Describe the pharmacology of intravenous sodium nitroprusside.
This was a straightforward pharmacology question relating to a relatively common and archetypal intensive care medication. The structure of the question was well handled by most of the candidates; easily falling into the classic pharmaceutics, pharmacokinetic and pharmacodynamics framework. Many candidates had a superficial knowledge of the presentation and formulation of the drug, aside from its light sensitivity. Better answers detailed the drug according to the above-mentioned framework but also accurately highlighted specific points relevant to the ICU practise such as the metabolic handling of sodium nitroprusside and relating this to the consequences of the various metabolic products.
|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|
|Target receptor||Soluble guanylyl cyclase (which is induced by NO)|
|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|
|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|
|Single best reference for further information||DBL PI document|
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