CNS (Anxiolytics/Antidepressants) - NICOLE Flashcards
do you need to taper CNS drugs?
YES!
behaviour modifying drugs the potential to result in
aggression
behaviour modifying drugs generally take ___________ ___________ to exert their full effect
several weeks - neurotransmitters adapt slowly to treatment
examples of anxiolytic drug classes
benzodiazepines
azopirones
antihistamines
barbiturates
examples of benzodiazepines
diazepam, midazolam
are benzodiazepines analgesics ????
NO
benzodiazepines clinical effects
-anxiolytic
-sedative and hypnotic at higher doses
-anterograde amnesia (good for pre-anesthetic, bad for long-term behaviour)
-muscle relaxant
-anticonvulsant
-appetite stimulant
-respiratory depressant
should you give oral diazepam to cats?
no - hepatic necrosis
different effects of benzodiazepines are due to
variations in the GABA receptor
benzodiazepines- chronic administration can cause
GABA receptor down-regulation
can you get tolerance to benzodiazepines
yeah boiiiii as soon as 1 week after chronic administration
when administering benzodiazepines do you need to gradually taper
chronic administration to prevent discontinuation syndrome - nervousness, tremors, seizures
what is an excellent sedative for small ruminants (especially goats)
diazepam - has a better safety profile than xylazine
however DOESNT PROVIDE ANALGESIA
midazolam - can it be given IM?
yes - DIAZEPAM CANNOT
Buspirone - the only clinically relevant
azapirone - but not licensed in vet med in Canada
serotonin is very important bc
regulates sleep, sensory perception, cognition, motor activity, appetite, intestinal motility, temperature regulation, mood, and behaviour
many hallucinogens have structures similar to
serotonin
there are many different subtypes of serotonin receptors - most are
G protein coupled
are serotonin receptors presynaptic or postsynaptic
either
the 5-HT1A receptor can get sensitized by
buspirone and SSRIS
buspirone is used for
fear/poor socialization in cats
- causes increased friendly behaviour and reduced anxiety and doesn’t affect memory, so animal learns behaviour
behavioural effects of buspirone seen after
1-4 weeks of regular administration
examples of antidepressants
-selective serotonin reuptake inhibitors (SSRIs)
-Tricyclic antidepressants
-monoamine oxidase inhibitors (MAOs)
-atypical antidepressants
how do antidepressants work (very general)
generally potentiate (ether directly or indirectly) the actions of serotonin and/or norepinephrine in the brain
antidepressants take how long to work
several weeks to see full effects
antidepressants work best if combined with
behavioural therapy
how to dose antidepressants
-start at low end of dose and assess response to minimize adverse effects
-wait an appropriate amount of time between dose adjustments (generally at least 2 weeks)
- CAN TAKE 4-6 WEEKS to see full response
examples of SSRIs
fluoxetine (most important), paroxetine, sertraline
SSRIs are antidepressants with what effects
anxiolytic, anti compulsive, and anti-aggressive effects
SSRIs work by
blocking the reuptake of serotonin, making more available at the synapse. VERY SELECTIVE
- competitive inhibitors of cytochrome P450 enzymes which may lead to increased concentrations of drugs metabolized by cytochrome P450 enzymes
SSRIs effect on blood glucose levels
can lower blood glucose levels, so use with caution in diabetic patients
is there a relationship between SSRI plasma concentrations and clinical effect?
very little relationship
should you discontinue SSRIs gradually
ya
Fluoxetine is also known as
prozac
use GREAT CAUTION if combining fluoxetine with
monoamine oxidase inhibitors (MAOIs) as this can lead to serotonin syndrome
serotonin syndrome occurs when
excessive stimulation of serotonin receptors results in muscle rigidity, myoclonus, salivation, agitation, and hyperthermia. It is more likely to occur if 2 SSRis are used together or and SSRI is combined with a MAOI.
CAN BE FATAL
tricyclic antidepressants examples
clomipramine (more important) and amitriptyline
tricyclic antidepressants work by
inhibiting serotonin and norepinephrine reuptake
- also have anticholinergic and antihistaminic effects
tricyclic antidepressants (TCA) have what effects
antidepressant, anxiolytic, anticompulsive, and antiaggressive
TCA mechanism of action
block NE and serotonin re-uptake
adverse effects of TCA are due to
lack of receptor specificity
adverse effects of TCA
sedation, miosis, urinary retention, + others related to anticholinergic effects
clomipramine is approved for use in
dogs for obsessive compulsive disorder and for dominance aggression & separation anxiety
when using clopramine, what do you need to do
increase & decrease doses gradually
- know cats metabolize it more slowly than dogs & require a lower dose
- know there’s a narrow therapeutic index - overdoses can be life threatening
Trazadone is an atypical antagonist - it works by
serotonin antagonist and reuptake inhibitor
trazadone effects
antidepressant, anxiolytic, hypnotic (sleep-inducing)
- used as anxiolytic prior to vet appointments in nervous dogs and cats +/- gabapentin
trazadone antagonizes which serotonin receptors
ALL except 5-HT1a - at low doses primarily acts as a 5HT2a antagonist, which is associated with neuronal excitation, anxiety, and learning
Monoazmine Oxidase is a mitochondrial enzyme found in the
NS, heart, liver, kidneys, spleen, platelets with 2 diff types -MAO-a and MAO-B
in the CNS, MAO-B catalyzes the oxidative deamination of
catecholamines, including dopamine, norepinephrine, epinephrine, 2-phenylethylamine, and serotinin
MAOIs inhibit the oxidative deamination of hormones/neurotransmiters listed in last question, which means
more neurotransmitters are available
example of MAO-B inhibitor
selegiline - used to treat cognitive dysfunction in older dogs
