| Class | Nitrate vasodilator |
|---|---|
| Chemistry |
Cyanide |
| Routes of administration |
IV only |
| Absorption |
0% oral availability, degraded into cyanide almost immediately on contact with mucosal surfaces |
| Solubility |
pKa -3.3; minimally fat soluble; highly water soluble |
| Distribution |
Virtually no protein binding. VOD ~ 0.25L/kg |
| Metabolism |
Two main mechanisms of metabolism: spontaneous decomposition into ferrous nitrosyl (FeNO) and five cyanide molecules, or reaction with haemoglobin to form cyanmethemoglobin and four cyanide molecules. It is also degraded by direct light, which requires opaque storage vessels and special handling techniques. |
| Elimination |
Immediate onset of effect (seconds); elimination half-life of 2 minutes |
| Time course of action |
Rapid onset and offset of effect; vasodilation is seen within seconds of beginning the infusion |
| Target receptor |
Soluble guanylyl cyclase (which is induced by NO) |
| Mechanism of action |
Acts as a donor of nitric oxide (NO) which activates guanylate cyclase, resulting in an increase of guanosine 3'5' monophosphate (cyclic GMP) in vascular smooth muscle. This hyperpolarises the membrane by increasing potassium channel conductivity and decreases the availability of inracellular calcium, thereby decreasing the resting tone and contractility of vascular smooth muscle |
| Clinical effects |
Systemic vasodilation - balanced venodilation and arterial dilation; reduced preload as well as reduced afterload. Increased intracranial pressure, headache, reflex tachycardia, methaemoglobinaemia. Tolerance develops over sustained use (tachyphylaxis). Significant cyanide toxicity can occur with doses in excess of 2mcg/kg/min |
| Literature reference |
DBL PI document |
| CICM details of understanding | Level 2 |
| Mentioned around Deranged Physiology | |
| Related SAQs |
Question 20 from the second paper of 2020 (sodium nitroprusside) Question 2 from the second paper of 2016 (sodium nitroprusside and GTN) Question 11 from the first paper of 2015 (sodium nitroprusside toxicity) Question 8(p.2) from the second paper of 2008 (sodium nitroprusside and GTN) Question 3(p.2) from the first paper of 2008 (sodium nitroprusside and GTN) |