Anxiolytic Agents Flashcards
What are the most commonly used txs for anxiety disorders?
SSRIs
What do you prescribe benzos for?
acute and situational anxiety
Why are barbs seldom used?
low safety margin, drug interactions, and abuse potential
Why is Buspirone used over benzos, even though it’s weaker?
fewer SEs
How do sedative/hypnotic drugs work, as a class?
they augment GABA neuronal inhibition and/or inhibit glutamate neuronal excitation
_______ drugs are described as decreasing activity, moderating excitement, and calming the recipient.
Sedative
______ drugs produce drowsiness and facilitate the onset and maintenance of sleep that resembles natural sleep and from which the recipient can be easily aroused.
Hypnotic
What does it mean that sedatives/hypnotics have a graded response? How do they act in the therapeutic range?
the CNS effects are dose-dependent; they produce antianxiety, anticonvulsant, muscle relaxant, sedative,
and hypnotic effects
Which drug class can be use for general anesthesia?
barbs
What is the major limiting SE of barbs?
respiratory and vasomotor depression –> coma/death
The great majority of sedative-hypnotic drugs act to facilitate the action of _______ at the GABAa receptor-chloride channel complex.
GABA (γ-aminobutyric acid)
The great majority of sedative-hypnotic drugs act to facilitate the action of GABA (γ-aminobutyric acid) at the _______.
GABAa receptor-chloride channel complex
GABA binding to its receptor ______.
opens an ion channel to increase Cl- conductance
Membrane hyperpolarization via GABA receptor binding causes?
decreased neuronal excitability and neurotransmission
Both benzodiazepines and barbiturates (each at a separate binding site) indirectly _______ to diminish neuronal excitability further.
increase the GABAergic effect
_______ intensify the effect of GABA, while _____ prolong the effect of GABA.
Benzos = intensify barbs = prolong
Benzodiazepines ______ the effect of GABA, while barbiturates ______ the effect of GABA.
Benzos = intensify barbs = prolong
At high concentrations, barbiturates interact directly with the ______ (presence of GABA is not required for effect).
GABA receptor
At _______, barbiturates interact directly with the GABA receptor (presence of GABA is not required for effect).
high concentrations
_____ action is less selective and also depresses excitatory neurotransmitters (glutamate).
Barbiturate
Barbiturate action is less selective and also depresses ______.
excitatory neurotransmitters (glutamate)
_____, _____, and _____ are non-benzodiazepines that interact with the benzodiazepine binding site as agonists and are commonly referred to as “Z”-drugs.
Zolpidem, eszopiclone, and zaleplon
Zolpidem, eszopiclone, and zaleplon are non-benzodiazepines that interact with ______ as agonists and are commonly referred to as “Z”-drugs.
the benzodiazepine binding site
Zolpidem, eszopiclone, and zaleplon are non-benzodiazepines that interact with the benzodiazepine
binding site as agonists and are commonly referred to as ______.
“Z”-drugs
______, an antagonist at the benzodiazepine binding site, reverses the CNS effects of benzodiazepines.
Flumazenil
Name an antagonist at the benzodiazepine binding site.
Flumazenil
Flumazenil reverses the CNS effects of ______.
benzodiazepines
What is Flumazenil?
an antagonist at the benzodiazepine binding site
reverses the CNS effects of benzodiazepines
GABA receptors with _____ subunits are highly expressed in the cortex and these receptors appear to mediate sedative (sleep), amnestic, and anticonvulsant actions of benzodiazepines.
α1
GABA receptors with α1 subunits are highly expressed in the ______, and these receptors appear to mediate sedative (sleep), amnestic, and anticonvulsant actions of benzodiazepines.
cortex
GABA receptors with α1 subunits are highly expressed in the cortex and these receptors appear to mediate _______ of benzodiazepines.
sedative (sleep), amnestic, and anticonvulsant actions
GABA receptors with α1 subunits are highly expressed in the cortex and these receptors appear to mediate sedative (sleep), amnestic, and anticonvulsant actions of _________.
benzodiazepines
GABA receptors with _____ subunits are highly expressed in the limbic system and brain stem and these receptors appear to mediate myorelaxant, motor impairing, anxiolytic, and ethanol-potentiating effects of benzodiazepines.
α2/α5
GABA receptors with α2/α5 subunits are highly expressed in the _______, and these receptors appear to mediate myorelaxant, motor impairing, anxiolytic, and ethanol-potentiating effects of benzodiazepines.
limbic system and brain stem
GABA receptors with α2/α5 subunits are highly expressed in the limbic system / and brain stem and these receptors appear to mediate _______ effects of benzodiazepines.
myorelaxant, motor impairing, anxiolytic, and ethanol-potentiating
GABA receptors with α2/α5 subunits are highly expressed in the limbic system / and brain stem and these receptors appear to mediate myorelaxant, motor impairing, anxiolytic, and ethanol-potentiating effects of _______.
benzodiazepines
_________ bind only to GABA-chloride channels with α1 subunits resulting in sleep without anxiolysis (reduced potential for dependence).
“Z-drugs” (zolpidem, zaleplon, eszopiclone)
“Z-drugs” (zolpidem, zaleplon, eszopiclone) are not benzodiazepines structurally and bind to GABA-chloride channels with _____ subunits resulting in sleep without anxiolysis (reduced potential for dependence).
α1
“Z-drugs” (zolpidem, zaleplon, eszopiclone) are not benzodiazepines structurally and bind only to GABA-chloride channels with α1 subunits resulting in ______.
sleep without anxiolysis (reduced potential for dependence)
Higher doses of most barbiturates and some benzodiazepines inhibit formation and spread of ______ in _____.
seizure activity in cortical neurons
What is the drug of choice for status epilepticus?
Diazepam
How do benzos/barbs cause muscle relaxation?
inhibit spinal cord polysynaptic reflexes may aid in muscle spasms (at high doses with CNS SEs)
Short-acting _______ (thiopental) are used to induce-maintain surgical anesthesia.
barbiturates
Short-acting barbiturates (_______) are used to induce-maintain surgical anesthesia.
thiopental
Name 3 benzos that have good oral absorption.
Diazepam, alprazolam, and triazolam
What benzo is good for IM administration?
Lorazepam
Many phase I metabolites of benzodiazepines are active with half-lives longer than the parent compounds. What is the significance of this fact?
Accumulation of these metabolites can occur when multiple doses are given, resulting in unwanted CNS effects such as daytime sedation, esp. in elderly pts
Accumulation of these metabolites can occur when multiple doses are given, resulting in unwanted CNS effects such as daytime sedation, esp. in elderly pts.
phase I metabolites of benzodiazepines
What benzos are safe to give your elderly and hepatic dysfunction pts and why?
Lorazepam and oxazepam are metabolized directly to the inactive glucuronides (NO P450 step) and as a result have shorter half-lives and fewer problems with cumulative and residual effects.
Lorazepam and oxazepam are metabolized directly to the inactive glucuronides (NO P450 step) and as a result have shorter half-lives and fewer problems with cumulative and residual effects. What is the significance of this fact?
safe to give these drugs to elderly and hepatic dysfunction pts
_______ are classic inducers of CYP450 enzymes and represent a major source of clinically significant drug interactions.
Barbiturates
Barbiturates are classic inducers of _______ enzymes and represent a major source of clinically significant drug interactions.
CYP450
Benzos can have an additive effect when given with what?
other agents that cause CNS depression (alcohol,
opioid analgesics, antipsychotic agents, anticonvulsants, antihistamines, TCADs)
Benzos can cause anterograde amnesia. How? Why is this significant?
because they enhance GABA-ergic neuronal function
good: procedural amnesia
bad: roofies/date rape
Why do benzos carry a black box warning?
strange sleep-related behavior and severe allergic reactions
Benzos are contraindicated in which patients?
those with breathing problems, chronic pulmonary disease, and symptomatic sleep apnea
Benzos can be used to treat which psych disorders?
acute: general anxiety
panic disorder
social anxiety
What is Buspirone?
a 5HT1A partial agonist located presynaptically on nerve terminals used as an anxiolytic
This is a 5HT1A partial agonist located presynaptically on nerve terminals used as an anxiolytic.
Buspirone
What are the SEs of Buspirone?
dizziness, nausea, headache
How must Buspirone be taken?
on a routine schedule for at least 2 weeks but 4-6 weeks for maximal efficacy
