sedative hypontic drugs

Question 1

barbituate vs benzos dose response relationship curves

Answer 1

barb: linear
benzo: non-linear (safer)

Question 2

benzodiazepines MOA

Answer 2

bind GABA(a) - between alpha and gamma subunit (BZ1 and BZ2)

GABA(a) is a chloride channel - activated by inhibitory GABA

increase in FREQUENCY of chloride influx

allosteric enhancement of GABA effect

Question 3

benzo receptor agonist, antagonist, inverse agonist

Answer 3

agonist: **positive allosteric modulators
antagonist: flumazenil (blocks benzo action)

inverse agonist: negative allosteric modulators of GABA (oppose GABA - cause anxiety and seizures) - only experimental drugs

Question 4

benzo actions

Answer 4

reduce anxiety
sedative and hypnotic actions
anticonvulsant
muscle relaxant
anesthesia

Question 5

benzo PK

Answer 5

lipophilic
various duration of actions
short, intermediate, long acting

Question 6

diazepam: short, intermed, long acting?

Answer 6

long 1 -3 days

Question 7

flurazepam: short, intermed, long acting?

Answer 7

long 1 - 3 days

Question 8

alprazolam: short, intermed, long acting?

Answer 8

intermediate: 10-20 hours

Question 9

lorazepam: short, intermed, long acting?

Answer 9

intermediate: 10-20 hours

Question 10

temazepam: short, intermed, long acting?

Answer 10

intermediate: 10-20 horus

Question 11

oxazepam: short, intermed, long acting?

Answer 11

short 3-8 hours

Question 12

triazolam: short, intermed, long acting?

Answer 12

short 3-8 hours

Question 13

all benzo’s undergo phase 1 by CYP3A4 except which 3 drugs

Answer 13

oxazepam
lorazepam
temazepam

good to use in pt with poor liver function or those with poor P450 function

Question 14

desmethyldiazepam

Answer 14

t 1/2 of >40 hours = active metabolite of several benzo’s

metabolized into oxazepam

Question 15

flurazepam

Answer 15

oxidized by liver enzymes to active metabolites with long half lifes (30-100 hours)

Question 16

diazepam use

Answer 16

muscular disorder

Question 17

benzo use for seizures

Answer 17

clonazepam

lorazepam and diazepam: status epilepticus

Question 18

tx drug withdrawal

Answer 18

diazepam
oxazepam

for etoh withdrawal

Question 19

benzo use for sleep disorders

Answer 19

flurazepam - long acting
temazepam - intermediate
triazolam - short

Question 20

benzo AE

Answer 20

drowsiness/confusion
ataxia
cognitive impariment

pysch effects = irritable, hostile, paranoia

dependence - withdrawal = confusion, agitation, insomnia

Question 21

flumazenil

Answer 21

only benzo receptor antagonist

reverses CNS depressant effects of benzo OD

Question 22

flumazenil PK

Answer 22

rapid onset, short duration (half life 1 hour)

for OD tx = keep giving flumazenil to maintain reversal

may precipitate withdrawal

Question 23

barbituates

Answer 23

less used b/c AE - tolerance, P450 inducers, coma

Question 24

barbituate MOA

Answer 24

(not as selective as benzo’s)

GABA(a) receptors - enhance transmission

increase DURATION of opening of chloride channels

also block glutamate receptors and sodium channels

Question 25

barbituate dose vs action

Answer 25

low - sedation

high - hypnosis

– anesthesia, coma, death

Question 26

barbituate action

Answer 26

resp depression: suppress hypoxic and chemoreceptor response to CO2

induces P540

anesthesia: thiopental
anticonvulsant: phenobarbital

Question 27

barbituate AE

Answer 27

drowsiness
paradoxical excitement
hypersensitivity
resp depression

• may worsen pain
• severe withdrawal

Question 28

zolpidem

Answer 28

non-benzo benzodiazepine receptor agonist

short duration - 1.5 - 3.5 hr half life

use: short term tx of insomnia

Question 29

zaleplon

Answer 29

non-benzo benzodiazepine receptor agonist

half life - 1 hour

use: short term insomnia tx

Question 30

eszopliclone

Answer 30

non-benzo benzodiazepine receptor agonist

s-enantiomer of zopiclone

tx: insomnia - decreases sleep latency AND improves sleep maintenance

half life - 6 hours (longer half life of z drugs)

Question 31

non-benzo benzodiazepine receptor agonist

Answer 31

act only at BZ1 subtype receptor

hypnotic
minimal muscle relaxant and anticonvuslant effects
little tolerance
dec AE

Question 32

5HT1a partial agonist

Answer 32

buspirone

Question 33

buspirone

Answer 33

5HT1a partial agonist

only anxiolytic effects (no hypnotic, anticonvulsant, relaxant)

use= anxiety disorders

onset - 2 to 3 weeks (MOA analogous to antidepressants)

Question 34

buspirone advantages

Answer 34

less psychomotor impairment
no drug interactions with EtOH, benzos, sedatives

no rebound anxiety or withdrawal signs

no dependence

Question 35

ramelteon

Answer 35

melatonin receptor agonist
at MT1 and MT2 receptors

tx: insomnia with difficult sleep onset

Question 36

hydroxyzine

Answer 36

antihistamine + antiemetic activity

sx relief of anxiety

Question 37

propanolol

Answer 37

performance anxiety

clonidine may also help with autonomic expression of anxiety

Question 38

other classes…

Answer 38

diphenhydramine
doxylamine

nonprescrip anti-histamines = tx mild insomnia