HowBehavioral Introduction Medications$Work$and …...Type(in(questions! Emailed(to(you48hours...

5/22/16

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How Behavioral Medications Work and How to Use Them

Lisa Radosta DVM, DACVBFlorida Veterinary Behavior Service

[email protected]

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Garret Pachtinger, VMD, DACVECC

COO, VETgirl

Introduction

Justine A. Lee, DVM,

DACVECC, DABT

CEO, VETgirl

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Lisa Radosta, DVM, DACVBFlorida Veterinary Behavior Service

[email protected]

Introduction RoadmapNeurotransmitters CompoundsMedicationsProductsDecision makingCases

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Cases

SupplementsMedications

Medication Classes

Roadmap

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Compounds

Neurotransmitters

Amino Acids

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GABA=

inhibitory

Glutamate =

excitatory

+-

Glutamate

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Most widespread NT in brain

Dysregulation:VigilanceAnxiety

Muscle tension

“Master Switch” of the

brain

GABA

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Regulatory Fxns:VigilanceAnxiety

Muscle tensionCognitionLearning

Major mediator of excitatory signals in most aspects of normal brain functioning

Compounds and Medications Affecting GABA and Glutamate

General PointsDogs and cats unless otherwise notedPVPAcute and chronic dosingFear, Anxiety and StressTest doses required for PVP useDose 2 hours prior to appt for PVP use

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Compounds/Medication Classes

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Benzodiazepinesα-casozepineMagnolia

Phellodendrongabapentinl-theanine

l-theanine

GlutamateGABA • Bovine protein supernatant• GABAA receptor• Lactose free• 15-30 mg/kg SID

Alpha-casozepine

• Green tea extract• Structural analogue of glutamate• Glutamate antagonist• Gabanergic• Dopaminergic• 5-10 mg/kg BI

l-theanine• Bark extract-honokiol• GABAA receptor• Glutamate antagonist• 250 mg/20.7 kg (w/phellodendron)• Effect rev by flumazenil

Magnolia officinalis

• Synergistic with Magnolia • Berberine• Diazepam/buspirone

Phellodendron amurense Ingredients/Products

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L-Theani neα-casozepine Magnolia offici onalis

Phellodendron amurense

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• S-50 mg tablets• M & L 100 mg tablets• Suntheanine• Blister packed• Chewable• Flavored

Anxitane• Thiamine-100 mg• L-tryptophan-75 mg• Colostrum Calming complex-25 mg• L-theanine-25 mg• Chewable• Flavored

Composure Pro

• L-theanine• Magnolia and Phellodendron• Whey protein concentrate• Chewable• Flavored• Small and med chewable• Med-large chewable tablet

Solliquin Solliquin

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• Alpha-casozepine• 75 mg, 225 mg, 450 mg• Non flavored• Capsule

Zylkene

Benzodiazepines30

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Benzodiazepines-Tips

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Try another benzo if first one is not effective

Single agent PVP: FAS w/ no aggressi on

Combi ne with other meds if potent sedati on

desired.

PVP: Use with pai n

medicati ons if patient is pai nful

Benzodiazepines-Pro

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Relieves FAS

Fast onset: 30-60 mi n

Increased appetite

Can use with many other medications and in many

different patients

Low incidence of physi ologic effects

Benzodiazepines-Con

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Paradoxical excitementMuscle

relaxationHyper phagiaDisinhi bitionSedati onBoldnessSociability

Cannot use diazepam in cats

Variable response withi n and between

indivi duals.

No anal gesia

Benzodiazepines

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Clonazepam (Cats)0.015-0.2 mg/kg

Clonazepam (Dogs)0.1-0.5 mg/kg

Diazepam (Dogs)0.5-2.2 mg/kg

Alprazolam (Cats)0.125-0.25 mg/cat

Alprazolam (Dogs)

0.02-0.2 mg/kg

Gabapentin

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Anticonvulsant, neuropathic pai n, mild sedati on, anxi olytic

Moderate sedati on

Low incidence of physi ologic si de

effects

AtaxiaIntensifies other

sedatives

Gabapentin

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Dogs20-40 mg/kg up to q8

Cats50-100 mg/cat

OR10-20 mg/kg up to q8

Effect: 1-2 hours

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SummaryGABA is inhibitoryGlutamate is excitatoryCompounds which enhance the binding of GABA or slow/block the binding of glutamate decrease the FAS response

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Compounds and Medications Affecting

Serotonin, Norepinephine and Dopamine

General guidelinesDogs and cats unless otherwise notedChronic dosing unless otherwise notedFear, Anxiety and Stress

3940

NE receptor

MNT

synaptic cleft

post synaptic membrane

pre synaptic neuronAnxious Patient

MNT=Monoamine Neurotransmitter

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MNTreceptor

vesicles

synaptic cleft


NT reuptake transporter

pre synaptic neuron

MonoaminesMNT=Monoamine Neurotransmitter

MNT

MonoaminesNE SE

DA

Pleasure MotivationEnergy Reward

VigilanceAlertness

ConcentrationEnergy

ImpulsivityObsessionsCognition

EmotionMoodPainFocus Appetite

Aggression

AnxietyImpulsivityIrritability

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Medication ClassesNE SE

DA

SARISSRI

l-tryptophan

TCA

MAO

Medications/ProductsNE SE

DA

fluoxetineparoxetinetrazodone

CALMi/d stressc/d stress

Clomicalmamitriptylline

selegiline

sertraline

• Essential amino acid• Competition for large neutral AA transporter• Poor intestinal absorption• Precursor to serotonin, melatonin• 2-10 mg/kg BID

L-Tryptophan Calm Diet

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l-tryptophan

α-casozepine

Nicotinamide (vitamin B3)

PRN or daily

2 weeks to effect

S/O diet base

C/D Stress

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α-casozepine

Kruger JM, Lulich JP, Merrills J, e t al. Proceedings. American College of Ve te rinary Internal Medicine Forum 2013.

L-tryptophan

Fatty aci ds

I/D Stress

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α-casozepine

Beet Pulp

Flax Seed

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SE receptor

serotonin

synaptic cleft


pre synaptic neuron

SE reuptake transporter

SSRI

SSRISE receptor

SE transporter

SSRI

SSRI

Sedati onAgitati on

Decreased appetiteReducti on

FearAnxiety

Impulsivity

Time to effect:4-6 weeks

SSRI

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Sedati onAgitati on

Decreased appetite

Reducti on in:Fear

AnxietyImpulsivityStressPhobia

SSRI

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Fluoxetine (Prozac®)

Dogs-0.5-2 mg/kg q24Cats-0.5-1.5 mg/kg q24

Paroxetine (Paxil®)Dogs-0.5-2 mg/kg q24Cats-0.5-1.5 mg/kg q24

Sertraline (Zoloft®)Dogs-1-3 mg/kg q24Cats-0.5-1.5 mg/kg q24

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SE receptor

serotonin

synaptic cleft


pre synaptic neuron


SARI

SARI

SE 5HT2 receptor

serotonin

SE receptor

SE transporter

SARI

SARI

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Medications Uses

trazodoneAcuteAnxietyFearPhobia

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Trazodone

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Sedati onAgitati onDecreased appetite

Monitor liver enzymes

Time to effect:1-2 hours

Consi der carefully use with TCAs,

MAOs, tramadol or SSRIs.

Durati on of ef fect 4-8 hours

No anal gesia

Trazodone

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Dogs3-8 mg/kg Cats

25-50 mg/cat

Give on empty stomach

Dose the night before and 2 hours prior to event

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SE receptor

synaptic cleft


pre synaptic neuron


TCA

TCA

H1receptor

NE receptorCholinergic

receptor

NE reuptake transporter

TCA

Dry MouthConsti pati onSedati on

Urinar y Retenti onChanges i n appetite

Time to effect:4-6 weeks

Calmi ng effect 3-5 days

IncreasedFocus

TCA

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Medications Uses

clomipramine (Clomicalm®)

amitriptylline (Elavil®)

AnxietyFearStressPhobia

Lack of focus

Tricyclic Antidepressants

Clomipramine (Clomicalm®)

Dogs-1-3 mg/kg q12Cats-0.5-1.5 mg/kg q24

Amitriptyline (Elavil®) Dogs-1-2 mg/kg q12Cats-0.5-1.0 mg/kg q24

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Clonidine

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alpha 2 agonist

Dogs0.01-0.05 mg/kg

Mild-moderate sedati on

Reducti on in noradrenergic activity less ar ousal and

vigilance

No anal gesia

SummaryRegulation of serotonin generally has a calming behavioral effectRegulation of norepinephrine generally has a calming behavioral effect and a reduction in SNS signs

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Making Prescribing Choices

• Medications•duration of effect, dosing, time to effect, metabolism

• Species• Patient health• Pain level• Temperament• Severity of FAS• Further sedation necessary• Disinhibition• Start low and go up

Prescribing Considerations

Manage Owner Expectations

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When to administer?

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Management affects response

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Questions

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Parameter PrescribeDo not

PrescribeRecovery long short

Welfare yes no

Environment no yesRisk yes no

Predictability no yes*Latency to

Arousal short long

Severity mod-sev mild

Questions

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When does the patient exhibit clinical signs?

What does the patient look like?

Which NT do you thi nk may be dysr egulated?

Risk?

PRN medicati on

Questions and Outcomes

Welfare?

Environment?

Severity?Latency to arousal ?

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No Medicati on

Predictable?

PRN Medication + Daily medication

Daily

Recovery?

PVPsSpecial Considerations

When to use

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Veterinary or travel FAS

Can the owner medicate the

pet?

Medications are not a last resort

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PVP combinations

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SedativeAnxi olytic

Benzodiazepineα-casozepineL-theanineMagnolia

Phellodendron

Anxi olytic/Sedative

Do not use cloni dine and acepromazine together

clonidi negabapentin

trazodoneacepromazi ne

Benzodiazepines-Tips

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Single agent PVP: FAS w/ no aggressi on

PVP: Use with pai n

medicati ons if patient is pai nful

Gabapentin-Tips

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Loading dose the night

before, then 2 hours prior

Clonidine-Tips

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Usually not enough

sedati on by itself for PVP.

No anal gesia

Loading dose the night before and 2 hours prior to visit.

Trazodone-Tips

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Loading dose the night before and 2 hours prior to visit.

Mild-moderate sedati on

No anal gesia

Supplements-Tips

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Administer 7 days prior to event.

Start at low end of range for 3 days, then i ncrease to upper end of range for remaini ng

days.

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Acepromazine

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Increased:Noise

sensitivityAggressi on

Not an anxi olytic

Moderate sedati on

Long durati on-patients may be groggy at home

No anal gesia

Do not use alone in patients with

FAS.

Acepromazine

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Dogs0.5-2.2 mg/kg up to q12

Cats0.25-2 mg/kg up to

q12

Review

Compounds/Medication Classes

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L-TheanineBenzodiazepinesα-casozepinegabapentinMagnoliaPhellodendron

L-theanine

Glutamat eGABA Norepinephrine

clonidineClomicalmamitriptyline

Serotonin

trazodoneClomicalmfluoxetinesertralineparoxetineamitriptyline

Cases

CasesStraightforwardSimilar diagnosesLots of optionsWhat is the best choice?

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• CS-Inappetence, depression, destruction• Dx-separation anxiety• Which PRN medication class?

Sweetie

Benzodiazepine

• Sweetie’s owner works 12 hour shifts• Which benzodiazepine?

Sweetie

clonazepam

• Sweetie’s owner is a stay at home mom and isn’t gone more than 2 hours at a time.• Which benzodiazepine?

Sweetie

alprazolam

• CS-phrenetic, pacing, panting, destruction• Eats treats when alone• Dx-separation anxiety• Which PRN medication class?

Maya

SARI

• Hiding, dilated pupils, tucked tail when visitors come over. • Owner has visitors daily and wants him to be more social.• What supplement would be most appropriate?

Sydney

Zylkene

• CS-Dilated pupils, tucked tail, attempts to escape, growling, barking at the veterinarian’s office• Dx-fear related aggression• Give 3 PVPs which may be appropriate.

Duke

gabapentin, trazodone, cl oni dine

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• CS-Dilated pupils, tucked tail. • No aggression, mild sedation.• Give 2 add on PVPs which may be appropriate.

Duke on trazodone

diazepam, clonidi ne

• CS-urination, salivation, urination, destruction when alone• Owner works long hours.• Dx-separation anxiety, impulsive behavior• Which daily medication would be a good choice?

Grady

Clomicalm

• CS-destruction when alone• Owner works long hours.• Dx-separation anxiety, generalized anxiety• Which daily medication would be a good choice?

Rusty

Fluoxeti ne

• CS (at vet clinic)-dilated pupils, in the back of carrier, hissing in carrier. When examined, swatting, biting• Dx-fear related aggression• List 3 first choice PVPs which would be a good options.

Fluff

Solliqui n, gabapentin, trazodone

• CS (at vet clinic)-dilated pupils, defensive body posture, no aggression• Dx-fear related aggression• List 2 first choice PVPs which would be a good options.

Gigi

Zylkene, alpraz olam

SummaryKnow what the neurotransmitters do.Know which neurotransmitters are likely to be in play given the clinical signs.Choose medications which dampen the clinical signs by affecting the neurotransmitters in play.

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#CPRwheel

Check out our 2016 upcoming VETgirl appearances!Dr. Justine Lee

AVMA, July 2016CVC, August 2016ACVC, October 2016

Dr. Garret PachtingerPVMA, May 2016SWVS, September 2016

@VetGirlOnTheRun

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