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PR3136 > Anxiolytics > Flashcards

Anxiolytics Flashcards

1
Q

Main type of anxiety disorder

A

Generalised anxiety disorder (GAD)

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2
Q

Main Therapeutic rationales for anxiety disorders

A
  • CNS is too aroused with continuous activation of adrenergic system
  • Therapy find ways to minimise this activation
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3
Q

Drugs for anxiety disorders are CNS depressants. A single drug can be anxiolytic, sedative, hypnotic, or anesthesic depending on what factor?

A

Depends on dose of drug

  • Low dose: Anxiolytic + Sedative
  • Higher dose: Hypnotic
  • Even higher dose: Anesthesia
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4
Q

List the Benzodiazepines (BZD) used as:

  1. anxiolytics/sedatives
  2. Hypnotics
  3. Pre-anaesthetics
  4. Anti-convulsants (may have anti-convulsant effects)
A
  1. Anxiolytic/sedative: Diazepam, Lorazepam
  2. Hypnotics: Diazepam, Triazolam, Temazepam
  3. Pre-anaesthetics: Diazepam, Midazolam
  4. Anti-convulsant effect: Diazepam
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5
Q

List some Non-BZD drugs / drug class also used in anxiety disorders

A
  1. Barbiturates (e.g. phenobarbital)
  2. Buspirone
  3. Zolpidem
  4. Propranolol
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6
Q

The most important biological target for anxiolytics

A

GABA-A receptor

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7
Q

Function of GABA

A

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

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8
Q

Outline the MoA of BZDs

A

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
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9
Q

There are three types of BZDs: Short, Intermediate and Long.

What type is suitable for GAD and why?

A

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
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10
Q

There are three types of BZDs: Short, Intermediate and Long.

What type is suitable for surgical procedures

A

Short-acting

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11
Q

What is the AE of overdose of BZD, and how to treat the overdose?

A
  • 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
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12
Q

Some side effects of BZDs and their caution

A
  1. Drowsiness
  2. Confusion
  3. Amnesia
  4. Impaired muscle co-ordination (avoid operating heavy machinery)
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13
Q

Describe tolerance and dependence of BZDs. Hence what is the precaution when using BZD?

A
  • 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
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14
Q

Outline the MoA of Zolpidem and state its use

A
  • 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
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15
Q

Outline the MoA of Buspirone. What does it show about the cause of GAD?

A
  • 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
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16
Q

How long is the onset of anxiolytic effects for Buspirone?

A

1-2 weeks

17
Q

Can Buspirone be used for seizure and epilepsey?

A

No, it lacks anticonvulsant and muscle relaxant properties

18
Q

Outline MoA of Barbiturates

A
  • Potentiates GABA-A mediated chloride currents, but a site distinct from BZDs
19
Q

What was Barbiturates used as? What has replaced it and why has it been replaced?

A
  • Used as sedative-hypnotic
  • Replaced by BZDs due to barbiturate’s tendency to develop tolerance and dependence, and also its severe withdrawal symptoms
20
Q

Can flumazenil be used to treat overdose of Barbiturates?

A

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.

21
Q

What happens when Barbiturates reach high doses in the body?

A
  • Can directly open Cl- channels without binding to GABA-A

- Can block Na+ channels

22
Q

Outline the MoA of Pregabalin and its use

A
  • GABA analogue: Increases synaptic GABA
  • Also acts on voltage-gated Ca channels
  • Use: GAD, has anticonvulsant effects
23
Q

Possible SE of pregabalin

A

Emergence of worsening of suicidal thoughts

24
Q

Outline the MoA of Hydroxyzine and its use

A
  • 1st generation antihistamine, also have activities on serotonergic and alpha-adrenergic receptors
  • Antagonist of serotonin 5-HT2 receptors hence its anxiolytic effects
25
Q

Advantages of Hydroxyzine

A
  1. Low addictive potential compared to BZDs and barbiturates

2. Helps to ease itching due to antihistamine activities

26
Q

Outline the MoA of Propranolol and its uses

A

Beta-adrenergic receptor antagonist

  • Uses: Performance anxiety, social phobias
27
Q

What is propranolol contraindicated in?

A
  • Asthma

- Heart conditions

28
Q

There are 3 duration classifications of barbiturates. What are they, and what are their uses? Give an example for each

A
  1. Ultrashort acting: As IV, induction of anesthesia
    E.g. Thiopental
  2. Short acting: Used as sedative and hypnotic
    E.g. Pentobarbital, amobarbital
  3. Long acting: Used as anticonvulsant
    E.g. phenobarbital
29
Q

List other anxiolytics

hint: many are also antidepressants

A
  1. NaSSA: Mirtazapine
  2. TCA: Clomipramine
  3. SSRI: Fluoxetine, Citalopram, Sertraline, Paroxetine
  4. SNRI: Venlafaxine, duloxetine
30
Q

There are some anxiolytics which can act as antidepressants. What does this show about the nature of these 2 conditions?

A

There might be close association between anxiety and depression. Hence there might be common receptor interactions

PR3136 (18 decks)

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