Anxiolytics(Sedatives) and Hypnotics

Role of GABA-A receptor

GABA-A is a chloride channel; activation → Cl- influx → hyperpolarization → CNS inhibition.

How benzos act on GABA-A

Benzodiazepines bind allosterically to GABA-A and increase frequency of Cl- channel opening.

How Z-drugs act on GABA-A

Zolpidem, zaleplon, eszopiclone bind same site as benzos and increase frequency of Cl- channel opening.

How barbiturates act on GABA-A

Barbiturates increase duration of Cl- channel opening; at high doses are GABA-mimetic. (Barbara is old so are her DURAl sinuses)

Drugs flumazenil inhibits

Flumazenil reverses benzodiazepines and Z-drugs; NOT barbiturates. benzo-receptor antagonist

Benzodiazepine major uses

Sedation, sleep, anesthesia adjunct, anxiety, muscle relaxation, seizures (status), alcohol withdrawal, anterograde amnesia.

Benzodiazepine major ADEs

Sedation, impaired motor skills, anterograde amnesia, dependence/withdrawal, respiratory depression (esp. w/ other CNS depressants), fall risk in elderly.

Short-acting benzos (ATOM)

Alprazolam(Xanax), Triazolam(Halcion), Oxazepam(Serax), Midazolam(Versed); higher withdrawal risk.

Long-acting benzos examples

Diazepam(Valium), chlordiazepoxide(Librium); active metabolites → prolonged effects.

Z-drugs uses and MOA

Zolpidem(Ambien), zaleplon, eszopiclone used for sleep (hypnotics). Same binding site on GABA-A receptor

Z-drugs ADEs

Sedation, less dependence than benzos, rebound insomnia at high doses, still risky in elderly.

Flumazenil MOA

Competitive antagonist at benzodiazepine binding site on GABA-A receptor. Reverses benzos and Z drugs

Flumazenil ADEs

Agitation, confusion, dizziness, can precipitate withdrawal bc you take someone out of benzos

Barbiturates MOA

Bind GABA-A; increase duration of Cl- channel opening; GABA-mimetic at high doses.

Barbiturates uses

Pediatric seizures, anesthesia, ICU sedation.

Barbiturates ADEs

Severe sedation, dependence, CYP enzyme induction, respiratory depression.

Buspirone MOA

Partial 5-HT1A agonist; also affects dopamine receptors.

Buspirone uses

Chronic(long term) anxiety; not effective for acute anxiety or panic.

Buspirone onset

Requires 2–4 weeks for effect.

Buspirone ADEs

Tachycardia, GI distress, paresthesias; minimal psychomotor impairment.

DORAs MOA and Use + Med name

Suvorexant, lemborexant, daridorexant block orexin receptors (OX1R/OX2R) → ↓ wakefulness. Used for insominia. ADE: Headache, next-day somnolence, fatigue. Dora makes me sleepy»orexin

Ramelteon MOA, Uses

MT1/MT2 melatonin receptor agonist. Used to Improve sleep latency (sleep onset). ADEs: Dizziness, somnolence, fatigue.

4 words when thinking of barbituates

Sedation, seizures(peds), enzyme-induction, GABA

Micellanous Meds used for insomnia

Antihistamines»diphenhydramine; Antidepressants: Doxepin and Trazodone

Summary of Anxiolytics

Zolpidem

aka Ambien. GABAa receptor and inc Cl movement

Clonazepam (Klonopin)

medium lasting benzo; used for seizures, anxiety, panic

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