Pharmacology of Anxiolytic Drugs Flashcards
What are some drugs used to treat anxiety?
Benzodiazepines, antidepressants, beta blockers, pregabalin, bispirone
What are some comorbid disorders of anxiety?
Substance abuse, ADHD, bipolar disorder, panic disorder, sleep disorder
What are the core symptoms of anxiety?
Significant symptom overlap with depression
Amygdala centred circuit = panic and phobia
Cortico-striatal-thalamic-cortical (CSTC) circuit = anxiety, apprehension, obsessions
What is the function of the amygdala in anxiety?
Integrates sensory and cognitive symptoms
Where in the brain is the affect of fear seen?
Anterior cingulate cortex and orbitofrontal cortex
What is the periaqueductal gray responsible for?
Fight or flight response
What part of the brain is ultimately responsible for increasing cortisol levels?
Hypothalamus
How does the locus coeruleus increase blood pressure and heart rate in fear?
Via autonomic output
What kind of memories is the hippocampus responsible for?
Traumatic memories
What neurotransmitters are involved in the amygdala centred circuit?
5-HT, GABA, glutamate, CRF, NE and voltage gated ion channels
What is GABA?
Main inhibitory transmitter in brain = reduces activity of neurons in the amygdala and CSTC circuit
What effect do benzodiazepines have on GABA?
Enhance GABA activity
What are the main GABA receptors?
GABA-A, GABA-B and GABA-C
What is GABA-A a target for?
Benzodiazepines, alcohol and barbiturates
What are some examples of benzodiazepines?
Lorazepam, diazepam and chlordiazepoxide
What effects do benzodiazepines have?
Reduce anxiety and depression, hypnosis and sedation, muscle relaxation, anticonvulsant, anterograde amnesia
What are the clinical uses of benzodiazepines?
Acute treatment of extreme anxiety, hypnosis, alcohol withdrawl, mania, delirium, rapid tranquillisation, status epilepticus
What are some side effects of benzodiazepines?
Paradoxical aggression, anterograde amnesia and impaired co-ordination, tolerance and dependence
What are some symptoms of benzodiazepine withdrawl?
Abdominal cramps, panic attacks, sweating, shaking, palpitations, blurred vision, depression, insomnia, dizziness, headaches, nausea/vomiting, tingling in hands/feet, restlessness, sensory sensitivity
What causes the symptoms of benzodiazepine withdrawl?
Chronic treatment reduces response to GABA = withdrawl results in anxiety or convulsions due to reduced density of benzodiazepine receptors
What is the first step when withdrawing a patient from benzoddiazepines?
Transfer patient to equivalent daily dose of diazepam or chlordiazepoxide preferably taken at night
How often do you reduce dose of benzodiazepines when withdrawing a patient from this drug?
Reduce dose every 2-3 weeks in steps of 2-2.5mg = if withdrawl symptoms occur then maintain dose until they clear, reduce dose further after this
How long can it take to withdraw a patient from benzodiazepines?
Can take anything from 4 weeks up to 1 year or more
Where does 5-HT innervate?
The amygdala
How do SSRIs and SNRIs increase 5-HT levels?
Block the 5-HT transporter
How do SSRIs increase 5-HT levels?
Inhibit reuptake of 5-HT = leads to increased levels in the synaptic cleft
What antidepressants can be used acutely to treat anxiety?
SSRIs = increase extracellular 5-HT
What does chronic use of antidepressants to treat anxiety cause?
Anxiolytic properties begin to appear
By which mechanisms do antidepressants treat anxiety?
Expression of receptors for 5-HT and glucocorticoids that depend upon sustained exposure to high extracellular concentrations of 5-HT
Enhanced neurosteroid synthesis
What anxiety disorders can SSRIs be used to treat?
Panic disorder, OCD, PTSD and phobias
Paroxetine and escitalopram used for GAD
What anxiety disorders are tricyclics used to treat?
Used for OCD
2nd line for panic disorder
What is venlafaxine (SNRI) used to treat?
GAD
What is moclobemide (MAOI) used to treat?
Social anxiety disorder
What are some features of pregabalin?
Ca2+ channel blocker and GABA enhancer = only considered if patient not responsive to other treatments
What are some features of propanolol?
Beta blocker = best used for somatic symptoms (e.g palpitations or tremor)
What are the steps for treating GAD?
1 = psychoeducation and self help/psychoeducation groups 2 = CBT or SSRIs ( consider <2 weeks benzodiazepines) 3 = SNRI 4 = Pregabalin 5 = combination of CBT and drug treatment
How often should you wait before reviewing treatment of GAD?
Up to 12 weeks to asses efficacy = unlikely to respond if no effect in 4 weeks
How long should you stay with the treatment for GAD?
Continue for 18 months
When stopping, reduce dose gradually to avoid discontinuation
What are the steps for treating panic disorder?
1 = self help 2 = CBT or SSRI (if no benefit from longstanding CBT) 3 = tricyclics (e.g clomipramine)
What drugs should be avoided when treating panic disorder?
benzodiazepines, sedating antihistamines, propanolol, bispirone, bupropion
How long do you stick with treatment for panic disorder?
6 months
What are the steps for treating OCD?
1 = low intensity psychological intervention 2 = more intensive psychological intervention or SSRI, continue for 1 year if effective 3 = consider dose increase after 4-6 weeks 4 = SSRIs plus CBT and ERP 5 = clomipramine 6 = augmentation with antipsychotic/clomipramine plus citalopram
What is the treatment of PTSD within 4 weeks of the traumatic event?
Watchful waiting
What is the treatment of PTSD within 3 months of the traumatic event?
Trauma focused CBT
Hypnotic medication for sleep disturbance
What is the treatment for PTSD over 3 months since the traumatic event?
Trauma focused CBT or EMDR
Are drugs used to treat PTSD?
Limited evidence for their use = paroxetine, mirtazepine, amitriptyline
What are the steps for treating social anxiety disorder?
1 = individual CBT 2 = SSRI (escitalopram, sertraline), review in 12 weeks 3 = SSRI plus CBT 4 = SNRI or alternative SSRI 5 = MAO inhibitor (moclobemide)
