Pharm 22 Sedative Hypnotic Drugs

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Pharm 22 Sedative Hypnotic Drugs

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Seditive Hypnotic Drugs

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seditive effect

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reduce anxiety exert calming effect

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hypnotic drug

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produce drowsiness and encourage sleep

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target for BZ drugs

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GABA a receptor

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subunits of GABA a receptor

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alpha, beta , gamma

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benzodiazepine receptor location

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gamma 2 subunit at interface with alpha (1 or 2)

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BZ1 vs BZ2

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if it includes alpha 1 it is a BZ1 if it includes alpha 2 it is a BZ2

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BZ increase the ____________ of Cl- channel oppening by GABA

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frequency "ben wants to do it more"

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low dose BZ activity

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reduction of anxiety, sedation

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high dose BZ activit

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hypnotic / muscle relaxant

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other effects of BZ

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anterograe amnesia, anticonvulsant

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effective for short term and long term panic disorders

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alprazolam

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useful for tx of skeletal muscle spasms in conitions such as MS and cerebral palsy

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diazepam

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DOA alprazolam

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intermediate (10-20h)

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DOA estazolam

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intermediate (10-20h)

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DOA clorazepate

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long (1-3 days)

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DOA oxazepam

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short (3-8h)

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DOA lorazepam

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intermediate (10-20h)

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DOA temazepam

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intermediate (10-20h)

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DOA chlordiazepoxide

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long (1-3 days)

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DOA flurazepam

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long (1-3 days)

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DOA triazolam

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short (3-8h)

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DOA quazepam

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long (1-3 days)

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drug used for induction of anesthesia

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midazolam

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diazepam and lorazepam used for what siezure d/o

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grand mal termination and status epilepticus

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BZ used for acute alcohol withdrawl

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chlordiazepoxite , clorazepate, diazepam, oxazepam

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commonly perscribed BZ for sleep disorders

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flurazepam (long) temazepam (intermediate) triazolam (short)

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BZ for people who cant fall asleep

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triazolam

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BZ for people who cant stay asleep

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temazepam

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withdrawl effects occur more rapidly with what BZ

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short acting

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most common SE for BZ

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drowsiness and confusion

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DOC for BZ overdose

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flumazenil

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MOA flumazenil

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GABA antagonist

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SE of flumazenil

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BZ withdrawl signs

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MOA of buspirone

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5-HT 2a receptor agonist

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indication buspirone

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chronic GAD management

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adverse effects of Buspirone

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nausea dizziness moreso than drowsiness fatigue and concentration issues (opposite trend for BZ drugs)

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disadvantages of barbituates

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tolerane, CYP induction, dependance, severe withdrawl, coma in toxic doses

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MOA barbituates

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interaction with GABA a receptor (distinct binding from BZ) ; keeps CL- channel open longer when GABA binds (BARB likes to do it longer)

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ultra short acting barbituate

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thiopental

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short acting barbituates (3)

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pento , seco, amobarbital

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long acting (1-2 days) barbituates

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phenobarbitol

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dose dependent effets of barbituates

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low to high (sedation, hypnosis, anesthesia, coma, death)

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enzyme activity barbituates

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CYP inducers

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barbituate used to induce anesthesia

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thiopental

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barbituate used in long term manangment of siezures

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phenobarbitol

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barbituates are synergistic with this CNS depressant

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ethanol

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doing this to urine will enhance phenobarbitol elimination

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alkalinization

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zolpiden acts on this receptor

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BZ1

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metabolism of zolpidem

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CYP450 (3A4)

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zaleplon

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similar to zolpidem but fewer residual effects, rapid elimination, CYP3A4 metabolism

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eszopiclone

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oral non BZ that acts on BZ1 and is used for tx of insomnia

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onset/duration for non BZ hypnotics (zolpidem, zaleplon, eszopiclone, ramelteon)

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all have rapid onset (20-30min) zaleplon is a 3 hour duration, zolpidem is 5, the other 2 are 7 hours

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MOA of ramelteon

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selective agonist of MT1 and MT2 melatonin receptors

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indication of ramelton

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long term management of insomnia with increased sleep latency as primary complaitn

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disadvantages of use of BZ class (2)

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impaired intellectual/motor function, potential for dependence/withdrawl

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advantages of clonazepam an clorazepate

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chronic siezure therapy

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advantages of flurazepam and quazepam

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less potent and more slowly eliminated, no rebound insomnia on withdrawl

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DOC for panic disorders

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alprazolam

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BZ with no Phase 1 metabolism and considered safe for pt with hepatic impairment

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lorazepam, temazepam

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withdrawl of this drug results in rebound insomnia

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triazolam

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low addiction potential, useful for long term anziety, doesn’t increase CNS depression of EtOH

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buspirone

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diadvantage to buspirone

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no muscle relaxation, no anticonvulsant, long time till onset of action

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advantae to eszopiclone

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useful tx for insomina for up to 6 months

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advantages to zaleplon and zolpidem

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minimal rebound insomnia, minimal withdrawl, little tolerance