Behavior Modifying Drugs Flashcards
What are CNS neutrotransmitters affected by behavior modifying drugs
SEROTONIN
Dopamine
NE
Gaba etc
What are the 3 FDA approved behavior modyifying drugs
Clomipramine (Clomicalm)
Fluoxetine (Renoconcile)
L-deprenyl; Selegilene (Anipryl)
“CFL”
What are 3 classes of BMD
Anxiolytics
Antidepressants
Monoamine Oxidase Inhibitors
Anxiolytic example
Buspirone
Antidepressant name 2 examples
Tricyclic Antidepressants
SSRI
Monoamine Oxidase Inhibitors example
Selegiline
Buspirone MOA
An anxiolytic.
It inhibits serotonin (5HT) synthesis by binding at pre-synaptic 5HT1A receptors
Possibly enhances dopamine activity
Buspirone adverse drug reactions
No sedative effects
Cats- increased aggression to other cats
Buspirone clinical use
Canine aggression, feline spraying
Thunderstorm phobias
Self mutilation
others
Name 2 other anxiolytics besides buspirone
Benzodiazepines
Butyrophenones
Antidepressants - which one is FDA approved in dogs
Clomipramine
Antidepressant use in dogs
We use antidepressants like clomipramine to treat behaviors we (humans) find unacceptable, i.e. chewing up the mattress
Antidepressants- MOA
enhances activity of NT (5HT, NE)
blocks physiologic inactivation (blocks reuptake pumps at synapse–> less reuptake)
Tricyclic antidepressants MOA
MAO degrades NE and 5HT into inactive metabolites
Clomipramine blocks BOTH pumps !!!!!! (both NE and serotonin receptor)
More NE and Serotonin
Antidepressants- adverse drug reactions (toxicity)
Describe therapeutic index? Less serious vs Serious toxicity ?
Narrow therapeutic index
Ranges from Mild to fatal
Less serious: behavior changes, lethargy, GI
Serious: cardiac arrhythmias, hypotension, CNS depression (coma, DEATH)
Antidepressants – what to remember when dispensing
use childproof containers!!!
adverse effects!! arrythmias, hyptension, coma/death
Antidepressants- metabolism
Metabolized by CYP450 enzymes!!
careful when concurrently using P450 inhibitors
Cyt P450 inhibitors
Ketoconazole
Fluoroquinolones
Cimetidine
Rifampin
“KFCR”
Cyt P450 inducers
Phenobarbital
Griseofulvin
Concurrent use of these drugs -> subtherapeutic [TCA]
What are other drugs that potentiate NE or 5HT
MAO inhibitors
Others (later)
May lead to Serotonin syndrome
Antidepressants are labeled for separation anxiety in dogs. What are some EL uses? How long does it take for effect?
Dog, cat, horse behaviors associated with: fear, aggression, obsessive-compulsive disorders, self mutilation
These are CNS changes –> takes several weeks
Selective Serotonin reuptake inhibitors: relative sedative effects?
These are newer class of antidepressants, less likely to cause sedation
SSRI examples (3)
Fluoxetine (Prozac)
Paroxetine (Paxil)
Sertraline (Zoloft)
SSRI MOA
Similar to TCA, but specific to Serotonin Reuptake pump (5HT pump gets inhibited –> less breaking down of serotonin to inactive metabolites)
Do SSRIs have more or fewer adverse drug reactions compared to TCAs
Fewer!
SSRI drug interactions
Can inhibit CYP 450, and cause serotonin syndrome
What is the FDA approved use for SSRI? Off label use?
FDA approved for Separation anxiety (like TCA)
Also clinically used for: Lick granulomas, Tail mutilation, Aggression, Psycogenic alopecia, other behavior disorders
Canine cognitive dysfunction- what is an FDA approved drug for treatment
Selegiline or I-deprenyl (Anipryl)
Selegiline MOA
It is a MAO inhibitor so less NE ,Dopamine, and 5HT are broken down into inactive metabolites
Selegiline is also metabolized to what two things
Amphetamine
Methamphetamine
Selegiline clinical uses
Canine cognitive dysfunction
Potential benefits in people with Alzheimer’s
Selegiline and horses
High abuse potential in performance horses
Can detect amphetamine and metamphetamine in urine of horses
Selegiline adverse drug reactions
Notes say “well tolerated”. May see anorexia, restlessness, repetitive movements. Potential for human abuse.
Selegiline drug interactions
Associated with serotonin syndrome in humans (interactions of selegiline with TCAs and SSRIs)
Serotonin syndrome occurs how
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)
Serotonin syndrome signs
V/D, abd pain Hypertension, hyperthermia, hypersalivation Seizures, tremors, hyperesthesia Ataxia, blindness Death!!! *medical emergency
What are some examples of MAO inhibitors and why is this important regarding serotonin syndrome
Anipryl
Amitraz (used for mange)
St John’s wort
These inhibit MAO which increases CNS Serotonin (and catecholamine) concentration!
What are some examples of TCAs and why is this important regarding serotonin syndrome
Clomipramine
Amitriptyline
Imipramine
These block both reuptake pumps (NE and 5HT) –> less serotonin (and NE) being uptaken! More Serotonin (and NE) in CNS
What are some examples of SSRIs and why is this important regarding serotonin syndrome
Fluoxetine (Prozac)
Sertraline (Zoloft)
Paroxetine (Paxil)
SSRIs block specifically the 5HT receptor –> Increased CNS Serotonin
Of MAO, TCAs, and SSRIs, which lead to increased CNS catecholamines and serotonin? Which lead to just increased serotonin?
MAO and TCAs- both
SSRIS- just increased Serotonin
Summary- describe drug combinations to avoid serotonin syndrome
SSRIs, TCAs, MAOs (Selegiline, Amitraz)
OTC (St johns wort, ginseng, dextromorphan)
Other compounds increasing CNS NE or Serotonin
What about Fluoxetine for treatment of compulsive disorders in dogs
clinical trials- showed improvement (70%)
Key= IMPROVEMENT (we don’t get complete ELIMINATION)
