Sedative, hypnotics, anxiolytivs Dr.Yang

Question 1

Sedative

Answer 1

calms anxiety, decrease excitement and activity, dose not produce drowsiness, or impair performance

Question 2

Anxiolytic

Answer 2

antianxiety, releives anxiety without sleep or sedation

Question 3

Hypnotic

Answer 3

induces sleep

Question 4

narcotic

Answer 4

now refers to opioids or illegal drugs

Question 5

Reticular formation

Answer 5

Extends through the central core of the medulla oblongata, pons, and midbrain
composed of loosely clustered neurons in what is otherwise white matter
contains dopamine, adrenergic, serotonergic, and cholinergic neurons. regulates sleep-wake transition and synchronization of EEG

Question 6

Stages of sleep

Answer 6

wakefulness, non rapid eye movement, rapid eye movement
NREM
stage 1 - dozing
stage 2 - unequivocal sleep
stage 3 - voltage increase, frequency decrease
stage 4 - delta wave

REM sleep (similar to awake in EEG)

SLEEP DEPRIVATION - TOTAL SLEEP, DELTA SLEEP, REM

Question 7

Factors that regulate sleep

Answer 7

Age, sleep history, drug ingestion, circadian rhythms

Question 8

Biological regulators of sleep

Answer 8

Neurotransmitters: catecholaines, serotonin, histamine, achetylcholine, adenosine, GABA
Neuromodulators: growth hormone, prolactin, cortisol, melatonin, enndogenous peptides

Question 9

GABAergic neurotransmission

Answer 9

GABAa receptors
GABAb receptors
GABA transporters
GABA-T (transaminase)

Question 10

GABAa receptor/ chloride ion channel complex

Answer 10

Targets for sedative-hypnotics
Orthosteric site: GABA
Allosteric site: benzodiazepine (BZD) side (alpha1 and gamma2), Barbiturate, ethanol, glucocorticoid
Channel pore: picrotoxin

Question 11

Ligands acting at the BZD receptor

Answer 11

Benzodiazepines: facilitate GABA action (alpha 1-5) increase frequency, require intact gaba system
Non-benzodiazepines: solpidem (ambien), Zaleplon (sonata, Esczopiclone (lunesta) - BZ1 receptors of alpha 1
BZD: antagonists: flumazenil (romazicon)
inverse BZD agonists: B carbolines

Question 12

Ligands acting on other non-orthosteric sites

Answer 12

BZDs: increase frequency of channel opening
Barbiturtates: increase duration of channel opening and direct effects on GABAa
Alcohol: enhances action of GABA at GABAa receptor

Question 13

Benzodiazepines Chemistry and metabolism

Answer 13

• special structure : 1 position alkylation provides active metabolites
  annealating the 1-2 bond with an electron rich rish (triazole or imidazole) yields high affinity and decreases half life

Question 14

Slow elimination rate

Answer 14

Diazepam (valium) - treatment of convulsive disorders, accumulation of metabolies
Chloridazepoxide (librium) - 1st benzo used for alcohol withdrawal
Flurazepam (dalmane) - used as a hypnotic
Clorazepate (tranxene) - alcohol withdrawal, convulsive disorders, accumulation of metabolites
Quazepam (doral) - hynotic
prazepam - not available in US

Question 15

Intermediate elimination rates

Answer 15

Clonazepam (Klonopin)- used as an anticonvulsant
alprazolam (Xanax) - withdrawal symptoms can present if abrupt d/c
lorazepam (ativan) - used as an anxiolytic and as a hypnotic
oxazepam (serax) - used as an anxiolytic and for alcohol withdrawl
temazepam (restoril) - used as a short term hypnotic

Question 16

rapid elimination rates

Answer 16

Midazolam (versed) - rapid anesthesia
Triazolam (halcion, d/c) - used as a short term hypnotic

Question 17

Benzodiazepines usage

Answer 17

Slow elimination: active metabolies, accumulation, drowsiness and sedation, useful in patients who wake up

intermediate to rapid elimination: preferable in patients with hepatic problems, preferable in elderly patients, drugs that alter liver enzymes, rapid tolerance, rebound insomnia

Question 18

General considerations

Answer 18

Readily absorbed (can delay with food)
Have active metabolites or are converted to active forms
Increased lipid solubility will increase speed of delivery to brain
redistribution to highly perfused tissue may decrease duration of action
cross placental barrier and are detected in breast milk
extensive protein binding, but not clinically significant

Question 19

Dose response curves for denzos vd barbiturates

Answer 19

Barbiturates are dangerous because by increasing duration of gaba receptor it can cause coma if dose is too high it can put people into a coma
benzos increase frequency of receptor, so increasing dose will not lead to coma

Question 20

Benzodiazepines use

Answer 20

not as commonly used for sleep aid due to its possibilities to Decrease rem sleep and Decrease stage 3 and 4 which can make you drowsy throughout the day
more used for Anticonvulsant activity

Question 21

Side effects of benzos

Answer 21

Dose dependant
sedation, weakness, headache, vertigo, nausea, paradoxical effects

Question 22

Precautions and interactions with benzos

Answer 22

Other sedatives, alcohol
pregnancy and breast feeding

Question 23

Flumazenil (romazicon)

Answer 23

Benzodiazepine antagonist
used for benzo overdose
initial dose - 0.2mg IV / 30sec
max dose - 3mg
SE: induce convulsions, panic attacks, agitation, confusion, nausea and vomiting, headache

Question 24

Non-benzodiazepines

Answer 24

Act at BZD binding site
zolpidem (ambien)
short term treatment of insomnia
Zaleplon (sonata) - short term treatment of insomnia
Eszopiclone (lunesta) - long term use of insomnia
SE: daytime drowsiness, dizziness, ataxia, nausea, and vomiting, causes less negative effects on sleep patterns, warn your patients about sleep driving, sleep cooking, sleep eating, sleep sex

Question 25

Long acting barbiturates

Answer 25

Phenobarbital (luminal) - anticonvulsants

Question 26

Short to intermediate acting barbituates

Answer 26

Phetobarbital (nembutal), amobarbital (amytal)- used for sedative -hypnotics

Question 27

Ultra short acting barbiturates

Answer 27

IV anesthetics
Thiopental
methohexital
thiamylal
SE: respiratory depression

Question 28

Comparing BBT, BZD, and Z-hypnotics

Answer 28

BBT: bint to all GABAa alpha1-5 increase duration, and direct effects on GABA
Benzo: bind to all GABAa alpha1-5 increase frequency of GABA channel
Z-hypnotics: bind to GABAa BZ1 receptors of alpha1 increase frequency of GABA channel opening
*Flumazenil is used for over dose of benzo but not for barbiturates