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# Acetylcysteine
## Overview
Acetylcysteine (NAC) is a mucolytic agent and an antidote for acetaminophen overdose. It works by breaking disulfide bonds in mucus, reducing its viscosity, and by replenishing glutathione stores depleted by acetaminophen toxicity.
## Primary Indications
* **Acetaminophen Overdose:** To prevent or reduce liver injury.
* **Mucolytic:** To thin mucus in conditions like cystic fibrosis, chronic obstructive pulmonary disease (COPD), and pneumonia.
## Adult Dosing
**Acetaminophen Overdose:**
* **Intravenous (IV) Dosing:** A 21-hour protocol is standard.
* Loading Dose: 150 mg/kg IV infused over 60 minutes.
* Second Dose: 50 mg/kg IV infused over 60 minutes, 4 hours after the loading dose.
* Subsequent Doses: 100 mg/kg IV infused over 16 hours.
* Maximum dose: Not to exceed 200 mg/kg/day, though higher single doses may be given if needed to reach the target infusion rate.
* **Oral (PO) Dosing:** Also a 72-hour protocol, though less common due to palatability and emesis.
* Loading Dose: 140 mg/kg PO.
* Subsequent Doses: 70 mg/kg PO every 4 hours for 17 doses.
**Mucolytic:**
* **Inhaled:** 3-10 mL of 20% solution or 5-10 mL of 10% solution nebulized every 2-6 hours. Frequency and concentration may vary based on protocol and patient response.
## Pediatric Dosing
**Acetaminophen Overdose:**
* **Intravenous (IV) Dosing:** Same as adult dosing (150 mg/kg, 50 mg/kg, then 100 mg/kg over 21 hours).
* **Oral (PO) Dosing:** Same as adult dosing (140 mg/kg, then 70 mg/kg every 4 hours for 17 doses).
**Mucolytic:**
* **Inhaled:** 1-2 mL of 20% solution or 2-5 mL of 10% solution nebulized every 2-6 hours. Frequency and concentration may vary based on protocol and patient response.
## Dose Adjustments
* **Renal Impairment:** No specific dose adjustment is typically required for IV administration in acetaminophen overdose. Caution advised for inhaled use.
* **Hepatic Impairment:** No specific dose adjustment is typically required for IV administration in acetaminophen overdose. Caution advised for inhaled use.
## Contraindications
* Hypersensitivity to acetylcysteine.
* Acute bronchospasm (for inhaled formulation).
## Adverse Effects
* **Intravenous:** Anaphylactoid reactions (rash, pruritus, urticaria, angioedema, bronchospasm, dyspnea), nausea, vomiting, fever, tachycardia, hypotension.
* **Inhaled:** Bronchospasm, nausea, vomiting, stomatitis, rhinorrhea, chest tightness.
## Key Drug Interactions
* **Activated Charcoal:** Can adsorb oral acetylcysteine, reducing its absorption. Administer oral acetylcysteine at least 1 hour after activated charcoal.
* **Nitroglycerin:** Potential for additive hypotension and headache. Monitor blood pressure closely.
## Monitoring
* **Acetaminophen Overdose:**
* Serum acetaminophen levels (at least 4 hours post-ingestion and repeated as needed).
* Liver function tests (AST, ALT, bilirubin, INR) every 24 hours.
* Renal function, electrolytes.
* Glucose (especially in IV protocol).
* Signs of anaphylaxis.
* **Mucolytic:**
* Pulmonary status, sputum production and viscosity.
* Bronchospasm.
## Clinical Pearls
* For IV administration in acetaminophen overdose, the goal is to initiate treatment as soon as possible, ideally within 8 hours of ingestion.
* Dilute IV acetylcysteine to reduce the risk of anaphylactoid reactions; typically infused in 5% dextrose or normal saline.
* Anticipate and manage anaphylactoid reactions promptly with antihistamines and/or epinephrine if necessary.
* Oral acetylcysteine may be effective when IV access is not feasible or if patient has vomited repeatedly with IV NAC. Antiemetics may be required.
* For inhaled use, patients may require bronchodilator pretreatment to prevent bronchospasm.
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*Please verify current prescribing information with the manufacturer's package insert or institutional protocols.*
