トピラマート
**トピラマート**は、主に犬や猫の難治性てんかんに対する追加（補助）療法として使用される、新しい第2世代の**抗てんかん薬**です。 * **臨床的有用性**：**部分（焦点）発作**や自動症（猫の「遊走発作」など）の管理に特に有用です。 * **薬物動態学的特徴**：犬での半減期は非常に短い（2〜4時間）ですが、脳内受容体への親和性が高いため、急速に消失しても持続的な治療活性を示します。 * **治療における役割**：フェノバルビタール、臭化カリウム、レベチラセタムなどの従来の発作治療薬では十分な効果が得られない場合によく検討されます。 * **実用上の考慮点**：ジェネリック医薬品が利用可能であり、費用の軽減に役立ちますが、頻繁な投与スケジュール（犬では通常1日3回）は飼い主の大きな負担となります。
作用機序: Topiramate has a multimodal mechanism of action that dampens excitatory pathways and enhances inhibitory neurotransmission in the central nervous system: * **Voltage-gated Sodium Channels** → Blocks repetitive action potentials in a time-dependent manner, preventing the spread of seizure activity. * **GABA Receptors** → Increases the frequency of **GABA** activation at **GABA_A receptors**, enhancing inhibitory signals in the brain. * **AMPA/Kainate Receptors** → Antagonizes these specific glutamate receptors, directly blocking excitatory neurotransmission (without affecting NMDA receptors). * **Carbonic Anhydrase** → Weakly inhibits isoenzymes **CA-II** and **CA-IV**, though this is believed to play only a minor role in its overall antiepileptic efficacy.
動物種別の用量
- Automatisms (running fits) and focal seizure activity · 12.5-25 mg PO (total dose) q8-12h · PO · q8-12h · Gradual adaptation in dosing is recommended. Inappetence is a major adverse effect with higher doses.
- Alternative second line anticonvulsant · 5-10 mg/kg PO q12h · PO · q12h
- Alternative treatment for refractory generalized and focal seizures · 5-10 mg/kg PO twice daily · PO · twice daily
- Seizures (Initial dose) · 2-10 mg/kg PO q12h · PO · q12h
- Seizures · 5-10 mg/kg PO twice daily · PO · twice daily · Start at the lower dosage to reduce adverse effects.
- Refractory epilepsy · 2.5-5 mg/kg PO three times daily · PO · three times daily · Presently, the author is using this drug at this dose, but at this stage there is not enough data to know how effective this treatment will be.
用量は獣医療従事者向けの臨床リファレンスです。必ず最新の添付文書と個々の患者で確認してください。
投与経路
禁忌
- Hypersensitivity to topiramate
- Known hypersensitivity to topiramate
有害事象
- GI distress (dogs)
- Inappetence (dogs, cats)
- Irritability (dogs)
- Sedation/Lethargy (cats, dogs)
- Ataxia (dogs)
- Somnolence (humans)
- Dizziness (humans)
- Acute myopia with secondary angle closure glaucoma (rare, humans)
- Calcium phosphate renal calculi (humans)
- Sedation
- Ataxia
- Anorexia
- Weight loss
- Gastrointestinal upset
薬物相互作用
- Amitriptyline · Topiramate may increase amitriptyline levels
- Carbonic Anhydrase Inhibitors (acetazolamide, dichlorphenamide) · Concomitant use may increase the risk of renal stone formation
- CNS Depressants · May exacerbate the adverse effects of topiramate · moderate
- Lamotrigine · May increase topiramate levels
- Phenytoin · May decrease topiramate levels; phenytoin levels may increase · moderate
- Valproic Acid · May decrease topiramate and VPA levels
- Phenobarbital · May increase clearance and decrease plasma concentrations of topiramate · moderate
モニタリング
- Seizure frequency and severity (Efficacy)
- Adverse effects (GI distress, sedation, inappetence)
- Seizure frequency and severity
- Body weight and appetite
- Renal function in compromised patients
過量投与
Overdoses in humans have caused convulsions, drowsiness/lethargy, slurred speech, blurred and double vision, impaired mentation/stupor, ataxia, metabolic acidosis, hypotension, agitation, and abdominal pain. In dogs, common findings reported to the ASPCA APCC include ataxia and lethargy. **Treatment**: * Gut emptying protocols if the ingestion was recent. * Supportive therapy. * Hemodialysis is effective in enhancing the elimination of topiramate from the body.
VetSheet の薬剤リファレンスは、獣医療従事者向けの臨床意思決定支援を目的としており、専門的判断やメーカーの最新添付文書に代わるものではありません。