PHARM - Anxiolytics Flashcards
discuss the role of the amygdala in anxiety
- 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
which two amygdala nuclei are involved in anxiety?
- basolateral amygdala complex (BLA)
- central nucleus (CeA)
how does GABA serve as an inhibitory NT?
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
summarize the mechanism by which benzodiazepenes (BZs) serve as an anxiolytic
(i.e, BZ MOA)
- 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
review - compare & contrast the major indications and MOAs of
- benzodiazapene - like drugs (BZLs)
- benzodiazapenes (BZs)
- 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
BZs
- includes which drugs?
- clinical uses
- MOA
- AE/CI
- drug-drug interactions
- 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
BZs are what schedule drug?
schedule IV
list which part of the CNS BZs interact with to
- reduce anxiety
- promote sleep (hypnosis)
- relax muscles
- anxiety - amygdala (limbic system)
- sleep - VLPO of hypothalamus
- muscle relaxation - supraspinal motor areas
in what situations would a patient on BZs be at a risk for for respiratory depression?
- those with COPD and/or OSA
- those taking other CNS depressants
BZs are in what pregnancy category?
what does this mean?
category D (warning)
are CI in pregnancy, L & D, breastfeeding
tolerance develops to which therapeutic effects of BZs?
anti-convulsant
little or no tolerance to hypnotic or anxiolytic effects
how do BZ withdrawal effects present?
- tachycardia
- systolic hypertension
- trembling
- GI distress
- sweating
alprazolam what kind of drug?
BZ
chlordiazepoxide - what kind of drug?
BZ
diazepam - what kind of drug?
BZ
lorazepam - what kind of drug?
BZ
which BZs are best for treatment of generalized anxiety disorder (GAD)?
in which situations should they be used?
lorazepam & alprazolam
used when immediate stabiliziation is needed
outline the treatment protocol for generalized anxiety disorder (GAD)
- chronic treatment: SSRIs, SNRIs, buspirone - have delayed onset*
- acute treatment (immediate stabilization): benzodiazapenes
- alprazolam
- lorazepam
what processes define Phase I vs Phase II metabolism?
- Phase I: oxidation, reduction, hydrolysis
- Phase II: conjugation pathway
a decrease in Phase I reactions can occur in which patient populations?
- those with liver disease
- geriatric patients
categorize the BZs using the following
which BZ is best for patients who are elderly and / or have impaired liver function?
why?
lorazepam (L for liver)
phase II metabolism only.
i.e, no Phase I metabolism, which can be impaired in both of these populations
flumanezil
- clinical use
- MOA
- AE
- drug drug interactions
- 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
what are the effects of GABA in a patient taking BZs and flumazenil?
why?
same as the therapeutic effects of GABA alone
how is BZ withdrawal treated?
- switch to long acting BZ drug (diazepam, chlordiazepoxide)
- then, gradually decrease the dose
which BZ is FDA approved as a muscle relaxant?
how does it work?
why is this significant?
- 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
buspirone
- clinical use
- MOA
- advantages
- 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
which drugs are used to treat a fear of public performance?
beta blockers
- propanalol (non-selective)
- metoprolol (B1 only) - if pt has COPD or asthma*
