Behaviour Modifying Drugs 1/2 Flashcards
Drug Classes used to modify behaviour target key neurotransmitters (5)
-Norepinephrine
-Serotonin
-Acetylcholine
-Dopamine
-GABA
4 ways to use drugs manage unwanted behaviours
-Decrease arousal
-Decrease excitability
-Decrease impulsivity
-Promote calming
Drug classes that ______ central serotonergic activity may produce a
______ in aggression
increase; decrease
-decrease tendency to engage in sudden outbursts
- increase threshold of tolerance to potentially aggressive stimuli
what type of drugs can be beneficial for compulsive disorders
TCA’s, SSRI’s and Opioid antagonists
what do fear/anxiety/phobia behaviours benefit from
anxiolytics
what will treatment duration vary with (4)
o Unwanted behaviour and species
o Drug class
o The “individual”
o Owner’s ability to comply with all aspects of therapy
most patients are on _______ therapy
long term
issues with transdermal drug delivery
-Generally, has yielded poor to variable drug levels and efficacy
- But Useful in animals that are challenging to medicate orally long-term
what happens if the drug doesnt work? (4)
-Remember clinical responses take time (~5 half-lives before steady-state, Modification of receptor systems also takes time)
-Dose modification possible; caution with ADRs
-Consider switching drug classes
-Consider combination drug therapy
most behaviour drugs are metabolized by the ____
liver
quality of CNS penetration of psychotropic drugs
generally very good…. for BBB and blood-CSF barrier
Many behaviour drugs used in veterinary medicine are ___ ____ and why
weak bases
o Good lipophilicity
o Protein binding generally low
drugs with long vs short 1/2 life
o Drugs with short t½’s do not accumulate; need to be given
frequently
o Drugs with long t½’s can partly explain the lack of immediate effects of some psychotrophic drugs
what are the principal anxiolytic in vet med
benzos
how do anxiolytics work
Work through potentiation of the GABA-A receptors; Anxiolytic effects believed due to modulation of 5-HT and NE neurons in the CNS
other effects of anxiolytics aside from anxiety
o Central muscle relaxation, sedation
o Seizure suppression
what is used to reverse benzos?
flumazenil, a benzo antagonist
side effects of benzos (4)
-Disinhibition possible; caution or avoid use in cases of aggression
-Paradoxical excitement and amnesia possible
-Idiosyncratic hepatotoxicity in cats possible with diazepam; not yet seen with other BZDs
-Sedation, muscle relaxation, ataxia and hyperphagia
what species can you use diazepam in chronically and why
-Has short half-life in dogs (~1 hr) compared to cats (~5.5 hr)
-Active metabolites with longer-half lives make it suitable for chronic use in cats only
three benzos used in vet med
-diazepam
-alprazolam
-lorazepam
when is use of alprazolam promising
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
when is lorazepam good to use
o Not as extensively metabolized by liver before excretion;
o Advantages in liver failure, geriatrics and cats possibly
what is the name of a nonbenzo anxiolytic
buspirone
how does buspirone work
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; No withdrawal effects; less abuse potential
general categories of anti-depressants in animals
-Tricyclic antidepressants (TCA’s)
-Selective serotonin re-uptake inhibitors (SSRI’s)
-Monoamine oxidase inhibitors (MAOI’s)
reasons to use anti-depressants in animals (3)
-Anti-anxiety effects
-Compulsive disorders
-Some forms of aggression
how do antidepressants work generally
These agents work by different mechanisms of action with the general property of altering primarily NE andserotonin (5-HT) levels in the CNS
how do tricyclic antidepressants work
The TCA’s inhibit re-uptake of NE and 5-HT, increasing levels in the CNS
what are 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
uses of tricyclic antidepressants
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 are some antidepressants (5)
TCA =clomipramine, amitriptyline
SSRIs = fluozetine, paroxetine, sertraline
how does clomipramine work
Clomipramine primarily blocks 5-HT re-uptake
o Major metabolite desmethyl-clomipramine blocks NE re-uptake
what is clomipramine approved for in dogs
Approved in Canada in dogs for…..
o Treatment of anxiety
o Treatment of stereotypies (compulsive disorders) such as lick dermatitis
-Has also been used for anti-aggressive effects
-Can also be used in storm and noise phobias
what is amitriptyline used for
-Used for behaviour modification and pain (neuropathic) mgmt
-Most common use is in cats for idiopathic interstitial cystitis
-Used to reduce arousal and promote calming
how does amitriptyline work
More selective for 5-HT reuptake inhibition vs NE reuptake
o Also blocks cholinergic, adrenergic and histamine receptors
what can SSRIs be used for
-Anxiolytic; separation and generalized anxiety disorder
-Panic disorder, storm and noise phobias
-Anticompulsive; eg. lick dermatitis and Anti-aggression
-Urine spraying and psychogenic alopecia
most common adverse effects of SSRIs
Sedation and axorexia are most common complaints
but overall excellent safety record
SSRIs more _____ in their action compared to TCAs
specific
what behaviours are opiate antagonists used for
-Tail chasing
-Self-traumatic licking (acral lick dermatitis), other self mutilation
what drug has been used successfully in some cases?
naltrexone
how do antipsycotics work
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 antipsycotics
-May produce sedation
-May decrease blood pressure
-May inhibit learning
-May cause extrapyramidal effects
use of antipsycotics
Limited to short-term and intermittent uses “as needed”
-Chemical restraint most common use
-Intense fear/phobias when quick effects required (Storm or noise phobia and anxiety, Prevent self-injury or damage to environment)
what are two examples of low potency antipsycotics and what they are used for primarily
acepromazine and clorpromazine
in noise or thunderstorm phobia
effects of progestins/how they work
-Act on GABA-A receptor similar to BZDs
-Possibly increase release of endogenous opioids
-Mild sedating effects thru actions on CNS steroid receptors
-More effective in males; Dominance aggression and other forms of aggression, Urine marking and roaming
adverse effecs of progestins
Adverse effects can include mammary enlargement, bone marrow suppression, possible Addison’s ds or diabetes mellitus, increased appetite and liver damage
name of a progestin used
medroxyprogesterone acetate
when are pheromones indicated
Indicated for stress/fear associated with….
-Transport
-Boarding
-New environment or stressful events
-Produces a calming effect in association with fear, anxiety and phobias
how are anticonvulsants used for behaviour and example drug
Have been used to manage behavioral problems that may have a seizure basis; not recommended unless a neurologic basis !!
gabapentin
how does trazadone work and when is it used
Trazadone produces NE and 5-HT reuptake inhibition; metabolites have some opiate effects
Used in dogs for thunderstorms and as an adjunct to TCA and SSRI treatment
why do you need to beware of increased possibility of ADRs through drug interactions
-Altered metabolism of one drug by another may lead to failure or
toxicity
-Increased effects of multiple drugs acting on the same NT system
additive or synergystic benefits of multiple drug examples
Partial 5-HT receptor agonist (buspirone) with a SSRI (fluoxetine);
increased serotonin levels
