N-Acetyl-Cysteine

Chemical

Synthetic N-acetyl derivative of endogenous a-acid L-cysteine

Use (in ICU)

  1. Antioxidant
  2. Paracetamol overdose
    • Irrespective of P level (staggered OD)
    • Doubt over time of P OD (despite level)
    • Paracetamol level > 100mg/L at 4hrs and 15mg/L at 15h
  1. Prophylaxis of radiocontrast induced kidney injury
  2. Acute and chronic bronchopulmonary disease

Presentation

Clear colourless solution for infusion

200mg/ml injection

Dose

Paracetamol OD:

  1. Initial loading 150mg/kg in 200ml infused over 1hr
  2. 50mg/kg in 500ml over next 4hrs
  3. 100mg/kg in 1L over next 16hrs
  4. Receiving 300mg/kg over 21hrs

Route

IV

Inhaled for mucolysis

DoA

t1/2b 5.6 hrs after IV dose

MoA

Reduces hepatic toxicity of NAPQI;

  1. NAC acts as precursor for the synthesis of antioxidant enzyme glutathione, replenishing stores to inactivate NAPQI
  2. Reduces oxidised thiol groups of Paracetamol’s reactive metabolite

Glutathione reduces disulfide bonds in mucoproteins, resulting in liquification of mucus

Antioxidant effects via reduction in free radicals

PK

A

Rapidly absorbed but low OBA 10-30%

M

Rapid.  Hepatic.  Deacetylated by liver to cysteine and subsequently metabolised

E

30% unchanged in urine

Adverse Effects

CNS: fever

CVS: chest tightness, hypotension, HTN, tachycardia

GI: N+V

ENT: rhinorrhea

Clamminess