Pharmacology of Anxiolytic Drugs Flashcards
what drugs are used to treat anxiety
benzodiazepines antidepressants busiprone pregabalin beta-blockers (propanolol)
when is anxiety a disorder
when it affects concentration, fatigue, sleep and arousal
what is anxiety commonly co morbid with
substance abuse, BPAD, pain and sleep disorders, other anxiety disorders
what are the core symptoms of anxiety and what part of the brain is responsible for them
fear: panic and phobia = amygdala centered circuit
worry: anxiety, apprehension, obsessions = cortico- striatal- thalamic- cortical circuit
what does the amygdala do
intergrates sensory and cognitive information
what part of brain: affect of fear
anterior cingulate cortex/ orbitofrontal cortex
what part of brain: avoidance
periaqueductal gray (fight/ flight)
what part of brain: endocrine element of fear
hypothalamus (increases cortisol)
what part of brain: autonomic output during fear
locus coeuleus (increase BP and HR)
what part of brain: re-experiencing of fear
hippocampus (traumatic memories)
what neurotransmitters are involves in amygdala centred circuits
5HT (Serotonin) GABA (gamm-aminobutyric acid) glutamate CRF (corticotophin releasing hormone) NE (norepinephrine) voltage gated ion channels
what is GABA
main inhibitory neurotransmitter
what does GABA do
reduced the activity of neurones in amygdala and CSTC (cortico-striato-thalamo-cortico) circuit
what do benzodiazepines do
enhance GABA action (inhibit neurones in maygdala and CSTC circuit)
what are the main GABA receptors
GABA-A
GABA-B
GABA-C
what else activates GABA-A
benzodiazepines, barbiturates, general anaesthetics: alcohol, steroids, propofol, haloethane
explain the action of benzodiazepines
binds at allosteric site on GABA receptor
this increases effect of GABA on channel and increases the activity of the GABA recpetor
=increases amount of Cl- passing into neurone
this hyperpolarises membrane potential making it less likely for the neurone to produce an AP
give examples of benzodiazepines
lorazepam midazolam diazepam (valium) alprazolam (xanax) chlordiazepoxide
all end in epam (-chlordiazepoxide)
what are the pharmacological effects of benzodiazepines
reduce anxiety and aggression hypnosis/ sedation muscle relaxant anticonvulsant effect anterograde amnesia
what are the clinical uses of benzodiazepines
acute treatment of extreme anxiety hypnosis alcohol withdrawal mania delirium rapid tranquilisation premedication before surgery or during minor procedure status epilepticus
what are potential problems with benzodiazepines
fairly safe in overdose (antagonist flumazenil)
paradoxical aggression
anterograde amnesia & impaired coordination
tolerance + dependence
what are the symptoms of benzodiazepine withdrawal
abdo cramps increased anxiety, panic attacks physical symptoms (muscle tension, chest pain, palpitations, sweating, shaking) blurred vision insomnia dizziness headaches inability to concentrate nausea and vomiting tingling in hands and feet restlessness sensory sensitivity
what causes benzodiazepine withdrawal symptoms
rapid withdrawal - confusion, psychosis, convulsions, tachycardia, sweating, hypertension, agitation, tremor
neuroadaption of the GABA response: chronic treatment- anxiety/ convulsions
how do you withdraw patient from benzodiazepines
transfer to equivalent dose of diazepam/ chlordiazepoxide- preferably taken at night
reduce tose every 2-3 weeks in 2-2.5mg steps (maintain dose is symptoms occur)
reduce dose further (if necessary in smaller steps)
stop completely (can take 4 weeks- year+)
what increases serotonin by blocking the serotonin transporter
SSRIs and SNRIs
how do antidepressants treat anxiety
acutely- SSRIs increase extracellular serotonin
chronically- anxiolytic properties appear (?neuroadaptove changes/ enhances neurosteroid synthesis)
what antidepressants are used for anxiety
SSRIs - panic disorder, OCD, PTSD, phobias, GAD (escitalopram, paroxetine)
tricyclics (clomipramine, imipramine)- 2nd line for panic disorder, OCD
venlafaxine (SNRI)- GAD
moclobemide (MAOI)- social anziety disorder
when should pregabalin be used for anxiety
only considered if not responsive to other treatments
how does pregabalin work
Ca2+ channel blocker, GABA enhancer
when should beta blocker be used for anxiety
best for somatic symptoms- palpitation, tremor
what is the management pathway for GAD
- psychoeducation
- self help/ 3. psychoeducation groups
- CBT/ SSRI (consider short term use of benzodiazepines <2 weeks)
- SNRI
pregabalin - combo of CBT and drugs
when do you review management of GAD
up to 12 weeks
no response in 4 weeks= unlikely to get response
what is the management pathway for panic disorder
- self help
- CBT or SSRI
(avoid benzos, propanalol, bupropion) - tricyclics (clomipramine, desipramine, imipramine, lofepramine)
continue treatment for 3 months
what is the management pathway for OCD
- low intensity psychological intervention (CBT and erp (exposure and response training), self help/ group)
- more intense psychotherapy/ SSRI
- if effective continue for a year - increase dose after 4-6 weeks
- SSRI plus CBT and ERT
- clomipramine (tricylic)
- antipsychotic/ clomipramine and citalopram
what is the management for PTSD
- watchful waiting if mild and within 4 weeks of trauma
- if within 3 months of trauma: CBT, hyponotic medication for sleep disturbance
- > 3 months: truama focussed CBT or eye movement desensitisation and reprocessing
- limited evidence for drugs
what is the management pathway for social anxiety
- individual CBT
- SSRI (escitalopram or sertaline
- SSRI plus CBT
- alternative SSRI (fluvoxamine or paroxetine) or SNRI (venlafaxine)
- MAOI (moclobemide)
how long should benzodiazepines be used for
2-4 weeks to prevent dependence
