咪達唑侖
咪達唑侖是一種短效的注射用**苯二氮平類藥物**，在獸醫學中廣泛用作麻醉前鎮靜劑、肌肉鬆弛劑和抗癲癇藥物。 **臨床要點：** * **獨特的溶解性：** 與地西泮（Diazepam）不同，咪達唑侖在藥瓶中（pH < 4）呈水溶性，但在生理體液 pH 值（7.4）下會變得具有高度脂溶性。這使其能安全地與其他水溶性藥物（如鴉片類藥物和氯胺酮）混合而不會產生沉澱。 * **肌肉注射吸收：** 由於不含丙二醇，咪達唑侖在肌肉注射（IM）時不會引起刺痛，且能迅速可靠地被吸收，因此在肌肉注射的應用上優於地西泮。 * **矛盾性興奮：** 當單獨給予健康、無焦慮的犬貓時，咪達唑侖通常無法提供可靠的鎮靜效果，反而可能引起矛盾的煩躁或興奮。與其他藥物（如鴉片類、氯胺酮或 alpha-2 致效劑）合併使用時效果最佳。 * **癲癇重積狀態：** 對於阻止活動性癲癇發作非常有效，可透過靜脈（IV）、肌肉（IM）或鼻腔（IN）給藥。
作用機制: 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.
各物種劑量
- 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
給藥途徑
禁忌症
- Hypersensitivity to benzodiazepines
- Acute narrow-angle glaucoma
- Intra-carotid artery injection (must be avoided)
- Neonates (avoid use)
不良反應
- 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)
藥物相互作用
- 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
監測
- 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
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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