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Nervous System: Unit IV > Anxiolytics > Flashcards

Flashcards in Anxiolytics Deck (16)
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Categories of drugs used in tx of Anxiety

  • Antidepressants (most common)
    • SSRIs - SNRIs
  • Benzodiazepines (sedative-hypnotic agent)
  • Busprione
  • Barbiturates (sedative-hypnotic agent)


(General) MOA of sedative-hypnotic drugs

  • graded dose-dependent depressant effects
  1. augment GABA neuronal inhibition and/or
  2. inhibit glutamate neuronal excitation
  • sedatve drugs = decreasing activity, moderating excitement, calming
  • hypnotic drugs = produce drowsiness, facilitate onset/maintenance of sleep that resembles natural sleep


Pharmacodynamics/dosing of barbituates vs. benzodiazepines

  • Barbiturates: Increase in dose above that needed for hypnosis-sleep ==> general anesthesia -==> depression of respiratory and vasomotor centers ==> coma and death
  • Benzodiazepines: Non-linear/less steep dose-response relationship ==> greater dosage increments are required to achieve CNS depression more profound than hypnosis-sleep - consistent with their greater margin of safety


Benzodiazepines: MOA

  • facilitate action of GABA @ GABAA receptor-chloride channel complex
    • ==> increased GABA channel opening ==> increased Clflow into cells ==> hyperpolarization ==> decreased neuronal excitability
  • Benzodiazepines intensify effect of GABA


Barbituates: MOA

  • facilitate action of GABA @ GABAA receptor-chloride channel complex
  • barbiturates prolong the effect of GABA @ therapeutic levels (requires presence of GABA)
  • @ high concentration: barbiturates interact directly w/GABA receptor (GABA not required)
  • ALSO barbiturates depress excitatory NTs (glutamate)
  • MOA ==> greater CNS depression + full surgical anesthesia ==> lower safety margin


GABA channel subunits and clinical relevance

  • GABA receptors with α1 subunits = @ cortex
    • receptors appear to mediate sedative (sleep), amnestic, and anticonvulsant actions of benzodiazepines
  • GABA receptors with α2/α5 subunits = @ limbic system / and brain stem
    • receptors appear to mediate myorelaxant, motor impairing, anxiolytic, and ethanol-potentiating effects of benzodiazepines


Benzodiazepines vs. "Z-drugs"

  • Benzodiazepines
    • bind to GABA-chloride channels with both α1 and α2/α5 subunits
    • ==> both sleep and anxiolysis
  • “Z-drugs” (zolpidem, zaleplon, eszopiclone)
    • not benzodiazepines structurally
    • bind only to GABA-chloride channels with α1  subunits
    • ==> sleep without anxiolysis (reduced potential for dependence)


Clinical indications of phenobarbital

  • e.g. of barbituate that inhibits spread of seizures in cortical neurons @ doses that don't cause severe sedation


Clinical indications of diazepam/lorazepam

  • e.g. of benzodiazepines
  • drugs of choice in status epilepticus


General pharmacologic effects of benzodiazepines/barbituates

  • anxiolysis
  • anticonvulsant effects
  • muscle relaxation
    • requires high doses, acoompanies by significant CNS depression
  • hypnosis (sleep)
  • anesthesia (short-acting barbiturates)
    • NOT benzodiazepines
  • ==> tolerance
  • ==> psychologic and physical dependence


Benzodiazepines: absorption/distribution

  • absorption
    • oral
      • rapid: diazepam, alprazolam, triazolam
      • slow: oxazepam, temazepam
    • IM = used for faster onset/if oral not possible
      • Lorazepam
  • distribution = lipid soluble ==> enters CNS rapidly


Benzodiazepines: metabolism

  • metabolism of most drugs = CYP450 enzymes @ liver
  • many phase I metabolites are active w/longer half-lives than parent compounds
    • ==> accumulation of metabolites
    • e.g. diazepam
  • others metabolized to active compounds but quickly conjugate
    • ==> short-lived effects
    • e.g. alprazolam
  • others metabolized directly to inactive form w/out P450 enzymes
    • ==> shorter half-lives
    • GOOD CHOICE @ elderly or hepatic dysfxn
    • e.g. lorazepam
    • e.g. oxazepam


Tx for GAD & Panic disorder

  • GAD
    • SSRIs
    • SNRIs
  • Panic disorder
    • Acute: high potency BDZs (alprazolam, clonazepam)
    • SSRIs


Tx for Social Phobia, OCD, PTSD

  • Social Phobia
    • Generalized: SSRI, SNRI
    • Performance: Beta-blockers, high-potency BDZs (alprazolam, clonazepam)
  • OCD
    • CBT
    • SSRIs, SNRIs
  • PTSD
    • CBT
    • SSRIs


Benzodiazepine use in axiety disorders (based on pharmacokinetic properties)

  • Oral onset:  Most rapid with alprazolam or diazepam for situational anxiety
  • IM absorption:  Lorazepam, rapid and  reliable
  • Elimination half-life
    • Agents with short-intermediate t1/2 (oxazepam, alprazolam, lorazepam) preferred in the elderly or in presence of hepatic disorder 
    • Agents with longer t1/2 (diazepam or chlordiazepoxide) may be dosed at bedtime if both hypnotic and daytime anxiolytic activity desired


Characteristics of buspirone

  • Buspirone is an alternative as an anxiolytic
  • Not a benzodiazepine, but a 5HT1A partial agonist located presynaptically on nerve terminals
  • NO sedation (or additive CNS depression), anticonvulsant, or myorelaxant action
  • Requires 2 weeks for onset of anxiolytic effect and 4-6 weeks for maximal efficacy (thus it is more useful and effective in chronic anxiety).  Less patient acceptance.
  • Must be administered on routine schedule (not on prn basis)
  • Side effects include dizziness, nausea, headache