フィゾスチグミン
フィゾスチグミンは可逆性の**コリンエステラーゼ阻害薬**であり、獣医療では主にイベルメクチン中毒の補助治療、犬や馬のナルコレプシー/カタプレキシーの誘発診断薬、および中枢性抗コリン薬中毒の解毒剤として使用されます。 **臨床上のポイント:** * 第4級アミン（ネオスチグミンなど）とは異なり、フィゾスチグミンは**第3級アミン**です。 * この構造の違いにより**血液脳関門（BBB）**を容易に通過できるため、「中枢性」の抗コリン毒性の治療に特異的な効果を発揮します。 * 中枢神経系に移行するため、中枢性の毒性作用（痙攣など）のリスクが高くなります。 * 治療域が狭く重篤な副作用の可能性があるため、通常は生命を脅かす中枢神経毒性の治療に限定して使用されます。
作用機序: Physostigmine reversibly inhibits the enzyme **acetylcholinesterase** → prevents the hydrolysis and destruction of **acetylcholine (ACh)** → increases the concentration of ACh at both muscarinic and nicotinic receptor sites. Because it is a lipophilic tertiary amine, it crosses the blood-brain barrier and exerts its cholinergic effects both **centrally** and **peripherally**. This widespread cholinergic stimulation leads to miosis, bronchoconstriction, hypersalivation, and increased gastrointestinal motility.
動物種別の用量
- For reversal of tall larkspur (Delphinium barbeya) poisoning · 0.04-0.08 mg/kg · IV · As needed · Administer rapidly; serial injections may be necessary.
- Provocative test in diagnosing cataplexy or narcolepsy · 0.05-0.1 mg/kg · IV · Once · Administer slow IV. Will precipitate a cataplectic attack within 3-10 minutes. Untoward effects may include colic or cholinergic stimulation. Note: RCI Class 3 drug.
- Provocative test in diagnosing cataplexy or narcolepsy · 0.06-0.08 mg/kg · IV · Once · Lack of positive response does not rule out diagnosis. Diarrhea can occur and caution is advised as horse can cause colic.
- To temporarily reverse the CNS effects of ivermectin toxicosis in support of the diagnosis · 1 mg (total dose) · IV · Once
- To temporarily reverse the CNS effects of ivermectin toxicosis in support of the diagnosis · 1 mg (total dose)/12 hours · IV · q12h · May reverse ivermectin-induced coma for 30-90 minutes. In comatose patients, it does not appear to induce seizures, but seizure-like activity can be observed in patients with only minor ataxia and confusion.
- Provocative test for narcolepsy/cataplexy · 0.025 mg/kg · IV · Once · Wait 9-15 minutes and observe response to stimulus. If clinical signs do not appear, may try a higher dose of 0.05 mg/kg. Subsequent testing can be done at doses of 0.075 mg/kg and 1 mg/kg. Increased severity of signs persisting for 15-45 minutes is indicative of cataplexy/narcolepsy.
用量は獣医療従事者向けの臨床リファレンスです。必ず最新の添付文書と個々の患者で確認してください。
投与経路
禁忌
- Prior hypersensitivity reactions to physostigmine or sulfites
- Bronchoconstrictive disease (asthma)
- Gangrene
- Diabetes mellitus
- Cardiovascular disease
- Mechanical obstruction of the GI or urinary tract
- Any vagotonic state
- Concurrent use of choline esters or depolarizing neuromuscular blocking agents
有害事象
- Miosis
- Bronchial constriction
- Hypersalivation
- Muscle weakness
- Sweating (in species with sweat glands)
- Seizures
- Bradycardia
- Tachycardia
- Asystole
- Nausea
- Vomiting
- Diarrhea
- Depolarizing neuromuscular block
- Pulmonary edema
- Respiratory paralysis
薬物相互作用
- Choline esters (bethanechol, carbachol, methacholine) · May cause additive adverse cholinergic effects.
- Organophosphates · May cause additive adverse cholinergic effects.
- Succinylcholine · High doses of physostigmine may cause muscle fasciculations or depolarization block, which may be additive to the effects of succinylcholine-like neuromuscular blockers.
モニタリング
- Direct patient supervision is required
- Heart rate
- Blood pressure
- ECG/Heart rhythm (especially if heart rate is abnormal)
- Signs of cholinergic crisis (salivation, lacrimation, urination, defecation, dyspnea, emesis)
過量投与
Overdoses or acute toxicity can be **life-threatening** and may result in a severe cholinergic crisis (seizures, bradycardia, asystole, respiratory paralysis). * **Supportive Care:** Because of the short duration of effect, supportive care (including mechanical ventilation and repeated bronchial aspiration) may be sufficient in some cases. * **Antidote (Muscarinic):** Administration of **IV atropine** is the primary treatment for cholinergic toxicity. Re-administration may be required. * **Antidote (Nicotinic):** **Pralidoxime (2-PAM)** may be useful in reversing the ganglionic and skeletal muscle effects of physostigmine. * Contact an animal poison control center for case management assistance.
VetSheet の薬剤リファレンスは、獣医療従事者向けの臨床意思決定支援を目的としており、専門的判断やメーカーの最新添付文書に代わるものではありません。