Sodium Nitroprusside

CLASS

• an inorganic complex

MECHANISM OF ACTION

• vasodiator & hypotension
• dilates both resistance & capacitance vessels by direction on vascular smooth muscle.
• acts by interacting with sulphdryl groups in smooth muscle membrane & preventing Ca2+ influx necessary for initiation of contraction

PHARMACEUTICS

• solution: 10mg/mL
• must be diluted before administration
• must be protected from light
• IV

DOSE

• 0.5 – 4mcg/kg/min
• titrated according to response
• need art line
• onset: immediate

Indications

(1) hypertensive crises
(2) aortic dissection
(3) LVF
(4) produce hypotension during surgery

Adverse Effects

• reversible decrease in PaO2 from decrease in hypoxic pulmonary vasoconstriction
• cerebral vasodilation -> increase in ICP
• increase in catecholamine
• increase in renin
• lactic acidosis may occur
• toxicity from cyanide production

PHARMACOKINETICS

• Absorption – n/a
• Distribution – confined to the plasma
• Metabolism

(1) reaction with sulphdryl groups on amino acids in plasma
(2) rapid, non-enzymatic hydrolysis within RBC’s

• 5 cyanide ions are produced by the degradation of each molecule of Na nitroprusside
• 1 reacts with metHb -> cyanometHb
• 3 react with thiosulphate -> thiocyanate (catalysed by hepatic rhodanese)
• 1 reacts with hydoxy-cobalamin -> forms cyanocobalamin (vitamin B12)

• Elimination – thiocyanate & cyanocobalamin -> urine, t1/2 of thiocyanate = 3 days

EVIDENCE

Major issue – liability to cyanide toxicity

• risk increased by hypothermia, malnutrition, vitamin B12 deficiency, hepatic or renal impairment
• related to rate of infusion rather than total dose.
• cyanide ion combines with cytochrome C -> impairment of aerobic metabolism -> metabolic lactic acidosis
• signs:

• tachycardia
• dysrhythmias
• hyperventilation
• sweating

• treatment:

• stop SNP infusion
• supportive measures
• sodium thiosulphate
• dicobalt edentate
• sodium nitrite