氯解磷定 (Pralidoxime Chloride)
氯解磷定（通常稱為 **2-PAM**）是一種特異性解毒劑，在獸醫學中主要用於治療**有機磷 (OP) 中毒**。有機磷常見於早期的殺蟲劑、農用化學品及某些神經毒劑中。它們會不可逆地結合並抑制乙醯膽鹼酯酶 (AChE)，導致神經突觸和神經肌肉接合處的乙醯膽鹼大量累積。 氯解磷定作為一種**膽鹼酯酶復活劑**，能在有機磷與酵素的結合變成永久性（此過程稱為「老化」）之前，有效地將有機磷分子從酵素上剝離。 > **臨床要點：** 氯解磷定幾乎總是與**阿托品 (Atropine)** 併用。阿托品能阻斷乙醯膽鹼過多引起的毒蕈鹼樣作用（SLUDDE 症狀：流涎、流淚、排尿、排便、呼吸困難、嘔吐），而氯解磷定則是緩解**菸鹼樣作用**（特別是嚴重的肌肉震顫、無力和包括呼吸肌在內的癱瘓）所必需的。它通常**不建議**用於氨基甲酸酯 (Carbamate) 中毒，因為氨基甲酸酯與 AChE 的結合會自發性逆轉，不需要使用肟類復活劑。
作用機制: 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.
各物種劑量
- 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
給藥途徑
禁忌症
- Hypersensitivity to pralidoxime
- Carbamate poisoning (generally not recommended as inhibition is rapidly reversible)
不良反應
- Tachycardia (especially with rapid IV injection)
- Muscle rigidity
- Transient neuromuscular blockade
- Laryngospasm
藥物相互作用
- 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.
監測
- 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
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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