thiobarbiturate

A thiobarbiturate is a type of barbiturate in which the carbonyl oxygen atoms of barbituric acid are replaced by sulfur, producing thio-barbiturates. This substitution increases lipid solubility and potency, contributing to rapid central nervous system penetration after intravenous administration.

Pharmacology and mechanism: Thiobarbiturates act as positive allosteric modulators of the GABA-A receptor, enhancing chloride ion influx and producing sedation, hypnosis, or anesthesia. Their high lipophilicity leads to rapid brain entry, contributing to swift onset of effects after IV dosing.

Pharmacokinetics and clinical use: Following an intravenous dose, thiobarbiturates have an ultra-short onset, often seconds to a minute, with a short duration of action (typically 5–20 minutes) due to rapid redistribution into muscle and adipose tissue, followed by hepatic metabolism. They have historically been used to induce anesthesia (notably thiopental) and for short procedures. Methohexital is another thiobarbiturate used for rapid induction and for short procedures, including electroconvulsive therapy.

Safety and adverse effects: Administration can cause respiratory depression or apnea, hypotension, and vascular irritation at the injection site. Histamine release and myocardial depression may occur in sensitive individuals. As with other CNS depressants, interactions with alcohol or other sedatives can enhance effects, and careful monitoring of airway and cardiovascular status is required.

Examples: Thiopental (pentothal), methohexital (methohexital), and thiopentone are representative thiobarbiturates, each with varying onset times and durations influenced by lipid solubility and formulation.