anxiolytics Flashcards
what are anxiolytics used to treat
anxiety, stress and sleep disorders such as panic disorders, phobias, social anxiety disorde, PTSD and OCD
what is general mechanism of anxiolytics
increased inhibition by increasing GABAergic activity
GABA receptors are site of action for benzos and barbiturates
no approved drugs target glutamate action
increased serotonergic activity reduces anxiety, 5HT1a agonists are anxiolytics
antagonism of beta receptors (adrenoceptors are upregulated in anxiety)
GABAa targets more common than 5HT targets which are more common than adrenoceptor targets
how do benzodiazepines effect GABA receptors
bind to GABAa receptors, increase inhibition at synapses by increasing frequency of channel opening
some are positive allosteric modulators of GABAa receptors, causing more chloride to enter the cell
some are negative modulators, e.g beta carboline ,causing inhibition of GABA action, these are not used clinically
what are benzodiazepine antagonists
some benzodiazepines which prevent benzo positive and negative allosteric modulators from binding, they themselves have no GABAa effect, e.g flumazenil
where do benzodiazepines bind on GABA receptors
bind to GABAa receptors, between alpha and gamma subunits
what are clinical uses of benzos and what are their unwanted effects
uses: anxiolytic effects for anxiety, anticonvulsant effects, hypnotic effects for insomnia, muscle relaxation effects, amnesic effects
unwanted effects: confusion, drowsiness, forgetfulness and muscle incoordination
there are also toxic adverse effects in overdose due to respiratory depression, depedence is also a major problem and cessation of treatment can cause rebound anxiety and disrupted sleep
what are Z drugs
are drugs which are not benzos but are agonists of GABA receptors and bind to same site, the aim of development was a non sedating anxiolytic
what are barbiturates, give examples and their use
derivatives of urea and malonic acid, first used for treatment of epilepsy
pentobarbitone is used as an anticonvulsant
thiopentone is used for rapid induction of general anaesthesia
how are barbiturates used for anxiety
not used or recommended for anxiety because anxiolytic effects are only apparent at sedative doses
drug dependance and abuse is also a notable problem, also dangerous in overdose which is problematic in patients with anxiety who are suicide prone
also have additive effects with other CNS depressants causing significant risk of accidental overdose
how do barbiturates effect GABA receptors
they potentiate action of GABA at GABAa receptor, they increase the duration of which chloride channel (benzos increase frequency of channel opening), unlike benzos they cause direct activation of receptor in absence of GABA
what are natural anxiolytics in the brain
neurosteroids; they are also positive allosteric modulators of GABA receptors, have similar effects to benzos (anxiolytic effects)
e.g allopregnanolone
how are drugs affecting 5HT activity used in anxiety
5HT1a receptor activation inhibits 5HT neurone firing (they are auto receptors)
5HT1a receptor activation may exacerbate anxiety, however persistant agonists may cause desensitisation, producing anxiolysis
only example of drug is busprione, does not have additive effects with alcohol and does not induce drug dependence
most effective in patients not previously treated with benzos
how are drugs affecting NA used in anxiety
beta antagonists inhibit NA function
anxiolytic effects due to reversal of increased sympathetic effects rather than central action
example is propranolol
rare use since only really effective in situiational anxiety such as in public speaking or competion nerves( altho it is banned by sporting organisations ) to counter CV and respiratory effects, so not really used
what are other drugs that effect anxiety
cough remedies that contain H1 antagonists can help although tolerance occurs rapidly
plant extracts such as valerian, active ingredient valerenic acid, acts by potentiating GABAa function
