Acetylcysteine
Acetylcysteine (often referred to as NAC) is a highly versatile therapeutic agent in veterinary medicine. It is most prominently utilized as a life-saving **antidote for acetaminophen (paracetamol) toxicity**, particularly in cats and dogs, where it prevents severe hepatic necrosis and methemoglobinemia. Beyond its antidotal properties, acetylcysteine is a potent **mucolytic agent**. When administered into the respiratory tract, it effectively breaks down thick, viscous mucus, aiding in the clearance of respiratory secretions. **Clinical Applications:** * **Toxicology:** Primary treatment for acetaminophen, xylitol, and phenol toxicities. * **Respiratory:** Used via nebulization or intratracheal instillation to treat chronic upper respiratory diseases or conditions with heavy mucus burden. * **Ophthalmic:** Applied topically to halt the progression of "melting" corneal ulcers by inhibiting collagenases. * **Equine Medicine:** Used locally to dissolve chondroids in the guttural pouch and administered as an enema for refractory meconium impactions in neonatal foals. * **Internal Medicine:** Used adjunctively for feline hepatic lipidosis and anecdotally for canine degenerative myelopathy.
Mechanism: **Antidote Mechanism (Hepatoprotection):** Acetaminophen is metabolized in the liver to a highly reactive and toxic intermediate called **NAPQI** (N-acetyl-p-benzoquinone imine). Normally, NAPQI is safely conjugated by endogenous **glutathione**. In an overdose, glutathione is rapidly depleted, allowing NAPQI to cause severe oxidative stress and hepatocellular necrosis. Acetylcysteine acts as a **glutathione precursor** and provides an alternate sulfhydryl substrate to conjugate directly with NAPQI, thereby neutralizing the toxin and restoring cellular antioxidant defenses. **Mucolytic Mechanism:** The free **sulfhydryl group (-SH)** on the acetylcysteine molecule directly interacts with mucoproteins in respiratory secretions. It cleaves the **disulfide bonds** linking these proteins, which drastically reduces the viscosity of both purulent and non-purulent mucus. This effect is optimal in an alkaline environment (pH 7-9). It has no effect on living tissue or fibrin.
Dosing by species
- Acetaminophen toxicity ยท 140 mg/kg PO loading dose, followed by 70 mg/kg PO q6h ยท PO ยท q6h ยท For 7 treatments (up to 12-17 doses for massive ingestions) ยท Dilute to 5% in dextrose or sterile water. May also be given slow IV over 15-20 minutes. Wait 2-3 hours after activated charcoal if giving PO.
- Acetaminophen toxicity ยท 150 mg/kg PO or IV initially, then 50 mg/kg q4h ยท PO/IV ยท q4h ยท For 17 additional doses
- Acetaminophen toxicity ยท 140 mg/kg PO loading dose, then 70 mg/kg PO every 6 hours ยท PO ยท q6h ยท For 7 treatments
- Phenol toxicity ยท 140 mg/kg PO or IV initially, then 50 mg/kg q4h ยท PO/IV ยท q4h ยท For 3 days ยท May be partially effective to reduce hepatic and renal injury.
- Hepatotoxicity secondary to xylitol poisoning ยท 140-280 mg/kg loading dose IV or PO; followed by 70 mg/kg four times daily ยท IV/PO ยท q6h ยท Used as part of a comprehensive protocol including vitamin K, plasma, SAMe, vitamin E, and silymarin.
- Degenerative myelopathy (anecdotal) ยท 25 mg/kg PO q8h for 2 weeks, then q8h every other day ยท PO ยท q8h ยท Indefinitely (every other day after 2 weeks) ยท Dilute 20% solution to 5% with chicken broth. Used in conjunction with aminocaproic acid. Note: No treatment has been shown to be effective in published trials.
- Mucolytic ยท nebulize 50 mg as a 2% (dilute with saline) solution over 30-60 min or instil directly into the trachea 1-2 ml of a 20% solution ยท Nebulization/Intratracheal ยท prn ยท As needed ยท Dilute with saline for nebulization.
- Paracetamol poisoning ยท 140-280 mg/kg diluted to a 5% solution using 5% dextrose by slow i.v. infusion over 15-20 min, followed by further slow infusions of 70 mg/kg (similarly diluted) every 6 hours ยท IV ยท q6h ยท for at least 7 doses ยท Administer after inducing emesis if appropriate (within 2 hours of ingestion). IV preferred for serious intoxications. Can be given PO but must be diluted to improve palatability.
Routes of administration
Contraindications
- Hypersensitivity to the drug (specifically for pulmonary indications)
Adverse effects
- Nausea and vomiting (especially with oral administration due to poor palatability)
- Urticaria (rare)
- Bronchospasm, chest tightness, and bronchial/tracheal irritation (when inhaled)
- Blood pressure changes and allergic reactions (reported with IV boluses in humans)
Drug interactions
- Activated Charcoal ยท May adsorb orally administered acetylcysteine, potentially reducing its systemic absorption and efficacy. A 2-3 hour wait between charcoal and oral acetylcysteine is recommended, or acetylcysteine should be given intravenously. ยท moderate
Monitoring
- Hepatic enzymes (especially in dogs)
- Acetaminophen levels (if available)
- Hemogram, specifically monitoring methemoglobin values (especially critical in cats)
- Serum electrolytes
- Hydration status
Overdose
Acetylcysteine is considered quite safe in overdose situations. The LD50 in dogs is reported to be 1 g/kg orally and 700 mg/kg intravenously. Massive overdoses may result in gastrointestinal distress (nausea, vomiting) or hypersensitivity reactions, but life-threatening toxicity from the drug itself is rare.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.