Pentobarbital Sodium
Pentobarbital sodium
Also known as: Nembutal · Pentobarbitone sodium
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Dosing by species
Dosing data for this drug is not yet available in the VetSheet formulary. Every other section below is complete. Consult the current product label before prescribing.
Overview
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 of action
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.
Safety & warnings
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)
Precautions
Administer IV SLOWLY (unless used for euthanasia). Very irritating if given SC or perivascularly; do NOT give intra-arterially (IA). Use cautiously in patients who are hypovolemic, anemic, or have borderline hypoadrenal, cardiac, or respiratory disease. Cats (especially females) are particularly sensitive to respiratory depressant effects. Use with caution in neonates due to higher CNS penetration.
Drug interactions
Increased risk for hepatotoxicity, particularly with large or chronic barbiturate doses.
Fatalities reported when treating lidocaine-induced seizures with pentobarbital; use diazepam instead.
Barbiturates may affect phenytoin metabolism and vice versa; blood level monitoring indicated.
May induce enzymes that increase the metabolism of barbiturates.
May increase the CNS depressant effect of pentobarbital.
May increase the CNS depressant effect of pentobarbital.
May increase the CNS depressant effect of pentobarbital.
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
Pharmacokinetics
Half-life
Absorption
Rapidly absorbed from the gut after oral or rectal administration. Peak plasma concentrations occur 30-60 minutes post-oral dosing. Onset of action is 15-60 minutes (PO) and <1 minute (IV).
Distribution
Distributes rapidly to all body tissues, with highest concentrations in the liver and brain. 35-45% bound to plasma proteins. Highly lipid-soluble; patient fat content alters distribution. Crosses the placenta and enters milk. Neonatal CNS levels can be up to 6 times higher than adults.
Metabolism
Metabolized in the liver principally by oxidation. Induces hepatic microsomal enzymes with extended use. Ruminants (sheep/goats) metabolize it very rapidly.
Elimination
Excreted via the kidneys. Excretion is not appreciably enhanced by increased urine flow or alkalinizing the urine.
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.
Available products
Formulations
- Injection
- Oral solution
Veterinary
- Nembutal® (Historical)
- Various Euthanasia Solutions (Combination products)
Human-labeled
- Nembutal® Sodium Injection
Regulatory status
No regulatory data for: 🇺🇸 US · 🇪🇺 EU · 🇬🇧 UK · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store at controlled room temperature. Protect from excessive heat and freezing.
Client information
Important Information for Pet Owners:
- Post-Anesthesia Care: Your pet may experience a rough recovery (vocalization, paddling, or excitement) as the drug wears off. Keep them in a quiet, dimly lit, and safe environment to prevent injury.
- Temperature Control: Pentobarbital can lower body temperature. Keep your pet warm and comfortable, but avoid direct heat sources like heating pads which can cause burns.
- Nursing Pets: This medication passes into breast milk and can cause drowsiness in nursing newborns.
- Toxicity Warning: Never allow pets to scavenge or consume the remains of animals that have been euthanized. Pentobarbital persists in tissues and can cause fatal poisoning if ingested.
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.