Pharmacology Flashcards
List 5 drugs used to treat anxiety
- benzodiazepines
- antidepressants
- pregabalin
- buspirone
- beta blockers
Why can SSRIs also be used to treat anxiety disorders?
Because symptoms overlap with depression in terms of concentration, fatigue, sleep and arousal
What are the 2 core symptoms and which circuits are responsible for each of these?
- fear -> amygdala-centred circuit
- worry -> cortico-striatal-thalamic-cortical circuit
In terms of neurobiology of fear what is the role of amygdala?
Integrates sensory & cognitive info
In terms of neurobiology of fear what is the role of the anterior cingulate cortex/orbitofrontal cortex?
Responsible for affect of fear i.e. feeling of fear
In terms of neurobiology of fear what is the role of periaqueductal gray?
Responsible for avoidance e.g. fight/flight
In terms of neurobiology of fear what is the role of the hypothalamus?
Responsible for increase in cortisol
In terms of neurobiology of fear what is the role of the locus coeruleus?
Responsible for autonomic output e.g. increase in BP/HR
In terms of neurobiology of fear what is the role of the hippocampus?
Responsible for re-experiencing i.e. traumatic memories
List 6 of the neurotransmitters involved in amygdala centred circuits?
- 5HT (serotonin)
- glutamate
- GABA
- corticotrophin releasing factor (CRF)
- Norephinephrine (NE)
- voltage gated ion channels
WHat is the main inhibitory transmitter in the brain, in what parts of brain does it reduce neuron activity and what drugs enhance its action?
- GABA
- amygdala and CSTC circuit
- benzodiazepines
How is GABA synthesised?
Glutamate made into GABA by glutamic acid decarbozylase
Which exact GABA receptor is the target of benzodiazepines, barbiturates and alcohol?
GABA-A
What channel is opened when GABA binds to GABA-A receptor?
Chloride channel opens and membrane is negatively polarised so action potential chance reduced
How does benzodiazepine act as a positive allosteric modulator?
Increases agonist affinity/efficacy
What are 2 types of drug that are anxiogenic?
- inverse benzodiazepine agonists e.g. beta Carbolines
- GABA antagonist e.g. flumazenil
List 3 common benzodiazepines in ?
Lorazepam - shorter effect, rapid tranquilisation
Diazepam - longer affect, anxiolytics
Chlodiazepoxide - used for alcohol withdrawal
What are 5 pharmacological effects of benzodiazepines?
- reduce anxiety and aggression
- hypnosis/sedation
- muscle relaxation
- anticonvulsant effect
- anterograde amnesia
What are clinical uses of benzos?
- acute treatment of extreme anxiety
- hypnosis
- alcohol withdrawal
- mania
- delirium
- rapid tranquilisation
- premedication before surgery
- status epilepticus
What is treatment for benzodiazepine overdose?
Flumazenil
What are 3 problems with benzos?
Paradoxical aggression
Anterograde amnesia & impaired coordination
Tolerance and dependence
Benzodiazepine withdrawal can cause symptoms such as abdo cramps, increased anxiety, muscle tension, chest pain, palpitations, sweating, blurred vision, depression, insomnia/nightmares, dizziness, headaches, N&V, tingling in hands & feet, restlessness, sensory sensitivity. What can cause these withdrawal symptoms?
- rapid withdrawal (extreme benzo withdrawal symptoms e.g. convulsions, psychosis etc)
- neuroadaptation of the GABA response due to chronic treatment causing reduced response to GABA or withdrawal causing reduced density of benzodiazepine receptors
How to withdraw benzodiazepines?
- Transfer patient to equivalent daily dose of diazepam/chlordiazepoxide at night (cos longer half-life)
- Reduced dose every 2-3 weeks in steps of 2/2.5mg
- Reduced dose further in smaller steps if needed
- Stop completely, can vary from 4 weeks - year
How do SSRIs and SNRIs increase serotonin?
By blocking the serotonin transporter
How long for SSRIs to see full affect and why?
Up to 12 weeks
Because acutely SSRIs increase extra cellular serotonin but chronically anxiolytics properties appear
What antidepressants are used for panic disorder, OCD, PTSD, phobias and GAD?
SSRIS
For GAD, specifically escitalopram/paroxetine
What antidepressants are used 2nd line for panic disorder or OCD? (However are unlicensed for panic)
Tricyclics such as clomipramine, imipramine
What antidepressants are used for GAD?
SNRI e.g. velafaxine
What antidepressant is used for social anxiety disorder?
Moclobemide (MAOI)
Pregabalin is only used if unresponsive to other treatments. What is the mechanism of action of pregabalin?
Calcium channel blocker, enhances GABA action
What is the following management plan for?
- Psycho education
- Self help/psychoeducation groups
- High intensity psychological intervention (CBT) OR drug treatment (SSRI) (maybe benzos for <2weeks)
- SNRI
- Pregabalin
- CBT & drugs combo
GAD
Treatment for GAD should continue for 18 months. If absence of effect within 4 weeks of treatment of GAD it is unlikely it will have an affect. True/false?
True
What is this the management plan for?
1. Self help
2. CBT/SSRI
Note: do not use benzos/sedating antihistamines as long term outcome not good & avoid propranolol, buspirone and bupropion
3. Tricyclics (clomipramine, desipramine, imipramine, lofepramine) and continue treatment for 6 months
Panic disorder
What is this the management plan for?
- Low intensity psychological intervention e.g. CBT & ERP
- CBT or SSRI (fluoxetine, fluvoxamine, paroxetine, sertraline or citalopram) - if effective continue for 1 year
- Consider dose increase after 4-6 weeks
- SSRI plus CBT & ERP
- Clomipramine
- Augmentation with antipsychotic or clomipramine + citalopram
OCD !
What is this the management for?
- Mild & <4 weeks from trauma - watch & wait
- Within 3 months of trauma: Brief psychological intervention and hypnotic meds for sleep
- More than 3 months after trauma: CBT/EMDR
- Not much evidence for drug treatment but maybe paroxetine/mirtazeprien or amitryptiline
PTSD
What is this the management plan for?
- CBT
- SSRI (escitalopram or sertaline) - review at 12 weeks
- SSRI plus CBT
- Alternative SSRI (Fluvoxamine or paroxetine) or SNRI (venlafaxine)
- MAOI (moclobemide)
Social Anxiety
