Introduction
This topic covers acute poisoning with barbiturates, a group of older sedative-hypnotic drugs now largely replaced by benzodiazepines but still important because of suicide attempts, accidental overdose and access to old stock. A good answer explains how these drugs act on the brain, why they are dangerous in overdose, how the poisoning develops and progresses, and how the patient is managed.
Definition and classification
Barbiturates are derivatives of barbituric acid that depress the central nervous system in a dose-dependent way. Low doses sedate, larger doses produce hypnosis, then anaesthesia, and in overdose coma with respiratory and circulatory collapse. Their therapeutic index is narrow, so the gap between a sedative dose and a toxic one is small. They are classified by duration of action, which depends mainly on lipid solubility and redistribution rather than on elimination alone.
Mechanism of action
Barbiturates bind to the GABA-A receptor, a ligand-gated chloride channel, at a site distinct from the benzodiazepine site. They prolong the time the channel stays open, so more chloride enters the neuron, and at high concentrations they can open it directly. They also activate GABA-B receptors, which increase potassium efflux. Together these effects cause membrane hyperpolarisation and reduced neuronal firing. Barbiturates additionally inhibit excitatory glutamate signalling, which adds to the depression of the reticular activating system, cortex and medullary centres. Respiratory centre depression, peripheral vasodilation and direct myocardial depression explain the main life-threatening effects.