Anxiolytics Flashcards
Main type of anxiety disorder
Generalised anxiety disorder (GAD)
Main Therapeutic rationales for anxiety disorders
- CNS is too aroused with continuous activation of adrenergic system
- Therapy find ways to minimise this activation
Drugs for anxiety disorders are CNS depressants. A single drug can be anxiolytic, sedative, hypnotic, or anesthesic depending on what factor?
Depends on dose of drug
- Low dose: Anxiolytic + Sedative
- Higher dose: Hypnotic
- Even higher dose: Anesthesia
List the Benzodiazepines (BZD) used as:
- anxiolytics/sedatives
- Hypnotics
- Pre-anaesthetics
- Anti-convulsants (may have anti-convulsant effects)
- Anxiolytic/sedative: Diazepam, Lorazepam
- Hypnotics: Diazepam, Triazolam, Temazepam
- Pre-anaesthetics: Diazepam, Midazolam
- Anti-convulsant effect: Diazepam
List some Non-BZD drugs / drug class also used in anxiety disorders
- Barbiturates (e.g. phenobarbital)
- Buspirone
- Zolpidem
- Propranolol
The most important biological target for anxiolytics
GABA-A receptor
Function of GABA
Inhibitory transmitter in brain. It binds to GABA-A receptors to cause chloride ion channels to open, leading to hyperpolarisation of the cell, making cell more difficult to depolarise and become neurally excited
Outline the MoA of BZDs
Similar to GABA:
- Binds to GABA-A receptor
- Increases frequency of GABA-induced chloride ion channel opening, hence enhancing entry of chloride ion via chloride ion channel
- Cause greater hyperpolarisation of the cell hence reducing cell neural excitability
There are three types of BZDs: Short, Intermediate and Long.
What type is suitable for GAD and why?
Intermediate and long
- Better as GAD may be chronic and long term
- Hence intermediate and long-acting BZDs allow low frequency of dosing, improving patients’ compliance
There are three types of BZDs: Short, Intermediate and Long.
What type is suitable for surgical procedures
Short-acting
What is the AE of overdose of BZD, and how to treat the overdose?
- Severe respiratory depression, especially if used concurrently with alcohol
- Treat using flumazenil, a BZD antagonist. It binds to GABA-A receptor and facilitate the closure of chloride ion channels to stop chloride ion influx
Some side effects of BZDs and their caution
- Drowsiness
- Confusion
- Amnesia
- Impaired muscle co-ordination (avoid operating heavy machinery)
Describe tolerance and dependence of BZDs. Hence what is the precaution when using BZD?
- Dependent on frequency of use
- Dependence can develop (hence abuse potential) and withdrawal effects includes: disturbed sleep, rebound anxiety, tremor, convulsions
- Hence, slowly taper dose and withdraw gradually
Outline the MoA of Zolpidem and state its use
- Potentiates GABA-A mediated chloride ion currents. Acts at the same site as BZDs
- Has good hypnotic effect, primarily used to treat insomnia (Insomnia is a common presentation of GAD)
- It is not effective as anxiolytics
Outline the MoA of Buspirone. What does it show about the cause of GAD?
- Serotonin 5-HT1A receptor partial agonist, and binds to dopamine receptors
- Shows that anxiety is not only caused by GABA, but other receptors and complex interactions as well
How long is the onset of anxiolytic effects for Buspirone?
1-2 weeks
Can Buspirone be used for seizure and epilepsey?
No, it lacks anticonvulsant and muscle relaxant properties
Outline MoA of Barbiturates
- Potentiates GABA-A mediated chloride currents, but a site distinct from BZDs
What was Barbiturates used as? What has replaced it and why has it been replaced?
- Used as sedative-hypnotic
- Replaced by BZDs due to barbiturate’s tendency to develop tolerance and dependence, and also its severe withdrawal symptoms
Can flumazenil be used to treat overdose of Barbiturates?
No, Flumazenil displaces BZD from BZD site in GABA-A receptor. However, Barbiturate binds to GABA-A at a different site, which Flumazenil does not bind.
What happens when Barbiturates reach high doses in the body?
- Can directly open Cl- channels without binding to GABA-A
- Can block Na+ channels
Outline the MoA of Pregabalin and its use
- GABA analogue: Increases synaptic GABA
- Also acts on voltage-gated Ca channels
- Use: GAD, has anticonvulsant effects
Possible SE of pregabalin
Emergence of worsening of suicidal thoughts
Outline the MoA of Hydroxyzine and its use
- 1st generation antihistamine, also have activities on serotonergic and alpha-adrenergic receptors
- Antagonist of serotonin 5-HT2 receptors hence its anxiolytic effects
