Diazepam

Class	Sedative
Chemistry	Benzodiazepine
Routes of administration	Oral, IV, IM, s/c
Absorption	Rapidly and completely absorbed; oral bioavailability is about 94%
Solubility	pKa 3.4; practically insoluble in water
Distribution	VOD = 0.8-1.0L/kg; 99% protein-bound
Metabolism	Hepatic metabolism: N-demethylated by CYP3A4 and 2C19 to the active metabolite N-desmethyldiazepam, and is hydroxylated by CYP3A4 to the active metabolite temazepam.
Elimination	Inactive glucouronides are renally excreted
Time course of action	Half-life of diazepam is 30-50 hours, and terminal elimination half-life of the active metabolite N-desmethyldiazepam is up to 100 hours.
Target receptor	GABA-A channel (a separate binding site from GABA)
Mechanism of action	Allosteric modulator of the GABA-A receptor: acts on GABA-A chloride channels, where it binds to a site distinct from the GABA binding site, and potentiates the effects of GABA, this increasing the chloride current and hyperpolarising the cell membrane of the neuron
Clinical effects	Sedation, amnesia, anticonvulsant effect, mild decrease in cerebral oxygen demand, no effect on ICP. Respiratory response to raised CO2 is flattened, but respiratory drive is not as suppressed as it would be with opioids. Airway reflexes are depressed. Haemodynamic effects (decreased blood pressure and heart rate) are related to its suppression of the sympathetic nervous system. These are less pronounced than those of propofol.
Literature reference	FDA PI document
CICM details of understanding	Level 1
Mentioned around Deranged Physiology	Pharmacology of anticonvulsant drugs, one must suppose.
Related SAQs	Question 21 from the second paper of 2014 (diazepam vs haloperidol?)

[Submit a comment or correction]