G7ii / 16B02: Compare and contrast the mechanisms of action and toxicity of sodium nitroprusside and glyceryl trinitrate (GTN)
16B02: Exam Report
Compare and contrast the mechanisms of action and toxicity of sodium nitroprusside and glyceryl trinitrate (GTN).
55% of candidates passed this question.
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.
G8iii / 16B02: Compare and contrast the mechanisms of action and toxicity of sodium nitroprusside and glyceryl trinitrate (GTN)
GTN
SNP
Comparison
Definition
GTN
An organic nitrate vasodilator
SNP
An inorganic peripheral vasodilator
MoA
GTN
Prodrug, needs to be denitrated to produce active NO
i.e. reacts with sulfyhydryl groups/ other enzyme reactions to liberate NO
SNP
Also a prodrug;
Diffuses into RBC & reacts with oxyHb to form:
- MetHb
- 5CN-
- NO
Comparison
Both have the same end point to produce NO
Both are prodrugs and require reactions
GTN / SNP
NO
↓
Diffuses into smooth m. cell
↓
Binds to & activates guanyl cyclase
↓
GTP \( \xrightarrow{\text{GC catalyses }} \) cGMP
↓
↑cGMP (2° messenger)
- Inhibits Ca2+ entry into smooth m. cell
- Activates K+ channels → hyperpolarises cell (inactive)
- Stimulates “cGMP-dependent-protein-kinase” → activates MLC phosphatases → dephosphorylates MLC
→ Smooth m. relaxation
Comparison
SNIP = equal relaxation of venous and arterial smooth muscle
GTN = Venous > Aterial diltation
Toxicity
GTN
80% dose absorbed by giving sets
Nitrates cause oxidation of Fe2+ → Fe3+ in Hb
This causes MetHb formation
MetHb cannot bind O2
Oxidation of one heme in the tetratmer causes the others to increase affinity for O2 and thus L ODC shift with Hb less readily releasing O2
Adverse Effects of GTN related to vessel dilatation-
CVS: ↓BP + ↑HR
GI: N & V
CNS: Headache
Haem: MetHb, platelet dysfunction
Tachyphylaxis
SNP
Rebound HTN
SNP toxicity (cyanide toxicity)
Build up of CN- impairs oxidative phosphorelation
Binds Cyt C Oxidase, blocking mitochondrial transport chain
Cellular hypoxia & depletion of ATP
Metabolic acidosis
CYANIDE TOXICITY symptoms:
↓BP
Headache
Dizziness
Palpitations
Comparison
Cyanide blood levels take time. Requires high index of suspicion
Lactate >8mmol/L is 94% sensitive and 70% specific
CN- toxicity is related to the rate of the infusion rather than the total dose
MetHb levels on ABG
- Author: Krisoula Zahariou