[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Antiseizure medicines](https://durgical.com/en/pharmacology/classes/antiseizure-medicines/) › Phenobarbital

[Pharmacology](https://durgical.com/en/pharmacology/) · [Antiseizure medicines](https://durgical.com/en/pharmacology/classes/antiseizure-medicines/)

# Phenobarbital

The oldest antiseizure medicine still in wide use, a barbiturate on the WHO essential list. It sedates, induces liver enzymes and can cause dependence.

Updated 2026-11-01

- Class: [Antiseizure medicines](https://durgical.com/en/pharmacology/classes/antiseizure-medicines/)
- Receptor: GABA-A receptor (α1β2γ2)
- ATC code: N03AA02
- WHO Model List of Essential Medicines

Also called: Phenobarbitone

◎**GABA-A receptor (α1β2γ2)**Phenobarbital

ⓘ The figure shows phenobarbital bound to the human GABA-A receptor of the α1β2γ2 subtype, with GABA also bound.

**Target in 3D:** GABA-A receptor (α1β2γ2). PDB structure 6X3W (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/6X3W) · Drag to rotate · pinch to zoom

## Mechanism of action

Phenobarbital binds the GABA-A receptor at a site different from GABA and benzodiazepines. It lengthens the bursts of opening of the receptor's chloride channel, so more chloride enters the neuron and it is harder to excite. It is also a strong inducer of liver enzymes.

- Binds the GABA-A receptor at the barbiturate site
- The chloride channel stays open longer with each GABA burst
- More chloride enters and the neuron hyperpolarizes
- Seizure discharges are suppressed

## Pharmacokinetics

**Absorption**
Absorbed by mouth; also given by injection

**Metabolism**
In the liver; it induces liver enzymes

**Elimination**
About a quarter to a half unchanged in the urine

**Half-life**
Very long: about 79 hours on average in adults (53 to 118 hours) and longer in newborns

## Indications

- Generalized and focal seizures [Epilepsy and seizures →](https://durgical.com/en/conditions/epilepsy-and-seizures/)
- Sedation and anxiety (now rarely)
- Controlled withdrawal in dependence on other barbiturates

## Adverse effects

### Common

- Drowsiness and slowed thinking
- Hyperactivity, irritability and learning problems in children
- Unsteadiness
- Confusion or excitement in older adults

### Serious (rare, important)

- Respiratory depression, especially with other sedatives or alcohol
- Tolerance, dependence and withdrawal seizures
- Fetal harm and respiratory depression in the newborn after use in labour
- Cognitive deficits in children

## Contraindications

- Hypersensitivity to barbiturates
- Manifest or latent porphyria
- Marked liver impairment
- Respiratory disease with dyspnoea or obstruction

## Key interactions

**Alcohol and other central nervous system depressants**
Added sedation and respiratory depression

**Oral anticoagulants**
Lower anticoagulant levels and weaker effect

**Hormonal contraceptives**
Contraceptive failure

**Doxycycline**
Shorter doxycycline half-life, even for weeks after phenobarbital is stopped

## What is monitored

- Level of sedation and breathing
- Serum phenobarbital level when needed
- Behaviour and school performance in children
- Liver function

## Administration and safety

- Given by mouth or injection; injection is used in hospital with breathing monitored
- Withdrawn slowly: stopping suddenly can cause withdrawal and seizures
- Controlled medicine: stored and recorded by the rules for controlled drugs

## Nursing care

- Check alertness, breathing and fall risk, especially in older adults
- Teach to avoid alcohol and other sedatives
- Teach that hormonal contraception may fail
- Teach not to stop suddenly

## Pregnancy and breastfeeding

Barbiturates can harm the fetus, and use near delivery can depress the newborn's breathing and cause withdrawal.

## Memory aid

Phenobarbital: «Barbiturates lengthen the burst» – longer chloride channel openings; and a very long half-life to match.

## Test yourself

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

## How do barbiturates such as phenobarbital differ from benzodiazepines at the GABA-A receptor?

Barbiturates lengthen the duration of the chloride channel's opening bursts; benzodiazepines increase how often the channel opens.

## In which hereditary disease is phenobarbital contraindicated?

Porphyria, manifest or latent, because barbiturates can trigger attacks.

## Why can phenobarbital make an oral anticoagulant or the pill less effective?

It induces the liver enzymes that metabolize them, so their levels fall.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/pharmacology/phenobarbital/)

## Related drugs

- [Phenytoin](https://durgical.com/en/pharmacology/phenytoin/)
- [Clobazam](https://durgical.com/en/pharmacology/clobazam/)

## Related conditions

- [Epilepsy and seizures](https://durgical.com/en/conditions/epilepsy-and-seizures/)

[← Back to the class: Antiseizure medicines](https://durgical.com/en/pharmacology/classes/antiseizure-medicines/)

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

Sources: [Phenobarbital: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a682007.html) (MedlinePlus (U.S. National Library of Medicine), 2020); [DailyMed - PHENOBARBITAL tablet](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fa09b4f2-edb0-4594-a2d2-b16f7b9686b4) (DailyMed (U.S. National Library of Medicine), 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 20 (McGraw Hill, 2023); [eEML - Electronic Essential Medicines List](https://list.essentialmeds.org/) (World Health Organization, 2025).

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Representative model, for educational purposes only.

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