupt withdrawal may lead to a rebound hypertension.

Longer term there is significant risk of cyanide accumulation and associated toxicity and impaired oxidative phosphorylation.

(See Special points below for further details)

Tolerance develops rapidly due to depletion of sulphydryl (thiol) groups reqrd for metabolism of GTN to NO2. Breaks for patches
CNS – headache (intracerebral vasodilatation) and ↑in ICP
CVS – at high doses ↓SVR → ↓afterload, however a compensatory tachycardia (baroreceptor induced) may reduce myocardial blood supply.
GIT – relaxes sphincter of oddi
HAEM – may precipitate methaemoglobinaemia

(See Special points below for further details)