Sedative, hypnotics, and anxiolytics Part 1

Question 1

Sedative

Answer 1

Calms anxiety, decreases excitement and activity, does not produce drowsiness, or impair performance

Question 2

Anxiolytic

Answer 2

Anti Anxiety, relieves anxiety without sleep or sedation

Question 3

Hypnotic

Answer 3

Induces sleep, implies restful, refreshing sleep, not “hypnotized!”, natural sleep

Question 4

Narcotic

Answer 4

Actually means “sleep producing”, now refers to opioids or illegal drugs

Question 5

Reticular formation

Answer 5

Extends through the central core of the medulla, pons, and midbrain

It is an intricate system composed of loosely clustered neurons in what is otherwise white matter

Question 6

Stages of sleep

Answer 6

Wakefulness

Non-rapid eye movement (NREM) slow-wave sleep

Rapid-eye movement (REM) sleep

Question 7

NREM Sleep

Answer 7

Stage 1 (dozing)
Stage 2 (unequivocal sleep)
Stage 3 (voltage increase, frequency decreases)
Stage 4 (delta waves)

Question 8

REM sleep

Answer 8

similar to awake in EEG

Question 9

Sleep deprivation

Answer 9

Total sleep
Delta sleep
REM

Question 10

Factors that regulate sleep

Answer 10

Age

Sleep history

Drug Ingestion

Circadian Rhythms: “Normal sleep cycle”

Question 11

Neurotransmitters

Answer 11

regulators of sleep

GABA: main target for current medication

Question 12

Neuromodulators

Answer 12

GH
Prolactin
Cortisol
Melatonin: “hormone of darkness”
Endogenous peptides

Question 13

GABAergic Neurotransmission

Answer 13

GABAa receptors
GABAb receptors
GABA Transporters
GABA-T (Transaminase)
SLIDE 11

Question 14

GABAa receptor/Chloride Ion Channel Complex

Answer 14

Orthostatic site: GABA alpha1 and beta2

Allosteric sites: benzodiazepines site alpha 1 and gamma 2

Barbiturate
Ethanol
Glucocorticoid

Channel pore (picrotoxin)

Most common

Question 15

Benzodiazepines

Answer 15

facilitate GABA action (alpha 1-5) increase frequency, require intact GABA system

Question 16

Non-benzodiazepines

Answer 16

zolpidem, zaleplon, eszopiclone–BZ1 receptors of alpha 1

Question 17

BZD antagonists

Answer 17

flumazenil, overdose treatment

Question 18

Inverse BZD agonists

Answer 18

B carbolines

Question 19

Ligands acting at “other” non-orthosteric sites

Answer 19

BZDs: Increase frequency of channel opening

Barbiturates: Increase duration of channel opening, and direct effects on GABAa

Alcohol: Enhances actions of GABA and GABAa receptor

GABA channel blockers: picrotoxin

Etomidate and Propofol: B2 and B3 subunit containing receptors

Neurosteroids for treating depression

Question 20

Structure activity relationships of benzodiazepines

Answer 20

1. Position alkylation