Compare and contrast the mechanisms of action and toxicity of sodium nitroprusside and glyceryl trinitrate (GTN).
Some excellent responses to this question showed a clear understanding of the pharmacology
of these agents – the differing mechanisms of action involving both involving nitric oxide. Better
answers were able to use this to explain the altered vascular specificity.
Toxicity was similarly well prepared for with a good understanding of the role of cyanide in
SNP and the low rates of toxicity with GTN. This question was best handled in a tabular format
which minimised omissions.
Some candidates focused on pharmaceutics, indications and side effects which were not
allocated any marks.
'Compare & contrast' means the similarities; differences & unique features need to be related
to each other. Several candidates confused ‘nitrous oxide’ with nitric oxide
This was not a straightforward "compare and contrast" question which one might be able to answer with one's brainstem. The examiners wanted to specifically see the differences in the mechanism of action and toxicity, which is slightly more novel and thought provoking. Specifically, one would have to dig deep to find differences in mechanism of action, as ostensibly both drugs exert their effect in basically the same way. You'd have to get creative with definitions of "mechanism" and "action". It does not appear as if pharmacokinetic maters would have attracted any marks, but it was tempting to include them because they attracted marks in previous versions of this question.
| Domain | Glyceryl Trinitrate (GTN) | Glyceryl Trinitrate (GTN) |
| Delivery of NO | Metabolised by enzymatic breakdown into dinitrate, mononitrate and ulimately glycerol, liberating NO2- | Degrades on contact with sulfhydryl groups and haemoglobin, liberating NO |
| Molecular target | Both drugs target soluble guanylate cyclase | |
| Molecular mechanism |
Both drugs act as a donor of nitric oxide (NO) which:
|
|
| Distinct pharmacodynamic features |
GTN is more selective for:
|
Nitroprusside is relatively nonselective and produces venodilation and arteriodilation equally |
| Metabolites | GTN is metabolised into glycerol, which is incorporated into glycolysis | Sodium nitroprusside deghrades into cyanide molecules |
| Toxicity | GTN toxicity is mainly the extension of its desirable effects, and includes hypotension, reflex tachycardia, and headache | Nitroprusside toxicity is mainly cyanide toxicity, and includes shock, lactic acidosis, multiorgan system failure, pulmonary oedema and seizures |
Münzel, Thomas, and Andreas Daiber. "Pharmacology of nitrovasodilators." Nitrite and Nitrate in Human Health and Disease. Humana Press, Cham, 2017. 195-216.
Torfgård, Kristina E., and Johan Ahlner. "Mechanisms of action of nitrates." Cardiovascular drugs and therapy 8.5 (1994): 701-717.
Schulz, V. "Clinical pharmacokinetics of nitroprusside, cyanide, thiosulphate and thiocyanate." Clinical pharmacokinetics 9.3 (1984): 239-251.