Anti-anxiety summary

Benzodiazepines

• alprazolam

• chlordiazepoxide

• clonazepam

• clorazepate

• diazepam

• estazolam

• flurazepam

• lorazepam

• midazolam

• oxazepam

• quazepam

• temazepam

• triazolam

Benzodiazepine MOA

bind to GABAA receptor subunits at CNS neuronal synapses to facilitate GABA- mediated chloride ion channel opening frequency to enhance membrane hyperpolarization

Benzodiazepine effects

• dose-dependent depressant

• sedation

• relief of anxiety

• amnesia

• hypnosis

• anesthesia

Benzodiazepine adverse effects

• coma

• respiratory depression

Benzodiazepine major clinical uses

• acute anxiety states

• generalized anxiety

• insomnia and other sleep disorders

Benzodiazepine toxicity

extensions of CNS depressant effects and dependence liability

Benzodiazepine interactions

additive CNS depression with ethanol and other drugs

Benzodiazepine Antagonists

Flumazenil

Benzodiazepine Antagonists MOA

antagonist at benzodiazepine-binding sites on GABAA receptor

Benzodiazepine Antagonists effect

block benzodiazepines and zolpidem but not other sedative-hypnotic drugs

Benzodiazepine Antagonists uses

management of benzodiazepine overdose

Benzodiazepine Antagonists toxicity

agitation and confusion. possible withdrawal symptoms in benzodiazepine dependence

Benzodiazepine Antagonists route of administration

IV

Barbiturates examples

• Amobarbital

• Butabarbital

• Mephobarbital

• Phenobarbital

• Secobarbital

Barbiturates MOA

bind to specific GABA A receptor subunits at the CNS neuronal synapses facilitating GABA-mediated chloride ion channel opening duration. Enhance membrane hyperpolarization

Barbiturates Effects

dose-dependent depressant effects on the CNS, steeper dose response relationship than benzodiazepines

Barbiturates clinical application

• anesthesia

• insomnia

• seizure disorders

what barbiturate is used for anesthesia?

thiopental

what barbiturate is used for insomnia ?

secobarbital

what barbiturate is used for seizure disorders?

phenobarbital

Barbiturates half lives

4-60 hrs wide range

Barbiturates toxicity

extensions of CNS depressant effects, dependence liability > benzodiazepines

Barbiturates interactions

additive CNS depression with ethanol and other drugs. induction of hepatic drug-metabolizing enzymes

Newer hypnotics examples

• eszopiclone

• zaleplon

• zolpidem

Newer hypnotics MOA

bind selectively to a subgroup of GABA A receptors. Acting like benzodiazepines to enhance membrane hyperpolarization

Newer hypnotics effects

rapid onset of hypnosis with few amnestic effects or day-after psychomotor depression or somnolence

Newer hypnotics clinical applications

sleep disorders, especially those characterized by difficulty in falling asleep

Newer hypnotics metabolism

CYP450 substrates

Newer hypnotics toxicity

extensions of CNS depressant effects, dependence liability

Newer hypnotics interactions

additive CNS depression with ethanol and many other drugs

5-HT-Receptor agonist

Buspirone

5-HT-Receptor agonist MOA

uncertain, partial agonists at 5HT receptors but affinity for D2 receptors possible

5-HT-Receptor agonist effects

slow onset (1-2 weeks) of anxiolytic effects, minimal psychomotor impairment, no additive CNS depression with sedative-hypnotic drugs

5-HT-Receptor agonist applications

generalized anxiety states

5-HT-Receptor agonist oral activity

forms active metabolite, short half life

5-HT-Receptor agonist toxicity

tachycardia, paresthesias, GI issues

5-HT-Receptor agonist interactions

CYP3a4 inducers and inhibitors

How are barbiturates excreted?

hepatic metabolism, renally excreted

Benzodiazepines metabolism

hepatic, forms some active metabolites

Melatonin receptor agonists

Ramelteon

Melatonin receptor agonists MOA

activates MT1 and MT2 receptors in suprachiasmatic nuclei in the CNS

Melatonin receptor agonists Effects

rapid onset of sleep with minimal rebound insomnia or withdrawal

Melatonin receptor agonists applications

sleep disorders especially those characterized by difficulty in falling asleep, not a controlled substance

Melatonin receptor agonists oral activity

forms activer metabolite via CYP1A2

Melatonin receptor agonists toxicity

dizziness, fatigue, endocrine changes

Melatonin receptor agonists interactions

fluvoxamine inhibits metabolism