Anxiolytics and Hypnotics Flashcards
What are anxiolytics and hypnotics used to treat?
A- anxiety.
H- insomnia
Give psychological and physical symptoms of anxiety.
Psychological- nervousness, fear, foreboding.
Physical- sweating, sleeplessness and palpitations.
Give the 5 treatments for anxiolytics and hypnotics?
barbiturates, benzodiazepines and Z drugs, 5HT1a receptor agonists, B adrenoceptor antagonists histamines,
How do barbiturates work?
Act as a GABAa positive allosteric receptor modulator.
What are GABAa receptors and what do they do?
Ligand gates receptors which have multiple binding sites. GABA binds- receptor opens and Cl ions flow into the cell causing hyper polarisation, this acts an inhibitory stimulus preventing AP firing.
Where are most GABAa receptors found?
Post synaptic neurones.
What is the structure of GABAa receptors?
Pentameric structure - most common, 2 alpha, 2 beta and a gamma.
What other substances bind to GABAa? (name 4)
Benzodiazepines, channel blockers (picrotoxin) channel modulators (GA) and allosteric modulators (barbiturates).
Function of barbiturates?
PAM- increase GABAa efficacy for GABA- binds for longer keeping the channel open for longer - enhances the functional response of the GABA receptor.
Why are barbiturates dirty?
They bind to other sites- high concentrations act as a direct agonist, block nACh receptors and block Ca dependant NT release.
What are benzodiazepines?
Positive allosteric modulators- although have their own binding site.
How to BZDs work?
They stabilise the GABA binding site, keeping the receptor in the form GABA can bind to rather than the receptor oscillating between forms. Increase GABA binding.
Where to the BZDs bind on the receptor?
To the alpha gama interface (only on alpha 1,2,3,5 as they have a histamine residue to bind to)
Name a competitive antagonist of BZDs
flumenazil- only used in severe ODs as it has bad side effects.
What are Z drugs?
Similar to BZDs, positie allosteric modulator that acts on the GABAa receptor at the BZD binding site causing a similar response. however they are structurally different.
How can BZDs and barbiturates cause addiction and withdrawal symptoms?
They increase GABA stimulation, in response there is an increase in glutamate receptors and simulation in order to balance excitation and inhibition. A withdrawal of BZDs or barbiturates will mean massive glutamate stimulation and no GABA- unbalances, causes withdrawal symptoms (seizures and addiction).
How to 5HT1a receptor agonists work? (example)
5HT1 receptors are metatropic auto inhibitory that decrease the release of serotonin. Agonists such as buspirone increase their action.
What do 5HT1a receptor agonists do?
Decrease serotonergic drive
How do B adrenoceptor antagonists work? (example)
Na binds to beta adrenoceptors, B adrenoceptor antagonists block the NA binding sites preventing the action NA.
Propanolol
What do B adrenoceptor antagonists do?
Block B receptors and decrease peripheral symptoms of anxiety. (stop renin release, prevent tachycardia)
How do antihistamines work?
they antagonise CNS H1 receptors which are responsible for wakefulness - therefore make people drowsy. Use as a hypnotic only.
