溴化鉀 / 溴化鈉
溴化物是歷史最悠久的抗癲癇藥物之一，自19世紀以來即應用於人類與獸醫學。它們是鹵化物鹽類，主要作為狗的難治性癲癇的第一線或輔助治療，特別是當單獨使用苯巴比妥（Phenobarbital）效果不佳或因肝毒性而有禁忌時。 **主要臨床特徵：** * **不具肝毒性：** 與苯巴比妥不同，溴化物不經肝臟代謝，完全由腎臟排泄，是患有肝功能障礙的癲癇犬的首選藥物。 * **半衰期極長：** 在狗體內的半衰期約為16-25天。因此，需要3到4個月才能達到穩態血清濃度。通常需要給予**負荷劑量（Loading doses）**以迅速控制癲癇。 * **飲食敏感性：** 溴離子在腎臟中會與氯離子競爭重吸收。飲食中鹽分（氯化物）攝取量的改變會直接且成反比地影響血清溴化物濃度。 * **貓的禁忌症：** 貓通常避免使用溴化物，因為有極高風險引發嚴重的、類似氣喘的下呼吸道疾病（貓肺炎），甚至可能致命。
作用機制: Bromide's anti-seizure activity stems from its generalized depressant effect on neuronal excitability. * **Mechanism:** The bromide ion (Br⁻) is a halide that closely mimics the chloride ion (Cl⁻) in the body. It competes with chloride for transport across cell membranes, particularly at the **GABA_A receptor** chloride channels. * **Pathway:** GABA binds to the receptor → channel opens → Bromide traverses the channel more readily than chloride → **membrane hyperpolarization**. * **Result:** This hyperpolarization lowers the resting membrane potential, making it significantly harder for the neuron to depolarize. This effectively raises the seizure threshold and limits the spread of epileptic electrical discharges across the brain.
各物種劑量
- Refractory seizures (3rd choice therapy) · 10-20 mg/kg/day PO · PO · q24h · Follow same guidelines as dogs. Use with extreme caution.
- Epilepsy (2nd line therapy) · 30 mg/kg PO once daily · PO · q24h
- Seizures (Maintenance) · 20-30 mg/kg PO once daily, with food · PO · q24h · Dose is for potassium bromide. If sodium bromide is used, decrease dose by 15% (i.e., 17-26 mg/kg).
- Seizures (Rapid Loading Dose) · 400 mg/kg PO divided into 8 doses given over a 48-hour period (i.e., 50 mg/kg every 6 hours for 2 days) · PO · q6h · 2 days · Giving entire loading dose at once will usually cause vomiting. Start maintenance dose after loading.
- Seizures (Alternative Loading Dose) · 400-600 mg/kg/day divided and given with food · PO · divided · 1 to 5 days · May be given over 24 hours or more gradually over 5 days. Then go to initial maintenance dose.
- Seizures (Alternative Loading Dose 2) · 125 mg/kg/day for 5 days PO divided q12h · PO · q12h · 5 days · Resume at 35 mg/kg PO once daily after loading.
- Status epilepticus / NPO · 100 mg/kg body weight every 4 hours for 6 total doses · Rectal · q4h · 24 hours
- Seizures (IV Loading - Sodium Bromide) · 600-1200 mg/kg, diluted in a solution and administered over eight hours · IV · once · 8 hours · Sodium bromide only. If target serum bromide concentrations are not reached, additional IV NaBr may be administered. Use with caution.
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
- Cats (relative to absolute contraindication due to severe pulmonary effects)
- Patients with severe renal dysfunction (requires extreme caution and dose adjustment)
- Pregnant or lactating animals (crosses placenta and enters milk, causing fetal growth retardation/intoxication)
不良反應
- Profound sedation (especially transiently during loading or when combined with phenobarbital)
- Polyphagia (increased appetite) and subsequent weight gain
- Polydipsia and polyuria (increased thirst and urination)
- Ataxia and hind limb paresis (signs of toxicity)
- Gastrointestinal upset (vomiting, anorexia, constipation)
- Pancreatitis (reported in combination with phenobarbital/primidone)
- Pruritic dermatitis (rare)
- Paradoxical hyperactivity (rare)
- Cats: Severe lower respiratory effects (cough, dyspnea, peribronchial infiltrates)
藥物相互作用
- CNS Sedating Drugs · Additive sedation and CNS depression.
- Diuretics (furosemide, thiazides) · May enhance the renal excretion of bromides, lowering serum levels and potentially causing seizure breakthrough.
- High Chloride/Salt Diets · Increases renal excretion of bromide, reducing serum bromide levels and affecting seizure control.
- Low Chloride/Salt Diets · Decreases renal excretion of bromide, increasing serum bromide levels and risking bromide toxicity.
- Drugs that lower seizure threshold (e.g., xylazine) · May potentially reduce the efficacy of antiseizure medications.
監測
- Serum bromide concentrations (Therapeutic range in dogs: 1-3 mg/mL)
- Seizure frequency and severity
- Signs of toxicity (sedation, ataxia, weakness)
- Renal function (BUN, Creatinine, USG)
- Body weight (due to polyphagia)
過量
Toxicity (bromism) is more likely with chronic overdoses, but acute overdoses can occur. **Clinical Signs of Bromism:** * Profound sedation to stupor * Ataxia, tremors, and hind limb paresis * Muscle pain * Conscious proprioceptive deficits * Anisocoria and hyporeflexia **Treatment:** * **Acute Ingestion:** Standard gut removal techniques (emesis, gastric lavage). Death from acute oral ingestion is rare as spontaneous vomiting usually occurs. * **Enhancing Excretion:** Administration of parenteral 0.9% sodium chloride (NaCl) or oral sodium chloride, parenteral glucose, and loop diuretics (e.g., **furosemide**) are highly effective in promoting renal excretion and reducing bromide loads in intoxicated patients.
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