撲米酮
撲米酮是一種巴比妥類抗癲癇前驅藥物，在犬隻體內會迅速轉化為**苯巴比妥 (Phenobarbital)** 和 **苯乙基丙二醯胺 (PEMA)**。 雖然過去常用於控制犬隻的癲癇發作，但**目前多數獸醫神經學專家已不建議將其作為首選藥物**。 > **臨床提示：** 與苯巴比妥相比，撲米酮引發嚴重肝毒性的機率較高，這是限制其長期使用的主要原因。 在犬隻中，撲米酮轉化為苯巴比妥的比例約為 4:1（250 毫克的撲米酮約等同於 60 毫克的苯巴比妥）。部分臨床獸醫師會將其保留用於對單獨使用苯巴比妥反應不佳的頑固性病例，理論上 PEMA 代謝物可能增強苯巴比妥的抗癲癇活性。該藥物對貓和兔子具有高度毒性。
作用機制: Primidone and its active metabolites, **phenylethylmalonamide (PEMA)** and **phenobarbital**, exert anticonvulsant effects by raising seizure thresholds and altering seizure patterns. **Mechanistic Pathway:** * **Phenobarbital (Primary active metabolite):** Binds to the allosteric barbiturate site on **GABA_A receptors** in the CNS → prolongs the duration of chloride channel opening → increases intracellular chloride influx → hyperpolarizes the postsynaptic neuron → globally depresses CNS excitability and raises the seizure threshold. * **PEMA:** Has weak intrinsic anticonvulsant activity but is believed to synergistically potentiate the effects of phenobarbital. * **Primidone (Parent drug):** May have some independent action on voltage-gated sodium channels, though its primary efficacy in veterinary species is attributed to its phenobarbital metabolite.
各物種劑量
- Seizure control · 20 mg/kg · PO · q12h · Extreme caution advised; many consider contraindicated in cats.
- Seizure control · 10-30 mg/kg per day divided into 2-3 doses · PO · divided into 2-3 doses · Initially
- Seizure control · 10 mg/kg · PO · q8h · Not recommended as first choice
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
- Severe liver disease
- Demonstrated previous hypersensitivity to primidone or barbiturates
- Nephritis (large doses contraindicated)
- Severe respiratory dysfunction (large doses contraindicated)
- Cats (considered contraindicated by many clinicians due to high toxicity risk)
不良反應
- Anxiety and agitation (especially during initiation)
- Elevated liver enzymes (ALT, ALP, GLDH)
- Decreased serum albumin
- Hepatic lipidosis
- Hepatocellular hypertrophy and necrosis
- Extramedullary hematopoiesis
- Depression and sedation
- Ataxia
- Polydipsia (PD)
- Polyuria (PU)
- Polyphagia
- Anorexia
- Tachycardia
- Dermatitis
- Episodic hyperventilation
- Urolith formation (primidone uroliths reported)
- Megaloblastic anemia (rare)
藥物相互作用
- Acetaminophen · Increased risk for hepatotoxicity, particularly with large or chronic doses of barbiturates.
- Carbonic Anhydrase Inhibitors (e.g., acetazolamide) · Oral administration may decrease the GI absorption of primidone.
- Monoamine Oxidase Inhibitors (e.g., amitraz, selegiline) · May prolong phenobarbital effects.
- Phenytoin · Barbiturates may affect phenytoin metabolism, and phenytoin may alter barbiturate levels; therapeutic monitoring indicated.
- Rifampin · May induce enzymes that increase the metabolism of barbiturates.
- Antihistamines · May increase the CNS depressant effects of phenobarbital.
- Chloramphenicol · May increase the effects of phenobarbital; phenobarbital may also decrease chloramphenicol levels.
- Opiates · May increase the CNS depressant effects of phenobarbital.
- Phenothiazines · May increase the effects of phenobarbital; phenobarbital may decrease phenothiazine serum concentrations.
- Valproic Acid · May increase the effects of phenobarbital.
- Warfarin · Phenobarbital may decrease anticoagulant effects by lowering serum concentrations.
- Beta-blockers · Phenobarbital may decrease effects by lowering serum concentrations.
監測
- Anticonvulsant efficacy (seizure frequency and severity)
- Adverse effects (CNS depression, PU/PD, weight gain, signs of liver disease)
- Serum phenobarbital levels (therapeutic range in dogs thought to be 15-40 mcg/mL) if lack of efficacy or adverse reactions are noted
- Routine CBCs and liver enzyme panels at least every 6 months during chronic therapy
過量
**Clinical Signs:** Because primidone is rapidly metabolized to phenobarbital in dogs, signs of acute toxicity mirror barbiturate overdose: sedation progressing to coma, anorexia, vomiting, ataxia, and nystagmus. **Treatment:** * **Decontamination:** Removal of ingested product from the gut if appropriate (emesis or gastric lavage). * **Adsorbents:** **Activated charcoal** is of considerable benefit in enhancing the clearance of phenobarbital (acts as a 'sink' for the drug to diffuse from the vasculature back into the gut), even if the drug was administered parenterally. * **Supportive Care:** Provide respiratory and cardiovascular support. * **Enhanced Elimination:** Forced alkaline diuresis can augment elimination in patients with normal renal function. Peritoneal dialysis or hemodialysis may be helpful in severe intoxications or anuric patients.
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。