sedative hypnotics Flashcards
intermediate-acting benzodiazepines
Use: perioperative medication, IV sedation, supression of seizures
-highly lipid soluble so enters the CNS readily
produces sedation (anxiolytic) at low doses and drowsiness at higher doses (hypnotic)
half-life: 6-24 hrs
Reversed by flumazenil, but its duration of action is 20 min and resedation may occur
-midazolam can be used by continuous infusion, because it has a shorter halftime; decreases systemic bp exacerbated by hypovolemia
-decrease CMRO2
-minimal respiratory depression
alprazolam (Xanax)
oxazepam (Serax)
lorazepam (Ativan)
short-acting benzodiazepine produces sedation (anxiolytic) at low doses and drowsiness at higher doses (hypnotic)
triazolam (Halcion)
long-acting active metabolite of benzodiazepines: chlordiazepoxide & diazepam
desmethyldiazepam
long-acting benzodiazepines
half-life: > 24 hrs
MOA: binds to BZ binding site on GABAa receptor and allosterically enhances the action of GABA, increasing Cl- conductance by increasing the frequency of channel opening resulting in hyperpolarization
produces sedation (anxiolytic) at low doses and drowsiness at higher doses (hypnotic)
Can be blocked by flumazenil
diazepam (Valium)
flurazepam (Dalmane)
chlordiazepoxide (Librium)
competes with benzodiazepines for BZ binding site
Class: synthetic benzodiazepine antagonist
MOA: blocks actions of benzodiazepines, eszopiclone, zaleplon, and zolpidem but does not antagonize the actions of barbiturates, meprobamate, or ethanol
Adverse: agitation, confusion, dizziness and nausea; seizures and cardiac arrhythmias may follow admin if patient has ingested both benzodiazepines & tricyclic antidepressants
flumazenil
Romazicon
MOA: binds to barbiturate binding site on the GABAa receptor increasing the duration of the Cl- channel opening resulting in hyperpolarization
At higher concentrations can directly activate the GABAa receptor
thiopental
secobarbital (Seconal)
phenobarbital (Luminal)
Class: hypnotic
MOA: selective agonist at BZ site on GABAa alpha1 receptors; increases total sleep time by increasing stage 2 nonREM sleep and has little effect on sleep patterns
high doses decrease REM sleep
no muscle relaxation effects
no anticonvulsive effects
Metab: CYP3A4, half-life 6 hours, minor active metabolites
eszoplicone
Lunesta
Class: sedative-hypnotic
MOA: selective agonist at BZ site on GABAa alpha1 receptors; decreases latency to persistent sleep, REM sleep, and increases slow-wave sleep
prolongs total time spent in sleep
-no active metabolites
-does not require GABA to be active
no muscle relaxation effects
no anticonvulsive effects
Metab: CYP450 (CYP3A4), half-life 1.5-3.5 hours
note: at higher doses rebound insomnia occurs
zolpidem
Ambien
Class:sedative-hypnotic
MOA: selective agonist at BZ site on GABAa alpha1 receptors
-decreases latency of sleep with little effect on total sleep time, REM sleep or NonREM sleep
no muscle relaxation effects
no anticonvulsive effects
Metab: CYP3A4
note: at higher doses rebound insomnia occurs
zaleplon
Sonata
Class: hypnotic
MOA: melatonin receptor agonist (MT1 and MT2) in the SCN of the brain
-reduces the latency of persistent sleep with no effects on sleep architecture, no rebound insomnia or significant withdrawal symptoms
Metab: undergoes first-pass metab to form active metabolite with longer half-life; Cyps
Interactions: ciprofloxacin, fluvoxamine, tacrine, zileuton, fluconazole
use with caution in patients with liver dysfunction
Adverse: dizziness, somnolence, fatigue, decrease in testosterone, increase in prolactin; pregnancy category C
Ramelteon
Rozerem
Class: anxiolytic that is a sedative-hypnotic
MOA: partial agonist at brain 5-HT1a receptors; interacts with D2 receptors
-minimal abuse liability
-no muscle relaxant or anticonvulsant activity
-no rebound or withdrawal anxiety
Adverse: chest pain, dizziness, nervousness, tinnitus, GI, paresthesias, pupil constriction
Metab: CYP34A (no grapefruit juice, erythromycin, ketaconazole)
Buspirone
BuSpar
increase the duration of the Cl- channel opening
bind to AMPA receptors and depress glutamate excitatory response
barbiturates
