Anxiety and Sleep disorder patho

Question 1

Sedative

Answer 1

-calms anxiety
-dec excitement/activity
-does not produce drowsiness or impair performance

Question 2

Anxiolytic

Answer 2

-antianxiety
-relieves anxiety w/o sleep or sedation (not all are sedatives)

Question 3

Hypnotics

Answer 3

-induces sleep
-restful, refreshing sleep
-natural sleep

Question 4

Narcotic

Answer 4

-sleep producing
-opioids or illegal drugs

Question 5

Reticular formation

Answer 5

-extends through central core of medulla, pons, and midbrain
-system of loosely clustered neurons in what is otherwise known as white matter
-DA, adrenergic, serotonergic, cholinergic
-sleep-wake

Question 6

Stages of sleep

Answer 6

-wakefulness
-non-rapid eye movement (NREM)
-REM (similar to awake in EEG)

Question 7

NREM stages

Answer 7

1. dozing
2. unequivocal sleep
3. voltage inc, freq dec
4. delta waves

Question 8

Sleep deprivation

Answer 8

-total sleep
-delta sleep
-REM

Question 9

Factors that regulate sleep

Answer 9

-age (dec w age bc changes in reticular formation)
-sleep history (rebound REM)
-drug indigestion (acute and withdrawal rebound effects)
-circadian rhythyms

Question 10

Circadian rhythm

Answer 10

-awake
-deep sleep alternating w REM dreaming sleep

Question 11

Chronopharmacology

Question 12

Biological regulators of sleep

Answer 12

-Neurotransmitters
-Neuromodulators

Question 13

Neurotransmitters involved in sleep regulation

Answer 13

-catecholamines (NE, EPI, DA)
-serotonin
-histamine
-ACh
-adenosine
-GABA (main target)

Question 14

Neuromodulators that regulate sleep

Answer 14

-growth hormone
-prolactin
-cortisol
-melatonin
-endogenous peptides

Question 15

GABAergic neurotransmission

Answer 15

-GABA A and B receptors
-transporters (GAT-1)
-GABA-T (transaminase)

Question 16

GABA A receptor

Answer 16

-pentameric structure
-5 subunits from several polypeptide classes (a,B,y,delta,e, pi, theta, smth else)

Question 17

GABA A receptor subtypes

Answer 17

?

Question 20

GABA A receptor/Chloride ion channel complex

Answer 20

-orthosteric site: GABA (a1 and B2)

-allosteric sites: benzodiazepine site: a1 and y2
-barbituate
-ethanol
-glucocorticoid
-?

-channel pore (picrotoxin

Question 21

Benzodiazepines acting at BZD receptor

Answer 21

-facilitate GABA action
-inc freq!
-require intact GABA system (internal safety system)

Question 22

Non-benzos (Z-hypnotics) at the BZD receptor

Answer 22

-BZ1 receptors of a1
-include: zolpidem, zaleplon, eszopiclone

Question 23

BZD antagonists

Answer 23

-flumazenil
-OD tx

Question 24

Inverse BZD agonists

Answer 24

-B carbolines

Question 25

Allosteric modulator MOA

Question 26

Ligands modulating GABA A receptor at other non-orthosteric sites

Answer 26

-BZDs: inc freq of channel opening
-barbiturates inc duration of channel opening and direct effects on GABA (high doses)
-alcohol: enhances actions of GABA at GABA A receptor
-GABA channel blockers: picrotoxin
-etomidate and propofol (diprovan/milk of magnesia): B2 and B3 subunit containing receptors
-Neurosteroids (progesterone) for tx depression

Question 27

Benzodiazepine SAR

Answer 27

-1 position alkylation!=source of active metabolites
-2 position NH2 or N(CH3)2 is active, oxo is active
-3 position has dec activity, 3-OH rapid excretion
-4-nonoxide is active
-sub on 5-phenyl has dec activity
-7 position w electronegative group is good
-annealating 1-2bond w electron rish ring (triazole or imidazole) yields high affinity and dec half-life

Question 28

Metabolism of diazepam

Answer 28

-long-half life
-slide 19

Question 29

Benzodiazepines w intermediate and rapid elimination rates

Answer 29

-slide 19

Question 30

Biotransformation of benzos

Answer 30

-slide 20

Question 32

Drugs w slow elimination rates

Answer 32

-all have active metabolites
-chlordiazepoxide
-diazepam?
-flurazepam
-clorazepate
-quazepam
-prazepam

Question 33

Diazepam

Answer 33

-slow elimination rate
-benzo
-tx convulsions (sz), accumulation of metabolites