1999B12 Briefly describe the mechanism and treatment of the toxicity of sodium nitroprusside.

Structure

·   Fe²⁺ surrounded by 5 x CN^- and 1 x NO

Appearance

·   Red powder

Reconstitution

·   With 5% dextrose -> orange solution

Problem

·   Light sensitive -> dark brown

·   Hence bottle and IV line covered with aluminium foil

Administration

·   0.3-10mcg/kg/min

Time course

·   Onset <1 min

·   Duration 1-10 mins

Absorption

N/A

Distribution

?

Metabolism

·   Reacts with oxyHb -> 1 x nitric oxide (NO) + 5 x cyanide (CN^-) + metHb

·   SNP t_1/2β 2 mins

Excretion

·   Thiocyanate t_1/2β 2 days

Mechanism

·   NO -> activate guanylyl cyclase -> ↑cGMP -> ↑MLCP activity, ↑Ca²⁺ reuptake, ↑K⁺ efflux

Vasodilation

·   Vasodilatation > venodilatation (unclear)

·   ↓SVR (used during aortic cross-clamping), ↓mAP

·   ↓PVR

·   ↓CVR -> ↑CBF, +/-↑ICP

Side effects

·   Reflex ↑HR

Cyanide toxicity

·   Pathophysiology: inhibit cytochrome C oxidase -> histiotoxic hypoxia

·   Toxic concentration: 8mcg/mL

·   Clinical: ↑HR, ↑RR, anxiety, sweating; can be lethal within minutes

·   Lab tests: ↑SvO₂, metabolic acidosis

·   Endogenous antidote:

o CN^- + metHb -> cyanmetHb

o CN^- -> thiocyanate (liver and kidney), 100x less toxic

·   Exogenous antidote:

o Sodium thiosulfate (cyanide -> thiocyanate)

o Dicobalt edetate (chelator)

o Nitrates: metHb binds CN^- more avidly

o Hydrocobalamin

Thiocyanate toxicity

·   Vasodilatation, tinnitus

Methaemoglobinaemia

·   Pathophysiology: NO: Fe²⁺ -> Fe³⁺; poor O₂ carrying capacity

·   SpO₂ trend to 84%

·   Significant if total dose SNP >10mg/kg

·   Endogenous antidote: NADH- or NADPH-metHb reductase

·   Exogenous antidote: methylene blue 1-2mg/kg Fe³⁺ -> Fe²⁺