ANXIOLYTICS & HYPNOTICS

Question 1

anxiety

Answer 1

an unpleasant emotional state characterized by fearfulness / distressing physical symptoms

CNS: worry, fear, obsession, rumination
PNS: sweating, tremors, tachycardia, vomiting

often connected with phobias, PTSD, OCD

Question 2

basis of anxiety

Answer 2

hypoactive (inactive) GABA receptors

inappropriate upregulation of CNS serotonergic neurons

overactivity of adrenergic neurons (cns/pns)

Question 3

what strongly innervates the hippocampus

Answer 3

serotonergic neurons

Question 4

what are anxiolytics

Answer 4

drugs that provide relief from symptoms of anxiety

Question 5

what are some anxiolytics

Answer 5

1. BENZODIAZEPINES - allosteric agonists on GABAa
2. modulators of SEROTONIN transmission
   (either increase /decrease)
3. B- ADRENERGIC receptor ANTAGONISTS
   (physical symptoms - b1 affect the heart)

Question 6

BENZODIAZEPINES

Answer 6

DIAZEPAM
. anxiolytic, hypnotic, anticonvulsant
. IV GE
. muscle relaxant 
= short-term treatment 

drug bings allosterically to GABAa R - increase binding of GABA to its normal binding site
=MORE FREQUENT opening of Cl- channels
=enhancement of inhibitory GABA response

Question 7

hypnotic

Answer 7

sleep-inducing

Question 8

what are benzodiazepines

Answer 8

allosteric agonists - bind to GABA R at a site distinct from binding site
= locks GABA b.s into confirmation where GABA can bind

inverse agonists (B-carboline)- lock GABA b.s into form that doesn’t favour GABA binding

Question 9

side effects of benzodiazepines

Answer 9

1. tolerance
2. physical dependance = rebound anxiety WORSE!
3. sedative effects
4. retrograde(before onset)/anterograde(while) AMNESIA
5. psychomotor effects (loss of coordination)

Question 10

how is diazepam metabolized into an active compound

Answer 10

by C450 enzyme
Diazepam (half-life 1-3 days)
» NORDAZEPAM (half-life 2-7 days)
half-life doubled in elderly = slower metabolism

Question 11

serotonin 5-HT has both excitatory/inhibitory functions

Answer 11

*chemical mediator in both CNS (behavioral effects)
PNS (vasoconstriction/dilation, platelet aggregation)
larger differences in receptor expression

Question 12

5-HT1A receptor

Answer 12

The 5-HT1A receptor = subtype of serotonin receptor located in presynaptic and postsynaptic regions
Activation of this receptor has been involved in the mechanism of action of anxiolytic, antidepressant and antipsychotic medications

Question 13

SSRI’s

Answer 13

Selective serotonin reuptake inhibitors (SSRIs)

= increase serotonin in synapse

Question 14

describe serotonin neurotransmission

Answer 14

Gs - stimulate adenylate cyclase = increase cAMP
Gi - inhibit adenylate cyclase = decrease cAMP
Gq - direct activator of protein kinase C

Question 15

modulators of serotonin transmission F

Answer 15

FLUOXETINE
. SSRI
. blocks SERT: prevents 5-HT uptake = increases serotonin in synaptic cleft
. treatment for chronic anxiety/depression

side effects:
sexual, anxiety, headache, insomnia, sedation

Question 16

modulators of serotonin transmission B

Answer 16

BUSPIRONE
. used for short/long term treatment of anxiety
. partial agonist at postsynaptic 5-HT1A
. full agonist at presynaptic autoinhibitory receptors
= Reduces activity of CNS serotonergic pathways
= antagonist of dopamine D2 receptors

side effects:
. no sedative/loss of coordination/ little risk of physical dependence
. doesn’t treat PNS symptoms

Question 17

B1- ADRENERGIC RECEPTOR ANTAGONISTS

Answer 17

PROPRANOLOL
. treats PNS symptoms of axiety
. competitive inhibitor of B-adrenergic receptors

side effects:
well-tolerated (// cardiac insufficiency, hypoglycemia, bradycardia, asthma)
- treats high BP as a result of decreasing HR

Question 18

BARBIUATES

Answer 18

GABA enhancers (bind different site to benzodiazepines)
. promote INCREASED DURATION of Cl- channel opening
. LOW TI (suppress CNS)
. serious problems with tolerance/dependence
NOT used

Question 19

other drugs to treat anxiety

Answer 19

monamine oxidase inhibitors (MAOI)

tricyclic antidepressants (TCAs)

future drugs: more selective 5-HT modulators
CRF antagonists = decrease cortisol

Question 20

comparison of anxiolytics

Answer 20

Benzodiazepines 
. fast onset -immediate symptom relief 
. produce tolerance/dependence 
. sedative/amnesic side effects 
. high potential for abuse

Fluoxetine/ Buspirone
. slow onset 
. most effective for general anxiety 
. few serious side effects
. treat comorbid depression

B-adrenergic anatagonists
. treat physical symptoms
. non-sedating/ few side effects

Question 21

sleep disorders

Answer 21

1. insomnia - state of wakefulness during normal sleep time
2. hypersomnia - excessive sleep
   - Narcolepsy - sudden periods of deep sleep that occur during normal wake hours

Question 22

describe stages of normal sleep

Answer 22

1. NonREM sleep = Serotonin + GABA
2. REM sleep = ACh + NE

normal sleep = repeated patterns of REM/NonREM sleep

Question 23

treatment of insomnia

Answer 23

1. BENZODIAZEPINES
   - decrease time taken to enter sleep
   - increase duration of sleep
   - inhibit REM sleep
   (habituation/dependance - not for long-term)

Question 24

other anti-insomnia drugs

Answer 24

2. ZOLPIDEM - non-benzodiazepine GABA R agonist
   . no effect on REM sleep / ineffective as anxiolytic
   . therapeutic effect long lasting
   . psychological dependence (hallucinations)
3. barbituates - reduces REM sleep - not used
4. choral hydrate - rarely used ^
5. Antihistamines - dry mouth
6. THC - decreases sleep latency + REM sleep

Question 25

2 modulators of serotonin transmission

Answer 25

fluoxetine

buspirone