Behaviour Modifying Drugs Flashcards
Drug Classes used to modify behaviour target key neurotransmitters. These are (5):
q Norepinephrine
q Dopamine
q Serotonin
q GABA
q Acetylcholine
most drugs used to modify behaviour in vet med are meant for what species?
Currently, most drugs used to modify behaviour in veterinary medicine are extra-label use of human products
common effects of behaviour modifying drugs, in general
q Decrease arousal
q Decrease excitability
q Decrease impulsivity
q Promote calming
are behaviour modifying drugs commonly curative? what can they be combined with?
-rarely curative
-can decrease latency response to behaviour modifying techniques
common categories of major behaviour problems
-aggression
-compulsive disorders (stereotypes)
-fear, anxiety, phobias
what types of aggression are there and which type is more concerning?
Offensive versus defensive aggression
q Offensive generally more of a concern
subtypes of aggression include:
Fear
Possessive
Dominance
Maternal
Territorial
Drug classes that increase central serotonergic activity may have what effects on aggression?
Decrease
-decreased tendency to engage in sudden outbursts
-increased threshold of tolerance to potentially aggressive stimuli
what are obsessions vs compulsions? what drugs are useful for this?
q Obsessions are persistent thoughts, ideas, impulses or images that cause marked distress
q Compulsions are repetitive behaviours eg. stereotypies
q TCA’s, SSRI’s and Opioid antagonists can be beneficial
when does fear become a problem? what are anxiety and phobias, and what drugs can we use to control behaviours related to these?
q Fear is a normal behaviour, but when excessive relative to the stimulus, then it is a problem
q Anxiety is marked by apprehension of “dread or a sense of danger”
q Phobias– fears of specific objects, persons or situations that result in panic
q These types of behaviour generally benefit from anxiolytics
treatment duration for unwanted behaviours depends on what? most patients receive treatment over what time frame?
o Unwanted behaviour and species
o Drug class
o The “individual”
o Owner’s ability to comply with all aspects of therapy
n Most patients are on long-term drug therapy
o Most drugs are not given “as needed”
o Severe or refractory cases may require life-long drug and behavior modification !
ideally, how will we change the dose of behaviour drugs over time?
n Ideally, gradually reduce (taper) dose; based on individual’s response
o Monitor signs while decreasing dose; identification of lowest effective dose if problem returns
o Withdrawal symptoms generally not significant
What if the behaviour drug does not work/isn’t working?
n Remember clinical responses take time
o ~5 half-lives before steady-state
o Modification of receptor systems also takes time
n Dose modification possible; caution with ADRs
n Consider switching drug classes
n Consider combination drug therapy
is transdermal drug therapy useful for behavioural cases?
n Generally, has yielded poor to variable drug levels and efficacy
n Useful in animals that are challenging to medicate orally long-term
q Knowledge of drug pharmacokinetics key
q Collaboration with experienced pharmacist; compounding required
what are the general characteristics of phsychotropic drugs in vet med? what are their chemical properties? what tissues can they penetrate? where are they metabolized?
o Many behaviour drugs used in veterinary medicine are weak bases
> Good lipophilicity
> Protein binding generally low
o CNS penetration is generally very good
> BBB and blood-CSF barrier
o Most behavior drugs are metabolized by liver
o Species variations in metabolism (CYP450’s)
Principal anxiolytics in veterinary medicine are
benzodiazepines (BZD’s)
mechanism of action of benzodiazepines?
o Work through potentiation of the GABA-A receptors
n Anxiolytic effects believed due to modulation of 5-HT and NE neurons in the CNS
mechanism of action of benzodiazepines?
o Work through potentiation of the GABA-A receptors
n Anxiolytic effects believed due to modulation of 5-HT and NE neurons in the CNS
effects of benzodiazepines
anxiolytic
o Anxiolytic effects separate from general CNS depressant effects; dose-related
n Anxiolytic effects can be immediate; may increase with continued dosing
n Other general CNS depressant effects include:
>central muscle relaxation, sedation
>seizure suppression
when do we use benzodiazepines
o Used in fear and anxiety related problems
n Separation and general anxiety
n Noise and storm phobia where immediate effects desired
>as needed basis
are benzodiazepines safe? what are some possible side effects?
o BZDs have an excellent history of safe use
n Disinhibition possible; caution or avoid use in cases of aggression
n Paradoxical excitement and amnesia possible
n Idiosyncratic hepatotoxicity in cats possible with diazepam; not yet seen with other BZDs
n Sedation, muscle relaxation, ataxia and hyperphagia
benzodiazepines used in vet med
Diazepam
Alprazolam
Lorazepam
what is flumazenil? how is it used?
BZD antagonist that may be employed to…..
n reverse overdose effects of BZD
n reverse unwanted behavior eg. paradoxical excitement, while taking BZD’s
use of diazepam? considerations and drawbacks?
n Has short half-life in dogs (~1 hr) compared to cats (~5.5 hr)
o Active metabolites with longer-half lives make it suitable for chronic use in cats only
n Potentially disappointing for immediate effects
o Higher doses needed in panic states ?
o Daily use over as needed basis ?
use of diazepam? considerations and drawbacks?
n Has short half-life in dogs (~1 hr) compared to cats (~5.5 hr)
o Active metabolites with longer-half lives make it suitable for chronic use in cats only
n Potentially disappointing for immediate effects
o Higher doses needed in panic states ?
o Daily use over as needed basis ?
what is alprazolam and what is its use?
anxiolytic, BZD
o Higher potency BZD; promising in dogs with panic disorders where a rapid response is needed
o Higher doses may also be needed for panic states over generalized anxiety
what is lorazepam and what is its use?
anxiolytic, BZD
o Not as extensively metabolized by liver before excretion;
o Advantages in liver failure, geriatrics and cats possibly
an important non-benzodiazepine anxiolytic
Buspirone; An azapirone class anxiolytic
what is the use of buspirone and how does it work? what are some advantages for it?
An azapirone class anxiolytic
o Acts as a partial agonist at 5-HT receptors
o Does not compete directly with BZDs
o Used for generalized anxiety; poor immediate effects
o Less sedating and other side effects than BZDs
o No withdrawal effects; less abuse potential
target behaviours for antidepressants in animals
In animals the lists of targets is great…..any type of “unacceptable” behavior
n Anti-anxiety effects
n Compulsive disorders
n Some forms of aggression
General category of antidepressants includes a number of classes of drugs:
n Tricyclic antidepressants (TCA’s)
n Selective serotonin re-uptake inhibitors (SSRI’s)
n Monoamine oxidase inhibitors (MAOI’s)
generally, what do antidepressants alter in the CNS?
general property of altering primarily NE and serotonin (5-HT) levels in the CNS
Tricyclic antidepressants primary mechanism of action
The TCA’s inhibit re-uptake of NE and 5-HT, increasing levels in the CNS
what are the effects of tricyclic antidepressants? what are they used for?
n The TCA’s reduce high arousal and reduce anxiety
o The TCA’s do not produce disinhibition of behaviour
o Used to manage mild aggression, anxiety and come compulsive disorders in dogs
o Used to manage inappropriate urination, some aggression, anxiety in cats
what is primarily responsible for the adverse effects of tricyclic antidepressants?
As a group, they also possess cholinergic and adrenergic (a-1) blocking effects that are largely responsible for ADRs
o Adverse cardiovascular, GI, and urinary tract effects
o Also produce sedation
o Contraindicated in CV disease, KCS and glaucoma
o Some agents also block histamine receptors
what is Clomipramine? how does it work and what does it treat?
a tricyclic antidepressant
n Clomipramine primarily blocks 5-HT re-uptake
>Major metabolite desmethyl-clomipramine blocks NE re-uptake
n Approved in Canada in dogs for…..
o Treatment of anxiety
o Treatment of stereotypies (compulsive disorders) such as lick dermatitis
n Has also been used for anti-aggressive effects
n Can also be used in storm and noise phobias
what is Amitriptyline? what is it used for and how does it work? most common use?
a tricyclic antidepressant
o Used for behaviour modification and pain (neuropathic) mgmt
o More selective for 5-HT reuptake inhibition vs NE reuptake
o Also blocks cholinergic, adrenergic and histamine receptors
o Used to reduce arousal and promote calming
n Separation anxiety, compulsive disorders and aggression in dogs n Anxiety, psychogenic alopecia in cats
n Most common use is in cats for idiopathic interstitial cystitis
o Unclear if efficacy is due to behavior modifying effects vs
analgesic and anti-spasmotic (antimuscarinic) effects
what are SSRIs used for in vet med?
o SSRI’s are classified as antidepressants, but display a variety of effects
n Anxiolytic; separation and generalized anxiety disorder
n Panic disorder, storm and noise phobias
n Anticompulsive; eg. lick dermatitis and Anti-aggression
n Urine spraying and psychogenic alopecia
adverse effects of SSRIs?
n Generally, have an excellent safety record
o Sedation and axorexia are most common complaints
n “Serotoninsyndrome” - reported in humans; possible when SSRI’s combined with:
o 5-HT agonists eg. Buspirone
o MAOI’s; decrease metabolism of SSRI’s
o TCA’s; also possess 5-HT re-uptake effect
o OTC herbal supplements; St. John’s Wort
what is fluoxetine? what is its mechanism of action and its uses?
n SSRIs more specific in their action than the TCAs
o Block 5-HT re-uptake; limited cholinergic/adrenergic effects
o Clinical uses in dogs/cats same as general SSRIs
what is the metabolic process that fluoxetine undergoes in the body?
n Fluoxetine metabolized to an active metabolite (norfluoxetine)
o Long wash out (~6 weeks) if switching to another agent that increases serotonin
o Accumulation occurs with multiple doses………long elimination half-life of parent and even longer for norfluoxetine
what is the route of admin for fluoxetine?
o Drug is compounded or human approved tablets, capsules or oral solution
Transdermal fluoxetine available but poor and variable
bioavailability
what are a few SSRIs used in vet med?
fluoxetine
paroxetine
sertraline
what is naltrexone and what has it been used for?
opiate antagonist
-some stereotypies are related to endorphin release
>this drug has been used successfully in some of these cases
what type of behavioural issues are antipsychotics used for?
o Limited to short-term and intermittent uses “as needed”
>chemical restraint most common use
>good for intense fear/phobias when quick effects required
what is the mechanism of action of antipsychotics? what effects do they have?
o Block central dopamine (D2) receptors
-Poor anxiolytics; usually inappropriate as sole agent
- Can produce state of ataraxia (relative indifference)
- Act as major tranquilizer
- Produce behavioral quieting
adverse effects of antipsychotics
q May produce sedation
q May inhibit learning
q May decrease blood pressure
q May cause extrapyramidal effects
what are two examples of low potency antipsychotics? what is the mechanism of these drugs, and what are they primarily used for?
acepromazine, chlorpromazine
> Less extrapyramidal signs (EPS) effects likely
> Greater anticholinergic (sedation) and a-adrenergic (hypotension) blocking effects; autonomic effects
o Used primarily in noise or thunderstom phobia
what is the use of progestins in behavioural medical therapy? what is an example of one? when would we use them?
Medroxyprogesterone acetate
Used as a last resort when newer safer approaches have failed
More effective in males
o Dominance aggression and other forms of aggression
o Urine marking and roaming
how is medroxyprogesterone acetate administered?
MPA is a depot injection given IM/SC that lasts for several months
mechanism and physiologic effects of progestins?
n Act on GABA-A receptor similar to BZDs
n Possibly increase release of endogenous opioids
n Mild sedating effects thru actions on CNS steroid receptors
adverse effects of progestins given as a behavioural therapy
Adverse effects can include mammary enlargement, bone marrow suppression, possible Addison’s ds or diabetes mellitus, increased appetite and liver damage
what pheromones can be used for behavioural therapy?
-Appeasing pheromones
Pheromone extracts of intermammary sebaceous tissue (dog) or facial pheromone glands (cat)
what is the use for pheromones for behaviour?
Indicated for stress/fear associated with….
o Transport
o Boarding
o New environment or stressful events
-Produces a calming effect in association with fear, anxiety and phobias
methods of administration for pheromones
n Diffusers and sprays; also incorporated into collars
n Diffusers released into animals environment
n Sprays are applied to objects, or environment
how are anticonvulsants used for behaviour? when are they appropriate?
Have been used to manage behavioral problems that may have a seizure basis; not recommended unless a neurologic basis !!
n Tail chasing, unprovoked rage (Bull Terriers)
what type of drug is gabapentin and what sort of issues may it be of value for treating?
n Newer anticonvulsant drug class
n May be of value in anxiety and other behavioral problems
what is the mechanism of action of trazadone?
Trazadone produces NE and 5-HT reuptake inhibition; metabolites have some opiate effects
what is trazadone generally useful for in behavioural therapy? is it safe?
n Used in dogs for thunderstorms and as an adjunct to TCA and SSRI treatment
n Trazadone is generally safe in dogs and cats
what is the use of dexmedetomidine for behavioural therapy and how is it administered?
Formulated for OTM delivery in a gel and approved for noise phobias in dogs in the USA
what are common and useful combination drug therapies for behavioural issues and their effects?
Partial 5-HT receptor agonist (buspirone) with a SSRI (fluoxetine);
increased serotonin levels
Combining antidepressants with rapid onset agents
o BZDs with TCA’s or SSRI’s
n Alprazolam with clomipramine; storm phobias
n Alprazolam with fluoxetine; urine spraying
when using a combination drug therapy, what should we be careful of?
Beware of increased possibility of ADRs thru drug interactions
n Altered metabolism of one drug by another may lead to failure or
toxicity
n Increased effects of multiple drugs acting on the same NT system
- Which one of the following drugs is not considered/classified as an antidepressant (1 mark)
a. Fluoxetine
b. Clomipramine
c. Buspirone
d. Amitriptyline
c. Busiprone (is an anxiolytic)
- You are treating a 12 year old male DSH cat (neutered) for generalized anxiety and urine spraying with benzodiazepines. You are concerned about possible liver problems. Which one of the following is your best treatment option (1 mark)
a. diazepam
b. flumazenil
c. alprazolam
d. lorazepam
Flumazenil - BZD antagonist??
Diazepam - anxiolytic, hepatotoxicity in cats
Alprazolam - higher potency, good for dogs where rapid onset is needed
Lorazepam - not as extensively metabolized in liver before excretion; advantages in liver failure, geriatrics, and cats possibly
D. lorazepam
- Which one of the following pairs is incorrect (1 mark)
a. Clopidogrel: antithrombotic
b. Vitamin K1: hemorrhagic disease
c. Tissue plasminogen activator (t-PA): growth factor
d. Heparin: systemic anticoagulant
c. Tissue plasminogen activator (t-PA): growth factor
