プラリドキシム塩化物
プラリドキシム（通称 **2-PAM**）は、獣医学において主に**有機リン（OP）中毒**の治療に使用される特異的な解毒剤です。有機リンは、古い殺虫剤、農薬、一部の神経剤に一般的に含まれています。これらはアセチルコリンエステラーゼ（AChE）に不可逆的に結合して阻害し、神経シナプスや神経筋接合部でのアセチルコリンの大量蓄積を引き起こします。 プラリドキシムは**コリンエステラーゼ再賦活薬**として働き、結合が永久的になる（「エイジング」と呼ばれるプロセス）前に、酵素から有機リン分子を効果的に引き離します。 > **臨床上のポイント:** プラリドキシムはほぼ常に**アトロピン**と併用されます。アトロピンはアセチルコリン過剰によるムスカリン作用（SLUDDE症状：流涎、流涙、排尿、排便、呼吸困難、嘔吐）をブロックしますが、プラリドキシムは**ニコチン作用**（特に重度の筋振戦、筋力低下、呼吸筋を含む麻痺）を軽減するために必要です。カルバメート中毒に対しては、カルバメートとAChEの結合がオキシム系再賦活薬を必要とせずに自然に可逆的となるため、一般的に**推奨されません**。
作用機序: Pralidoxime works by directly reactivating the acetylcholinesterase enzyme that has been inhibited by organophosphates. * **Organophosphates** bind to the esteratic site of **acetylcholinesterase (AChE)** via phosphorylation, inactivating the enzyme. * Accumulation of **acetylcholine (ACh)** occurs at muscarinic and nicotinic receptors → severe overstimulation. * **Pralidoxime** possesses a high affinity for the AChE enzyme. * Via **nucleophilic attack**, the oxime group of pralidoxime binds to the offending phosphoryl group of the organophosphate. * The pralidoxime-organophosphate complex breaks away from the enzyme → **AChE is reactivated** and resumes breaking down ACh. > **Important Mechanistic Note:** If the phosphorylated enzyme undergoes a chemical change (loss of an alkyl group) before pralidoxime is administered, the bond becomes permanent. This is known as **"aging"**. Therefore, pralidoxime is most effective when given **within 24 hours** of exposure, though some benefit may be seen up to 36-48 hours in massive exposures.
動物種別の用量
- Organophosphate poisoning · 20 mg/kg · IM or slow IV · 2-3 times a day · Works best when combined with atropine. Initial dose IM or slow IV; subsequent doses IM or SC.
- Organophosphate poisoning · 10-15 mg/kg · IM or SC · q8-12h · 36 hour minimum
- Organophosphate poisoning · 50 mg/kg · slow IV · May repeat in one hour if severe · Recovery should occur gradually over 48 hours · Give atropine first. Dilute in 10% glucose. May administer IM or IP. Reduce dose in renal failure.
- Organophosphate poisoning · 20 mg/kg · IV · Repeat in one hour if signs persist, then q8h · 24-48 hours · Give slowly or with fluids over a 30-minute period.
- Organophosphate poisoning · 20 mg/kg · IM or IV · May repeat q6-8h · Give within first 24 hours of exposure. Combine with atropine or give separately. Do not use in carbamate toxicity.
- Organophosphate poisoning · 30 mg/kg · IM · q8h · FARAD recommends a 28-day meat and a 6-day milk withdrawal time.
- Organophosphate poisoning · 25-50 mg/kg · IV · Single dose, or maximum of 100 mg/kg/day as an IV drip · Give as a 20% solution over 6 minutes.
- Organophosphate poisoning · 20 mg/kg (may require up to 35 mg/kg) · IV · q4-6h
投与経路
禁忌
- Hypersensitivity to pralidoxime
- Carbamate poisoning (generally not recommended as inhibition is rapidly reversible)
有害事象
- Tachycardia (especially with rapid IV injection)
- Muscle rigidity
- Transient neuromuscular blockade
- Laryngospasm
薬物相互作用
- Barbiturates · Anticholinesterases can potentiate the action of barbiturates; use with caution.
- Cimetidine · Use should be avoided in patients with organophosphate toxicity.
- Succinylcholine · Use should be avoided in patients with organophosphate toxicity.
- Theophylline · Use should be avoided in patients with organophosphate toxicity.
- Reserpine · Use should be avoided in patients with organophosphate toxicity.
- Respiratory Depressants (e.g., narcotics, phenothiazines) · Use should be avoided in patients with organophosphate toxicity.
モニタリング
- Clinical signs associated with organophosphate poisoning (SLUDDE signs, muscle fasciculations, weakness)
- Heart rate and rhythm (especially during IV administration)
- Respiratory rate and effort
過量投与
The acute LD50 of pralidoxime in dogs is 190 mg/kg. At high dosages, it causes signs associated with its own anticholinesterase activity. Clinical signs of toxicity in dogs may be exhibited as: * Muscle weakness * Ataxia * Vomiting * Hyperventilation * Seizures * Respiratory arrest * Death
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