Barbiturate Mechanism

Barbiturates may have been abandoned as sedatives and tranquillizers due to their high abuse and dependence potential and risk of side effects, but they continue to hold an important place in neurology practice today.

There are several uses of these agents and at present there are two major uses – as an agent that induces general anesthesia and as an agent that may control seizures.

Mechanism of action

The primary mechanism of action of barbiturates is inhibition of the central nervous system. It causes central nervous system depression. This is brought about by stimulating the inhibitory neurotransmitter system in the brain called the [gamma]-aminobutyric acid (GABA) system.

The GABA channel is a Chloride channel that has five cells at its gate. When barbiturates bind to the GABA channel they lead to prolonged opening of the channel letting in Chloride ions into the cells in the brain. This leads to increased negative charge and alters the voltage in the brain cells.

This change in voltage makes the brain cells resistant to nerve impulses and thus depresses them.

Barbiturates used in anesthesia including Thiopentone sodium (also known as pentothal) also act by decreasing Calcium flow between the membranes.

Barbiturates for controlling seizures and maintaining sleep

Barbiturates that are used in controlling seizures include phenobarbitone. These are found to be effective in partial, complex partial and secondarily generalised seizures.

There are other first line and more effective agents useful for these conditions, but phenobarbitone remains one of the effective agents that may be used when all others fail.

Barbiturates are also used for inducing and maintaining sleep. Due to the narrow therapeutic dose range that leads to an increased risk of over dosage these agents are not routinely prescribed in sleep disorders. Another use of these agents is in the evaluation of patients with medically intractable seizure disorders for possible surgical therapy.

Uses of barbiturates

• Sedation – these agents have largely been replaced by more modern and safer agents like benzodiazepines in this area.
• Sleep induction or hypnosis – in short term insomnia, barbiturates may be effective. This is because they tend to lose their effectiveness in sleep induction and maintenance after 2 weeks of use.
• Before surgery as a preanesthetic agent – sedation is given prior to surgery to allay anxiety and to ease the process of induction of general anesthesia. This is also an area where benzodiazepines have replaced barbiturates.
• Induction of general anesthesia – Thiopentone or pentothal is routinely used as an injectable induction agent in general anesthesia.
• Treatment of seizures - treatment of partial and generalized tonic-clonic and cortical focal seizures could still utilize barbiturates including mephobarbital, Phenobarbital.
• Acute convulsions – acute onset convulsions including  status epilepticus, eclapmsia during pregnancy, meningitis, tetanus and toxic reactions to strychnine or local anesthetics, convulsions during cholera etc. are indications for use of barbiturates.

Onset and duration of action

• Long-Acting Barbiturates – these are generally used in seizures. The action starts slow (30-60 minutes) and lasts longer (10-16 hrs).
• Intermediate-Acting Barbiturates – these are generally used in inducing and maintaining sleep. The action starts slow (45-60 minutes) and lasts for an intermediate duration (6-8 hrs).
• Short-Acting Barbiturates – these are also used as sedatives. Relatively rapid onset (10-15 minutes) and relatively short duration of action is seen (3-4 hrs).
• Ultra-Short-Acting Barbiturates – these are used in induction of anesthesia. These have an immediate onset of action that lasts for a very short duration.