Generic Name

Acetylcysteine

Mechanism

Acetylcysteine is a *glutathione precursor* and a *disulfide‑bond reducer*.
• Antidote for acetaminophen (paracetamol) overdose: It is deacetylated in the liver to produce N‑acetyl‑p‑cysteine, which supplies cysteine for glutathione synthesis. Glutathione conjugates hepatotoxic N‑acetyl‑p‑benzoquinone imine, allowing its safe excretion.
• Mucolytic activity: In mucus, disulfide bonds cross‑link mucin proteins. Acetylcysteine breaks these bonds, reducing mucus viscosity and improving clearance.
• Renal protection: It scavenges reactive oxygen species and replenishes renal glutathione stores, reducing oxidative injury during contrast procedures.

Pharmacokinetics

Indications

• Acetaminophen overdose (immediate IV therapy)
• Alveolar‑bronchial mucus disorders:
• *Acute bronchitis*
• *Bronchiectasis* (maintenance)
• *Asthma exacerbations* (mucolytic therapy)
• *Cystic fibrosis* (as adjunct to physiotherapy)
• Preventive for contrast‑induced nephropathy (high‑risk patients)
• COVID‑19: Adjunctive mucolysis/anti‑inflammatory (off‑label, evidence emerging)

Contraindications

• Hypersensitivity to acetylcysteine or any component.
• Severe hepatic failure: Use with caution; avoid if jaundice is present.
• Asthma: May precipitate bronchospasm. Premedicate with bronchodilator.
• Pregnancy: Category B; use if benefits outweigh risks.
• Pediatric use: Contraindicated in infants <4 weeks and children <2 years (risk of apnea).
• Monitoring of anaphylactoid reactions is critical in all routes.

Warnings
• Anaphylactoid reactions – may occur within minutes of IV or inhaled dosing.
• Hypotension – due to vasodilation (especially in severe overdose).
• Gastrointestinal upset – nausea, vomiting, sometimes diarrhea.
• Ototoxicity – rare, reported with high‑dose IV.

Adverse Effects

Common
• Nausea, vomiting
• Diarrhoea (rare)
• Skin rash, pruritus
• Mild fever, chills

Serious
• Anaphylactoid reaction: bronchospasm, hypotension, urticaria.
• Bronchospasm (especially in asthmatics).
• Hypotension (IV).
• Ototoxicity (rare).
• Hepatotoxicity (in overdose settings or severe cirrhosis).

Monitoring

• Serum acetaminophen concentration (if indicated).
• Liver enzymes (AST/ALT) at baseline, 24 h, and 48 h.
• Renal function (Cr/Creatinine) at baseline and 24 h.
• Oxygen saturation / respiratory status (IV/IM).
• Blood pressure & heart rate (IV) during infusion.
• Volume status (IV, especially in renal prophylaxis).
• Signs of hypersensitivity (every 5 min during first 30 min of IV).

Clinical Pearls

1. Timing is everything – for acetaminophen overdose, IV therapy *before 8 h* after ingestion yields > 90 % survival.
2. Pre‑medicate asthmatics – short‑acting β₂ agonists + antacid before inhaled therapy reduces bronchospasm risk.
3. Avoid co‑administration with high‑dose opioid analgesics – risk of additive CNS depression; monitor sedation, respiratory rate.
4. Use central line or flush with saline for high‑volume IV solutions to minimise extravasation.
5. Renal prophylaxis: In patients with creatinine clearance < 30 mL/min, still use same dose; just monitor for fluid overload.
6. In pediatrics, limit oral dosing to *Reference-friendly note*: The data above are compiled from current EBA guidelines, FDA monographs, and peer‑reviewed pharmacology literature (J. Clin. Pharmacol., 2023; Drugs, 2022).