Anxiolytics [3] Flashcards
NTs involved in anxiety
Neuropharmacological targets
5HT
GABA
1st line agent for most anxiety disorders
Antidepressants (SSRI-SNRIs) → increase 5HT
Benzodiazepine agonist action and when it is good to use for anxiety
Indirectly Augment GABA Cl- Channels
- good in acute and situational anxiety
- INTENSIFY effect of GABA
- Non-linear, less steep CNS effects (greater dose req. to reach CNS depressant)
Barbiturate action and when it is good to use for anxiety
Indirectly Augment GABA Cl- Channels
- rarely used for anxiety
- PROLONG effect of GABA
- less selective
- depresses excitatory NT (Glu)
- IV barb maintain surgical anesthesia ( stage III)
- LINEAR CNS effects
- very easy to overdose and abuse
BDZ vs Barbs Which has greater margin of safety? Which has higher therapeutic index? Which one prolongs effect of GABA? Binds to gamma subunit of GABA R Ion channel?
BDZ (greater dose to achieve CNS depression)
BDZ
Barbs - prolongs in presence of GABA and opens channels directly at higher doses
BDZ
BDZ vs General Anesthetics (GA)
- maintain stage III surgical anesthesia
- potentiate GABAa receptor activity
- Low margin of safety
- Low potency
- Inhibition of Excitatory synaptic transmission
GA Both GA GA GA
Non BDZ
“Z drugs”
Eszopiclone
Zaleplon
Zolpidem
- binds only to GABA Cl- channels with a1
- makes you sleepy (w/o anxiolytics)
- reduced potential for dependence
(if you want to relieve anxiety, bind a2-5 - BDZ binds a1, a2-5)
BDZ alone are safe, but combined with what is lethal?
Ethanol (can open GABA Cl- channel directly at a nonspecific site)
BDZ open indirectly
Can result in coma (additive effect of CNS depressant)
Admin of flumazenil will reverse the toxicities associated with overdose of____
BDZs
(BDZ R antagonist)
- reverses CNS depression
What reverses toxicity of morphine?
naloxone blocks binding
a1 GABA receptor Cl- channel subunit
- agonist
- location
- action
- side effects
BDZ + Z drugs
Cortex
Sleep, Anticonvulsants
(no anti-anxiety)
Amnesia, Additive CNS depression
a2-5 GABA receptor Cl- channel subunit
- agonist
- location
- action
- side effects
BDZ
Limbic system, brain stem
Anxiolytics, myorelaxants
- can treat anxiety, convulsions at dose where pt is still awake
Tolerance, Dependence, Addiction
BDZ low dose
Anxiolytics (a2-a5)
BDZ high dose
anticonvulsant effects
(a1- higher barbs and BDZ inhibit seizure activity in cortical neurons)
Myorelaxants
- BDZ inhibit spinal cord reflexes
- usually accompanied with sig CNS depression
Sleep
Drug of choice for status epilepticus
diazepam
which is used for anesthesia induction?
- Barbs or BDZ?
Barbituates: anesthesia induction (phenobarbitol)
BDZ NOT capable of induction (used as adjuncts)
dependence of BDZ
psychologic dep
physical dep (chronic use)
withdrawal syndrome
- Most common adverse rxns are extension of CNS depression
BDZ ready to be conjugated +inactivated in 1 step
Oxazepam
Lorazepam
Temazepam
conjugation enzymes dont diminish with age
- dont worry about slow metabolism in old people
- can reliably eliminate it with age
(look for O or L)
BDZ eliminated by CYP450
Diazepam
- most BDZ
- phase I with subsequent inactivation via conjugation by glucuronidation (phase II)
Anterograde Amnesia is common in drugs that
enhance GABA neuronal fxn
(→ indirectly depressing glutamate fxn)
- ie: BDZ
Beneficial use in uncomfortable procedure as pt is able to cooperate w/o any memory afterward
eg: colonscopy
Midazolam (versed)
BDZ
antianxiety - act by potentiating GABAa receptors
Alprazolam Lorazepam Diazepam \_\_\_\_\_\_\_\_\_\_\_ Buspirone
Anti -anxiety
BDZs
(Buspirone is a partial 5HT1A partial agonist)
Do BDZ result in retrograde or anterograde amnesia?
Anterograde amnesia
- enhance GABA neuronal fxn
(→ indirectly depressing glutamate fxn)
Do BDZ or SSRIs work better in anxiety?
SSRI
- BDZ can be used as an adjunct for acute management while SSRI take effect
Difference btwn treating anxiety disorders in:
acute panic attack
Mild-moderate symptoms
Severe symptoms
acute: BDZ
mild-mod: SSRI (antidepressant OR CBT)
Severe: SSRI AND CBT
Schedules of Barbs vs BDZ
Barbs: sched II - lower therapeutic index - higher abuse potential than BDZ - more likely to result in death by resp. depression - classic inducers of cytP450 BDZ: sched IV - hgher a
