Anxiolytic and Hypnotics

Question 1

Define sedative

Answer 1

Decreases activity
Moderates 
Excitement
Calms
-Doesn't put you to sleep though

Question 2

Define hypnotic

Answer 2

Produces drowsiness
Facilitates onset and maintenance of sleep that resembles natural sleep
Easily aroused sleep

Question 3

GABA is

Answer 3

Major inhibitory NT

Question 4

GABA(A)

Answer 4

Ligand operated

Permeable for Cl- which leads to hyperpolarization

Question 5

GABA(B)

Answer 5

Metabotropic receptor
Inhibits adenylate cyclase, reduces NT release
Mostly in SPINE
Not helpful for anxiety

Question 6

More Cl =

Answer 6

More inhibition = less anxiety

Question 7

**Benzodiazepines MOA

Answer 7

Potentiate the action of GABA which increases the flux of chloride which makes more pronounced hyperpolarization and less excitable neurons
DOES NOT DIRECTLY ACTIVATE GABA(A) RECEPTOR

Question 8

Flunitrazepam (BZ), pentobarbital and ethanol all

Answer 8

Cause sedation, CNS depression, anxiolysis and euphoria

Question 9

GABA(A) has

Answer 9

different subunits

Question 10

BZ are activators of which receptors

Answer 10

alpha 1/2/3/5 (not 4/6

Question 11

Alpha 6 involved in

Answer 11

motor and balance coordination

Question 12

Alpha 1 responsible for

Answer 12

Hypnotic/sedative
Anticonvulsant
Antergrade Amnesia

Question 13

Alpha 2 responsible for

Answer 13

Anxiolysis

Question 14

Pi pi stacking

Answer 14

Week form of bonding between groups when aligned parallel

Weak but multiple can be strong

Question 15

Benzodiazepines are strictly :

Answer 15

allosteric modulators of the GABA(A) receptor

DO NOT directly open the receptor

Question 16

What combination can be lethal?

Answer 16

Benzo and Alcohol

Question 17

Antidote of Benzodiazepines

Answer 17

Flumazenil

Question 18

Flumazenil MOA

Answer 18

Binds to GABA(A) receptor and competitively antagonizes BDZ

Question 19

Overall Effects of BDZ

Answer 19

Reduction of anxiety and aggression
Sedation (little suppression of REM)
Anti-convulsant effect
Anterograde amnesia
Paradoxical effect (excitation)

Question 20

PK of BDZ

Answer 20

Lipophilic
Liver
Active metabolites
No enzymes

Question 21

Dizepam –>

Answer 21

Temazepam –> Oxazepam

Question 22

Dexomoxepam –>

Answer 22

Diazepam

Question 23

Prazepam –>

Answer 23

Diazepam

Question 24

Short half life BZs

Answer 24

Triazolam

Oxazepam

Question 25

Intermediate half life of BZ

Answer 25

Estazolam Temazepam Lorazepam Alprazolam

Question 26

Long half life of BZ

Answer 26

``` Flurazepam Diazepam Quazepam Nitrazepam Clonazepam ```

Question 27

Rapid onset BZ

Answer 27

``` Triazolam Estazolam Flurazepam Diazepam Quazepam Nitrazepam Clonazepam ```

Question 28

Slow onset BZ

Answer 28

Oxazepam | Temazepam

Question 29

Intermediate onset of BZ

Answer 29

Lorazepam | Alprazolam

Question 30

Overall side effects BZ

Answer 30

``` Daytime sedation Reduction of reaction time Ataxia, falls COGNITIVE DEFICITS Addictive!!! ```

Question 31

BZ Approved for Insomnia

Answer 31

Flurazepam and Quazepam (long half life) Triazolam (short) Estazolam and temazepam (int)

Question 32

Problem with ultra-long half-life

Answer 32

Sleep through the night and then sleep through the day | Then you take another and it keeps increasing until its toxic

Question 33

Problem with ultra-short half-life

Answer 33

Fall off around 3-4 hours so then you wake up

Question 34

Problem with moderate half-life

Answer 34

Stay during the day and you have a hangover effect

Question 35

Zolpidem is what?

Answer 35

Non-BZ hypnotic (Z drugs) | Selective for alpha 1 subunit (which is great)

Question 36

Zolpidem effects

Answer 36

Pronounced sedative | Onset: 15 minutes and last for 2-3 ours

Question 37

Other Z drugs

Answer 37

Zaleplon (1 hr) and Eszopiclone (6 hr)

Question 38

Thiopental

Answer 38

Pentothal | Induction of anesthesia

Question 39

Pentobarbital

Answer 39

Nembutal

Question 40

Secobarbital

Answer 40

Seconal Pre-OP sedation Insomnia

Question 41

Phenobarbital (luminal)

Answer 41

Anti-consulvant

Question 42

Barbiturates PD PK

Answer 42

High doses: open the channel directly (overdose) | Strong induction of P450s so drugdrug interactions

Question 43

Acute effects of barbiturates

Answer 43

``` Strong sedation Some anticonvulsants No anxiety Suppresses REM Repiratory and CV depression at high doses Paradoxical excitement ```

Question 44

BZ as drug of choice... But why?

Answer 44

``` High therapeutic index Few peripheral effects Low tolerance Low dependence Few drug interaction No respiratory depression (death) ```

Question 45

Ramelteon is a

Answer 45

Melatonin MT1/2 receptor agonist Extensive first pass Cyp1A2 which is induced in smokers MEEEEHHHH

Question 46

Belsomra

Answer 46

``` Suvorexant Orexin antagonist (NT protein that regulate arousal and wakefulness) ```

Question 47

Belsomra AE

Answer 47

Daytime somnolence Suicidal thinking COPD Sleep paralysis, hallucinations

Question 48

Belsomra Interactions

Answer 48

Digoxin | CYP3A