sedative hypontic drugs Flashcards
barbituate vs benzos dose response relationship curves
barb: linear
benzo: non-linear (safer)
benzodiazepines MOA
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
benzo receptor agonist, antagonist, inverse agonist
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
benzo actions
reduce anxiety sedative and hypnotic actions anticonvulsant muscle relaxant anesthesia
benzo PK
lipophilic
various duration of actions
short, intermediate, long acting
diazepam: short, intermed, long acting?
long 1 -3 days
flurazepam: short, intermed, long acting?
long 1 - 3 days
alprazolam: short, intermed, long acting?
intermediate: 10-20 hours
lorazepam: short, intermed, long acting?
intermediate: 10-20 hours
temazepam: short, intermed, long acting?
intermediate: 10-20 horus
oxazepam: short, intermed, long acting?
short 3-8 hours
triazolam: short, intermed, long acting?
short 3-8 hours
all benzo’s undergo phase 1 by CYP3A4 except which 3 drugs
oxazepam
lorazepam
temazepam
good to use in pt with poor liver function or those with poor P450 function
desmethyldiazepam
t 1/2 of >40 hours = active metabolite of several benzo’s
metabolized into oxazepam
flurazepam
oxidized by liver enzymes to active metabolites with long half lifes (30-100 hours)
diazepam use
muscular disorder
benzo use for seizures
clonazepam
lorazepam and diazepam: status epilepticus
tx drug withdrawal
diazepam
oxazepam
for etoh withdrawal
benzo use for sleep disorders
flurazepam - long acting
temazepam - intermediate
triazolam - short
benzo AE
drowsiness/confusion
ataxia
cognitive impariment
pysch effects = irritable, hostile, paranoia
dependence - withdrawal = confusion, agitation, insomnia
flumazenil
only benzo receptor antagonist
reverses CNS depressant effects of benzo OD
flumazenil PK
rapid onset, short duration (half life 1 hour)
for OD tx = keep giving flumazenil to maintain reversal
may precipitate withdrawal
barbituates
less used b/c AE - tolerance, P450 inducers, coma
barbituate MOA
(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
barbituate dose vs action
low - sedation
high - hypnosis
– anesthesia, coma, death
barbituate action
resp depression: suppress hypoxic and chemoreceptor response to CO2
induces P540
anesthesia: thiopental
anticonvulsant: phenobarbital
barbituate AE
drowsiness
paradoxical excitement
hypersensitivity
resp depression
- may worsen pain
- severe withdrawal
zolpidem
non-benzo benzodiazepine receptor agonist
short duration - 1.5 - 3.5 hr half life
use: short term tx of insomnia
zaleplon
non-benzo benzodiazepine receptor agonist
half life - 1 hour
use: short term insomnia tx
eszopliclone
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)
non-benzo benzodiazepine receptor agonist
act only at BZ1 subtype receptor
hypnotic
minimal muscle relaxant and anticonvuslant effects
little tolerance
dec AE
5HT1a partial agonist
buspirone
buspirone
5HT1a partial agonist
only anxiolytic effects (no hypnotic, anticonvulsant, relaxant)
use= anxiety disorders
onset - 2 to 3 weeks (MOA analogous to antidepressants)
buspirone advantages
less psychomotor impairment
no drug interactions with EtOH, benzos, sedatives
no rebound anxiety or withdrawal signs
no dependence
ramelteon
melatonin receptor agonist
at MT1 and MT2 receptors
tx: insomnia with difficult sleep onset
hydroxyzine
antihistamine + antiemetic activity
sx relief of anxiety
propanolol
performance anxiety
clonidine may also help with autonomic expression of anxiety
other classes…
diphenhydramine
doxylamine
nonprescrip anti-histamines = tx mild insomnia
