Anxiolytics and Insomnia Therapeutics

Anxiolysis use

• reduce anxiety

• Anterograde amnesia: prevents memory formation

  • benzodiazepines

Anxiolytic and Sedative Medications

• Benzodiazepines: anterograde amnesia, sedative

• Antihistamines: benzodiazepines intolerance, sedative, NO anterograde amnesia

• Narcotics/ opioids: Codine, morphine, fentanyl

• Nitrous oxide: anterograde amnesia

• Do Not drive while under the influence: Pt needs driver!

Benzodiazepines

• Bind to GABA receptors in CNS and enhance the inhibitory action os GABA: CNS depression (sedation)

  • GABA agonist = CNS depression

• Sedative effects

• Anxiolytic effects

• No analgesic effects: still feel pain

• Cause anterograde amnesia

• Cause muscle relaxation

Flumazenil

• IV injection only

• Competitive GABA receptor antagonist

  • Benzodiazepine antidote

Diazepam

• Type of benzodiazepine

• Mild to mod. levels of sedation and amnesia

• Onset of action: 30mins

• Long duration of action

• PO/IV

Lorazepam

• type of benzodiazepine

• Onset action: 30 mins

• greater t1/2, long duration, shorter than diazepam

• PO/ IV

Triazolam

• common benzodiazepine used in dentistry

• high levels of sedation and amnesia

• same onset as diazepam and lorazepam

• shorter duration of action: fast acting

• 1 dose: taken before appointment

• 2 doses: first taken the night before, second taken an hour prior to procedure

Midazolam

• type of benzodiazepine

• shortest duration of action, fastest acting (15-30 mins)

• ideal for dent.

• IM/IV/PO

Antihistamines

• H 1 receptor antagonist

• Induces mod. levels of sedation w/o amnesia

Hydroxyzine

• type of antihistamine

• rapid onset: 15 mins

• pro-dug:

  • metabolized to cetirizine in liver

  • Cetirizine: non-sedating (BN: Zyrtec)

• No amnesia, only sedation/ dizzy

Promethazine

• type of antihistamine

• Histamine-1 receptor antagonist

  • sedative w/o amnesia

  • antiemetic: prevent or relieve nausea and vomiting

Antihistamines ADRs and Precautions

• Anticholinergic effects (w/ daily use)

  • Dry mouth (xerostomia)

  • Urinary retention

Non-benzodiazepine Anxiolytics

Zaleplon

Zolpidem (BN: Ambien)

• Non-BZD but bind to BZD site on GABA receptors

• Sedative and amnesia effects

• Onset: 30 mins

• Reversed by flumazenil

Zaleplon

• Non-Benzodiazepine Anxiolytics

• bind to BZD site on GABA receptors

• sedative and amnesia

• onset: 30 mins

• reversed by flumazenil

Zolpidem (BN: Ambien)

• Non-Benzodiazepine Anxiolytics

• bind to BZD site on GABA receptors

• sedative and amnesia

• onset: 30 mins

• reversed by flumazenil

Nitrous Oxide (N20)

• inhalation anesthetic agent (gas)

• CNS depression

  • stabilizing axonal membrane

  • sedative and amnesia

• rapid onset: 3 mins

• 25-50% conc.

• reversed by oxygen 100%

• may also act on opioid receptor: analgesic effects (pain reliever)

Insomnia medications

• meds stopped after 2-3 nights of adequate sleep

• CNS depressing agents: GABA agonists

examples:

• Barbiturates: Phenobarbital

• Benzodiazepines: Triazolam

• Non-BZD GABA enhancers: Zolpidem

• Melatonin receptor agonists: Ramelteon

• Orexin receptor antagonists: Suvorexant

Phenobarbital

Barbiturate used to treat insomnia

Triazolam

• Benzodiazepine used to treat insomnia

• Tolerance may develop

• Residual daytime sedation

Zolpidem

Non-BZD GABA enhancer used to treat insomnia

Ramelteon

Melatonin receptor agonists used to treat insomnia

Suvorexant

Orexin receptor antagonists used to treat insomnia

• Diphenhydramine (BN: Benadryl)

• Doxylamine

• H1RBs, 1st generation

  • Antihistamine used to treat insomnia

• Trazodone

• Paroxetine

• Mirtazapine

Antidepressants used to treat insomnia

BZDs for insomnia

• tolerance may develop

• residual daytime sedation

• rebound insomnia

• anterograde amnesia

• impaired memory, risk of falls (elderly)

• accumulated in hepatic/ renal insufficiencies

• withdrawal: must be tapered off

  • worsening insomnia, anxiety, muscle twitches, photophobia (sensitivity to light), tinnitus, auditory and visual hypersensitivity, seizures

Zaleplon

• Non-BZD GABA agonist used for insomnia

• short t1/2, appropriate for sleep initiaion not maintenance problems

  • fewer daytime issues

• cause anterograde amnesia

Eszopiclone

• Non-BZD GABA agonist used for insomnia

• longer t1/2

• cause anterograde amnesia

Zolpidem

• Non-BZD GABA agonist used for insomnia

• longer t1/2, similar to eszopiclone

• cause anterograde amnesia

Non-BZD GABA agonists compared to BZDs

• lack muscle relaxant properties

• much lower respiratory depression

• lower risk of developing tolerance

• cause anterograde amnesia

Ramelteon

• insomnia med

• Melatonin agonist

• no dependence/ tolerance

• no respiratory depression

• no anterograde amnesia

Suvorexant

• Insomnia med: Orexin receptor antagonist

• for sleep maintenance

• 10 mg PO, 30mins before bed

Melatonin

OTC insomnia med

Doxepin

• Antidepressant used for insomnia

• TCA: tricyclic antidepressant

• with lower doses