N-Acetyl-Cysteine

Drug toxicity used against

  • Treatment of acute Acetaminophen toxicity
  • Prevention of CIN (contrast induced nephrotoxicity)

Mechanism of action

  • Acetaminophen metabolism
    • ~5% oxidized by CYP450
  • Produces toxic metabolite  N-acetyl-p-benzoquinone imine (NAPQI)
    • Precursor to cellular injury
    • Normally detoxified by liver glutathione
  • Overdose
    • Depletes the glutathione reserves
  • NAC
    • Glutathione inducer – providing cysteine, an essential precursor in glutathione production
    • Directly conjugate NAPQI
    • Antioxidant-  binds to toxic metabolites and scavenges free radicals
    • Also increases oxygen delivery to tissues, increases ATP production, and alters the microvascular tone to increase blood flow and oxygen delivery to the liver and other vital organs

Effects offset

  • Liver-Prevent  cellular necrosis
  • Kidneys-reduces oxidative stress
    • Improves blood flow 

Time to clinical effect

  • Nebuliser: 1-2 hours
  • Oral: 2 hours
  • IV: No data available

Digoxin FAb

Drug toxicity used against

  • Acute
  • Chronic Digoxin toxicity

Mechanism of action

  • Immunoglobulin – Antibody binding (Fab)fragment which binds digoxin molecule
    • Makes it unavailable for binding at the site of action on cells
    • Fab fragment-digoxin complex is excreted by the kidney

Effects offset

  • Prevents the toxic effects of digoxin eg:
    • Bradycardia
    • VF
    • VT,
    • Asystole,
    • Heart blocks

Time to clinical effect

  • 30 – 45 minutes

Naloxone

Drug toxicity used against

  • Opioid toxicity

Mechanism of action

  • Competitive inhibitor of the µ-opioid receptor
    • Block or reverse the effects of opioids

Effects offset

  • Abates the effects like respiratory depression
  • Reduced heart rate
  • Slurred speech,
  • Drowsiness
  • Constricted pupils

Time to clinical effect

  • IV / Nasal spray
  • 2-5 minutes

Lipid emulsion (i.e. Intralipid)

Drug toxicity used against

  • Local anaesthetic systemic toxicity (LAST)
  • Including cardiac arrest Eg
    • Bupivacaine
    • Cocaine
  • Class I antiarrhythmic cardiotoxicity
  • Studied in other Lipophilic drugs Eg
    • Bupropion
    • Lamotrigine

Mechanism of action

  • Precise mechanism unclear
  • Several theories exist
  • Weinberg’s “lipid sink” theory
    • A lipid compartment is created in the blood into which the lipophilic drugs may dissolve and remove them from the aqueous plasma circulation
  • Dynamic “lipid shuttle” or “lipid subway”
    • Lipid compartment scavenges local anesthetic from high blood flow sensitive organs (ie, heart and brain), then redistributes to muscles for storage and the liver for detoxification
  • Cardiotonic and postconditioning effects
    • Directly increases cardiac contractility
  • Cardioprotective effects through multiple biochemical pathways

Effects offset

  • Reverses both neurologic and cardiac toxicity

Time to clinical effect

  • ? Minutes

Author: Nazma Navilehal Rajasab