Let's move on to the barbiturates. The barbiturates
receptors, the GABA A receptors are also present in the brain
and we see those ones often in the reticular activating system
of the brain. Barbiturates may also antagonize glutamic acid.
Barbiturates are not antagonized by flumazenil. So think
about this. Look where flumazenil is and where it binds to the
gamma subunit and then take a look at where the receptor
binding site is for barbiturates. They are quite far apart.
Flumazenil is an antidote to benzodiazepine poisoning or
overdose. It does not work against the barbiturates.
Barbiturates also cause increased flow of chloride through
the channel but it does so a little bit differently than
benzodiazepines. It helps the GABA to inhibit the gamma
subunit. So the gamma subunit is now inhibited and it opens up
but it increases the duration of chloride
flow through opening. And so that's different
than the benzos. The benzos increase frequency, barbiturates
increase duration. Barbiturates are binding on both the alpha
and the beta units. And through many types of receptors it
exerts many levels of sedation throughout the brain.
We often use barbiturates for induction of anesthesia. So
thiopental is the prototypical drug and the one that you
should remember. In terms of the benzodiazepines, we also use
diazepam and midazolam for induction. I personally use
lorazepam in the intensive care unit. Seizure control
is excellant with the barbiturate phenobarbital,
and we've used it many times for status epilepticus
where we can't get control of patients.
It's sort of our go to strong drug for seizure control.