BARBITURATES

1. Functions at the GABA-A receptor
   • In contrast to BZD, it increases the duration of GABA-A channel opening.
   • At higher concentrations, it may be GABA-mimetic (that is, they can open the channel themselves)
   • Also depress excitatory transmission of glutamate by binding to AMPA channels.
   • Also has some non-synaptic membrane effects

Overall, due to their effect on many channels, barbiturates producing more pronounced central depression and having a lower margin of safety than BZDs. They may also be used as induction agents.

1. IV

1. It is very rapidly distributes into and then away from the CNS, which accounts for its quick onset and offset.

1. Hepatic, by microsomal enzymes.
   • Note that overall, metabolism rate is slow and therefore, accumulation does occur if there is repeated dosing/infusion. It is not suitable for long term sedation, e.g. in ICU.
   • Remember that barbiturates are enzyme inducers.

1. Excreted in the urine mainly as glucuronide derivative.
   • One exception is phenobarbital, which is excreted 20-30% unchanged in the urine. Phenobarbital is a weak acid with a pKa of 7.4. Therefore, alkalinizing the urine may increase its elimination significantly.

1. Used to terminate status epilepticus
2. Used as an induction agent (e.g. thiopental)

1. Absolute CI in porphyria (barbiturates may precipitate porphyria crisis)

1. Elderly patient
2. Liver disease

1. Additive effects if given with other CNS drugs (opioids/anti-psychotics/alcohol)
2. It is an enzyme inducer, so reduced effects of warfarin/digoxin/carbamazepine

1. Extension of its pharmacologic properties – CNS depression and respiratory depression.