Midazolam
Midazolam is a short-acting parenteral **benzodiazepine** widely used in veterinary medicine as a preanesthetic sedative, muscle relaxant, and anticonvulsant. **Clinical Pearls:** * **Unique Solubility:** Unlike diazepam, midazolam is water-soluble in the vial (at a pH < 4) but becomes highly lipid-soluble at physiologic body pH (7.4). This allows it to be mixed safely with other water-soluble drugs (like opioids and ketamine) without precipitating. * **IM Absorption:** Because it does not contain propylene glycol, midazolam does not sting upon intramuscular (IM) injection and is rapidly and reliably absorbed via the IM route, making it superior to diazepam for IM use. * **Paradoxical Excitement:** When given alone to healthy, non-anxious dogs and cats, midazolam often fails to provide reliable sedation and can cause paradoxical dysphoria or excitement. It is most effective when combined with other agents (e.g., opioids, ketamine, or alpha-2 agonists). * **Status Epilepticus:** It is highly effective for arresting active seizures and can be administered IV, IM, or intranasally (IN).
กลไกการออกฤทธิ์: 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.
ขนาดยาตามชนิดสัตว์
- 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
วิธีการให้ยา
ข้อห้ามใช้
- Hypersensitivity to benzodiazepines
- Acute narrow-angle glaucoma
- Intra-carotid artery injection (must be avoided)
- Neonates (avoid use)
อาการไม่พึงประสงค์
- 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)
อันตรกิริยาระหว่างยา
- 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
การติดตาม
- 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
การได้รับยาเกินขนาด
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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