ANXIOLYTIC Flashcards
Psychological component of anxiety state
Insomnia
Arousal
Lack of concentration
Negative emotions (worry, nervousness, unease)
Physical component of anxiety state
Tachycardia Shortness of breath Nausea Gastric acid hypersecretion Trembling
Generalised Anxiety Disorder (GAD)
- at least 6 months
- excessive and uncontrolled worry over everyday matters
- interferes with daily functioning
Anxiolytic and sedative benzodiazepines
- Diazepam
2. Lorazepam
Hypnotic benzodiazepines
- Diazepam
- Triazolam
- Temazepam
Pre-anaesthetic benzodiazepines
- Diazepam
2. Midazolam
3 categories of benzodiazepines according to their onset of action
- Short acting
- few hours (3-8h)
- Triazolam (insomnia) & Midazolam (general anaesthesia) - Intermediate acting
- several hours (10-20h)
- Temazepam (insomnia) & Lorazepam (insomnia & status epilepticus) - Long acting
- days
- Diazepam (epilepsy, status epilepticus & refractory seizures)
MOA of benzodiazepines
Benzodiazepines bind to benzodiazepine binding site on GABA receptor.
This enhance and promote the binding of GABA to its binding site which then opens the Cl- channel to allow influx of negatively charged Cl- into the cell, causing neuronal membrane to be hyperpolarised.
Hence, it is harder for the neuron to be depolarised and fired.
Can benzodiazepines work without GABA agonists?
No.
Benzodiazepines potentiate GABA action by increasing the frequency of GABA-induced channel opening.
Side effects of benzodiazepines
- Severe respiratory depression, especially with alcohol use
- Confusion, amnesia and drowsiness
- Impaired muscle coordination
- High risk of dependency development
- withdrawal effects (disturbed sleep, rebound anxiety, tremors and convulsion) - High risk of tolerance development (req higher dose to exhibit same therapeutic effect)
- depends on the frequency of use
Treatment for overdosage of benzodiazepines
Flumazenil, benzodiazepine-site antagonist
Non-benzodiazepines (6)
- Zolpidem
- Buspirone
- Barbiturates
- Pregabalin (GABA analogue)
- Hydroxyzine
- Propranolol
MOA of Zolpidem
- binds to benzodiazepine-binding site to potentiate GABA binding to its receptor
- primarily used to treat insomnia (NO ANXIOLYTIC EFFECT)
MOA of Buspirone
- partial 5-HT receptor agonist & dopamine receptor angonist
- for GAD but onset takes 1-2 weeks
- lack muscle relaxant and anti-convulsant properties
MOA of Barbiturates
- bind to barbital binding site on GABA receptor
- higher tendency for dependence and tolerance
- severe withdrawal symptoms
- at anaesthetic doses, it can directly open Cl- channels and block Na+ channels
- CANNOT use flumazenil for overdosage treatment
MOA of Pregabalin
- GABA agonist analogue which increase synaptic GABA agonists
- also act on voltage-gated Ca2+ channels
- for GAD and anti-convulsant effect
- risk of suicidal thoughts
MOA of Hydroxyzine
- antihistamines with activities on serotonergic and alpha-adrenergic receptors
- anxiolytic effect due to 5-HT receptors activities
- low addictive potential compared to benzodiazepines and barbiturates
- helps with itching
MOA of Propranolol
- beta-adrenergic receptor antagonist
- for performance anxiety and social phobias
- reduce physical symptoms
- CI in asthma and heart diseases
3 categories of barbiturates according to their onset of action
- Ultra-short acting
- mins
- thiopental (IV anaesthesia) - Short acting (sedative & hypnotic)
- 3-8h
- pentobarbital & amobarbital - Long acting
- days
- phenobarbital
Anti-depressants as anxiolytics (4)
- NaSSA : Mirtazapine
- TCA : Clomipramine
- SSRI : Fluoxetine, citalopram, sertraline and paroxetine
- SNRI : Venlafaxine and duloxetine
serotonergic agents
Buspirone vs Buproprion
Buspirone
- partial 5-HT agonist
- activities on dopamine receptors
Buproprion
- NDRI
ADR of Pregabalin
Suicidal tendency
