Anxiolytics Flashcards
What is the biochemical basis of anxiety states?
CNS noradrenergic activation -> Fight/Flight response
PNS adrenergic/epinephrine activation -> Fight/Flight
Stress response -> HPA axis -> Secretion of stress hormones (cortisol)
List the type of Anxiety Disorders
- Generalised Anxiety Disorder (GAD)
- Post-traumatic stress disorder
- Phobias
- Panic disorder
- Obsessive Compulsive Disorder
Generalised Anxiety Disorder
- Interferes with daily functioning
- Both psychological & phy symptoms
- Diagnosed when >= 6mths (not the same as anxiety)
- Most common cause of disability in the workplace
Therapeutic rationale for Anxiety Disorders
CNS Depressant:
Sedative: Cause sedation, relaxation
Hypnotic: Induce drowsiness & sleep (may have amnestic effects)
Anxiolytic: Reduce anxiety
Note: same drug can have > 1 action depending on dose
Low dose: Anxiolytic & sedative effects
Higher dose: Hypnotic
Even higher doses: Can cause anesthesia,
used for surgery
Therapeutics for Anxiety Disorders
1) Benzodiazepines
i) Anxiolytics/sedative: diazepam, lorazepam
ii) Hypnotics: diazepam, triazolam, temazepam
iii) Pre-anaesthetics: diazepam, midazolam
iv) May also have anti-convulsant effects: diazepam
2) Non-Benzodiazepines
i) Barbiturates
ii) Buspirone
iii) Zolpidem
iv) Propanolol etc.
MOA of Benzodiazepines
Potentiate GABA actions by increasing frequency of GABA-induced channel opening
- Binds to Benzodiazepine site (allosteric site) of GABA^A Receptor complex
- Potentiates influx of Cl- ions leading to hyperpolarization
- > Less active firing of neurons, decrease arousal
Effect depends on site:
Limbic system - Mood alteration
Reticular activating system - Cause drowsiness
Motor cortex - Relax muscles
How are Benzodiazepines classified based on?
Duration of action (how long they work, does not necessarily mean faster ooa)
Short-Acting Benzodiazepines
Midazolam: Induction of general anaesthesia
Anxiety, Procedural sedation
Triazolam: Insomnia
Intermediate-Acting Benzodiazepines
Alprazolam: Anxiety, panic disorder
Clonazepam: Panic disorder, seizure
Lorazepam: Anxiety, insomnia, status epilepticus
Oxazepam: Alcohol withdrawal syndrome, anxiety
Temazepam: Insomnia
Long-Acting Benzodiazepines
- For more chronic conditions
Diazepam: Status epilepticus, sedation, anxiety, seizure, alcohol withdrawal syndrome, refractory seizure, adjunct skeletal muscle spasm
Flurazepam: Insomnia
Chlordiazepoxide: Alcohol withdrawal syndrome, anxiety
Adverse effects of Benzodiazepines
- Acute toxicity/overdose
- > Can cause severe respiratory depression (especially used concurrently with alcohol)
- > Treatment: Flumazenil (benzodiazepine antagonist)
- Drowsiness, confusion, amnesia
- Impaired muscle co-ordination (impairs manual skills)
- Tolerance & dependence:
- > Depends on frequency of use
- > Dependence can develop
- > Importance to withdraw gradually
- > Has abuse potential
Classification of Barbiturates & examples
though seldom in use except for ultrashort acting
[Duration of Action]
1) Ultrashort (20min)
- IV induction of anaesthesia (eg. thiopental)
2) Short (3-8hrs)
- Sedative & Hypnotic (eg, pentobarbital & amobarbital)
3) Long-acting (1-2days)
- Anticonvulsant (eg. phenobarbital: last line for anti-epilepsy, not suitable for long-term use)
[Non-benzodiazepine] Zolpidem
MOA: Potentiates GABA^A mediated Cl- currents at the same site as benzodiazepines
Use: Insomina (Good hypnotic effect)
- not effective as anxiolytic
[Non-benzodiazepine] Buspirone
MOA: Serotonin 5-HT^1A receptor partial agonist, also binds to dopamine receptors
Use: GAD (anxiolytic effects take 1-2weeks)
- Lacks anticonvulsant & muscle relaxant properties
[Non-benzodiazepine] Barbiturates
MOA: Potentiates GABA^A mediated Cl- current but at different site
- @ anaesthetic doses can directly open Cl- channels as well as block Na+ channels (only at much higher doses)
Adverse Effects:
- Tendency to develop tolerance & dependence
- Severe withdrawal symptoms
- Flumazenil not effective for treating barbiturate overdose
