Anxiolytic Drugs Flashcards
Give an example of an ANTIDEPRESSANT which is a Selective serotonin (5-HT) reuptake inhibitor (SSRI) used to treat anxiety
citalopram
Give an example of an ANTIDEPRESSANT which is a serotonin/noradrenaline reuptake inhibitor (SNRI) used to treat anxiety
venlafaxine
What is a disadvantage of using ANTIDEPRESSANTS to treat anxiety?
the onset of action is delayed
Are ANTIDEPRESSANTS anxiolytic, sedative, or hypnotic?
Anxiolytics
Give two examples of older ANTIDEPRESSANTS used to treat anxiety
MAOIs
Tricyclics
The disadvantages of using older ANTIDEPRESSANTS to treat anxiety
more side effects
What are the clinical uses of BENZODIAZEPINES
- anti-anxiety
- sedative
- hypnotic
- anticonvulsant
- muscle relaxant
What are the side effects of BENZODIAZEPINES
- drowsiness
- confusion
- amnesia
- impaired motor coordination
- lack of depth perception
- reduced REM sleep
What is the half life and therapeutic usefulness of the BENZODIAZEPINE Zolpidem?
1-2h
hypnotic
What is the half life and therapeutic usefulness of the BENZODIAZEPINE Triazolam
2-4h
hypnotic
withdraw from UK market due to side effects
What is the half life and therapeutic usefulness of the BENZODIAZEPINE Loprazolam
6-12h
hypnotic and anxiolytic
What is the half life and therapeutic usefulness of the BENZODIAZEPINE Nitrazepam
16-40h
hypnotic and anxiolytic
What is the half life and therapeutic usefulness of the BENZODIAZEPINE Diazepam
20-40h
anxiolytic and anticonvulsant
Describe the tolerance of BENZODIAZEPINES in relation to their anticonvulsant, anxiolytic, and hypnotic uses.
- greatest to anticonvulsant action
- may occur to anxiolytic action
- little to hypnotic actions
Do BENZODIAZEPINES induce a physical or psychological dependance?
physical
In the use of BENZODIAZEPINES what does withdrawal induce with physical dependance?
- anxiety
- dizziness
- tinnitus
- tremor
- weight loss
- sleep disturbances
What occurs if BENZODIAZEPINES are taken with alcohol
respiratory depression
What is the mechanism of action of BENZODIAZEPINES
1) Bind to GABAa receptor
2) Enhance the affinity of GABA binding
3) Increase the probability of channel opening
4) increase Cl- into cell leading to hyperpolarisation 5)inhibition of nerve cell
What is the structure of the GABAa receptor?
It is a ligand gated chloride channel with a pentameric structure
What is the most abundant GABAa receptor?
α1β2γ2
Where do benzodiazepines bind to on the GABAa receptor?
α-γ interface
Where does GABA bind to on the GABAa receptor?
α-β interface
Which alpha subunits are insensitive to benzodiazepines?
α4
α6
At which alpha subunit does the binding of benzodiazepines induce sedation and amnesia?
α1
At which alpha subunits does the binding of benzodiazepines induce anxiolytic effects?
α2
α3
Which gamma subunit is required for benzodiazepine binding?
γ2
Ideal receptor subunit combinations for effective anxiolytic action of benzodiazepines
α2β3γ2
α3β1-3γ2
What is the mechanism of action of the endogenous benzodiazepine βCCE (ethyl-β-carboline-3-carboxylate)
Binds to the benzodiazepine binding site as an inverse agonist
Diazepam binding inhibitor
Give an example of a benzodiazepine antagonist
Flumazenil
when is Flumazenil used
Reverse actions of benzodiazepines, for example in patients who become excessively drowsy after BZ admin or after overdose
What would happen if Flumazenil was administered to benzodiazepine–naïve patients?
Will produce anxiety
Give an example of a BARBITUATE used to treat anxiety
phenobarbitone
Mechanism of action of barbiturates
e.g. phenobarbitone
binds to the GABAA receptor
low concentrations prolongs openings produced by GABA
high concentrations it opens the channel (in absence of GABA)
Barbiturates are non-selective. Where else do they bind and what is there action?
bind to AMPA receptors inhibiting glutamate release
why are barbituates no longer used?
Produce tolerance and dependence
Produce anaesthesia and death in overdose
Give an example of 5-HT1A agonists used to treat anxiety
Buspirone (mst comonly used)
ipsapirone
gepirone
what is the mechanism of Buspirone?
5-HT1A receptor partial agonist
What are the benefits of using Buspirone over other anxiolytic drugs?
- less sedation
- less motor in-coordination
- No reports of tolerance and physical dependence
What are the side effects of Buspirone?
- nausea
- dizziness
- headache
- restlessness
What are the disadvantages of Buspirone?
Ineffective against panic attacks or severe anxiety
Therapeutic action takes days or weeks to develop
Does not suppress benzodiazepine withdrawal
What is the mechanism of action of 5-HT1A agonists like buspirone to relieve anxiety?
5-HT1a receptors are somatodendritic autoreceptors on raphe neurones
5-HT1a receptors on 5-HT containing nerves desensitize
Eventually 5-HT release is enhanced
Give an example of an anxiolytic which is a β-adrenoceptor antagonists
propanolol
What is the effect of propanolol
remove the peripheral symptoms of anxiety
palpitations
sweating
tremor
Block peripheral receptors – not a CNS effect
Give two examples of antipshychotics used to treat anxiety
olanzepine
risperidone
When are antipshychotics used to treat anxiety
may be used to treat GAD or post-traumatic stress disorder in some cases
Give two examples of other hypnotics used to treat anxiety
zopiclone
zolpidem
What is the mecahnism of action of zopiclone and zolpidem?
chemically distinct from benzodiazepines but bind to same site and act in similar way
short lasting
Give two examples of antihistamines used to treat anxiety?
diphenhydramine (NYTOL)
promethazine
What is the side effect of antihistamines?
drowsiness
