Behavior Modifying Drugs Flashcards
What 4 behavior modifying drugs have been FDA-approved for dogs?
- Reconcile (fluoxetine) - separation anxiety
- Clomicalm (clomipramine) - separation anxiety
- Anipryl (selegiline, L-deprenyl) - canine cognitive dysfunction
- Sileo (dexmedetomidine transmucosal gel) - noise aversion
How do most clients receive behavior-modifying drugs?
extra-label with veterinarian recommendation (cheaper)
Why are psychotropics used in vet med? How do fear, anxiety, and stress factor into learning?
reduce underlying emotional arousal that contributes to undesirable behaviors and improve the quality of life for pet and owner
interferes with learning and other normal behaviors
What is needed to be used with psychotropics to reach the desired outcome?
behavior modification —> address behavior and train
What are the 5 domains of welfare?
- NUTRITION: water, food, food quality
- ENVIRONMENT: temperature, confinement, shelter
- HEALTH: disease, injury
- BEHAVIOR: choices, limitations
- MENTAL STATE: pain, thermal comfort, boredom, frustration, happiness
What are the 3 circles of animal needs?
- functioning
- natural living
- affective states
What must be done before recommending psychotropics?
rule out underlying medical causes/etiology of behavior after thorough history taking and behavioral diagnosis
What are the 2 classes of neurotransmitters targeted by psychotropics? What are the 6 most common ones?
BIOGENIC AMINE
1. serotonin
2. dopamine
3. norepinephrine
4. acetylcholine
AMINO ACIDS
5. GABA
6. glutamate
What does serotonin do in the brain? Where is most of it found in the body?
regulates mood, appetite, sleep, and some cognitive functions
1-2% in brain, most in the enteric nervous system
How can serotonin be gained from the diet?
dietary tryptophan
(5-hydroxytryptamine)
How is serotonin stored in the brain at rest? What happens during stimulation? When does action of serotonin stop?
stored in vesicles of presynaptic neurons
serotonin is released into synapses and binds to the postsynaptic receptor, activating the neuron
high-affinity reuptake of serotonin into presynaptic terminal by serotonin transporters (SERTs) proteins
What are the 2 major categories of psychotropics based on use?
- long-term (daily) for chronic use —> weeks to effect
- short-term (event) for acute use —> quick onset to last for a set amount of hours in stressful situations
(some short-term meds can be used long-term)
In what 8 situations are long-term (daily) psychotropics used?
- generalized anxiety
- fearful behavior leading to aggression
- inter-pet conflict
- separation anxiety
- cognitive dysfunction syndrome
- urine marking in cats
- stress-related house soiling
- repetitive behaviors (spinning, licking, fly-biting)
What are the 4 classes of long-term psychoactives?
- selective serotonin reuptake inhibitors (SSRIs) - Fluoxetine
- tricyclic antidepressants (TCAs) - Clomipramine
- azapirones (serotonergics) - Buspirone
- monoamine oxidase inhibitors (MAOIs) - Selegiline
How are all long-term psychoactives administered?
orally
What are the most commonly used psychotropics? Why are they preferred?
SSRIs
efficacy and few side effects
What is the mechanism of action of SSRIs?
inhibits the reuptake of serotonin by blocking the reuptake transporter (SERT) for serotonin, allowing serotonin to accumulate in the synapse and act for longer periods of time = INCREASE in serotonergic neurotransmission
What is the side effect theory of SSRIs? Why are side effects able to stop?
initially, serotonin floods ALL of its receptors because reuptake is blocked, leading to different subtypes of serotonin receptors getting saturated
most receptors downregulate over 4-6 weeks, while the postsynaptic autoreceptor remains more active with time —> therapeutic effect
How long does it take for SSRIs to work? What happens when the presynaptic serotonin receptor is activated?
3-6 weeks
inhibits serotonin synthesis and decreases release from the axon —> must wait for desensitization of serotonin autoreceptor that can take weeks
What are SSRIs classified as? What are some other properties?
antidepressants
- anxiolytic
- anti-compulsive
- anti-aggression
What are the 4 situations in which SSRIs are typically used? When can it be used as an acute/event drug?
- generalized anxiety
- obsessive-compulsive or repetitive/stereotypic behaviors
- urine marking
- aggressive behaviors
- in conjunction with behavior modification
What is the efficacy onset of SSRIs? How does this affect use?
onset of improvement is slow (3-6 weeks) and response cannot be evaluated until at lead a month
CAN’T be used as needed —> ineffective
Is there a relationship between SSRI plasma levels and response?
no
Why should SSRI use not be abruptly discontinued?
rebound withdrawal effect —>. taper to stop
What are 5 possible adverse effects of SSRIs?
- decreased appetite or GI upset (extra careful with cats - hepatic lipidosis)
- mild sedation, lethargy, decreased grooming in cats
- anxiety, restlessness
- decreased sexual motivation
- RARE: urine retention, seizures, aggression
What enzyme are SSRIs competitive inhibitors of? What can this lead to?
cytochrome P450 in the liver
elevated levels of SSRI when using other medications metabolized by cytochrome P450
In what 3 situations is it contraindicated to use SSRIs?
- animals with diabetes because it may alter blood glucose concentrations
- dogs with epilepsy or history of seizure disorders
- animals with severe hepatic impairment
What is serotonin syndrome? How does this affect SSRI usage?
taking excessive quantities of medications that increase serotonin levels or impact serotonin metabolism results in tachycardia, muscle tremors/rigidity, restlessness, panting, pacing, agitation, disorientation, confusion, seizures, and death
DO NOT combine SSRIs with TCAs, MAOIs, serotonin precursors, St. John’s Wort
What are 3 common SSRIs used? Which is FDA-approved?
- Fluoxetine (Prozac/Reconcile***)
- Paroxetine (Paxil)
- Sertraline (Zoloft)
In what 2 situations is Fluoxetine (Prozac) most commonly used? What else can it be used for?
- canine separation anxiety (Reconcile) with behavioral modification
- urine marking/spraying and house soiling in cats
- repetitive behaviors/stereotypies/compulsive behaviors
- generalized anxiety
- lessen, manage aggression
Why isn’t Fluoxetine given transdermally?
very poor bioavailability
How does Paroxetine compare to Fluoxetine?
- no dog/cat placebo-controlled clinical trials
- may be appetite enhancing
- mild anticholinergic effects —> constipation***
- shorter half-life —> dosing 2x a day
How does Sertraline compare to Fluoxetine?
- no dog/cat placebo-controlled clinical trials
- safer in animals with epilepsy
Why is Sertraline safer to used in patients with chronic kidney disease?
primarily fecal excretion, skips kidney
What is the mechanism of action of TCAs?
inhibits both serotonin and norepinephrine reuptake, increasing the availability of the NTs at the synapse
- antihistaminic
- anticholinergic
Why are TCAs able to cause significant changes evolving over time?
chronic administration leads to decreased numbers and altered function of serotonin receptors in the forebrain
How are TCAs classified? What other properties do they have?
antidepressants
- anxiolytic
- anti-compulsive
- anti-aggression
- antihistamine = more calming
How do TCA action compare to SSRIs?
less selective due to anticholinergic effects, leading to a higher side-effect profile (second line)
What are 3 uses/indications of TCAs? What is their efficacy onset?
- generalized anxiety
- urine marking
- aggressive behaviors
several days to weeks (start low and titrate up)
What 2 TCAs are most commonly used? Which is FDA-approved?
- Clomipramine (ClomiCalm***)
- Amitriptyline
What is the most serotonin-specific of veterinary TCAs? In what 5 situations is it most commonly used?
Clomipramine
- canine separation anxiety (ClomiCalm)*** with behavior modification
- urine marking in cats
- compulsive disorders
- noise aversion
- generalized anxiety
What are 5 possible side effects of Clomipramine?
- sedation (antihistamine)
- moderate anticholinergic effects - dry eye, urine retention, constipation
- arrhythmogenic (longer p-wave)
- lower seizure threshold
- RARE: severe urine retention leading to functional blocking
In what 4 situations is it contraindicated to used Clomipramine?
- pets with history of constipation, dry eye, and glaucoma
- pets with cardiovascular compromise
- pets with history of seizures or epilepsy
- breeding males —> testicular hypoplasia
Why isn’t Amitriptyline the first choice of TCAs for anxiety disorders?
- may cause neuropathic pain and acral lick in dogs
- “old school” usage for cats with feline interstitial cystitis and house soiling
What 2 additional side effects does Amitriptyline have compared to those in Clomipramine?
- moderate to severe sedation (zombie cat)
- arrhythmogenic (decreased Q-T interval)
What azapirone is most commonly used as a psychotropic? What is its mechanism of action?
Buspirone
serotonin 1A partial agonist that binds at the presynaptic serotonin autoreceptors and increases serotonin production or binds at the postsynaptic serotonin autoreceptor to mimic the effects of serotonin
What are the 2 main effects Buspirone is responsible for?
- decreases anxiety
- increases boldness (bravery drug)
In what 5 situations is Buspirone most commonly used?
- fearful, NON-aggressive pets (inter-pet conflict recipients)
- generalized anxiety
- urine marking/spraying in cats (Fluoxetine has better results)
- separation anxiety
- motion sickness in cats?
Why is it difficult to give pets Buspirone, making it less commonly prescribed?
usually needs to be given 2-3x daily
What are 4 possible side effects of Buspirone?
- increased friendliness in cats
- more assertive social interactions
- exacerbation of existing aggression
- RARE: sedation, agitation, bradycardia, GI issues, stereotypic behaviors
In what 2 situations is it commonly contraindicated to use Buspirone?
- liver and kidney disease —> decreased clearance and higher levels
- use with caution in animals with aggressive behaviors
What do MAOIs act on? What is their mechanism of action?
monoamine oxidase responsible for the oxidative deamination of dopamine, NE, and serotonin causing their breakdown
prevent the action of MAO enzymes (MAO-A +/- MAO-B) allowing the accumulation of dopamine, serotonin, and NE at the synapse
- enhances catecholamines
What MAO-B inhibitor is most commonly used as a psychotropic?
Selegiline (Anipryl)
How are neurotransmitters affected as dogs age?
decreases dopamine production in the brain —> increases free radicals (unpaired electron damages cells) or their damage
What are the 4 general mechanisms of Selegiline?
- irreversible inhibitor of MAO-B, which increases dopamine
- produced metabolites are CNS stimulants: amphetamine and methamphetamine, which contributes to efficacy and side effects
- reduces oxidative stress caused by dopamine degradation
- increases levels of superoxide dismutase that is responsible for reducing free radical formation - neuroprotective
In what 4 situations is Selegiline used? What is its efficacy onset?
- canine cognitive dysfunction (Anipryl - FDA approved)
- off-label for cognitive dysfunction in cats
- chronic anxiety?
- noise aversion?
2-6 weeks (be patient, start early)
What are 3 uncommon side effects of Selegiline?
- GI upset
- lethargy/restlessness
- irritability
