Behavior Modifying Drugs

Question 1

What are CNS neutrotransmitters affected by behavior modifying drugs

Answer 1

SEROTONIN
Dopamine
NE
Gaba etc

Question 2

What are the 3 FDA approved behavior modyifying drugs

Answer 2

Clomipramine (Clomicalm)
Fluoxetine (Renoconcile)
L-deprenyl; Selegilene (Anipryl)

“CFL”

Question 3

What are 3 classes of BMD

Answer 3

Anxiolytics
Antidepressants
Monoamine Oxidase Inhibitors

Question 4

Anxiolytic example

Answer 4

Buspirone

Question 5

Antidepressant name 2 examples

Answer 5

Tricyclic Antidepressants

SSRI

Question 6

Monoamine Oxidase Inhibitors example

Answer 6

Selegiline

Question 7

Buspirone MOA

Answer 7

An anxiolytic.

It inhibits serotonin (5HT) synthesis by binding at pre-synaptic 5HT1A receptors

Possibly enhances dopamine activity

Question 8

Buspirone adverse drug reactions

Answer 8

No sedative effects

Cats- increased aggression to other cats

Question 9

Buspirone clinical use

Answer 9

Canine aggression, feline spraying
Thunderstorm phobias
Self mutilation
others

Question 10

Name 2 other anxiolytics besides buspirone

Answer 10

Benzodiazepines

Butyrophenones

Question 11

Antidepressants - which one is FDA approved in dogs

Answer 11

Clomipramine

Question 12

Antidepressant use in dogs

Answer 12

We use antidepressants like clomipramine to treat behaviors we (humans) find unacceptable, i.e. chewing up the mattress

Question 13

Antidepressants- MOA

Answer 13

enhances activity of NT (5HT, NE)

blocks physiologic inactivation (blocks reuptake pumps at synapse–> less reuptake)

Question 14

Tricyclic antidepressants MOA

Answer 14

MAO degrades NE and 5HT into inactive metabolites
Clomipramine blocks BOTH pumps !!!!!! (both NE and serotonin receptor)

More NE and Serotonin

Question 15

Antidepressants- adverse drug reactions (toxicity)

Describe therapeutic index? Less serious vs Serious toxicity ?

Answer 15

Narrow therapeutic index
Ranges from Mild to fatal
Less serious: behavior changes, lethargy, GI
Serious: cardiac arrhythmias, hypotension, CNS depression (coma, DEATH)

Question 16

Antidepressants – what to remember when dispensing

Answer 16

use childproof containers!!!

adverse effects!! arrythmias, hyptension, coma/death

Question 17

Antidepressants- metabolism

Answer 17

Metabolized by CYP450 enzymes!!

careful when concurrently using P450 inhibitors

Question 18

Cyt P450 inhibitors

Answer 18

Ketoconazole
Fluoroquinolones
Cimetidine
Rifampin

“KFCR”

Question 19

Cyt P450 inducers

Answer 19

Phenobarbital
Griseofulvin
Concurrent use of these drugs -> subtherapeutic [TCA]

Question 20

What are other drugs that potentiate NE or 5HT

Answer 20

MAO inhibitors
Others (later)
May lead to Serotonin syndrome

Question 21

Antidepressants are labeled for separation anxiety in dogs. What are some EL uses? How long does it take for effect?

Answer 21

Dog, cat, horse behaviors associated with: fear, aggression, obsessive-compulsive disorders, self mutilation

These are CNS changes –> takes several weeks

Question 22

Selective Serotonin reuptake inhibitors: relative sedative effects?

Answer 22

These are newer class of antidepressants, less likely to cause sedation

Question 23

SSRI examples (3)

Answer 23

Fluoxetine (Prozac)
Paroxetine (Paxil)
Sertraline (Zoloft)

Question 24

SSRI MOA

Answer 24

Similar to TCA, but specific to Serotonin Reuptake pump (5HT pump gets inhibited –> less breaking down of serotonin to inactive metabolites)

Question 25

Do SSRIs have more or fewer adverse drug reactions compared to TCAs

Answer 25

Fewer!

Question 26

SSRI drug interactions

Answer 26

Can inhibit CYP 450, and cause serotonin syndrome

Question 27

What is the FDA approved use for SSRI? Off label use?

Answer 27

FDA approved for Separation anxiety (like TCA) Also clinically used for: Lick granulomas, Tail mutilation, Aggression, Psycogenic alopecia, other behavior disorders

Question 28

Canine cognitive dysfunction- what is an FDA approved drug for treatment

Answer 28

Selegiline or I-deprenyl (Anipryl)

Question 29

Selegiline MOA

Answer 29

It is a MAO inhibitor so less NE ,Dopamine, and 5HT are broken down into inactive metabolites

Question 30

Selegiline is also metabolized to what two things

Answer 30

Amphetamine | Methamphetamine

Question 31

Selegiline clinical uses

Answer 31

Canine cognitive dysfunction | Potential benefits in people with Alzheimer's

Question 32

Selegiline and horses

Answer 32

High abuse potential in performance horses | Can detect amphetamine and metamphetamine in urine of horses

Question 33

Selegiline adverse drug reactions

Answer 33

Notes say "well tolerated". May see anorexia, restlessness, repetitive movements. Potential for human abuse.

Question 34

Selegiline drug interactions

Answer 34

Associated with serotonin syndrome in humans (interactions of selegiline with TCAs and SSRIs)

Question 35

Serotonin syndrome occurs how

Answer 35

Excessive concentrations of serotonin in CNS (such as selegiline use with TCAs, SSRIs, Tramadol; also OTC things like ginseng, tryptophan, dextromethorphan, St John's wort should not be used concurrently)

Question 36

Serotonin syndrome signs

Answer 36

``` V/D, abd pain Hypertension, hyperthermia, hypersalivation Seizures, tremors, hyperesthesia Ataxia, blindness Death!!! *medical emergency ```

Question 37

What are some examples of MAO inhibitors and why is this important regarding serotonin syndrome

Answer 37

Anipryl Amitraz (used for mange) St John's wort These inhibit MAO which increases CNS Serotonin (and catecholamine) concentration!

Question 38

What are some examples of TCAs and why is this important regarding serotonin syndrome

Answer 38

Clomipramine Amitriptyline Imipramine These block both reuptake pumps (NE and 5HT) --> less serotonin (and NE) being uptaken! More Serotonin (and NE) in CNS

Question 39

What are some examples of SSRIs and why is this important regarding serotonin syndrome

Answer 39

Fluoxetine (Prozac) Sertraline (Zoloft) Paroxetine (Paxil) SSRIs block specifically the 5HT receptor --> Increased CNS Serotonin

Question 40

Of MAO, TCAs, and SSRIs, which lead to increased CNS catecholamines and serotonin? Which lead to just increased serotonin?

Answer 40

MAO and TCAs- both | SSRIS- just increased Serotonin

Question 41

Summary- describe drug combinations to avoid serotonin syndrome

Answer 41

SSRIs, TCAs, MAOs (Selegiline, Amitraz) OTC (St johns wort, ginseng, dextromorphan) Other compounds increasing CNS NE or Serotonin

Question 42

What about Fluoxetine for treatment of compulsive disorders in dogs

Answer 42

clinical trials- showed improvement (70%) Key= IMPROVEMENT (we don't get complete ELIMINATION)