Behavior Modifying Drugs

What general categories of drugs affect the CNS?

• anesthetic drugs

• Anti-seizure medications

• Analgesics

• Behavior modifying drugs

What is the main inhibitory neurotransmitter?

GABA

Give an example of an antipsychotic.

acepromazine

What two categories of antidepressants are present in vet med?

• Tri-cyclic

• SSRI

Give two examples of SSRIs.

• Fluoxetine

• Trazadone

Give an example of a tri-cyclic antidepressant.

Clomipramine

Give two examples of MAOIs.

• selegiline

• L-deprenyl

Give three categories of anxiolytics.

• Benzodiazepines

• Alpha-2 agonists

• Calcium channel blockers

Give an example of a benzodiazepine.

diazepam

Give an example of an alpha 2 agonist.

Dexmedetomidine

Give two examples of calcium channel blockers.

Gabapentin and Pregabalin

What is the target receptor for Phenothiazines or antipsychotics? What is its action?

D2 dopaminergic receptor

• block post synaptic dopamine receptors in CNS

What are the neuroleptic effects of Acepromazine?

• suppression of spontaneous movements

• Suppression of complex behaviors

• Impulse behaviors gradually diminished

• Inhibit appetite and vomiting

True or False: acepromazine is an ideal medication for behavior modification.

FALSE

What is acepromazine commonly used for?

sedative or pre-anesthetic to reduce anesthetic gas

In horses, Acepromazine has a _____ half-life which makes it have a ____ onset.

fast; rapid

True or False: Acepromazine has poor oral bioavailability

TRUE

What are the three adverse effects of Acepromazine use?

• hypotension (adrenergic alpha 1)

• Paraphimosis (horses)

• Decreases tear production in cats (adrenergic alpha 1)

What are three contraindications of Acepromazine?

• organophosphate toxicity

  • Due to mild cholinersterase inhibitor

• Avoid in cardiovascular dz

  • Due to alpha 1 block

• Avoid in epileptic patients

  • Lowers seizure threshold

Clomipramine is a ________ (drug class).

tricyclic antidepressant (TCA)

What is the mechanism of action of clomipramine?

• presynaptic reuptake inhibition which prolongs neurotransmitter action

  • MOSTLY serotonin

• Anticholinergic

• Antihistamine

• Adrenergic receptor agonist

What is the clinical use of clompramine?

OCD, ± seperation anxiety

What is the active metabolite in clomipramine?

desmethylclomipramine

Where is desmethylclompramine excreted?

urine

How does drug interaction change the drug elimination in clomipramine?

It is metabolized in the liver and can inhibit P450 enzymes. it also interacts with P450 substrates

Do you need to taper dose of a TCA before DC?

YES

What are some adverse effects of clomipramine?

• serotonin syndrome

• Antihistamine - sedation

• Anticholinergic - urine retention & constipation

• tachycardias

True or False: Cats are more sensitive to anticholinergic effects.

TRUE

What is the treatment for adverse effects associated with Clomipramine overdose?

NONE → symptomatic care only

When is clomipramine contraindicated?

patients also on a MAOI

What is the mechanism of action of fluoxetine?

selective serotonin reuptake inhibitor

What is fluoxetine approved for in dogs?

Seperation anxiety

What is fluoxetine used for in cats?

manage urinary spraying or repetitive behaviors

• off-label

What is the active metabolite of fluoxetine?

norfluoxetine

Where is fluoxetine metabolized?

liver via P450 enzymes

The active metabolite of fluoxetine, norfluoxetine, has a much longer half life than fluoxetine. What is it and why is it important?

50+ hrs

• Importance: delayed onset for behavior change & gradually decreases in plasma on its own

Why do you not need to taper the dose of fluoxetine when DC?

the half life is VERY long and slowly decreases in the plasma on its own

What are the contraindications of fluoxetine?

• epileptic dogs

• Hypersensitivity

• Patients on MAOIs

True or False: trazodone is only available in a human preparation and is used off-label in animals.

TRUE

What is the mechanism of action of trazodone?

serotonin reuptake inhibitor and antagonizes norepinephrine, serotonin 2, histamine 1, and alpha 1 and 2

What is trazodone used for?

anxiety related conditions

Why is trazodone a preferred anti-anxiety medication in animals?

It has a rapid onset so it will work within 2-3 hrs without needing a loading dose

What are the contraindications of trazodone?

• epileptic patients

• Hypersensitivity

• patients using MAOI

What are the neuromuscular signs of serotonin syndrome?

• tremors

• Hyper reflex is

• Myoclonus

• Hypertonia

What are the autonomic signs of serotonin syndrome?

• mydriasis

• Tachycardia

• Tachypnea

• Vomiting

• Arrthymias

What are the neurological signs of serotonin syndrome?

• agitation

• Excitement

• Restlessness

• Insomnia

• Confusion

What is the treatment of serotonin syndome?

• inducing Emesis

• Supportive care

What is the ONLY MAOI being used now?

Selegiline

How long does it take for selegiline to reach its maximal effect?

5-10days

What is the mechanism of action of selegiline?

inhibition of mitochondrial MAO B which prevents the degradation of dopamine

WHat is selegiline used for?

• canine Hyperadrenocorticism

• Senile cognitive dysfunction

What are the two metabolites produced with selegiline?

• Amphetamine

• Metamphetamine (METH)

What are the adverse effects of selegiline?

• vomiting

• CNS hyperactivity

What behavior modifying drug can easily be abused bu clients? Why?

Selegiline

• active metabolite is metamphetamine

Selegiline is a ______ (drug class)

MAOI

Benzodiazepines are a ______

anxiolytic

What is the mechanism of action of benzodiazepines?

binds to GABAa receptors

What are the uses of benzodiazepines?

pre-med, muscle relaxant, breakthrough seizure control

True or False: Tolerance will never build up with benzodiazepines.

FALSE

Following oral administration in cats with diazepam, what can occur?

acute fulminating hepatotoxicity

Dexmedetomine is a _______(drig class)

alpha 2 adrenergic agonist

What is the mechanism of action of dexmedetomidine?

pre-synaptic alpha 2 adrenergic agonist to work as a negative feedback

What is dexmedetomidine approved for in dogs? Horses?

Dogs - noise aversion

Horses - sedative or analgesia`

What is the reversal of dexmedetomidine?

atipamezole

What is the mechanism of action of gabapentin?

inhibits voltage gated calcium channels

True or Fale: gabapentin affects GABA receptors.

FALSE

What is the clinical use of gabapentin?

• pain managmenet

• adjunct in seizure therapy

• anti-anxiety (CATS)

What are the adverse effects of gabapentin?

• sedation

• ataxia

• impaired balance

Which drug is similar to gabapentin but has a longer duration of action?

Pregabalin