Pentobarbital Sodium
Pentobarbital sodium is a short-acting **barbiturate** historically used as a general anesthetic and sedative in veterinary medicine. Due to the advent of safer inhalant anesthetics and injectable agents like propofol, its therapeutic use is now largely restricted to managing **refractory status epilepticus** (e.g., secondary to strychnine or tetanus toxicity) and as a primary agent in **euthanasia solutions**. * **CNS Depression:** Capable of inducing all levels of CNS alteration, from mild sedation to deep coma and death. * **Cardiovascular & Respiratory Effects:** Causes dose-dependent respiratory depression and cardiovascular alterations (tachycardia, decreased myocardial contractility, and hypotension). > **Clinical Pearl:** Pentobarbital has a narrow therapeutic index and provides **no intrinsic analgesia**. It is a DEA Schedule II controlled substance (when not formulated as a combination euthanasia product).
Mechanism: Pentobarbital acts as a profound **CNS depressant** through multiple mechanisms: * **GABA-A Receptor Modulation:** Binds to the barbiturate site on the GABA-A receptor, **prolonging the duration** of chloride channel opening → hyperpolarization of the postsynaptic membrane → profound CNS inhibition. At high doses, it is directly GABA-mimetic. * **Glutamate Inhibition:** Inhibits excitatory neurotransmission by blocking glutamate release and AMPA/kainate receptors. * **Neurotransmitter Release:** Inhibits the release of acetylcholine and norepinephrine. * **Calcium Channels:** At high anesthetic doses, it inhibits calcium uptake at nerve terminals.
Routes of administration
Contraindications
- Known hypersensitivity to barbiturates
- Severe liver disease
- Nephritis
- Severe respiratory depression
- Lidocaine-induced seizures
- Pregnancy (Category D - embryotoxic/teratogenic)
Adverse effects
- Respiratory depression (can be severe)
- Hypothermia
- Paradoxical excitement during recovery (especially in dogs)
- Cardiovascular depression (decreased contractility, hypotension)
- Severe tissue irritation and necrosis (if given perivascularly or SC)
Drug interactions
- Acetaminophen · Increased risk for hepatotoxicity, particularly with large or chronic barbiturate doses.
- Lidocaine · Fatalities reported when treating lidocaine-induced seizures with pentobarbital; use diazepam instead.
- Phenytoin · Barbiturates may affect phenytoin metabolism and vice versa; blood level monitoring indicated.
- Rifampin · May induce enzymes that increase the metabolism of barbiturates.
- Antihistamines · May increase the CNS depressant effect of pentobarbital.
- Chloramphenicol · May increase the CNS depressant effect of pentobarbital.
- Opiates · May increase the CNS depressant effect of pentobarbital.
- Phenothiazines · May increase the CNS depressant effect of pentobarbital.
Monitoring
- Respiratory rate, depth, and effort (ventilatory support must be available)
- Heart rate and rhythm
- Blood pressure
- Body temperature (monitor for hypothermia)
- Depth of anesthesia/sedation
Overdose
In dogs, the reported oral LD50 is 85 mg/kg and IV LD50 is 40-60 mg/kg. **Fatalities from ingestion of meat from animals euthanized by pentobarbital have been reported in dogs.** **Treatment:** * Removal of ingested product from the gut if appropriate (e.g., gastric lavage, activated charcoal). * Provide aggressive respiratory (ventilatory) and cardiovascular support. * Forced alkaline diuresis is of little benefit. * Peritoneal dialysis or hemodialysis may be beneficial in severe intoxications.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.