Chapter 11: Barbiturates
The principal mechanism of action of the barbiturate class of drugs is best described as:
(A) blockade of CNS sodium channels
(B) inhibition of NMDA receptors
(C) potentiation of GABA-mediated chloride currents
(D) stimulation of mu- and kappa-opioid receptors
(E) stimulation of alpha-2 adrenergic receptors
The answer is C. The mechanisms by which barbiturates produce unconsciousness have been extensively researched. Barbiturates exert their effect at the GABAA receptor, but appear to have a concentration-dependent effect. At low concentrations, barbiturates bind to the receptor, preventing the dissociation of GABA from the receptor and thereby prolonging its effect; at higher concentrations, there appears to be a direct activation of the chloride channels, mimicking GABA without requiring its binding to the receptor. Either mechanism increases the flow of chloride through the central pore of the receptor. This hyperpolarizes the postsynaptic cell membrane and results in inhibition of postsynaptic neuron.
Barbiturates are known to have an inhibitory effect on excitatory neurotransmitters (including glutamate and acetylcholine), although the extent to which these contribute to sedation and hypnosis is unclear.
Ref: Longnecker DE, Brown DL, Newman MF, Zapol WM. Anesthesiology. 2nd ed. New York, NY: McGraw Hill; 2012.
In which of the following circumstances should the induction dose of barbiturates be reduced?
(D) nonpregnant female patients
(E) patients taking barbiturates regularly
The answer is B. The usual induction dose for thiopental (the most commonly used barbiturate) in adults is 3–4 mg/kg. Neonates and small children often require more due to increased clearance (5–8 mg/kg), whereas pregnant patients and the elderly require less (1–3 mg/kg). When dosed for lean body mass rather than total body mass, no adjustments need to be made for sex, age, or obesity.
The concentration of barbiturate in the CNS is influenced by the degree of unbound drug. Therefore, disease states that reduce overall plasma protein levels (e.g., cirrhosis, renal failure) increase the concentration of free barbiturate, necessitating a reduction in dose by approximately 40–50%.
Chronic use of barbiturates is known to induce the same oxidative microsomal enzymes that are responsible for metabolism. For this reason, patients that take barbiturates often require a higher induction dose.
Barbiturates are weak acids, and both thiopental (7.6) and methohexital (7.9) have a ...