CNS Behaviour Pharmacology Flashcards
What are 4 types of anxiolytics
benzodiazepine
- diazepam/midazolam
azapirones
- buspirone
antihistamine
barbituate
What are the clinical effects of benzodiazepines?
anxiolytic
anterograde amnesia
muscle relaxant
anticonvulsant
appetite stimulate
- dont give PO to cats tho - cause liver necrosis
- respiratory depression but not apnea (reduce response to hypercapnea)
What is the general mechanism of benzodiazepines
GABA receptor impacts
What are the pharmacokinetics of benzodiazepines
short half lives
- dog = 15m - 3h
- cat 5.5h
metabolized to active metabolite with 1/3 potency of diazepam
- diazepam > nordiazepam > oxazepam
How does duration of administration of benzodiazepines impact its efficacy?
tolerance can develop if chronic
GABA is downregulated
What is benzodiazepines mainly used for
sedation for small ruminants (safer than xylazine)
neonatal foals
mus add analgesia
What is the mechanism of azapirones?
serotonin 1A agonist
- partial agonist = pre synaptic effect on 5HT1A
- full agonist = post synaptic
dopamine receptor agonist
What is an example of azapirones?
buspirone
What is serotonin? How is it made?
5-hydroxytryptamine
from tryptophan
What does serotonin do?
regulate sleep/perception/motor activity/mood/behaviour
excess can cause serotonin syndrome
What receptors does serotonin act on?
G protein couples receptors on pre and post synaptic membranes
What is the mechanism of buspirone?
reduce serotonin synthesis and inhibit neural firing
long term it will have the opposite effect because receptors will be down regulated
What is the effect of buspirone?
anxioselective
no sedation/muscle relaxation/anti-seizure
What consideration should you have when monitoring buspirone’s efficacy?
It takes time for effect to be seen
presynaptic receptor desensitization causes increased serotonin in the synapse
- down regulation of inhibitory pre synaptic receptor
What is buspirone used for
cats - social anxiety
- causes friendly behaviour
What are the pharmacokinetics of buspirone
short half life
non linear - released dosing will give higher blood levels than if it was dose associated
What considerations should you have when giving anti-depressants
it takes weeks to see an effect (4-6wk)
should start at a low dose and adjust as needed
What are 4 types of antidepressants
SSRI
tricyclic antidepressants
atypical antidepressants
monoamine oxidase inhibitors
What is an example of an SSRI commonly used
fluoxetine
What is the effects of fluoxetine
antidepressant
antianxiolytic
anticompulsive
decrease glucose
What is the mechanism of fluoxetine
blocks serotonin transporter in the synapse
downregulated pre-synaptic 5H1A receptor
What are 2 other names for fluoxetine
prozac aka reconcile
What are the pharmacokinetics of fluoxetine and why is it important?
Good PO absorption
- SID
- metabolize slower if given more frequently
It is metabolized in the liver
competitive inhibitor of CYP450 = lots of drug interactions
also impacts CYP2319
kidney excretion
What are the adverse effects of fluoxetine
sedation and reduced appetite
How do you recommend stopping prozac administration
taper
What drugs should you not give (or be cautious) with prozac
monoamine oxidase inibitors
can cause serotonin syndrome
What are the effects of tricyclic antidepressants
antidepression
anxiolytic
anticompulsive
antiaggression
anticholinergic
antihistamine
varied efficacy
What is the mechanism of action of tricyclic antidepressants
inhibit serotonin and norepi reuptake
What are the adverse effects associated with tricyclic antidepressants
miosis
sedation
urinary retention
+/- anticholinergic effect
- constipation
- arrhythmia
- ataxia
- reduced tear production
- appetite change
- mydriasis
-tachycardia
- bp change
What are 2 examples of tricyclic antidepressants
clomipramine
amilriptyine
How does clomipramine metabolism vary between species
cats = slower because it is metabolized via glucuronidation
narrow therapeutic index
What is clomipramine used for
OCD in dogs
seperation anxiety
dominance/aggression
off label use in cats
What is an example of an atypical antidepressant
trazadone
What is the mechanism of trazadone
serotonin antagonist and reuptake inhibitor
antagonize all except 5HT1A
mainly 5HT2A (excitatory post synaptic serotonin receptors)
What is the function of 5HT2A receptors
neuronal excitation
anxiety
learning
hallucinogens
What are the effects of trazadone
antidepression
anxiolytic
hypnotic (sleep)
What is trazadone is used for?
post surgery
anxiety
phobia
+/- combo with gabapentin pre-appointment
What are monoamine oxidase inhibitors
mitochondrial enzymes in the NS/heart/liver/kidney
MAO A
MAO B - catalyze oxidative deamination of catecholamines (dopamine/epi/norepi/2-phenylethylamine/serotonin)
inhibition of MAO = increase neurotransmitter
What is an example of a MAO inhibitor
selegine HCL
What is the mechanism of action of selegine
MAO B inhibitor
inhibits dopamine metabolism in the CNS
What is another name for selegine
anipyrl
What is selegine used for
cognitive dysfunction in dogs
(also used for parkinsons and alzheimers in humans)
