Sedative Hynotics Flashcards
Hypnotics uses?
produce drowsiness
encourages onset and maintenance of sleep
What are some sedative-hypnotics?
- benzodiazepines
- barbiturates
- non-benzodiazepine benzodiazepine recpetor agonists
- 5HT1A receptor partial agonists
- melatonin agonists
Benzodiazepines
MOA?
bind to GABAa receptors (chloride channel) b/w adjacent alpha and gamma subunit -> opens channel -> increase Cl influx.
What is benzodiazepine receptor AGONIST interaction?
- positive allosteric modulators
- exert anxiolytic and anticonvulsant effects.
What is benzodiazepine receptor ANTAGONIST interaction?
flumazenil: blocks actions of benzodiazepines
What is benzodiazepine receptor INVERSE AGONIST interaction?
- negative allosteric modulators of GABA receptr function
2. cause anxiety and seizures.
what are the actions of benzodiazepines?
- reduction of anxiety
- sedative and hypnotic actions
- anticonvulsant
- muscle relaxant
- anesthesia
benzodiazepines
PK?
lipophilic
rapidly and completely absorbed after oral administration
distributed throughout body
what are long-acting benzodiazepines?
- diazepam
2. flurazepam
what are intermediate-acting benzodiazepines?
- alprazolam
- lorazepam
- temazepam
what are short-acting benzodiazepines?
- oxazepam
2. triazolam
how is desmethyldiazepam metabolized?
desmethyldiazepam = active metabolite of several benzo
- then metabolized to the active compound oxazepam
how is oxazepam, lorazepam, and temazepam metabolized?
oxazepam, lorazepam, temazepam are conj. directly (no P450)
how is flurazepam metabolized?
flurazepam is oxidized to active metabolites hydroxyethyl-flurazepam and desalkyl-flurazepam.
What are therapeutic uses of benzodiazepines?
- anxiety disorders
- muscular disorders
- diazepam: skeletal muscle spasm, spasticity from degenrative disorders (MS or cerebral palsy) - seizures
- clonazepam: epileptic seizures
- lorazepam & diazepam: status epilepticus - drug withdrawal
- diazepam & oxazepam: EtOH withdrawal - anesthesia
- Sleep disorders
- flurazepam (long), temazepam (intermediate), triazolam (short)
what are some benzodiazepines a.e’s?
- drowsiness and confusion
- ataxia
- cognitive impairment
- psychological effects
- anxiety, irritability, hostility/rage, paranoia, depression, suicial ideation - dependence
- withdrawal sx’s when d/c abruptly
- confusion, anxiety, agitation, restlessness, insomnia, tension
what is a benzo antagonist?
flumazenil
flumazenil
uses?
reverse CNS depressant effects of benzo overdose
hasten recovery following use in anesthetic and diagnostic procedures.
flumazenil
A.E?
precipitate withdrawal in physiologically dependent pts or
cause seizures if a benzodiazepine is used to control seizures.
why has benzo replaced barbiturates?
- induced tolerance
- induced drug-metabolizing enzymes
- physical dependence
- severe withdrawal sx’s
- coma c high dose
barbiturates
MOA?
- act on GABAa receptors -> increases duration of GABA-gated Cl channel openings.
- block glutamate receptors and Na channels
barbiturates
actions?
- depression of CNS
- low dose = sedation
- high dose = hypnosis -> anesthesia -> coma, death - respiratory depression
- enzyme induction (P450)
barbiturates
uses?
- anesthesia (thiopental)
- anticonvulsant (phenobarbital)
- tonic-clonic seizures, status epilepticus and eclampsia. - anxiety
- hepatic metabolic
- tx hyperbilirubinemia and kernicterus
barbiturates
A.E?
- CNS - drowsy, impaired concentration, metnal/physical sluggishness
- paradoxical excitement
- hypersensitivity
- hangover
- increase porphyrin synthesis - contraindicated pts c porphyria.
- respiratory depression in pts c pulmonary insuff.
- pain
- dependence
- poisoning: respiratory depress and central CV depress.
what is non-benzodiazepine benzodiazepine receptor agonists?
act only on the BZ1 subtype of benzo receptors.
- Zolpidem
- Zaleplon
- Eszopiclone
eszopiclone
uses?
insomnia
decreases sleep latency and improves sleep maintenance.
zolpidem
uses?
insomnia, difficulties c sleep initiation.
short action
Zaleplon
uses?
short term tx of insomnia
what is a 5HT1A partial agonists?
buspirone
buspirone
uses?
anxiety disorders
analogous to antidepressants MOA.
buspirone
advantages?
- less psychomotor impairment
- no rx interaction c EtOH
- no rx interactions c benzo and other sedative-hypnotics
- no rebound anxiety or withdrawal signs on abrupt d/c
- no dependence.
what is a melatonin receptor agonist?
ramelteon
ramelteon
uses?
agonist at MT1 and MT2 melatonin receptors
insomnia, difficulty c sleep onset.
what are other sedative-hypnotics?
- hydroxyzine
- relief anxiety - propranolol
- control performance anxiety - clonidine
- diphenhydramine and doxylamine
- mild insomnia
Sedative uses?
reduce anxiety
calming effect c little or no effect on motor or mental functions.
