Behavioural Drugs and their uses Flashcards
What is anxiety?
Apprehensive anticipation of future threat or danger accompanied by somatic signs of tension
What physical observations are made in an anxious animal?
Sympathetic arousal, muscle tension, acute anorexia, scanning/hypervigilance, increased motor activity, impaired concentration and conditionability, loss of selective attention, hesitancy
What are common symptoms that owners of anxious animals report?
Fatigue easily, irritability, sleep disturbance, impaired concentration and response to trained commands, hesitancy, elimination problems and PU/PD
In what type of situation are anxious attacks more likely?
In an environment or situation that is unfamiliar to it or when it meets a novel stimulus
What are some anxiety related behavioural conditions?
Separation anxiety, aggression, elimination problems, destructiveness especially chewing and stereotypy/compulsive disorder
What are panic attacks?
Discrete episodes of intense anxiety
What behaviours have been seen in dogs thought to be experiencing panic attacks?
Retching/gagging, ataxia, collapses, faints, extreme sympathetic arousal, trembling/shaking, nausea/vomiting, increased locomotor activity
What is fear?
Apprehension of a specific object, person or situation
Normal adaptive experience that enables an individual to avoid harm
What behaviours have been observed in a fearful animal?
Facial and postural expressions, sympathetic arousal, urination/defecation, anal sac expression, muscle tremor, flight-escape response, threat/aggression directed towards stimulus
What is a phobia?
Irrational, excessive fear of object/situation that is out of proportion to the real threat or risk
How can phobias develop?
Single aversive event
Minor aversive experiences for poorly socialised and habitual animals
What are the principles behind approach-avoidance conflict?
In normal conditions there is a natural tendency to approach and investigate a novel object or situation
This conflicts with a simultaneous tendency to apprehensively avoid new or fear eliciting things
The interaction between these tendencies can be expressed as a pair of intersecting lines
How is the amount of fear represented on a approach-avoidance graph?
The height of the point of intersection
What affect do factors that lower/raise the strength of approach tendency do to the line?
They raise/lower the height of the line without affecting its gradient
How can the approach-avoidance graph make predictions about the behaviours of dogs in fearful situations?
Suddenly more fearful = closer than approach equilibrium = attack
Even if strong tendency to approach can be a high level of fear
Reduce fearfulness so that avoidance line is lowered
Potentially explosive situation if an animal with strong avoidance is subjected to flooding
Forced approach is likely to increase fearfulness
What are some physiological measurements of stress?
Catecholamine levels Corticosteroid levels (decreased ACTH response under stress) Altered neutrophil:lymphocyte ratio Immunosuppresion Cognitive impairment
What diseases can be associated with anxiety related disorders?
Cardiac and pulmonary disease, hypothyroidism, pain and fear, hyperthyroidism, high FSH and prolactin levels, hypoglycaemia
What is a typical approach to treating a fearful animal?
Identify fear provoking stimuli, identify threshold, establish a gradient of stimuli, control the pet’s environment, desensitisation and counter-conditioning
What is a typical approach to an anxious animal?
Identify context and conditions of anxiety, identify cues, desensitise, counter-condition and reduce predicative value of cues that cause anxiety, train some specific commands to relax, teach animal to relax in situations where anxiety has occurred
Why use drugs in treating behavioural problems in animals?
When anxiety or fear is great making therapy difficult or dangerous bearing in mind the risk of disinhibition, conditions causing fear/anxiety are unavoidable in normal life, animal is suffering as a result of chronic anxiety or repeated fearful experiences, prognosis is likely to be improved
Which two specific psychoactive drugs are specifically licensed for use in companion animals?
Clomipramine
Selegiline
What unlicensed psychoactive drugs are also used in companion animals?
Buspirone (atypical antidepressent)
Fluoxetine, Sertraline and Fluvoxamine (SSRIs)
Amitriptyline (non-SSRIs)
Which common veterinary drugs are also used to treat behavioural problems?
Propanolol
Phenobarbitone
Diazepam
What class of drug is clomipramine?
Non-selective serotonin re-uptake inhibitor and is a member of the tricyclic group of antidepressants (TCA)
Chemically similar to phenothiazines and has similar adverse effects
What is the mode of action of clomipramine?
Blocks the re-uptake of serotonin and nor-adrenaline causing a build up of these NTs in the synapse
What effect does clomipramine have?
Elevates mood, reduces anxiety and blocks the development of panic
What are the main targets of clomipramine?
Locus Coeruleus (LC) which is the area of the brain that relies on nor-adrenaline as a major NT
Raphe nuclei which rely on serotonin as a major NT
Togehter LC and Raphe nuclei form parts of the ascending reticular activating system involved in mood, wakefulness, sleep cycles and arousal
How long does it take for clomipramine to have a therapeutic effect?
About 3 weeks
Why does clomipramine take so long to have an effect?
Lasting correlations in mood are the result of intracellular changes in receptor numbers so is dependent on secondary messenger systems, gene expression and protein synthesis which take time to happen
Which drugs can lead to dangerous disinhibition of dogs?
Benzodiazepines
What other effect of benzodiazepines also limits their effectiveness as a behavioural drug?
Inhibit memory formation so can’t use as part of learning new behaviours
What is clomipramine licensed for use for in dogs?
Separation related disorders
What unlicensed uses are there for clomipramine?
Anxiety related problems, especially those involving panic
Sterotypy/compulsive disorders
Aggression where anxious apprehension is an obstacle for treatment
Spraying where anxiety is a factor
What are the adverse effects of clomipramine?
Sedation, hypotension, increased appetite, weight gain and anti-allergic activity due to H1 blockade
Delirium, hyperthermia, insomnia, seizure induction, tachycardia, constipation, decreased bronchial secretion, blurred vision, narrow angle glaucoma, photophobia and dry mouth due to Ach blockade
What drug interations does clomipramine have?
Morphine - enhanced analgesia and resp. depression
MAOIs - risk of serotonin syndrome, wash out period of 2-3 weeks
Phenothiazines - increased shared adverse effects
Fluoxetine and cimetidine inhibit cytochrome p450=toxic levels of TCAs
Fibre rich diets reduce bioavailability
What is serotonin syndrome?
GIT disease, head pain, agitation, increased HR body temp and RR, muscular rigidity, convulsions, coma, death
What class of drug is selegiline?
Selective monoamine oxidase type B inhibitor
What is the mechanism of action of selegiline?
Increases the availability of dopamine for inclusion into secretory vesicles by the vesicular monoamine transporter (VMAT) proteins on the surface of cytoplasmic vesicles in dopaminergenic neurones
What dietary modification needs to be considered with selegiline?
Reduce dietary tyramine as it becomes toxic in the presence of excess dietary tyramine
What effect does selegiline have?
Reduces anxiety and depression mainly through its effect on dopamine
Increases the tendency to explore and then enhances the reward for behaviours
What is the main use of selegiline?
Treatment of fears and phobias
What is the licensed use of selegiline in dogs?
Treatment of behavioural problems of emotional origin
What are some unlicensed uses of selegiline?
Other fear related problems including aggression
Spraying
Hyperactivity
Compulsive/stereotypical disorders predominantly involving fears
What are the adverse effects of selegiline?
Agitaiton, GI signs, drowsiness, headache, abdominal pain, hallucinations, increased competitiveness and shifts in status relationships
What drug interactions does selegiline have?
TCS/SSRI - serotonin syndrome
Benzodiazepine - potentiated by selegiline
Buspirone - isolated human cases of non-fatal hypertension
Pethidine - in humans - hyperpyrexia, resp failure, impaired consciousness, neuro signs
Phenylpropanolamine/phenylephrine/ephedrine/pseudoephedrine - life-threatening hypertension in man
