Week 7 - Behavior Modifying Drugs Part 2

Question 1

2 Major Categories
1. Long-term or “Daily” for chronic use
▪ Weeks to effect
2. Short-term or “Event” medication for acute use
▪ Stressful events
▪ Quick onset, last for set # of hours
▪ Sometimes daily as multimodal/poly-therapy
*A few of the short-term meds can also be used long-term

Question 2

Indications for short-term (event)

▪ Veterinary visits!
▪ Car travel
▪ Separation anxiety (poly)
▪ Visitors
▪ Noise aversion
▪ New baby!
▪ “Bridge” medication (switching from 1 med to another or trying to wait for a medication to take effect
▪ Adjunct to daily medication; if already on long term med but have acute event that needs addressing

Question 3

Common classes: Short-term psychoactives
1. Serotonin
2.
3
4
5
bolded = FDA approve

Question 4

1. Serotonin antagonist and
   reuptake inhibitors (SARIs)
   ▪ Trazodone (really the only one that is used within this class)

Question 5

2. Alpha-2 agonists
   ▪ Clonidine
   ▪ Dexmedetomidine gel
   (Sileo®) - oral transmucosal gel

Question 6

3. GABA analogues
   ▪ Gabapentin
   ▪ Imepitoin (Pexion®): FDA approved but not
   available in U.S

Question 7

4. Benzodiazepines
   ▪ Diazepam (Valium)
   ▪ Alprazolam (Xanax)
   ▪ Clonazepam (Klonipin)
   ▪ Lorazepam (Ativan)

Question 8

5. Phenothiazine neuroleptics
   ▪ Acepromazine (PromAce®): FDA approved but not really anti-anxiety; not anti-
   anxiety psychoactive med/approval

Question 9

ALL of the drugs that will be discussed in this
section of short-term psychotropic medications are
ORALLY (and 1 is orotransmucosal) administered

Question 10

SARIs: Trazodone
Mechanism of action
▪ Blocks serotonin 2A (5-HT2A) and 2C (5-HT2C) receptors
▪ Blocks serotonin re-uptake
***▪ Trazodone strongly binds to / affinity for the 5-HT2A receptors
▪ Also blocks histamine H1 receptors AND alpha-1
adrenergic receptors
▪ Partial agonist at 5-HT1A

Answer 10

5-HT2C = serotonin

Question 11

Trazodone Uses/Indications
▪ Most common drug used for situational fear and anxiety (mostly dogs, but effective in cats)
▪ Event stress: Common (Veterinary/in-hospital, thunderstorm,
fireworks, etc.)
▪ Post-operative confinement
▪ 90% owners satisfied
▪ Stress in shelters

Question 12

Trazodone Uses/Indications
▪ Noise aversion
▪ “Bridge” medication: immediate relief while waiting for
SSRI/TCA
▪ Adjunct med: synergy w/ SSRIs/TCAs (but caution serotonin)
▪ antagonize 5-HT2 receptors
→ augment efficacy of SSRIs
▪ CAN use long-term (although typically not 1st choice)

Question 13

How many/what percent of dog owners seek treatment for their dog for noise aversion (storm phobia, fireworks, etc.), per recent studies?

Answer 13

Few (<20%)

Question 14

Noise aversion reminder
▪ Only intervention with high success:
psychopharmaceuticals (Riemer 2020; Albright and Ballantyne 2020)
▪ Desensitization occurs → maladaptive behavior responses
decrease → medication dosages and frequencies reduced
(Gruen et al 2020)

Question 15

Trazodone Uses/Indications
▪ Noise aversion
▪ “Bridge” medication: immediate relief while waiting for
SSRI/TCA
▪ Adjunct med: synergy w/ SSRIs/TCAs (but caution serotonin)
▪ d/t antagonize 5-HT2 receptors
→ augment efficacy of SSRIs
▪ CAN use long-term (although typically not 1st choice but it can be)

Question 16

Trazodone
▪ Atypical antidepressant (via SERT inh → incr serotonin)
▪ Some sedative properties (d/t antihistaminic, alpha-1 adrenergic antagonist )

Question 17

Trazodone
Pharmacologic
▪ 2nd generation triazolopyridine
derivative (good to know; not going to be asked)
▪ When taken with food → slower absorption
▪ Good oral availability

Question 18

Trazodone
Dosing
▪ Can be used every 8 hours every day, orally
▪ Large, bitter pills (so typically not 1st
choice for cats)

Question 19

Trazodone
Efficacy onset
▪ Quick onset of action: median 30-45 minutes (can occur in 15 min)
▪ Duration of action: 4+ hours

Question 20

Trazodone: Side effects and contraindications
NON-Adverse
▪ WELL-tolerated
▪ High margin of safety
▪ 5HT2A/C antagonism
→ less side effects vs SSRIs, TCAs
▪ Fewer anticholinergic effects than
TCAs
▪ **Lower seizure risk than other
▪ Less cardiac issues than TCAs

Question 21

Trazodone
Adverse
▪ GI (vomiting, hyporexia)
▪ Tachycardia, increased anxiety
▪ Behavior disinhibition, aggression

Question 22

Trazodone
Contraindications / Cautions
▪ AVOID in pets with:
▪ Severe cardiac disease
▪ Hepatic, renal impairment,
glaucoma
▪ **Those taking MAOIs

Question 23

Trazodone
Serotonin syndrome (but
trazodone often used
together with SSRI’s)
▪ Fluoxetine may inhibit
metabolization of
trazodone (not going to ask)

Question 24

Dexmedetomidine orotransmucosal (Sileo®)
▪ Indications/Uses:
▪ Noise aversion in dogs (Sileo® FDA-approved)
▪ Thunderstorm, fireworks, etc.
▪ Reduce fear/anxiety during vet visits
▪ Dosing:
▪ Applied to GUMS (btwn cheek/gum), not
swallowed (if swallowed
→ loss of
absorption/efficacy)
▪ No food or treats within 15 minutes
▪ Administer 30-60 minutes before
aversive stimulus
▪ If event > 2-3 hours → re-dose
▪ During 1 event, up to 5 doses w min 2 hour
interval
▪ Efficacy/Onset
▪ ~ 30 minutes for peak
concentration
▪ Half-life: 30 min – 3
hours

Question 25

Sileo® Side Effects/Contraindications
Side effects / Contraindications
▪ Sedation
▪ Emesis
▪ Depression of CNS (peripheral and cardiac
vasoconstriction, bradycardia, respiratory depression)
▪ FYI’s for owners:
▪ Adjust dose stopper BEFORE dispensing
▪ Wear gloves
▪ Tube lasts only 4 weeks once opened
Reversal for dexmedetomidine: Atipamezole (but owners
won’t have access to that)

Question 26

Clonidine
▪ Alpha-2A and imidazoline receptor agonist
▪ Slows NE release in reticular activating system →
decr anxiety and alertness = sedation
▪ Few clinical trials and limited evidence
▪ Uses/indications
▪ Fear-based behavior problems & anxiety in dogs
▪ Quick calming in overly “hyperkinetic” dogs
▪ Efficacy/onset
▪ ~ 30 minutes to onset
▪ May only last 4 hours in some dogs

Question 27

Clonidine adverse effects/contraindications
▪ Very sedation
▪ Transient hyperglycemia
▪ Dry mouth, constipation
▪ Aggressive behavior
▪ Hypotension, collapse, bradycardia
▪ Gradual reduction over 2-4 days should be considered
d/t withdrawal symptoms (agitation, nervousness,
hypertension in humans)

Question 28

Gabapentin
▪ GABA analogue; anti-convulsant; traditionally treatment
for chronic and neuropathic pain (spinal cord injuries,
limb amputation in humans)
▪ Uses/Indications:
▪ At high doses: Sedative, anxiolytic
▪ Reduce fear responses associated with handling and vet clinic
visits in cats (100 mg/~5 kg cat) (several studies). Most common use these days.
▪ Storm phobia in dogs (but….)
▪ Other non-behavior uses for long-term /chronic (pain)
▪ Efficacy/Onset and Duration of Action
▪ Peak plasma conc 1 to 2 hours after admin
▪ Half-life 2-4 hours (dogs and cats)

Question 29

Gabapentin Adverse/Contraindications
▪ Eliminated near exclusively via kidney
▪ Caution with kidney disease! (adjust dose)
▪ Sedation, ataxia at higher doses
▪ Low side effect profile
▪ Some cats: hypersalivation and vomiting (resolves in 8
hours)
▪ MUST be weaned off of if given chronically (for pain)

Question 30

** FYI: Gabapentin is now a controlled drug in some states **
Alabama, Kentucky, Michigan, North Dakota, Tennessee, Virginia,
West Virginia

Question 31

Imepitoin (Pexion®)
▪ Indications/Uses:
▪ Noise aversion in dogs (Pexion® FDA-approved); however,
not available in U.S.
▪ Reduce fear/anxiety
▪ Issues with use
▪ Administration must start at least 2 days prior to noise event
▪ Administration should continue 2x daily as long as noise stimuli
expected
▪ Caution w/ hepatic, renal, CV disease
▪ Adverse: ataxia, lethargy, emesis, aggression, hypersalivation in
cats

Question 32

Imepitoin (Pexion®)
▪ Indications/Uses:
▪ Noise aversion in dogs (Pexion® FDA-approved); however,
not available in U.S.
▪ Reduce fear/anxiety
▪ Issues with use (not going to ask this)
▪ Administration must start at least 2 days prior to noise event
▪ Administration should continue 2x daily as long as noise stimuli
expected
▪ Caution w/ hepatic, renal, CV disease
▪ Adverse: ataxia, lethargy, emesis, aggression, hypersalivation in
cats

Question 33

Benzodiazepines
▪ More common ones used:
▪ Diazepam (Valium)
▪ Alprazolam (Xanax)
▪ Clonazepam (Klonipin)
▪ Lorazepam (Ativan)

Question 34

▪ Reversal for
benzodiazepines: flumazenil

Question 35

Benzos
▪ Generally fast onset of action within 30 minutes
▪ Typically choose (in behavior med) based on duration of
action

Question 36

Benzos
Good for panic and profound
fear
▪ Sedative/hypnotic (potential
amnesic → learning?)
▪ Anxiolytic (anti-panic)
▪ Muscle relaxant
▪ Appetite stimulant = good for
b-mod
▪ Anticonvulsant = good if
seizures

Question 37

Benzos
HOWEVER
▪ Paradoxical “excitation”
reactions (up to 1/3 of dogs)
▪ Contraindicated in AGGRESSIVE
animals
▪ Disinhibition of aggression
▪ Ataxia common
▪ Dependance/tolerance if use
daily (not recommended)
▪ Withdrawal: anxiety, seizures

Question 38

Alprazolam
▪
**Shortest acting
▪ Duration: 2-3 hours
▪ Good for events of BRIEF duration:
▪ Storm phobia, anxiety-related events

Question 39

Diazepam
▪ Short duration of action: 4-6 hours
▪ Slightly more sedating than alprazolam
▪ Better for storm phobias in case storm is delayed –
lasts longer
▪ Do NOT use in cats (idiosyncratic hepatic failure)

Question 40

Lorazepam
▪ Longer duration of action: 6-8 hours
▪ Maybe best benzo choice for cats (IF choose benzo)
▪ No active liver metabolites (so no hepatic necrosis)
▪ Less sedating than other benzos
▪ Increases appetite → good for b-mod

Question 41

Clonazepam
▪ Longest acting: 10-12 hours
▪ Readily available and affordable
▪ May be best for daily treatment of global fear and a
daily panicking dog

Question 42

Acepromazine * IMPORTANT POINTS *
▪ **NOT an ANXIOLYTIC → it does NOT DECREASE ANXIETY
▪ It is a SEDATIVE / TRANQUILIZER
▪ FDA-approved for use in dogs, cats, horses as aid in controlling intractable
animals (and anti-pruritic, antiemetic, preanesthetic)
▪ It is best used IN ADDITION to anxiolytic meds when greater SEDATION is
needed
▪ CLINICAL doses are SIGNIFICANTLY LOWER than those listed on the label
▪ CAUTION:
▪ In aggressive dogs if only using acepromazine
→ startle response AND
worsening of aggression and CNS stimulation
▪ Dogs with multidrug sensitivity gene (MDR1) mutation: need dose reduction or
avoidance
▪ Time to onset: 15 – 30 minutes
▪ Duration of action: 3-4 hours; up to 6-8 in some animals

Question 43

Separation anxiety: fluoxetine or clomipramine

Question 44

Repetitive, obsessive-compulsive behaviors: fluoxetine

Question 45

Aggression (ONLY IF ALSO with behavior modification and
THOROUGH behavioral work-up): fluoxetine

Question 46

Inter-cat conflict: fluoxetine

Question 47

Noise aversion: Sileo transmucosal or trazodone

Question 48

Canine cognitive dysfunction: Selegiline (FDA-approved)

Question 49

Polytherapy: Daily and/or Event Meds
▪ Is patient’s behavior concerning enough that immediate
relief is needed? Safety? Welfare? Or client impatience?
▪ Start event med Q8-12 hours, then add daily med in
▪ May be able to wean off event med after daily drug reaches
therapeutic levels
▪ Maybe a pain component to behavior?
▪ Gabapentin as a “bridge” med
▪ Are there anticipated stressful events that trigger panic
that’s likely to override the effects of daily therapy alone?
▪ Start daily med and have client give test doses of an event
med in a few days

Question 50

Which psychoactive drugs can be used for daily (long-term) AND/OR event (short-term) use? (you may choose more than 1)
A. Fluoextine
B. Trazodone
C. Clomipramine
D. Gabapetin
E. Buspirone
F. Acepromazine
G. Lorazepam

Answer 50

Trazodone, Gabapentin

Question 51

Case: Johann the dog
Signalment: Johann is a 5-year-old, 32-kg (70 pounds) male, neutered
mixed breed dog.
History: Johann was adopted from a shelter when he was 1.5 years old.
He had been surrendered to the shelter when he was 5 months old
because of malodorous dermatologic issues. He was treated at the
shelter for juvenile generalized demodicosis and secondary bacterial
infections for the subsequent 3 months and was then adopted by
another owner. That owner returned Johann to the shelter after 3
weeks for being unruly, destructive, and “too much to handle.” Johann
then stayed at the shelter for another month before adoption by the
current owner.
Johann lives with 2 other male, neutered dogs and 2 male, neutered cats
in the home. He gets along very well with the other pets and all humans.
Physical exam: Unremarkable; healthy, well-muscled dog
Bloodwork and urinalysis are unremarkable
Presenting complaint: thunderstorm and firework associated anxiety behaviors
~ 30 minutes prior to storm event → ~ 30 minutes after;
* during fireworks also
* always occurred
* Pacing, whining, barking, panting, owner-directed
severe attention-seeking (climbing on top of the
owners), wide dilated pupils, trying to “escape” from
room – scratching and biting at baby gate.
* No play or toys, no interaction other dog friends during
* Not during loud music or television, vacuum cleaners, road noise, or other
loud noises.
* No separation anxiety

Answer 51

1. Medications: Trazodone 5mg/kg (150
   mg) PO, 30-60 min prior or 1st sign
2. Pheromone collar (Dog Appeasing
   Pheromone by Ceva) and diffusers
3. ThunderShirt
4. Behavior: Desensitization and counter-
   conditioning VERY important for
   success
   Diagnosis: Noise aversion (aka: noise phobia or anxiety, thunderstorm phobia or anxiety)

Question 52

Case: Pedro the cat
➢Signalment: Pedro is a 6-year-old 4.9-kg (10.8 pounds) male,
neutered domestic shorthair cat.
➢History: Pedro was adopted from a shelter when he was 4 months
old. In his new home, he had been living with his owners (a couple)
and 2 other adult male, neutered cats for the past 4 years. All 3 cats
got along well. Approximately 1.5 years ago, the owners adopted a 4th
cat, another 4-year-old male, neutered domestic shorthair cat.
➢Physical exam: Pedro is bright, alert, responsive. He received 100 mg
gabapentin prior to his veterinary visit so he was very amenable to his exam.
His physical exam was unremarkable other than dermatological findings: coat
somewhat unkempt, ungroomed with a greasiness and some dander/scaling
noted
➢Bloodwork and urinalysis are unremarkable
➢Presenting complaint:
➢Pedro’s interactions with newest cat, Bart, problematic: stares,
growls, chases
➢After family relocation 1 yr ago → Pedro antagonism worse →
swats, scratches, bites, displaces Bart from rooms &
litterboxes, and…
➢Pedro backs up to wall, quivers tail, sprays w urine (mostly)
➢Pedro guards access to 2nd floor; Bart spends time in basement
➢Owners: verbal reprimands → Pedro walks away → tail flicks,
quiver, spray → more verbal reprimands and “shoo’ing”
➢Other 2 cats in home: allogrooming, bonded to both Pedro & Bart
➢Pedro hides from visitors
➢Pedro scared of loud noises
➢Past 6 months: Pedro paces, isolating

Answer 52

Diagnoses: Inter-cat conflict with territorial aggression;
urine marking secondary to anxiety; generalized anxiety disorder

1. Medications:
   a. Fluoxetine at 0.25 mg/kg (1.25 mg) PO Q24 x 14 days, then 0.5 mg/kg
   (2.5 mg) PO Q24
   a. After 2 month recheck, increased to 0.8 mg/kg (4 mg) PO Q24
   b. Gabapentin at 5 mg/kg (25 mg) PO Q24 x 5 days, then Q12
2. Pheromone diffusers (Ceva Optimum) and Feliway spray (Ceva)
3. Behavioral and environmental modification VERY critical
   to success