氯拉西泮
氯拉西泮（Clorazepate）是一種**苯二氮平類（Benzodiazepine）**藥物，在獸醫學中主要用作輔助抗癲癇藥，以及治療與焦慮或恐懼相關的行為障礙。 * **臨床要點**：它是一種前驅藥，需要胃酸環境才能迅速脫羧成為活性代謝物**去甲地西泮（Nordiazepam）**，隨後被吸收。 * 在犬隻中，常與苯巴比妥合用治療難治性癲癇。雖然對其抗癲癇效果可能會產生耐受性，但據報導其耐受速度慢於氯硝西泮（Clonazepam）。 * 在貓咪中，可用作抗焦慮藥，有時也作為苯巴比妥的替代品來控制癲癇，但由於口服苯二氮平類藥物在貓咪中有引發特異質性肝毒性的風險，因此需要謹慎使用。
作用機制: Benzodiazepines exert their effects by enhancing the inhibitory activity of **gamma-aminobutyric acid (GABA)** in the central nervous system. * **Mechanism**: They bind to specific allosteric sites on the **GABA-A receptor** complex → increases the frequency of chloride channel opening → cellular hyperpolarization → decreased neuronal excitability. * This depression of subcortical CNS levels (primarily limbic, thalamic, and hypothalamic) produces the characteristic anxiolytic, sedative, skeletal muscle relaxant, and anticonvulsant effects. * Other postulated mechanisms include antagonism of serotonin and diminished release or turnover of acetylcholine in the CNS.
各物種劑量
- Anxiolytic or for compulsive behaviors · 0.2-0.5 mg/kg PO q12-24h · PO · q12-24h
- Alternative drug to phenobarbital for seizures · 3.75-7.5 mg (total dose per cat) PO once to twice daily · PO · q12-24h · Similar precautions are necessary as described for diazepam use in cats (risk of hepatic necrosis).
- Adjunctive medication in the treatment of seizures (in combination with phenobarbital) · 1-2 mg/kg PO q12h, but may need to divide q12h dose and give q8h to minimize adverse effects and maintain therapeutic levels · PO · q8-12h
- Adjunctive medication in the treatment of seizures (in combination with phenobarbital) · 0.5-1 mg/kg PO q8h · PO · q8h · No advantage gained with using sustained release products. May affect phenobarb levels; monitor 2 and 4 weeks later.
- Adjunctive medication in the treatment of seizures · 1-2 mg/kg PO q12h · PO · q12h
- Adjunctive medication in the treatment of seizures · 2-4 mg/kg PO twice daily, some dogs may require three times daily · PO · q8-12h
- Third-line agent for seizures · 1-2 mg/kg PO q8-12h · PO · q8-12h
- Management of cluster seizures · 0.5-2 mg/kg two to three times daily · PO · q8-12h · 48-96 hours · Give immediately after first seizure and stop after 48-96 hours. Used only during seizure activity, not as maintenance.
- Adjunctive therapy for fears and phobias · 11.25-22.5 mg per dog PO once to twice daily · PO · q12-24h · Recommends the sustained-delivery product (Tranxene-SD).
給藥途徑
禁忌症
- Hypersensitivity to benzodiazepines
- Significant liver disease/dysfunction
- Acute narrow angle glaucoma
- Fear-induced aggression (relative contraindication; may disinhibit bite inhibition)
不良反應
- Sedation (most common)
- Ataxia
- Physical dependence (with chronic use)
- Acute hepatic necrosis (idiosyncratic in cats)
- Paradoxical excitation or disinhibition of aggression
藥物相互作用
- Azole Antifungals (itraconazole, ketoconazole) · May increase serum levels of benzodiazepines by inhibiting their metabolism.
- Cimetidine · May decrease the metabolism of benzodiazepines, leading to prolonged effects.
- CNS Depressants (barbiturates, narcotics, anesthetics) · Additive CNS depression; may cause profound sedation or respiratory depression.
- Erythromycin · May decrease the metabolism of benzodiazepines.
- Phenobarbital · Complex interaction: Clorazepate may initially increase phenobarbital serum levels. Over time, clorazepate levels may decrease, leading to decreased phenobarbital levels. Requires close monitoring.
- Phenytoin · May decrease clorazepate concentrations.
- Rifampin · May induce hepatic microsomal enzymes and decrease the pharmacologic effects of benzodiazepines.
監測
- Clinical efficacy (seizure frequency or behavioral improvement)
- Adverse effects (sedation, ataxia)
- Liver enzymes (especially critical in cats due to risk of acute hepatic necrosis)
- Phenobarbital serum levels (if used concurrently, monitor at 2 and 4 weeks after adding clorazepate)
過量
When used alone, clorazepate overdoses are generally limited to significant **CNS depression** (confusion, coma, decreased reflexes, profound sedation). * **Treatment**: Consists of standard protocols for removing and/or binding the drug in the gut (e.g., emesis if asymptomatic and recent, activated charcoal) and supportive systemic measures. * The use of analeptic agents (CNS stimulants such as caffeine, amphetamines) is generally **not recommended**. * **Flumazenil** (a specific benzodiazepine reversal agent) may be considered for very serious, life-threatening overdoses.
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