苯巴比妥
**苯巴比妥 (Phenobarbital)** 是一種長效巴比妥類藥物，在獸醫學中是控制癲癇發作的基石。 * **主要用途**：被廣泛認為是治療貓原發性癲癇的首選藥物，同時也是狗和馬最常見且有效的第一線或輔助抗癲癇藥物之一。 * **臨床優勢**：具有良好的藥代動力學特性、相對安全性高、療效確切且成本低廉。它能在亞催眠劑量下有效控制癲癇。 * **肝臟自我誘導**：苯巴比妥的一個獨特藥理特徵是它能誘導肝臟細胞色素 P450 酵素。隨著時間推移，病患肝臟代謝該藥物的效率會提高，這通常需要增加劑量以維持治療血清濃度。 * **其他用途**：除了控制癲癇外，偶爾也用作口服鎮靜劑（例如用於貓咪旅行焦慮或過度鳴叫），並可用於在使用苯二氮平類藥物初步控制後的癲癇重積狀態管理。
作用機制: Phenobarbital exerts its antiseizure and sedative effects through multiple mechanisms within the central nervous system: * **GABA-A Receptor Modulation**: Phenobarbital binds to the allosteric barbiturate site on the **GABA-A receptor**. Unlike benzodiazepines (which increase the *frequency* of chloride channel opening), phenobarbital increases the **duration** of chloride channel opening → enhanced influx of chloride ions → hyperpolarization of the postsynaptic neuronal membrane → increased seizure threshold and decreased spread of seizure activity. * **Glutamate Inhibition**: It inhibits the release of excitatory neurotransmitters, specifically **glutamate**, thereby dampening CNS excitability. * **Calcium Channel Blockade**: At high (anesthetic) doses, it inhibits the uptake of calcium at nerve endings, further reducing neurotransmitter release. * **Other Neurotransmitters**: It has also been shown to inhibit the release of acetylcholine and norepinephrine.
各物種劑量
- Idiopathic epilepsy (initial dose) · 2-2.5 mg/kg · PO · q12h · Optimum therapeutic levels 23-30 mcg/mL.
- Idiopathic epilepsy (maintenance) · 1-2 mg/kg · PO · q12h · Adjust based on serum levels.
- Idiopathic epilepsy (rapid loading) · 16-20 mg/kg once IV loading dose, then 1-5 mg/kg PO q12h · IV/PO · Once then q12h
- Status epilepticus · 2-5 mg/kg bolus (repeat at 20 min intervals up to 2x), or add to diazepam infusion at 2-10 mg/hour · IV · PRN · If seizures persist after diazepam therapy.
- Emergency seizure control · 3 mg/kg (repeat q20m up to 24 mg/kg/24h) OR 10 mg/kg bolus · IV · PRN · Given along with IV diazepam.
- Sedation (situational distress/travel) · 2-3 mg/kg · PO · PRN · For controlling excessive vocalization.
- Seizures · 1-2 mg/kg · PO · q8-12h (2-3 times daily)
- Seizures (rapid loading) · Loading dose of 16-20 mg/kg once IV; maintenance dose of 1-2 mg/kg PO q8-12h · IV/PO · q8-12h
- Enzyme induction in organochlorine toxicity · 5 grams · PO · Daily · 3-4 weeks on, 3-4 weeks off, repeat
給藥途徑
禁忌症
- Known hypersensitivity to barbiturates
- Severe liver disease
- Nephritis (large doses)
- Severe respiratory depression
- Hepatic dysfunction
- Severe renal impairment
- Hypersensitivity to barbiturates
不良反應
- Dogs: Transient anxiety, agitation, or lethargy upon initiation
- Dogs: Polydipsia (PD), polyuria (PU), and polyphagia (PP)
- Dogs: Sedation and ataxia (especially at higher serum levels)
- Dogs: Elevated liver enzymes (ALT, ALP) - common and not always indicative of failure
- Dogs: Hepatotoxicity (uncommon, usually at levels >30-40 mcg/mL)
- Dogs: Rare blood dyscrasias (anemia, thrombocytopenia, neutropenia)
- Dogs: Rare superficial necrolytic dermatitis (SND)
- Cats: Ataxia, persistent sedation, lethargy
- Cats: Polyphagia, weight gain, PU/PD
- Cats: Rare immune-mediated reactions and bone marrow hypoplasia
- Cats: Coagulopathies (at very high doses)
- Sedation
- Ataxia
- Polyuria (PU)
- Polydipsia (PD)
藥物相互作用
- Acetaminophen · Increased risk for hepatotoxicity, particularly with large or chronic doses of barbiturates.
- Carprofen · Increased risk for hepatotoxicity secondary to carprofen metabolites.
- MAO Inhibitors (e.g., Selegiline) · May prolong phenobarbital effects.
- Phenytoin · Barbiturates may affect phenytoin metabolism, and phenytoin may alter barbiturate levels.
- Rifampin · May induce enzymes that increase the metabolism of barbiturates.
- Levetiracetam · Phenobarbital reduces levetiracetam elimination half-life by about 50% in dogs.
- Warfarin · Phenobarbital may decrease anticoagulant effects by lowering serum concentrations.
- Corticosteroids · Phenobarbital increases the metabolism and clearance of corticosteroids, potentially reducing their efficacy. · moderate
- Doxycycline · Phenobarbital decreases doxycycline serum concentrations; effect may persist for weeks after discontinuation.
- Theophylline · Phenobarbital increases theophylline metabolism, lowering its serum concentrations.
- Chloramphenicol · May increase the effects of phenobarbital while phenobarbital may decrease chloramphenicol levels. · major
- Levothyroxine · Increased hepatic metabolism and clearance of T4 · moderate
監測
- Anticonvulsant efficacy (seizure frequency and severity)
- Adverse effects (CNS depression, ataxia, PU/PD, weight gain)
- Serum phenobarbital levels (Dogs: 20-35 mcg/mL; Cats: 23-30 mcg/mL). Wait 5-6 half-lives (12-14 days in dogs, 9-10 days in cats) before measuring steady-state levels.
- Routine CBC, liver enzymes (especially ALT and AST), and bilirubin at least every 6 months during chronic therapy.
- Serum phenobarbital concentrations (trough levels)
- Liver enzymes (ALT, ALP, GGT)
- Serum bile acids
- Complete Blood Count (CBC)
- Renal function
過量
**Clinical Signs of Toxicity**: * **Dogs**: Ataxia, lethargy, sedation, recumbency, depression, hypothermia, and coma. * **Cats**: Ataxia, sedation, and recumbency. **Treatment**: * **Decontamination**: Removal of ingested product from the gut if recent. **Activated charcoal** is highly effective and acts as a 'sink' to draw the drug from the vasculature back into the gut, enhancing clearance even if the drug was given parenterally. * **Supportive Care**: Provide intensive respiratory and cardiovascular support. * **Enhanced Elimination**: Forced alkaline diuresis can substantially augment elimination in patients with normal renal function. Peritoneal dialysis or hemodialysis may be helpful in severe intoxications or anuric patients.
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