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PSYCH > PHARM - Anxiolytics > Flashcards

PHARM - Anxiolytics Flashcards

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1
Q

discuss the role of the amygdala in anxiety

A
  • thalamus → input to BLA (basolateral amygdala complex)
  • BLA → CeA (central nucleus), also in the amygdala. input is either
    • excitatory, via direct projectections
    • inhibitory, via GABAnergic interneurons onto a2 - containing GABAA receptors
  • CeA → BNST (brainstem + hypothalamus)
  • BNST → anxiety
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2
Q

which two amygdala nuclei are involved in anxiety?

A
  • basolateral amygdala complex (BLA)
  • central nucleus (CeA)
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3
Q

how does GABA serve as an inhibitory NT?

A

by inducing hyperpolarization of post-synaptic neurons such that any excitatory NTs from their pre-synaptic neuron cannot induce a potential high enough overcome threshold & initiate firing

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4
Q

summarize the mechanism by which benzodiazepenes (BZs) serve as an anxiolytic

(i.e, BZ MOA)

A
  • bind the benzodiazapene binding site of a2 - containing GABAA receptors on the central nucleus (CeA) of the amygdala
  • this increases GABAa receptor affinity for GABA
  • binding of GABAa to these post-synaptic receptor i_nduces Cl- influx_
  • Cl- influx hyperpolarizes the membrane
  • hyperpolarization reduces any potential produced by exctitatory amino acids from the pre-synapse
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5
Q

review - compare & contrast the major indications and MOAs of

  • benzodiazapene - like drugs (BZLs)
  • benzodiazapenes (BZs)
A
  • MOAs: GABAA receptor binding
    • BZL: a1 subunit - containing only (selective)
    • BZs a2 & a3 subunit - containing mostly (non-selective)
  • indications:
    • BZL: hypnotic
    • BZs: ​anxiolytic > hyponotic, amnesia, muscle relaxing
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6
Q

BZs

  • includes which drugs?
  • clinical uses
  • MOA
  • AE/CI
  • drug-drug interactions
A
  • drugs: -pams (diazepam, lorazepam), aprolezam, chlordiazepoxide
  • clinical use: anxiety > hyponosis, muscle relaxation, AED
  • MOA: enhance GABA affinity of a2 & a3 containing GABAA receptors
  • PK: metabolized by CYP-3A4
  • AE:
    • CV / respiratory depression - usually mild
    • decreased motor skills
    • anterograde annesia
  • CI: pregnancy, L & D, breast-feeding
  • drug-drug interactions:
    • CNS depressants - inc risk of respiratory depression
    • CYP-3A4 inhibitors - inc plasma levels overall
    • flumazenil - antagonist
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7
Q

BZs are what schedule drug?

A

schedule IV

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8
Q

list which part of the CNS BZs interact with to

  • reduce anxiety
  • promote sleep (hypnosis)
  • relax muscles
A
  • anxiety - amygdala (limbic system)
  • sleep - VLPO of hypothalamus
  • muscle relaxation - supraspinal motor areas
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9
Q

in what situations would a patient on BZs be at a risk for for respiratory depression?

A
  • those with COPD and/or OSA
  • those taking other CNS depressants
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10
Q

BZs are in what pregnancy category?

what does this mean?

A

category D (warning)

are CI in pregnancy, L & D, breastfeeding

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11
Q

tolerance develops to which therapeutic effects of BZs?

A

anti-convulsant

little or no tolerance to hypnotic or anxiolytic effects

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12
Q

how do BZ withdrawal effects present?

A
  • tachycardia
  • systolic hypertension
  • trembling
  • GI distress
  • sweating
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13
Q

alprazolam what kind of drug?

A

BZ

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14
Q

chlordiazepoxide - what kind of drug?

A

BZ

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15
Q

diazepam - what kind of drug?

A

BZ

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16
Q

lorazepam - what kind of drug?

A

BZ

17
Q

which BZs are best for treatment of generalized anxiety disorder (GAD)?

in which situations should they be used?

A

lorazepam & alprazolam

used when immediate stabiliziation is needed

18
Q

outline the treatment protocol for generalized anxiety disorder (GAD)

A
  1. chronic treatment: SSRIs, SNRIs, buspirone - have delayed onset*
  2. acute treatment (immediate stabilization): benzodiazapenes
    • alprazolam
    • lorazepam
19
Q

what processes define Phase I vs Phase II metabolism?

A
  • Phase I: oxidation, reduction, hydrolysis
  • Phase II: conjugation pathway
20
Q

a decrease in Phase I reactions can occur in which patient populations?

A
  • those with liver disease
  • geriatric patients
21
Q

categorize the BZs using the following

A
22
Q

which BZ is best for patients who are elderly and / or have impaired liver function?

why?

A

lorazepam (L for liver)

phase II metabolism only.

i.e, no Phase I metabolism, which can be impaired in both of these populations

23
Q

flumanezil

  • clinical use
  • MOA
  • AE
  • drug drug interactions
A
  • clinical use: used to reverse
    • ​sedative affects of BZ post - anesthesia
    • BZ overdose
  • MOA: is a competive antagonist of BZs
  • AE: could precipitate BZ withdrawal
  • drug-drug interactions: cancels BZ effects
24
Q

what are the effects of GABA in a patient taking BZs and flumazenil?

why?

A

same as the therapeutic effects of GABA alone

25
Q

how is BZ withdrawal treated?

A
  1. switch to long acting BZ drug (diazepam, chlordiazepoxide)
  2. then, gradually decrease the dose
26
Q

which BZ is FDA approved as a muscle relaxant?

how does it work?

why is this significant?

A
  • diazapem
  • MOA: hyperpolarization of the pre-synaptic neuron in the spinal cord → decreased release of excitatory NTs onto NNJ
    • different than anxiolytic MOA, in which post-synaptic GABAnergic tranmission in enahnced
27
Q

buspirone

  • clinical use
  • MOA
  • advantages
A
  • clinical use: GAD only
  • MOA: partial agonist of 5-HT1A receptor
  • advantages: less sedation (CNS depression)
    • less likely to lead to withdrawal sx
    • not C/I with other CNS depressants
28
Q

which drugs are used to treat a fear of public performance?

A

beta blockers

  1. propanalol (non-selective)
  2. metoprolol (B1 only) - if pt has COPD or asthma*

PSYCH (7 decks)

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