托吡酯
**托吡酯 (Topiramate)** 是一種新型的第二代**抗癲癇藥物**，主要作為犬貓難治性癲癇的附加（輔助）治療。 * **臨床應用**：對於控制**局部性（病灶性）癲癇**及自動症（例如貓的「奔跑性發作」）特別有效。 * **藥代動力學特徵**：在狗體內的半衰期極短（2-4小時），但由於其對大腦受體具有高親和力，儘管清除迅速，仍能維持持續的治療活性。 * **治療角色**：通常在傳統第一線療法（如苯巴比妥、溴化鉀或左乙拉西坦）無法有效控制癲癇時考慮使用。 * **實務考量**：目前已有學名藥上市，有助於降低治療成本，但頻繁的給藥頻率（狗通常需要一天三次）需要飼主的高度配合。
作用機制: 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.
各物種劑量
- 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.
劑量為持牌獸醫專業人員的臨床參考。請務必對照最新藥品說明書及個別病患確認。
給藥途徑
禁忌症
- Hypersensitivity to topiramate
- Known hypersensitivity to topiramate
不良反應
- 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
藥物相互作用
- 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
監測
- 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
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 藥物參考供持牌獸醫專業人員作臨床決策輔助之用,不能取代專業判斷或廠方最新藥品說明書。