Anxiolytics

Question 1

what’s the difference between anxiety and fear

Answer 1

anxiety = anticipated threat, vague
fear = present danger

Question 2

similarities between fear and anxiety

Answer 2

the threat may be real or perceived

both responses: defensive behaviours, autonomic reflexes, arousal, corticosteroid production, negative emotions

Question 3

Psychological manifestations of anxiety states

Answer 3

• negative emotions: worry, nervousness, unease
• arousal
• lack of concentration
• insomnia

Question 4

Physical manifestation of anxiety states

Answer 4

• tachycardia
• SOB
• nausea
• gastric acid hypersecretion
• trembling (skeletal muscles activated)

Question 5

what is the biochemical basis that cause psychological and physical manifestation of anxiety states

Answer 5

• central and peripheral noradrenergic/adrenergic activation –> flight or fight response
• stress response –> HPA axis –> secretion of stress hormones (cortisol)

Question 6

main anxiety disorder that is discussed in lecture

Answer 6

generalised anxiety disorder (GAD)

Question 7

what is GAD?

Answer 7

• excessive worrying over everyday matters
• interferes w daily functioning
• both psychological and physical manifestation
• diagnosed when present for at least 6 months
• most common cause of disability in the workplace

Question 8

what are the 3 different therapeutic effects that can be seen in anxiolytic drug?

Answer 8

CNS depressant:

1. sedative = cause sedation/relaxation but still aware
2. hypnotic = induce drowsiness and sleep,may have amnestic effects
3. anxiolytic = reduced anxiety

Question 9

at what doses can i see the different types of therapeutic effect?

Answer 9

1. low dose: anxiolytic, sedative effects
2. higher dose: hypnotic
3. even higher dose –> cause anaesthesia, used for surgery

Question 10

which BZDs is used as anxiolytics /sedatives?

Answer 10

diazepam, lorazepam

Question 11

which BZDs is used as hypnotics?

Answer 11

diazepam, triazolam, temazepam

Question 12

which BZDs is used as pre-anaesthetics?

Answer 12

diazepam, midazolam

Question 13

which BZDs used for anti-convulsant effect?

Answer 13

diazepam

Question 14

MOA of BZDs

Answer 14

binds to the BZD site (allosteric site) away from the GABA site

potentiate GABA actions by increasing the frequency of GABA-induced channel opening

potentiates influx of CL- ions leading to greater hyperpolarization –> neurons not firing

Question 15

what happens when the GABA is activated or potentiated in this case with BZDs?

Answer 15

• alters mood via the limbic system
• cause drowsiness via reticular activating system
• relax muscles vis motor cortex

Question 16

what are the short acting BZDs and their uses?

Answer 16

midazolam (anaesthetic), triazolam (hypnotic)

Question 17

what are the intermediate BZDs and their uses?

Answer 17

Temazepam (hypnotic), Lorazepam (anxiolytic/sedative)

Question 18

what are the long acting BZDs and their uses

Answer 18

diazepam
(anxiolytic/sedative, hypnotic, anaesthetic, status epilepticus (anti-convulsant)

• longer acting for chronic conditions

Question 19

Adverse effects of BZDs

Answer 19

1. acute toxicity/ overdose –> severe respiratory depression, esp w concurrent use of alcohol

–> treated w flumazenil, a benzodiazepine antagonist

2. SE: drowsiness, confusion, amnesia
   - impaired muscle co-ordination (impair manual skills - cannot use machinery)
3. tolerance: depends on freq of use
   - develops faster for epilepsy than for use to induce sleep
4. dependence: withdrawal effect = disturbed sleep, rebound anxiety, tremor, convulsion
   - to withdraw GRADUALLY
   - has abuse potential

Question 20

What are the names of the non-BZDs

Answer 20

• zolpidem
• buspirone
• barbiturates
• pregabalin
• hydroxyzine
• propanolol

Question 21

MOA of Zolpidem

Answer 21

• potentiates GABAa mediated CL- currents at the same site as BZD

Question 22

Therapeutic effects of zolpidem

Answer 22

• good hypnotic effect: PRIMARILY used to treat insomnia

- NOT effective as an anxiolytic

Question 23

MOA of buspirone

Answer 23

• serotonin 5-HT1A receptor partial agonist

- bind to dopamine receptors

Question 24

Therapeutic effects of buspirone

Answer 24

• GAD, but anxiolytic effect takes 1-2 weeks

- lacks anti-convulsant and muscle relaxant properties

Question 25

MOA of barbiturates

Answer 25

potentiates the GABAa mediated CL- current, at barbiturate site (not at BZD site)

Question 26

Therapeutic effect of barbiturates

Answer 26

- sedative-hypnotic BUT - NOT used freq due to higher tolerance and dependence compared to BZDs (barbiturates: directly proportional vs BZDs: increases and plateaus) - severe withdrawal symptoms - flumazenil not effective in treating barbiturate overdose - at anaesthetic doses (higher doses) --> e.g. phenobarbital can DIRECTLY open CL- channels and block Na+ channels

Question 27

3 different types of barbiturates

Answer 27

- long-acting (1-2 days) - short (3-8hrs) - ultra-short (20min)

Question 28

therapeutic effect of long acting barbiturates?

Answer 28

- anticonvulsant --> phenobarbital

Question 29

therapeutic effect of short acting barbiturates?

Answer 29

sedative & hypnotic --> pentobarbital, amobarbital

Question 30

therapeutic effect of ULTRA short acting barbiturates?

Answer 30

IV induction of anesthesia --> thiopental

Question 31

MOA of pregabalin

Answer 31

- GABA analogue increases synaptic GABA --> GABA receptor mediated CL- current --> hyperpolarization - acts on voltage-gated Ca2+ channels

Question 32

SE of pregabalin

Answer 32

- assoc w worsening of suicidal thoughts

Question 33

Therapeutic effect of pregabalin

Answer 33

- treat GAD, also has anticonvulsant effect

Question 34

MOA of hydroxyzine

Answer 34

- first gen antihistamine; - anxiolytic effect: antagonism of serotonin 5-HT2 receptors - activity on a-adrenergic receptors as well

Question 35

Use of hydroxyzine

Answer 35

- low addictive potential (compared to BZD/barb) | - helps w itching and nausea manifestation of anxiety

Question 36

MOA of propanolol

Answer 36

BB: b-adrenergic receptor antagonist

Question 37

Use of propanolol

Answer 37

- treat performance anxiety and social phobias | - reduce PHYSICAL symptoms assoc w adrenergic activation

Question 38

CI of propanolol

Answer 38

asthma and heart conditions

Question 39

Other anxiolytics names:

Answer 39

NaSSA: Mirtazapine TCA: Clomipramine SSRI: fluoxetine, citalopram, sertraline, paroxetine SNRI: venlafaxine, duloxetine