奧沙西泮
奧沙西泮是一種短至中效的**苯二氮平類 (Benzodiazepine)** 藥物，在獸醫學中主要用於犬貓的**食慾促進劑**和**抗焦慮藥**。 **臨床要點與藥理優勢：** * **代謝特徵：** 與地西泮 (Diazepam) 不同，奧沙西泮不經過第一階段肝臟代謝（氧化），且無活性代謝物。它僅透過第二階段的葡萄糖醛酸結合反應進行代謝。 * **老年與肝病患者的安全性：** 由於其代謝途徑較簡單，對於老年病患或患有輕至中度肝功能障礙的動物，通常被認為是比地西泮更安全的替代選擇。 * **貓咪注意事項：** 儘管其代謝特徵良好，但由於有少數軼事報告指出其可能引發特異體質性猛暴性肝衰竭，因此在患有肝炎或嚴重肝功能障礙的貓咪中使用仍具爭議。 * **行為治療用途：** 可作為口服輔助抗焦慮藥，用於治療恐懼、恐懼症和尿液標記行為，但偶爾可能出現矛盾的興奮反應。
作用機制: Oxazepam acts as a positive allosteric modulator at the **GABA-A receptor** complex in the central nervous system. * **Binding:** It binds to specific benzodiazepine recognition sites on the **GABA-A** ligand-gated chloride channel. * **Mechanism:** It enhances the inhibitory effect of **gamma-aminobutyric acid (GABA)** by increasing the *frequency* of chloride channel openings. * **Pathway:** Influx of chloride ions → **neuronal hyperpolarization** → decreased neuronal excitability. * **Clinical Effect:** This depression of subcortical CNS levels (primarily limbic, thalamic, and hypothalamic) produces the characteristic anxiolytic, sedative, skeletal muscle relaxant, and anticonvulsant effects.
各物種劑量
- Appetite stimulant · 2 mg per cat (total dose) · PO · every 12 hours
- Appetite stimulant (hepatic lipidosis) · 0.1-0.3 mg/kg · PO · q12-24h · If cat has a small interest in eating
- Appetite stimulant · 0.25-0.5 mg/kg · PO · one to two times daily
- Fears and phobias · 1-2.5 mg per cat (total dose) · PO · every 12 hours
- Fears and phobias · 0.2-0.5 mg/kg · PO · q12-24h
- Feline urine marking · 0.2-0.5 mg/kg · PO · once to twice a day
- Spraying or overgrooming · 0.2-0.5 mg/kg · PO · q12-24h
- Fears and phobias · 0.2-1 mg/kg · PO · q12h or q6h · The lowest dose and longest frequency between doses that alleviate the fear should be used.
- Fears and phobias · 0.2-0.5 mg/kg · PO · q12-24h
- Fears and phobias · 0.2-1 mg/kg · PO · q12-24h
- Fears and phobias · 0.2-1 mg/kg · PO · one to two times a day
- Fears and phobias · 0.04-0.5 mg/kg · PO · q6h · The lowest dose and longest frequency between doses that alleviate the fear should be used.
給藥途徑
禁忌症
- Known benzodiazepine hypersensitivity
- Acute narrow angle glaucoma
不良反應
- Sedation (most common)
- Ataxia
- Paradoxical excitability, vocalization, or aggression
- Rebound anxiety or behavior worsening (if withdrawn abruptly)
- Rare precipitation of tonic-clonic seizures
- Rare idiosyncratic fulminant hepatic failure (cats)
藥物相互作用
- CNS Depressant Drugs (barbiturates, narcotics, anesthetics) · Additive CNS depression effects may occur.
- Phenytoin · May decrease oxazepam concentrations.
- Probenecid · May impair glucuronide conjugation (in dogs) and prolong effects.
- Rifampin · May induce hepatic microsomal enzymes and decrease the pharmacologic effects of benzodiazepines.
- St. John's Wort · May decrease oxazepam effectiveness.
- Theophyllines · May decrease oxazepam effectiveness.
監測
- Clinical efficacy (improved appetite, reduced anxiety/fear)
- Adverse effects (degree of sedation, ataxia, paradoxical excitement)
過量
**Signs of Toxicity:** When used alone, overdoses are generally limited to significant CNS depression (confusion, coma, decreased reflexes, profound sedation). **Treatment:** * **Decontamination:** Standard protocols for removing and/or binding the drug in the gut (e.g., emesis induction if asymptomatic and recent, activated charcoal) if taken orally. * **Supportive Care:** Systemic supportive measures (IV fluids, warming, respiratory support if needed). * **Antidote:** **Flumazenil** (a specific benzodiazepine antagonist) could potentially be used in life-threatening overdoses. * **Contraindications:** The use of analeptic agents (CNS stimulants such as caffeine, amphetamines) is generally not recommended.
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