Sodium Nitroprusside (SNP)

Chemical

An INORGANIC peripheral vasodilator

Use

  1. Hypertensive crisis
  2. Aortic dissection prior to surgery

Presentation

IV solution for injection 50mg/2mL

Dose

0.5mcg/kg/min (IV)

MoA

A PRODRUG

Diffuses into RBC & reacts with OxyHb to form

  • MetHb
  • 5CN–
  • NO

NO → diffuses into smooth m. cell → binds to & activates GUANYLYL CYCLASE → GTP \( \xrightarrow{\text{GC }} \) cGMP → ↑cGMP

  1. Inhibits Ca2+ entry into smooth m. cell
  2. Activates K+ channels → hyperpolarises cell (inactive)
  3. Stimulates ‘cGMP-dependent-protein-kinase’ → activates MLC phosphatases → dephosphorylates MLC

↓

Smooth m. relaxation

PD

CVS: ↓BP, ↓afterL, ↑HR

RESP: blunts HPVC → ↓PaO2

CNS: Cerebral VD → ↑ICP; shifts autoregulation curve LEFT

GI: ↓LES tone, paralytic ileus

Metabolic:

  • ↑plasma catecholamines
  • ↑RENIN
  • Metabolic acidosis

PK

A

Nil oral absorption

D

Confined to plasma

VD = ECF = 15L

M

Pathway 1

In RBC to 5CN– + NO

  • 1CN– → reacts with MetHb → forms CyanoMetHb
  • 80% 4CN– → enter plasma → in liver metabolised by RHODANESE EN2 → uses thiosulfate ions as ‘sulfur donors’ to detoxify CN–
  • Rest 20%: react with hydroxycobalamin → CYANO-COBALAMIN

NB: CyanoMetHb = non toxic

Pathway 2

  • Low [ ] SNP
  • Reacts with sulphydryl groups of amino-acids present in plasma

E

Thiocyanate & cyanocobalamin excreted in urine

Adverse Effects

CYANIDE TOXICITY

↓BP

Headache

Dizziness

Palpitations