20 - Sedatives, hypnotics and anxiolytics

Question 1

What is sedation

Answer 1

Reduction in excitement, vigilance and physiological arousal so that the person is relaxed, calm and possibly sleepy

Question 2

What is hypnosis

Answer 2

Ability to induce drowsiness and sleep

Question 3

What do lesions of the anterior hypothalamus cause

Answer 3

Insomnia

Question 4

What do lesions of the posterior hypothalamus cause

Answer 4

somnolence

Question 5

What systems are part of the ARAS

Answer 5

NorA
5HT
ACh
DA
HA
Orexin

Question 6

What systems are sleep promoting

Answer 6

GABA
Adenosine
Melatonin

Question 7

What is insomnia

Answer 7

Unsatisfactory sleep onset, maintenance or early waking

Question 8

What are some treatments for insomnia (5-6)

Answer 8

COGNITIVE BEHAVIOURAL THERAPY
PHARMACOTHERAPY
Barbiturates
Benzodiazepines
z-drugs
Melatonin
Antihistamines

Question 9

Why did benzodiazepines replace barbiturates

Answer 9

Lower risk of abuse, overdose and induction of liver enzymes

Question 10

How do benzodiazepines help with insomnia

Answer 10

Promote onset of sleep and ongoing sleep

Question 11

What are most GABAA receptors made of

Answer 11

2 a, 2b and 1 y

Question 12

What will the y subunit be replaced with in different brain regions

Answer 12

d, e and t

Question 13

What subunits are benzodiazepines selective for

Answer 13

a1, a2, a3, a5

Question 14

Benzo vs barbiturate action

Answer 14

Increase affinity and no. of openings vs

Increase length opening and increase channel

Question 15

Are benzos active without GABA

Answer 15

No, but boosts GABA response

Question 16

What are the clinical effects of benzodiazepines

Answer 16

Hypnotic
Sedative
Anxiolytic
Amnesic
Antiepileptic
(Produce strange sleep behaviours)

Question 17

What are some benzodiazepine sensitive GABAA receptor brain regions

Answer 17

Amygdala
Prefrontal cortex
Hypothalamus
Striatum
Bed nucleus of striatum
Hippocampus

Question 18

What does the a1 subunit mediate

Answer 18

Sedation
Hypnosis
Anticonvulsion

Question 19

What do the a2 and a3 subunits mediate

Answer 19

Anxiolysis

Question 20

What do the a3 and a5 subunits mediate

Answer 20

Myorelaxation

Question 21

What are z-drugs

Answer 21

Chemically not benzodiazepines but act at BZ site

Question 22

What are the effects of Z-drugs

Answer 22

Same benefits and problems of BZ

Possibly less memory/cognition side effects, shorter half life (no daytime sedation)

Question 23

Which subunit do z-drugs show some preference for

Answer 23

a1

Question 24

What are some issues with benzodiazepines

Answer 24

Ongoing use
Tapered stopping
Dependence liability
Strange sleep behaviours
Amnesiac 
Falls in elderly
Combining with other sedatives

Question 25

How do antihistamines help with insomnia

Answer 25

Histamines are arousing

Question 26

What are first generation antihistamines

Answer 26

H1 inverse agonist

Question 27

Why do antihistamines cross the BBB

Answer 27

Lipophillic | LMW, not PGP target

Question 28

What are side effects of antihistamine

Answer 28

``` Dry mouth Constipation Blurred vision Urinary retention More daytime sedation Fog Memory issues even when drug no longer present ```

Question 29

Where is endogenous melatonin synthesised

Answer 29

Pineal gland

Question 30

What reduces melatonin production

Answer 30

Light, via thalamus, reduces melatonin production

Question 31

What are the two receptors for melatonin

Answer 31

2 GPCR MT1 MT2

Question 32

What are the two functions of the two melatonin receptors

Answer 32

MT1 - sleep onset | MT2 - circadian timing

Question 33

What is a synthetic analogue of melatonin

Answer 33

Ramelteon

Question 34

Which neurotransmitters are activating

Answer 34

NorA, 5HT, ACh, DA, HA, Orexin

Question 35

Which neurotransmitters are sleep promoting

Answer 35

GABA, adenosine and melatonin

Question 36

What is fear

Answer 36

Threatening stimulus: | State of preparation for danger and results in arousal, vigilance, increased ability to respond and negative feelings

Question 37

What is anxiety

Answer 37

State of preparation for danger and results in arousal, vigilance, increased ability to respond and negative feelings BUT NO immediate threatening stimulus

Question 38

What is the criteria for anxiety

Answer 38

Patients have to experience symptoms causing significant personal distress with associated impairment in function

Question 39

What appears to play a central role in anxiety

Answer 39

Amygdala activity up-regulated | Issues with synaptic plasticity

Question 40

What are treatments for anxiety

Answer 40

``` Cognitive and behavioural therapy Benzodiazepines Selective serotonin reuptake inhibitors Serotonin/noradrenaline reuptake inhibitors Tricyclics Pregabalin Buspirone ```

Question 41

What is the first line of treatment for anxiety

Answer 41

Benzodiazepines

Question 42

What are pros and cons of benzodiazepines

Answer 42

+ act rapidly | - dependence potential, drowsiness

Question 43

Which benzodiazepines are used for anxiety

Answer 43

Alprazolam | Clonazepam

Question 44

Which drugs are not a good choice for anxiety

Answer 44

'z drugs'

Question 45

Where is serotonin released from

Answer 45

Raphe nuclei

Question 46

What do serotonin axon projections influence

Answer 46

``` Sleep Arousal Attention Sensory processing in the cortex Emotion Mood ```

Question 47

What are some SSRIs for anxiety

Answer 47

Fluoxetine and paroxetine

Question 48

What is the first treatment for most anxiety disorders

Answer 48

SSRIs

Question 49

What are pros and cons of SSRIs

Answer 49

``` Pros: Less side effects May allow dual treatment for depression Cons: Very slow to act Sometimes side effects difficult Have discontinuation syndrome ```

Question 50

What are some other anxiolytics

Answer 50

Serotonin/noradrenaline reuptake inhibitors Other antidepressants Pregabalin (GABA analgoue) Buspirone (Partial 5HT1A agonist for treatment of GAD) Alcohol