What class of drug is sodium nitroprusside?

Aka. SNiP

CLASS

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
  • T1/2 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  
  • Malnutrition – vitamin B12 deficiency
  • Hepatic or renal impairment
  • High rate and/or prolonged infusion
• Signs
• 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 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

LITFL

References

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of three amazing children.

On Twitter, he is @precordialthump.

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