Lecture 6- Nervous System Drug Overview 2

Common behavioral issues

Separation anxiety, noise phobia, aggression, compulsive disorders, inappropriate elimination, cognitive dysfunction.

Behavioral treatment approach

Thorough assessment, documentation, rule out pathology, behavioral intervention + medical intervention.

Integrated treatment program goals

Protect patient/owner, provide suitable environment, implement behavior modification, perform risk assessment before medication.

Diagnostic criteria: separation anxiety

• Distress only when client absent

• physical injury, physiologic signs, behavioral/cognitive/emotional changes

Diagnostic criteria: noise phobia

Profound, nongraded extreme response to noise with avoidance/escape/anxiety + sympathetic signs.

Diagnostic criteria: panic disorder

• Sudden, profound fearful response

• stimulus may be unknown

• differs from phobia (less discrete trigger)

Nonspecific signs of anxiety

Panting, trembling, salivation, vocalization, pacing, hiding, hypervigilance, GI changes, grooming changes, ritualized behaviors.

Medical behavioral modification: drug categories

Situational medications + daily maintenance antidepressants.

Situational vs daily maintenance

• Situational = predictable events, rapid onset

• Maintenance = persistent anxiety, slow onset, daily dosing.

Situational medication examples

Dexmedetomidine, tasipimidine, benzodiazepines, trazodone, gabapentin.

Daily maintenance examples

Fluoxetine, clomipramine, other SSRIs/TCAs.

FDA-approved situational meds

Dexmedetomidine (Sileo®), Tasipimidine (Tessie®).

Alpha-2 agonist MOA

Bind presynaptic α2 receptors → ↓ norepinephrine release → ↓ CNS transmission → anxiolysis.

Alpha-2 agonist adverse effects

Vomiting, cardiovascular depression, bradycardia, hypotension, reduced alertness

• potentiated by CNS depressants.

Dexmedetomidine (Sileo®) indication

Canine noise aversion.

Sileo® administration

Oromucosal (cheek/gum); swallowing reduces efficacy.

Sileo® timing

30–60 min before noise or at first fear signs.

Sileo® adverse effects

Sedation, bradycardia, ↓ body temperature.

Sileo® cautions

Cardiovascular, respiratory, hepatic, renal disease; hypotension, hypoxia, bradycardia.

Tasipimidine (Tessie®) indication

Noise aversion AND separation anxiety.

Tessie® administration

Oral solution, swallowed.

Tessie® timing

~1 hour before event.

Tessie® adverse effects

Lethargy, GI effects.

Tessie® cautions

Do not give if dog still drowsy from prior dose; food delays absorption.

Sileo vs Tessie: key difference

• Sileo = oromucosal

• Sileo = noise only

• Tessie = swallowed

• Tessie = noise + separation anxiety.

Benzodiazepines situational uses

• Calming, anxiolysis, sedation

• panic/phobia

• rapid onset

Benzodiazepine MOA

GABA-A positive allosteric modulator → ↑ GABA affinity → ↑ Cl⁻ influx → inhibition.

Benzodiazepine unwanted effects

Excessive sedation, cognitive/motor impairment, tolerance, dependence, paradoxical excitement/aggression.

Benzodiazepine contraindications

• Households with substance abuse

• caution with hepatic disease

Diazepam behavioral notes

• Anxiety in dogs

• first-pass metabolism

• metabolites

• PO causes fatal hepatic necrosis in cats

Clorazepate notes

• Anxiety in dogs

• oxidized in stomach to nordiazepam

• crosses placenta/milk

• teratogenic

Alprazolam notes

• Rapid response

• panic disorder/storm phobia

• no extensive hepatic metabolism

• sedation, paradoxical excitement, dependence

Oxazepam notes

• Fears/phobias

• appetite stimulant in cats

• glucuronidated

• sedation, paradoxical excitement

Lorazepam notes

• Fears/phobias

• short t½

• appetite stimulant in cats

Chlordiazepoxide notes

• Appetite stimulant, anxiety, sedation

• zoo animals; long t½

• sedation, ataxia, rage, liver dysfunction

Other pre-event adjuncts

Trazodone, gabapentin, clonidine, benzodiazepines.

Trazodone MOA

Serotonin antagonist/reuptake inhibitor (SARI).

Trazodone uses

Previsit anxiety, confinement, travel, postoperative restriction.

Trazodone concerns

Sedation, ataxia, serotonergic interactions.

Gabapentin MOA

α2δ calcium-channel ligand.

Gabapentin uses

• Previsit anxiety, handling, travel

• useful in cats

Gabapentin concerns

• Sedation, ataxia

• renal elimination

Clonidine MOA

Alpha-2 adrenergic agonist.

Clonidine uses

Fear/anxiety/hyperarousal situations.

Clonidine concerns

Bradycardia, hypotension, sedation.

Five-step separation anxiety plan

1. management

2. tools

3. social cues

4. desensitization/counterconditioning

5. medications

Quicker-onset meds for separation anxiety

Trazodone, gabapentin, clonidine, benzodiazepines.

Slower-onset meds for separation anxiety

SSRIs (fluoxetine), TCAs (clomipramine).

Monoamine hypothesis

Impaired monoamine activity → depression; increased activity → mood elevation.

Main monoamines

Dopamine, serotonin, norepinephrine.

Antidepressant general MOA

Modulate monoamine neurotransmission (5-HT, NE).

Antidepressant onset

• Pharmacologic effect hours/days

• clinical response weeks

Antidepressant mechanisms

• Reuptake inhibition (SSRIs, TCAs, SNRIs)

• MAO inhibition (MAOIs)

TCA mechanism

• Inhibit serotonin + norepinephrine reuptake; block muscarinic, H1, α1 receptors

• cardiac ion-channel effects

TCA adverse effects

Dry mouth, urinary retention, constipation, sedation, hypotension, cardiotoxicity.

Clomipramine indication

FDA-approved for canine separation anxiety with behavior modification.

Clomipramine concerns

GI effects, sedation, anticholinergic effects; cardiovascular effects; seizure risk; serotonergic interactions.

Clomipramine cautions

Avoid MAOIs, cardiac disease, seizure disorders, urinary retention, reduced GI motility.

SSRI mechanism

Selective inhibition of serotonin reuptake → ↑ synaptic serotonin.

SSRI uses

Separation anxiety, generalized anxiety, compulsive disorders, selected aggression, feline urine marking.

SSRI adverse effects

Reduced appetite, GI signs, lethargy/agitation, sleep changes, tremors.

SSRI risks

Serotonergic interactions, seizure-threshold concerns, abrupt behavioral changes.

Fluoxetine indication

FDA-approved for canine separation anxiety with behavior modification.

Fluoxetine PK issue

Long-lived active metabolite → prolonged washout.

Fluoxetine adverse effects

Reduced appetite, GI effects, lethargy, restlessness, trembling, weight loss.

Fluoxetine restrictions

Epilepsy/history of seizures; MAOIs; serotonergic drugs.

Fluoxetine vs clomipramine: anticholinergic effects

• Fluoxetine minimal

• clomipramine more significant

Fluoxetine vs clomipramine: cardiovascular concerns

• Fluoxetine fewer

• clomipramine more

Fluoxetine vs clomipramine: seizure concerns

• Fluoxetine contraindicated with epilepsy

• clomipramine caution

Serotonergic interaction contributors

SSRIs, TCAs, trazodone, tramadol, buspirone, dextromethorphan, SNRIs, MAOIs.

Serotonin syndrome cause

Excess serotonergic activity due to overdose, dose increase, interaction, inadequate washout.

Serotonin syndrome signs

Agitation, restlessness, disorientation, vocalization; tremors, myoclonus, hyperreflexia; hyperthermia, tachycardia, BP changes, vomiting/diarrhea.

Transition principles

• Account for active metabolites

• fluoxetine requires long washout

• MAOI transitions require explicit planning

Canine cognitive dysfunction syndrome

• Age-related neurodegenerative condition

• treated with MAOI selegiline (Anipryl®)

MAOI mechanism

Inhibit monoamine oxidase → ↓ degradation of serotonin/norepinephrine.

Selegiline indication

Canine cognitive dysfunction syndrome

Selegiline risks

Serotonergic interactions; avoid with SSRIs/TCAs.

Key exam trap: Sileo administration

• Must be oromucosal

• swallowing reduces efficacy

Key exam trap: alprazolam

• Rapid onset

• paradoxical excitement possible

Key exam trap: trazodone

• Serotonergic interactions

• sedation

Key exam trap: fluoxetine

Long washout due to norfluoxetine.

Key exam trap: clomipramine

• Anticholinergic + cardiac effects

• seizure risk

Key exam trap: serotonin syndrome

Recognize triad: mental-status changes + neuromuscular signs + autonomic instability.

Key exam trap: gabapentin

• Sedation/ataxia

• renal elimination

Key exam trap: clonidine

Bradycardia/hypotension.