Sodium Nitroprusside

Aka. SNiP, SNP

CLASS

• an inorganic nitrate

INDICATIONS

1. Acute hypertensive crisis
2. Perioperative BP control
3. Left ventricular failure

ADMINISTRATION / DOSING

• Intravenous (IV) either peripherally (requires more dilute concentration) or centrally
• Infusion:
  • Rate: 0.5-10 microgs/kg/min
    • Start: 1500 microgs/h (3 mL/h of central concentration) and adjust every 2-3 mins by 500 microgs (1 mL/h of central concentration)
  • Central infusion: 50 mg in 100 mL of 5% dextrose = 500 microgs/mL
  • Peripheral infusion: 50-100 mg in 500 mL of 5% dextrose (100-200 microgs/mL)
• An arterial line is required for close monitoring while using this medication
• It is compatible via Y-site with multiple other infusions frequently used in critical care (please undertake due diligence and check prior to same)

MECHANISM OF ACTION

• It works on both arterial and venous smooth muscle, however, it is more active in the veins than the arteries (and GTN is much more venous-acting than SNiP)
• Prodrug bioactivation to nitric oxide (NO) in erythrocytes by NO synthase
  • A by-product of metabolism is methaemoglobin and five cyanide ions (see metabolism)
• NO acts by activating/increasing the activity of guanylate cyclase (GC)
  • GC converts GTP –> cGMP which:
    • Activates myosin light-chain phosphatases causing smooth muscle relaxation
    • Activates calcium-sensitive potassium channels increasing potassium efflux and inhibiting L-type calcium influx channels
      • This inhibits calcium release from the sarcoplasmic reticulum via Inositol Triphosphate (IP3)
  • Net action: relaxation of smooth muscle via NO and decreases available intracellular calcium for further muscle contraction

PHARMACEUTICS

• Solution: 50 mg in 2 mL
• Must be diluted before administration
• Must be protected from light
• Must be given as an infusion

PHARMACOKINETICS

• Absorption
  • IV only
  • Almost immediate onset and offset of action
• Distribution
  • Limited information, however, confined only to the plasma
• Metabolism
  • Metabolism of SNiP in erythrocytes by NO synthase produces: methaemoglobin, nitric oxide and five cyanide ions
  • Of the five cyanide ions:
    • 1x binds to methaemoglobin and produces cyanomethaemoglobin
    • 3x form thiocyanate via rhodanese enzyme in the liver with sodium thiosulphate
    • 1x forms cyanocobalamin from vitamin B12a (hydroxocobalamin)
    • When the above mechanisms are saturated the cyanide ions are free to cause mischief in the mitochondria
• Elimination
  • T_1/2 of SNiP = 2 min and of thiocyanate = ~ 2 days
  • Predominantly renal elimination
  • Sodium nitroprusside is dialysable

PHARMACODYNAMICS

• CVS
  • Dose-dependent reduction in systemic vascular resistance
  • Venous vasodilation = reduced venous return –> reduction in preload –> reduction in myocardial oxygen consumption
  • Reflex tachycardia
  • Coronary artery vasodilator (less so than GTN)
• CNS
  • Increases cerebral blood flow thus increasing ICP
  • May cause cerebral steal in SAH
• RESP
  • Reduces hypoxic pulmonary vasoconstriction leading to increased shunt
  • Pulmonary artery vasodilator
• OTHER
  • Increase in methaemoglobinaemia
  • Sphincter relaxation
  • Cyanide toxicity (see below) and resulting lactic acidosis

TOXICITY

See Cyanide Poisoning on CCC.

• The primary cause of SNiP toxicity is related to the activity of free cyanide ions, with increased risk associated with higher doses and increased duration of therapy.
• Prolonged therapy leads to depletion of sodium thiosulphate and/or vitamin B12 with resulting saturation of cyanide metabolism/elimination pathways
• Increased cyanide-free ions have a high affinity for cytochrome oxidase which interrupts the electron transport chain in the mitochondria thus preventing aerobic metabolism (a form of histotoxic hypoxia)
• Risks
  • Hypothermia
  • Malnutrition – vitamin B12 deficiency
  • Hepatic or renal impairment
  • High rate and/or prolonged infusion
• Signs
  • Hypotension
  • Tachycardia
  • Arrhythmias
  • Hyperventilation
  • Sweating
  • Tachyphylaxis
  • Hyperlactataemia
• Treatment
  • Cease infusion, give supplemental oxygen
  • Give organic nitrate such as amyl nitrate –> increases methaemoglobin which has a high affinity to bind cyanide (higher than cytochrome oxidase)
  • Give sodium thiosulphate
  • Give di-cobalt edetate – chelates cyanide ions
  • Give Vitamin B12 (Hydroxocobalamin) which is less effective acutely
  • Consider giving methylene blue – also acts as a reducing agent and can increase methaemoglobin production

References and links

LITFL

• CCC – Cyanide Poisoning
• Toxicology Library – Cyanide Toxicity

References

• Australian Injectable Drugs Handbook, 8th Edition. (2022). Retrieved 07 October 2022, from https://aidh.hcn.com.au/
• Australian Medicines Handbook. (2022). Retrieved 07 October 2022, from https://amhonline.amh.net.au/
• IBM Micromedex. (2022). Retrieved 07 October 2022, from https://www.micromedexsolutions.com

Cite this article as:

Pearlman, J., & Nickson, C. (2023, July 21). Sodium Nitroprusside. Life in the Fast Lane. https://litfl.com/sodium-nitroprusside/