Anxiolytics & Hypnotics

Question 1

What is the definiton for anxiolytic?

Answer 1

Reduces anxiety

Question 2

What is the definiton of hypnotic?

Answer 2

Assists sleep (also called soporifics)

Question 3

What is the definition of relaxants?

Answer 3

Usually mean muscle relaxants

Question 4

Minor tranquillisers are AKA

Answer 4

Sedatives

Question 5

Major tranquillisers are AKA

Answer 5

Antipsychotics

Question 6

What is anxiety?

Answer 6

Normal human emotional state: we have things we rationally need to worry about.

Question 7

The difference between normal and pathological anxiety is not clear, true or false?

Answer 7

True

Question 8

What are the two concepts of anxiety?

Answer 8

Fear

Generalised anxiety

Question 9

What are the different types of anxiety disorders?

Answer 9

• Panic disorder
• Social anxiety disorder (SAD)
• Phobias
• Obsessive-compulsive disorder (OCD)
• Generalised anxiety disorder (GAD)
• Post-traumatic stress disorder

Question 10

What part of the brain is responsible for anxiety & emotional processes ?

Answer 10

Amygdala & prefrontal cortex (PFC)

Question 11

In anxiety disorders, what happens in the brain?

Answer 11

Dysfunctional PFC-amygdala communication

Amygdala hyperactivity

Question 12

Amygdala hyperactivity is associated with?

Answer 12

Anxiety

Question 13

5-HT associated with

Answer 13

Mood stability

Question 14

What are the pharmacological strategies for Anxiolytics?

Answer 14

Increased monoaminergic / serotinergic activity:
Antidepressants, especially SSRIs
5-HT1A agonists (buspirone)
Atypical antipsychotics

Increase GABAergic (inhibitory) activity:
           GABAA receptor stimulation

Question 15

What are the other options for anxiolytics?

Answer 15

Beta-blockers (propranolol) for physical symptoms

Pregabalin

Ketamine? Cannabidiol?

Question 16

Main anxiolytics drugs used are?

Answer 16

Antidepressants drugs (5-HT) - Work through monoaminergic (esp. serotonergic) pathways

Question 17

5-HT antidepressant drugs in anxiolytics are poor at dealing with?

Answer 17

Acute anxiety attacks

Question 18

What are the preferred antidepressants as anxiolytics?

Answer 18

SSRIs preferred (e.g. sertraline, citalopram, fluoxetine)

Question 19

Antidepressants as anxiolytics are effective against?

Answer 19

generalised anxiety, phobias, social anxiety disorder and post-traumatic stress

may also treat depression associated with anxiety

Question 20

Buspirone, function and effect?

Answer 20

5-HT1A partial agonist

• Used for general anxiety states; weak for panic attacks and severe anxiety. No antidepressant action.
• Clinical effects not observed for up to 2 weeks.
• Also binds to dopamine receptors; possible function in anxiety unclear

Question 21

Most common GABAA receptors subunit combination is?

Answer 21

a1b2g2

Question 22

In GABAA receptors, a1 subunits more associated with?

Answer 22

Hypnotic effects

Question 23

In GABAA receptors, a2/3 subunits more associated with?

Answer 23

Anxiolytics effects (amygdala)

Question 24

What are Benzodiazepines?

Answer 24

BDZs are GABAAR positive allosteric modulators; increase likelihood of channel opening

Question 25

What happens when benxodiazepines ( i.e. diazepam) binds to GABA

Answer 25

With GABA bound, receptor flits between open and closed states > more CL- enter

Question 26

GABAA receptors are ionotropic, which means?

Answer 26

Cl- channels

Question 27

Administration and use of Benzodiazepines

Answer 27

Orally active Useful for acute anxiety; fast acting (~30 mins)

Question 28

All BDZs largely identical in side effects True or false

Answer 28

True

Question 29

Therapeutic use of benzodiazepines are determined by duration of effect: long lasting? Medium acting? Short acting?

Answer 29

Long lasting – anticonvulsants, anxiolytics Medium acting – anxiolytics Short acting – anxiolytics, hypnotics

Question 30

Side effects of benzodiazepines in abuse, dependency, tolerance, overdose & toxicity

Answer 30

Abuse: calming, dream state, also + alcohol Dependency: withdrawal rebound anxiety: hallucinations, tremor, seizures Tolerance: downregulation of a2-containing GABAARs? OD & toxicity: relatively safe except with alcohol. Treat with flumazenil, BDZ site antagonist

Question 31

Side effects of benzodiazepines

Answer 31

Side effects: Well tolerated; drowsiness, confusion, amnesia, loss of co-ordination, enhancement of other depressants

Question 32

Diazepam

Answer 32

Anxiolytic, muscle relaxant, anticonvulsant. ~70% of BDZ prescriptions

Question 33

Clobazam

Answer 33

Anticonvulsant only

Question 34

Clonazepam

Answer 34

Anticonvulsant – very uncommon as anxiolytic

Question 35

Midazolam

Answer 35

Ultra-short-acting, i.v. surgical sedation, i.v. anaesthesia induction (rare), i.v. anticonvulsant oral hypnotic (rare in UK)

Question 36

Some old literature may refer to “benzodiazepine receptors”. These are AKA?

Answer 36

GABAA receptors

Question 37

What is used for benzodiazepines overdose?

Answer 37

Flumazenil

Question 38

What was the preferred medication for anxiolysis before BDZs?

Answer 38

Barbiturates

Question 39

Barbiturates are very similar in MoA and effects to but more powerful?

Answer 39

Benzodiazepines

Question 40

Side effects of Barbiturates

Answer 40

Higher abuse risk Higher addiction risk Dangerous in OD

Question 41

What benzodiazepines drugs can be used as hypnotics?

Answer 41

“Z-drugs”: e.g. zolpidem, zopiclone & zaleplon

Question 42

moa of “Z-drugs”?

Answer 42

Structurally dissimilar, but bind to same site as BDZs Only active at a1 subunit-containing GABAARs. Hypnotic >>> anxiolytic Ultrashort duration (<4h)

Question 43

Side effects of “z drugs”

Answer 43

tolerance & dependency, abuse risk

Question 44

Which Z drug is thought to improve function after brain damage?

Answer 44

Zolpidem

Question 45

Diazepam subunit selectivity

Answer 45

a1, a2, a3, a4, a5, a6

Question 46

Flunitrazepam subunit selectivity

Answer 46

a1, a2, a5

Question 47

Midazolam subunit selectivity

Answer 47

a1, a2, a3, a4, a5, a6

Question 48

Flumazenil subunit selectivity

Answer 48

(antagonist) a1, a2, a3, a4, a5, a6

Question 49

Zolpidem subunit selectivity

Answer 49

a1