Pentobarbital

Barbiturates
Barbiturates
High alert
An error with this medicine can cause serious harm: double checks and protocols are used.
Pregnancy: avoid
Avoided when possible: barbiturates cross the placenta and can harm the fetus; use near delivery can depress the newborn's breathing and cause withdrawal.

A short-acting barbiturate given by injection for refractory seizures and sedation. Strongly alkaline, habit-forming and deadly in overdose.

Updated Nov 12, 2026

Quick facts

Group: Barbiturates
Target: GABA-A receptor (barbiturate site)
Used for: Emergency control of acute convulsions
Key effects: Drowsiness · Paradoxical excitement
Monitor: Breathing · Blood pressure and heart rate
ATC: N05CA01

No doses: the clinician sets them by the current guideline.

Mechanism of action

GABA-A receptor (barbiturate site)Pentobarbital

No structure of pentobarbital in the GABA-A receptor is available; the figure shows phenobarbital, another barbiturate at the same site, in the human α1β2γ2 receptor with GABA.

Target in 3D: GABA-A receptor (barbiturate site). PDB structure 6X3W (RCSB PDB, public domain). View the structure at RCSB PDB

Pentobarbital binds a barbiturate site on the GABA-A receptor and keeps its chloride channel open longer each time GABA binds; at higher concentrations it opens the channel directly, even without GABA, and also reduces glutamate excitation. Neurons are hyperpolarised and the whole CNS is depressed in a dose-related way: sedation, sleep, anaesthesia, then coma with depression of breathing. Because the effect does not stop at a ceiling, as with benzodiazepines, overdose is far more dangerous. It also induces liver enzymes.

Binds the barbiturate site of GABA-A
Chloride channel stays open longer; opens directly at high levels
Dose-related CNS depression: sedation to coma
No ceiling: breathing can stop in overdose

Indications

Emergency control of acute convulsions (status epilepticus, eclampsia, toxic reactions), including induced coma for refractory status epilepticus Status epilepticus →
Sedation and preanaesthetic use; induced coma to lower raised intracranial pressure Raised intracranial pressure and brain herniation →
Short-term treatment of insomnia (largely replaced) Insomnia disorder →

Adverse effects

Common

Drowsiness, hangover, confusion
Paradoxical excitement (older people, children, people in pain)
Low blood pressure
Pain at the injection site

Contraindications

Known barbiturate sensitivity
Manifest or latent porphyria

Key interactions

Alcohol, opioids, benzodiazepines and other CNS depressants: Additive, potentially fatal CNS and respiratory depression.
Warfarin, corticosteroids, oral contraceptives and other enzyme substrates: Enzyme induction lowers their effect; another contraceptive method may be needed.
Valproate and MAO inhibitors: Raise or prolong barbiturate effects.
Phenytoin: Unpredictable effect on phenytoin levels; levels are checked more often.

What is monitored

Breathing, oxygen saturation and airway; ventilatory support ready
Blood pressure and heart rate
EEG when used for induced coma
Injection site, and limb pain during injection

Administration and safety

Given slowly intravenously; fast injection causes apnoea and hypotension.
Strongly alkaline: not mixed with other drugs or solutions; cloudy or precipitated solution is discarded.
Into a large vein; the injection is stopped at once if the patient feels pain in the limb (risk of intra-arterial injection).
Used only where airway support and ventilation are available.

Pregnancy and breastfeeding

Avoided when possible: barbiturates cross the placenta and can harm the fetus; use near delivery can depress the newborn's breathing and cause withdrawal.

Nursing care

Before: check airway equipment, IV access patency and porphyria history.
During: monitor breathing, saturation and blood pressure continuously.
Watch the site for swelling or pallor; stop for pain.
After prolonged use: taper rather than stop abruptly; watch for withdrawal.

Pharmacokinetics

Absorption: Injection, usually intravenous; also intramuscular.
Metabolism: Liver microsomal enzymes; metabolites excreted in the urine. It also induces these enzymes.
Half-life: Long and dose-dependent (roughly 15 to 50 hours in adults).
Onset and duration: Almost immediate after intravenous injection.

Test yourself

Think of the answer, then tap the question to see it.

How does a barbiturate differ from a benzodiazepine at the GABA-A receptor?

It prolongs each channel opening and can open the channel directly at high levels; benzodiazepines only increase opening frequency when GABA is present.

Why is pentobarbital overdose more dangerous than benzodiazepine overdose?

There is no ceiling: increasing doses deepen CNS and respiratory depression to coma and death.

Which inherited condition is a contraindication to barbiturates?

Porphyria (barbiturates induce ALA synthase).

Why must pentobarbital not leak out of the vein?

The solution is strongly alkaline and causes tissue necrosis; intra-arterial injection can cause gangrene.

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Connections

← Back to the class: Barbiturates

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: PENTOBARBITAL SODIUM injection, solution (DailyMed (U.S. National Library of Medicine), 2026); Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus phenobarbital (RCSB Protein Data Bank, 2020); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.