アセチルシステイン
アセチルシステイン（NACとも呼ばれる）は、獣医学において非常に多用途な治療薬です。特に犬や猫における**アセトアミノフェン（パラセタモール）中毒の救命解毒剤**として最もよく知られており、重篤な肝壊死やメトヘモグロビン血症を防ぎます。 解毒作用に加えて、アセチルシステインは強力な**粘液溶解剤**でもあります。気道に投与されると、ドロドロとした粘液を効果的に分解し、気道分泌物の排出を助けます。 **臨床応用：** * **毒物学：** アセトアミノフェン、キシリトール、フェノール中毒の主な治療。 * **呼吸器系：** ネブライザーまたは気管内注入により、慢性上部呼吸器疾患や粘液過多の状態を治療。 * **眼科：** コラゲナーゼを阻害し、「融解性」角膜潰瘍の進行を止めるために局所塗布。 * **馬の医学：** 喉嚢内の軟骨様物質を溶解するための局所使用、および新生仔馬の難治性胎便停滞に対する浣腸として使用。 * **内科：** 猫の肝リピドーシスの補助治療、および犬の変性性脊髄症に対する経験的治療。
作用機序: **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.
動物種別の用量
- Acetaminophen toxicity · 140 mg/kg PO loading dose, followed by 70 mg/kg PO q6h · PO · q6h · For 7 treatments (up to 12-17 doses for massive ingestions) · 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 · 150 mg/kg PO or IV initially, then 50 mg/kg q4h · PO/IV · q4h · For 17 additional doses
- Acetaminophen toxicity · 140 mg/kg PO loading dose, then 70 mg/kg PO every 6 hours · PO · q6h · For 7 treatments
- Phenol toxicity · 140 mg/kg PO or IV initially, then 50 mg/kg q4h · PO/IV · q4h · For 3 days · May be partially effective to reduce hepatic and renal injury.
- Hepatotoxicity secondary to xylitol poisoning · 140-280 mg/kg loading dose IV or PO; followed by 70 mg/kg four times daily · IV/PO · q6h · Used as part of a comprehensive protocol including vitamin K, plasma, SAMe, vitamin E, and silymarin.
- Degenerative myelopathy (anecdotal) · 25 mg/kg PO q8h for 2 weeks, then q8h every other day · PO · q8h · Indefinitely (every other day after 2 weeks) · 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 · 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 · Nebulization/Intratracheal · prn · As needed · Dilute with saline for nebulization.
- Paracetamol poisoning · 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 · IV · q6h · for at least 7 doses · 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.
投与経路
禁忌
- Hypersensitivity to the drug (specifically for pulmonary indications)
有害事象
- 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)
薬物相互作用
- Activated Charcoal · 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. · moderate
モニタリング
- Hepatic enzymes (especially in dogs)
- Acetaminophen levels (if available)
- Hemogram, specifically monitoring methemoglobin values (especially critical in cats)
- Serum electrolytes
- Hydration status
過量投与
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.
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