Psychopharmacology of Anxiolytics Flashcards
Enumerate structures modulating fear
- Amygdala
- Anterior cingulate cortex
- Orbitofrontal cortex
Avoidance, a primarily motor response, is regulated by which structures?
Reciprocal connections between the amygdala and periaqueductal gray (PAG)
Which hormone is secreted in the fear response?
Cortisol
What are the physiologic responses to fear?
- Changes in respiration (regulated by parabrachial nucleus)
- Increases in HR and BP (regulated by connections between amygdala and locus ceruleus)
What is re-experiencing?
Traumatic memory stored in the hippocampus triggering the amygdala to initiate a fear response
Neurotransmitters involved in symptoms of anxiety and fear associated with malfunctioning of amygdala-centred circuits
- Serotonin (5HT)
- GABA
- Corticotropin releasing factor
- norepinephrine
Structure associated with symptoms of worry
Cortico-striato-thalamic-cortical (CSTC) loop
Drug treatments for Anxiety
- GABAergic anxiolytics/Benzodiazepines
- Serotonergic anxiolytics
- Noradrenergic anxiolytics
Most widely used anxiolytics
Benzodiazepines
Principal inhibitory neurotransmitter
GABA
Benzodiazepine mode of action
Enhancement of GABA action at amygdala and prefrontal cortex within CSTC loops
Types of GABA receptors
- GABAa: gatekeepers of chloride channel, allosterically modulated
- GABAb: Not allosterically modulated, binds exclusively to Baclofen
Benzodiazepine receptors
- Omega 1 (cerebellum: anxiolytic, sedative-hypnotic.)
- Omega 2: (spinal cord and striatum: muscle relaxant)
- Omega 3: peripheral
Actions of benzodiazepines
- Anxiolytic
- Anticonvulsant
- Muscle relaxation
- Hypnosis and stupour in high doses
NOT
- Analgesia
- Anaesthesia
Clinical uses of benzodiazepines
- Anxiety disorders
- Muscle relaxation
- Anticonvulsant
- Alcohol withdrawal
Adverse effects of benzodiazepines
- Drowsiness
- Confusio
- Ataxia
- Amnesia
Benzodiazepines not metabolised in the liver, thus safe to give in liver disease
- Oxazepam
- Temazepam
- Lorazepam
Benzodiazepine antagonist given for poisoning, reverses the effect of benzodiazepines
Flumazenil
Neurotransmitter innervating the amygdala and CSTC, which regulates fear and worry
Serotonin
Serotonergic anxiolytics
- Buspirone
- Gepirone
- Tandospirone
Identify:
Serotonin 1A partial agonist, a generalised anxiolytic used as an augmenting agent to antidepressants which does not interact with alcohol, benzodiazepines, or sedatives; has no dependence or withdrawal symptoms even with long term use
Buspirone
Clinical uses for Buspirone
- Chronic and persistent anxiety
- Comorbid substance abuse
- Elderly
Neurotransmitter with important regulatory output to the amygdala, prefrontal cortex, and thalamus in CSTC circuits
Norepinephrine
Noradrenergic anxiolytic that is an alpha 2 agonist (stimulates alpha-2 receptors) effective at decreasing tachycardia, dilated pupils, sweating, and tremors, but not at blocking subjective and emotional aspects of anxiety
Clonidine
Anxiolytics useful in cases of social phobia
Beta blockers
Novel approaches to treatment of anxiety disorders
- Fear extinction
2. Reconsolidation
Benzodiazepine advantages
- Rapid-onset
- Effective
- Well-tolerated
- General anti-anxiety effects
- Safe in overdose
Benzodiazepine disadvantages
- Withdrawal reaction
- Sedation
- Multiple daily dosing may be required
- Abuse potential
- Poor antidepressant
SSRI advantages
- Effective
- Benign side effects
- No dependence issue
- Once a day dosing
Tricyclic antidepressant (TCA) advantages
- Single daily dose
- Antidepressant effect
- No abuse potential
- Well-studied
- Effective
- Generics available
TCA disadvantages
- Delayed-onset
- Anticholinergic side effects
- Postural hypotension
- Weight gain
- Dangerous in overdose
Pharmacotherapeutic agents for insomnia
- Nonbenzodiazepine short-acting hypnotics (e.g. Zateplon, Zolpidem, Zopiclone)
- Benzodiazepines (decrease sleep latency, diminish wakenings, increase duration of sleep)
- Melatonergic hypnotics
- Sedative-hypnotic antidepressants
- Sedating antihistamines
- OTC agents
- Older sedative hypnotics e.g. Chloral hydrate