Anxiolytics Flashcards
6 types of anxiolytics?
SSRI’s (e.g., sertraline, fluoxetine)
SNRI’s (e.g., venlafaxine)
Pregabalin
Benzodiazepines (e.g., diazepam)
Buspirone
𝛽-noradrenergic receptor antagonists (e.g., propranolol)
Insomnia: compare transient vs short-term vs chronic
Transient insomnia: occurs in those who normally sleep well and may be due to noise, jet lag
Short-term insomnia: related to an emotional problem or illness – it may last for a few weeks
Chronic insomnia can be caused by psychiatric disorders such as anxiety and depression
Hypnotics are used to treat insomnia. - 4 types?
Anti-histamines (e.g., promethazine)
Melatonin
Z-drugs (e.g., zolpidem, zopiclone)
Benzodiazepines (e.g., temazepam)
These drugs rarely benefit chronic insomnia - the underlying psych complaint should be treated instead
compare benzodiazepinesvs Z Drugs vs Buspirone vs B-Noradrenergic receptor antagonists
what type of drug they r + receptor they work on!
Explain how the GABA a receptor is a key target of anxiolytics and hypnotics
It is a ligand gated channel with a pentameric structure - has 6 subtypes
2α 2β γ most common configuration
This allows for multiple binding sites of drugs on GABA receptors
Describe the multiple binding sites for each of the drugs on GABA receptors
agonist/ antagonist vs bzd vs allosteric modulator
channel blocker vs channel modulator
Note- Z drugs also bind to same location as bzd’s
3 mechanisms of Barbiturates + overall effect?
Increases GABA-a channel opening
Stabilises opening of glycine receptor channel
Blocks nicotinic ACh, 5-HT3 and AMPA receptors normally activated by glutamate, which decreases CNS excitation.
The above overall severely depresses CNS, hence why no longer used for anxiety & insomnia, tho used for epilepsy + anaesthesia
What are the benzodiazepines?
how long used for, mechanism, what receptors don’t they activate, what is the antidote available
Short term use only, bc can build up tolerance
Benzodiazepines stabilise the GABA-A receptor binding site in the open configuration - So bzd’s are positive allosteric modulators = increase GABA affinity + inhibitory action
These drugs don’t activate other receptors like Glut & glycine.
Antidote available: flumazenil = competitive antagonist of benzodiazepine- used in OD
compare 6 bzd’s + their overall duration of action & therefore their usage!
mtladc
Benzodiazepines and barbiturates can only be used short term. Why is this?
BZD’s increase GABA signalling
Neuroadaptation (receptor trafficking): new glutamate receptors inserted - therefore patient has to increase bzd dose for same effect!
Sudden withdrawal leads to excess excitation, extra glut activity + convulsions
What are Z drugs?
Z-drugs, e.g., zolpidem, zopiclone bind to the bzd binding site on the GABAA receptor ( alpha-gamma)
BUT, Z-drugs are structurally different to bzd’s - therefore Z-drugs are v. short-acting – suitable for hypnotics but NOT as anxiolytics
Gaba - between alpha and beta
Benzo - between alpha and gamma
Zdrugs - between alpha and gamma
What is Buspirone?
mechanism, 3 side effects, when is effect seen
Buspirone: 5-HT1A auto-receptor agonist for GAD ( inhibits 5-ht release)
Side effects: nausea, dizziness, headache
Several days-weeks before anxiolytic effects are seen
Use this question to explain the moa of buspirone
Buspirone = 5-HT1A receptor agonist - this initially inhibits 5-HT release
However, over time buspirone desensitises auto-inhibitory 5-HT1A receptors, which leads to downregulation of 5-HT1A receptors
This desensitisation + downregulation causes heightened excitation of serotonergic neurons + enhanced 5-HT release, suppressing GAD
How can 𝛽-noradrenergic receptors antagonists be used to treat some forms of anxiety?
Propranolol is non-selective between 𝛽1 & 𝛽2 noradrenergic receptors
𝛽-noradrenergic antagonists do not affect worry, but do reduce autonomic symptoms (palpitation, tremor)
Doesn’t reduce non-autonomic anxiety symptoms (eg muscle tension)
Indicated for those w mostly somatic symptoms to in turn prevent psych symptoms
abuse in some sports (reduce tremor) + the performing arts (reduce stage fright)
