Anxiolytics and Hypnotics Flashcards
Why are benzodiazapenes sometimes used?
They are CNS depressant drugs that act as anxiolytics or hypnotics immediately. When the dose is increased they have a sedative/hypnotic effect.
What other class of drugs can be used as anxiolytics?
Antiepileptic drugs such as pregabalin and gabapentin Beta blockers can reduce sweating, tachycardia and tremors Barbiturates Buspirone (delayed action of 1 - 3 weeks and can be used if someone has generalized anxiety disorder) Antidepressant drugs
What classes of drugs beside benzodiazapenes can be used to induce sleep?
Sedating antihistamines such as diphenyhydramines can be used to induce sleep. Newer sedatives used
How do benzodiazapenes work?
They affect the GABAergic system. Benzodiazapenes, zolpidem, and barbiturates act on GABAa receptor. (they do not affect GABAb)
What kind of receptor is GABAa?
Ionotropic receptor
What kind of receptor is GABAb?
Metabotropic
What kind of structure does GABAa have? What protein subunits make it up?
They are pentameric ion channel proteins and most are composed of α, β, and γ2 subunits.
Where do benzodiazapenes act on the GABAa protein?
Between the γ2 and α subunits
Where do barbiturates act on the GABAa protein?
They bind to the β subunit and increase the time of channel being open thus making cell more hyperpolarized.
Where does GABA bind on the GABAa protein?
On the 2 interfaces between α and β subunits
What does the GABAa receptor do?
When both GABAa receptors are bound by the GABA molecules the channel opens up and allows chloride ions into the cell making it hyperpolarized and harder to stimulate.
What kinds of situations are barbiturates dangerous in?
Large doses due to large inhibitory effect.
What kind of effect do benzodiazapenes have on GABAa channels?
Benzodiazapenes are positive allosteric modulators thus increasing the frequency of opening of the GABAa channels.and increasing inhibitory effect.
What kinds of protein targets are benzodiazapenes reactive to?
α1, α2, α3, and α5 subunits
What is the advantage of using benzodiazapenes over barbiturates?
Benzodiazapenes are reversible more easily via
How is zalpoden different to other benzodiazapenes?
zalpoden are selective for α1 unlike diazapenes which act on all receptors equally.
Which receptor is responsible for addictive properties of benzodiazapenes?
α1 is the receptor responsible for addictive properties of benzodiazapenes so zalpoden still has addictive effects.
How is the response different between using benzodiazapenes and barbiturates?
Less probability of overdose problems with benzodiazapenes
Additional disadvantage of barbiturates relative to benzodiazapens:
They induce hepatic cytochrome P450 which doesn’t happen with benzodiazapenes
What are the therapeutic benefits of using benzodiazapenes?
Reduction in anxiety (diazepam, oxazepam, alprazolam)
Induction of sleep (temazepam)
Skeletal muscle relaxation (diazepam, clonazepam) [note: may not be a good idea for elderly with muscular weakness]
Anticonvulsant effects (clonzepam, clobazam)
Intravenous sedation (midazolam) [anterograde amnesia may be caused by this but that brings about a positive effect when administered intravenously]
How are benzodiazapenes metabolised?
Initial demethylation of diazepam at the 1 position -> desmethyldiazepam -> temazepam (minor portion) + oxazepam (major portion)
What is the difference between the onset of action in temazepam/oxazepam and diazepam?
When you compare the onset of action of temazepam and oxazepam it is faster than diazepam due to hydroxyl group making them more water soluble and so there is a faster onset of action in the brain after taking temazepam/oxazepam compared to diazepam.
