ミダゾラム
ミダゾラムは、獣医療において麻酔前鎮静薬、筋弛緩薬、および抗てんかん薬として広く使用される短時間作用型の注射用**ベンゾジアゼピン系薬物**です。 **臨床上のポイント：** * **独自の溶解性：** ジアゼパムとは異なり、ミダゾラムはバイアル内（pH < 4）では水溶性ですが、生理的な体内のpH（7.4）では高い脂溶性を示します。これにより、他の水溶性薬物（オピオイドやケタミンなど）と沈殿することなく安全に混合できます。 * **筋肉内吸収：** プロピレングリコールを含まないため、筋肉内（IM）注射時に痛みを伴わず、迅速かつ確実に吸収されるため、IM投与においてジアゼパムより優れています。 * **逆説的興奮：** 健康で不安のない犬や猫に単独で投与した場合、確実な鎮静が得られず、逆説的な不快感や興奮を引き起こすことがよくあります。他の薬剤（オピオイド、ケタミン、アルファ2作動薬など）と組み合わせて使用すると最も効果的です。 * **てんかん重積状態：** 活動性の発作を止めるのに非常に効果的であり、静脈内（IV）、筋肉内（IM）、または経鼻（IN）投与が可能です。
作用機序: Midazolam exerts its effects by enhancing the activity of **gamma-aminobutyric acid (GABA)**, the primary inhibitory neurotransmitter in the central nervous system. * **Target:** Binds to specific allosteric benzodiazepine receptors on the **GABA-A receptor** complex. * **Mechanism:** Binding increases the *frequency* of chloride channel openings → influx of chloride ions → hyperpolarization of the postsynaptic neuronal membrane → decreased neuronal excitability. * **Effects:** This depression of subcortical levels (limbic, thalamic, and hypothalamic) produces anxiolytic, sedative, skeletal muscle relaxant, and anticonvulsant effects. Midazolam has approximately twice the affinity for benzodiazepine receptors compared to diazepam, making it more potent with a faster onset and shorter duration of action.
動物種別の用量
- As a preoperative agent · 0.2-0.4 mg/kg IV or IM with an opioid such as hydromorphone (0.1 mg/kg IV or 0.2 mg/kg IM) · IV/IM · Once
- As a preoperative agent · 0.05-0.5 mg/kg; a dose of 0.3 mg/kg being the most effective when mixed with ketamine to allow for intubation. May be used in combination with ketamine in a 50:50 mixture (volume/volume) at a dose of 1 mL/9.1 kg (1 mL/20 lb), this equates to a dose of 0.28 mg/kg of midazolam and 5.5 mg/kg of ketamine. · IV/IM · Once
- As a preoperative agent · 0.1-0.5 mg/kg IV · IV · Once
- For status epilepticus · 0.07-0.2 mg/kg IV or IM; effects are short-lived, so if seizures recur a CRI can be helpful given at 0.05-0.5 mg/kg/hour. · IV/IM · Once or CRI
- Emergency management of seizures including status epilepticus · 0.2-0.3 mg/kg · IV/Intrarectal · Repeat q10min up to 3 times if no clinical effect · As needed for emergency control · Intrarectal route used if venous access is not available.
- As a preoperative agent · 0.011-0.0.44 mg/kg IV · IV · Once
- For seizure control in foals · 2-5 mg (total dose) for a 50 kg foal given IV; rapid IV administration may result in apnea and hypotension. A CRI may be used at a dose of 1-3 mg/hour for a 50 kg foal. · IV · Once or CRI
- For seizure control in foals · 2-5 mg (total dose) for a 50 kg foal given IV or IM; may be repeated to effect. · IV/IM · To effect
投与経路
禁忌
- Hypersensitivity to benzodiazepines
- Acute narrow-angle glaucoma
- Intra-carotid artery injection (must be avoided)
- Neonates (avoid use)
有害事象
- Respiratory depression (especially when combined with opioids or other CNS depressants)
- Paradoxical excitement, dysphoria, or agitation (especially in cats and dogs when used alone)
- Hypotension and bradycardia (when combined with other anesthetics like isoflurane or ketamine)
- Pain on injection or local irritation (rare compared to diazepam)
- Respiratory depression
- Severe hypotension
- Paradoxical excitement (occasionally)
薬物相互作用
- Inhalational Anesthetics (e.g., Isoflurane) · Midazolam may decrease the dosages required for inhalant anesthetics.
- Azole Antifungals (ketoconazole, itraconazole, fluconazole) · May inhibit midazolam metabolism, increasing midazolam blood levels.
- Calcium Channel Blockers (diltiazem, verapamil) · May increase midazolam levels.
- Cimetidine · May increase midazolam levels by inhibiting hepatic metabolism.
- Other CNS Depressants · May increase the risk of profound sedation and respiratory depression.
- Macrolide Antibiotics (erythromycin, clarithromycin) · May increase midazolam levels.
- Opiates · May increase the hypnotic effects of midazolam; hypotension has been reported when used with meperidine. Combination causes greater respiratory depression.
- Phenobarbital · May decrease peak levels and AUC of midazolam via enzyme induction.
- Rifampin · May decrease peak levels and AUC of midazolam.
- Thiopental · Midazolam may decrease the dosages required for induction.
- Propofol · Potentiates effect, reducing the dose required for induction · major
- Inhalation anaesthetics · Potentiates effect, reducing the dose required · major
モニタリング
- Level of sedation and central nervous system depression
- Respiratory rate, effort, and oxygenation (especially when combined with other drugs)
- Heart rate and blood pressure
- Respiratory rate and effort
- Blood pressure
- Heart rate and rhythm
- Level of sedation and consciousness
過量投与
Accidental overdoses should be managed with **supportive care** (e.g., cardiovascular and respiratory support), similar to diazepam. * **Reversal Agent:** **Flumazenil** is a specific benzodiazepine antagonist and can be used to reverse midazolam's effects. * However, because midazolam has a very short duration of effect and flumazenil is costly, supportive therapy is usually sufficient for all but the most massive overdoses.
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