アルファキサロン
**アルファキサロン (Alfaxalone)** は、速効性の中枢神経系抑制薬および全身麻酔薬として機能する神経活性ステロイド分子です。主に獣医療における麻酔の導入および維持に使用されます。 **臨床上のポイントと薬理学的特徴：** * **製剤の進化：** 現代の製剤（Alfaxan®）は、可溶化剤として2-ヒドロキシプロピル-β-シクロデキストリン（HPCD）を使用しています。これは、ポリエトキシ化ヒマシ油（Cremophor EL）を含み、特に猫において重篤なヒスタミン放出やアナフィラキシーを引き起こした過去の製品（Saffan®）からの大きな進歩です。 * **心肺機能への影響：** 一般的に安全域が広いと考えられていますが、特に急速に静脈内投与した場合、用量依存性の呼吸抑制や導入後の無呼吸を引き起こす可能性があります。代償性の頻脈が起こることはありますが、心血管系のパラメータは通常良好に維持されます。 * **鎮痛作用：** アルファキサロンには**鎮痛作用がほとんどありません**。痛みを伴う処置には、適切な純粋な鎮痛薬（オピオイドなど）を併用する必要があります。 * **回復：** 半減期が短く蓄積性がないため、回復は通常迅速かつスムーズですが、刺激を受けたり、前投薬/鎮痛が不十分な場合、精神運動性の興奮（パドリング、発声、痙攣）を経験することがあります。
作用機序: Alfaxalone exerts its anesthetic effects by interacting with **GABA_A (gamma-aminobutyric acid type A) receptors** in the central nervous system. * **Mechanism:** It binds to specific transmembrane domains on the GABA_A receptor complex. * **Pathway:** Binding → Enhances the binding of the inhibitory neurotransmitter GABA to the receptor → Increases the frequency and duration of **chloride (Cl⁻) ion channel** opening → Influx of chloride ions into the neuron → **Hyperpolarization** of the postsynaptic cell membrane → Inhibition of neural action potential transmission → Dose-dependent CNS depression (ranging from sedation to general anesthesia).
動物種別の用量
- Anesthesia Induction (Premedicated) · 3 mg/kg · IV · once · Administer over first 60 seconds to effect. If intubation not possible, one further similar dose may be administered.
- Anesthesia Induction (Unpremedicated) · 2 mg/kg · IV · once · Administer over first 60 seconds to effect.
- Anesthesia Induction (Alternative) · 1-2 mg/kg · IV · once · Slowly over 20-30 seconds while assessing degree of anesthesia.
- Anesthesia Maintenance (CRI, Premedicated) · 0.1-0.12 mg/kg/minute · IV · CRI · Up to 1 hour · Equivalent to 6-7 mg/kg/hour.
- Anesthesia Maintenance (CRI, Unpremedicated) · 0.13-0.15 mg/kg/minute · IV · CRI · Up to 1 hour · Equivalent to 8-9 mg/kg/hour.
- Anesthesia Maintenance (Bolus, Premedicated) · 1-1.2 mg/kg · IV · q10m · Up to 1 hour · Administer every 10 minutes as needed.
- Anesthesia Maintenance (Bolus, Unpremedicated) · 1.3-1.5 mg/kg · IV · q10m · Up to 1 hour · Administer every 10 minutes as needed.
- Anesthesia Maintenance (Alternative Bolus) · 5-12 mg/kg total dose · IV · incremental · 5-7 mg/kg total for short procedures; 8-12 mg/kg total for longer procedures.
- Anesthesia Induction · 5 mg/kg · IV · once · Premedicated or unpremedicated. Administer over first 60 seconds to effect.
投与経路
禁忌
- Concurrent use with other injectable general anesthetic agents (e.g., propofol, thiopental)
- Situations where endotracheal intubation, positive pressure ventilation, and oxygen support are unavailable
- Animals less than 12 weeks of age (safety not established)
有害事象
- Respiratory depression
- Post-induction apnea
- Hypotension (dose-dependent)
- Cardiac arrhythmias (primarily secondary to hypoxemia/hypercapnia)
- Psychomotor excitement during recovery (especially if unstimulated or lacking premedication)
薬物相互作用
- CNS Depressants (e.g., acepromazine, opioids, alpha-2 agonists, benzodiazepines) · Potentiates the CNS and respiratory depressant effects. Significantly reduces the required induction and maintenance doses of alfaxalone.
- Propofol · Should not be used concurrently according to the manufacturer label.
- Thiopental · Should not be used concurrently according to the manufacturer label.
- Other IV anaesthetic agents · Increased risk of severe CNS and respiratory depression · major
- Premedicants (e.g., sedatives, opioids) · Synergistic CNS depression; significantly reduces the required induction dose of alfaxalone · moderate
- Opioids (e.g., methadone, buprenorphine) · Synergistic CNS depression; reduces the required induction dose of alfaxalone. · moderate
- Alpha-2 agonists (e.g., dexmedetomidine) · Profound synergy; significantly reduces alfaxalone dose requirements and may exacerbate cardiovascular and respiratory depression. · major
- Phenothiazines (e.g., acepromazine) · Enhanced sedation and increased risk of hypotension. · moderate
- Opioids (e.g., butorphanol, methadone) · Synergistic CNS depression; significantly reduces the required induction dose of alfaxalone. · moderate
- Benzodiazepines (e.g., midazolam) · Synergistic CNS depression; reduces alfaxalone dose requirements. · moderate
モニタリング
- Level of anesthesia / CNS depression (jaw tone, palpebral reflex)
- Respiratory rate, rhythm, and depth (capnography and pulse oximetry highly recommended due to apnea risk)
- Cardiovascular status (heart rate, ECG rhythm, blood pressure)
- Body temperature (monitor for hypothermia during anesthesia)
過量投与
Overdoses up to 25 mg/kg primarily result in severe cardiorespiratory depression. **Clinical Signs of Toxicity:** * Severe hypoventilation and prolonged apnea * Hypotension * Cardiac arrhythmias **Treatment:** * Immediate endotracheal intubation and positive pressure ventilation with 100% oxygen. * Cardiovascular support (IV fluids, vasopressors/inotropes if hypotension is severe). * Continuous monitoring until the drug is metabolized and cleared.
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。