Psychopharmacological agents used in practice Flashcards
When would drug therapy be advocated?
- Behavioural response extreme and well established
- Difficult to start any form of behavioural therapy due to response at a low threshold
- Strong ‘organic’ component (eg. neuro pathologies)
- Rapid changes are needed for client compliance/motivation
What 3 things should be considered when thinking about drug use?
Possible side effects/costs/risk of misuse v pros.
Owner aware that drugs are an adjunct not alternative?
Non-specific action of drugs -> Disinhibitoin risk?
Why is off-label drug usage common with behavioural drugs?
Few licensed in the species we need them for.
- ensure sufficient quality scientific evidence to support use
- ensure owner has given informed written consent
- use in accordance with published guidelines
What are the six main NTs behavioural drugs will work on?
Ach (Achetylcholine) DA (Dopamine) NA (Noradrenaline) GABA (Gama-aminobutyric acid) 5-HT (Serotonin) Melatonin
List the 8 classes of anxiolytic drug
Benzodiazepenes B Blockers Azapirones Barbituates Antihistamines Tri-Cyclic Antidepressants (TCAs) Selective serotonin reuptake inhibitors Monoamine oxidase inhibitors
List the anxiolytic medications useful for SHORT TERM use.
- Benzodiazepenes (Diazepam, Alprazolam)
- B Blockers (Propanolol)
List the anxiolytic medications useful for LONG TERM use.
- Azapirones (Buspirone)
- TCAs (Amytriptaline, clomipramine (Clomicalm), Imipramine, Doxepin, Desiprsamine, Nortriptyline
- SSRIs (Fluoxetine (Prozac), Paroxetine (Paxil), Sertraline (Zoloft), Citalopram, Fluvoxamine)
- MAO inhibitors (Selegiline, MAO-B inhibitor)
What is another name for Diazepam? What is it commonly used for?
Valium
Seizure medication in dogs and cats
What is the main effect of the benzodiazepines?
Facilitate the INHIBITORY effect of GABA in the CNS -> dampen excitation in the brain
Why are benzodiazepines well formulated to affect the CNS? What repercussions does this have?
They are highly lipophilic.
Pharmacokinetics/dynamics affected depending on obesity level of dog
- fat dog -> absorption and slow release
- skinny dog -> rapid ^conc and then vconc
What side effects are associated with benzodiazepines and how soon is their onset?
Very quick onset
- sedation
- ataxia
- mm relaxation
- ^apetite esp in cats
- paradoxical excitement in 10-20% cases
- memory deficits
- hepatic necrosis in cats (rare)
Why are benzodiazepines not good to give in conduction with behaviour therapy?
Block consolidation of memory so will not learn new things
How might these effects change with time?
Tolerance to sedation and ataxia after a few days
How can these side effects be predicted?
Give test doses to evaluate reaction
What are benzodiazepines useful for in behavioural medicine?
Anxiolytic
Amnesic if given ~1 hour before event
What are the potential problems associated with benzo use?
Disinhibition of aggression Interference with learning Risk of fatal liver failure in cats Human abuse potential Addictive properties/dependence Teratogenic properties Drug interactions
How should benzos be stopped?
Gradually
- suddenly stopping -> recurrence, extreme nervousness, seizures
What is the half life of diazepam in dogs?
Hours (v short)
What is the greatest risk associated with the use of diazepam in cats? Other risks?
Hepatic necrosis
Reduced depth perception (do not let outside!)
Apetite stimulant
What is the efficacy of diazepam like?
Varied - dose adjusted to effect
Sometimes dose required causes unacceptable level of ataxia
How does alprazolam compare to diazepam?
Higher potency
Better retrograde amnesia (NB: no anxiolytic effect until given obviously)
Longer half life - 12 hrs, peak levels in 1-2hrs
Increased friendliness in cats (but still loss of depth perception and ataxia)
How do B-blockers work?
Selective blocking of b1 and/or b2 adrenergic receptors in myocardium, bronchi and vascular smooth muscle
Reduced sympathetic response in a fearful situation -> v feeling of anxiety feedback loop
Possibly also central activity
When would B-Blockers be useful in a behavioural therapy programme?
When animal is too hyper-reactive to even begin training.
Only mild anxiolytics but no cognitive impairment
What are the potential side effects of B-blockers?
Bradicardia Hypotension Lethargy Depression Hypoglycaemia Bronchoconstriction Syncope Diarrhoea
What is syncope?
Fainting
Where are B-blockers contra-indicated?
Hypotension
Heart failure
Bronchospastic disease
Bradycardia
What type of drug is Propanolol?
Non-selective B-blocker (b1+b2)
Metabolised in liver
What is the half life of propanolol in dogs?
0.77-2hours
What four mechanisms of actions do azapirones have?
Serotonergic, noradrenergic, dopaminergic and cholinergic
“Dirty”
What is the only azapirone used in behavioural therapy?
Buspirone
What is buspirone’s main mechanism of action?
Partial 5-HT1a agonist at PRE and POST synaptic receptors.
Mixed ag/ant properties on DA receptors
How is buspirone excreted?
Inactive metabolite in the urine
Why will buspirone have varying effects in individual animals?
As it acts on PRE and POST synaptic receptors, effects will depend on number of receptors in individual animal.
- if more PRE synaptic receptors to be affected, will DEcrease activity
- if more POST synaptic receptors to be affected, will INcrease activity
How and why do effects of buspirone differ in the short and long term?
Short term: ^ likelihood of 5-HT impulses
Long term: Downregulation of post synaptic receptors -> v likelihood of 5-HT impulses
How commonly is buspirone used?
RARELY
- some success reported in feline spraying but high relapse rate, no placebo controlled trials
- poor efficacy in specific fears
How quickly does Buspirone act?
Slow onset of action (1-3 weeks)
Short half life - BID/TID
What are the side effects of buspirone?
GI disturbance, irritability, ^aggression, paradoxical excitability, humans - headaches, dizziness, insomnia, bradycardia, cramps, stereotypic behaviours
What makes buspirone a good choice of drug? (despite not commonly used)
Wide safety margin
No sedative/hypotic effect
No withdrawal phenomenon
No abuse potential
Give examples of TCAs
Amitryptaline Clomipramine (licensed for dogs) Imipramine Doxepin Desipresamine Noritryptaline
How do TCAs work?
Block reuptake of 5HT and NA (different compounds block each to a different degree)
- Most have active metabolites
Which behaviour problems are TCAs advocated for?
Wide variety - compulsive disorders, separation anxiety, urine marking
How long does it take for TCAs to reach therapeutic levels?
Long time - 2-4 weeks
What are the side effects of TCAs and when do they begin?
RAPID ONSET (despite therapeutic action slow onset)
- mild transient sedation
- Anticholinergic effects (urinary retention, constipation, dry mouth)
- Antihistiminic effects - Hypotension, motor incoordination, cardiac conduction disturbance (in healthy animals this is not pathological), agranulocytosis (rare)
When may the antihistaminic effects of TCAs be useful? Which TCA is particularly antihistaminic?
Itching/scratching based problems
Cystitus
- amytriptaline good
Which two drugs should NEVER be given together?
Clomipramine and Selegeline
- inexact with MAObs -> SEROTONIN SYNDROME
- hyperthermia, rigidity, myoclonus, confusion, delerium, coma - fatal
What conditions are TCAs contraindicated for?
Heart disease Hypertension Hypothyroidism Epilepsy (lowers seizure threshold) Concurrent use with MAOBs Other potential problems - bitter taste - potential for human misuse - OD fatal with no antidote
When is amitryptaline usually used?
Greater NA and H1/2 effects required
- FLUTD (although beware urine retention due to Anticholinergic side effects)
- Pyschogenic alopenia
- ALD in dogs
What is the most common use of Clomipramine?
Clomicalm - licensed for separation anxiety in dogs
- multi centre, palcebo controlled, blinded trial
- Main effect 5HT
> used in cats off label but tolerated less well than dogs, side effects worse and more variable
Give examples of` SSRIs
Fluoxetine (Prozac) Paroxetine (Paxil) Sertraline (Zoloft) Citaloproam Fluvoxamine (also NA effects -> anxiety)
What are SSRIs most commonly used for?
Fear responses - sudden, immediate and unconsidered, sometimes anxiety
sometimes compulsive disorders
Which response is NA responsible for?
Panic/stress
What is serotonins role?
Anti depressive, antianxiety
What is the time until therapeutic onset of SSRIs?
Long - 3/4 weeks
What may occur with short term SSRI use?
^anxiety due to v 5HT (negative feedback of serotinergic auto receptors)
with longterm use v anxiety due to receptor (up?) regulation and ^ [5HT]
How may the initial antigenic properties of SSRIs be combatted?
Short course benzodiazepenes
Where other than the CNS are serotinergic pathways found? How does this impact side effects?
The gut
-GI irritability
(can be reduced by gradual increase of dose)
What other side effects of SSRIs?
Insomnia, sedation, potential for human misuse
Which SSRI is licensed for separation anxiety?
Fluoxetine “Reconcile” (USA)
- long half life active metabolite
- rapid onset side effects
>GI irritation, inappetance , lethargy, nervousness
What kind of molecule are all NTs?
Monoamines
How do MAO inhibitors work?
Prevent mono amine oxidase working to break down generalised NTs in synaptic clefts -> ^[NT]
- NTs include NA, Adrenaline, DA, 5HT, tyramine
What are the 2 different forms of MAO inhibitors?
MAO a - inhibtis all monoamines, has dietary requirements - no tyramine containing foods (not used in dogs therefore)
MAO b - inhibits all monoamines except 5HT, NO dietary requirements
Give an example of a MAOb inhibitor. Is it licensed?
Selegeline
- licensed in Europe (disorders of emotional origin) and USA(cognitive dysfunction=alzheimers)- different purposes
- some evidence of neuroprotective effect
What should Selegeline never be given in conjunction with?
SSRIs, TCAs or St Johns Wort- Serotonin syndrome can be fatal
Remember long half life (20d!)
Give 4 antipsychotics/neuroleptics (=tranquillisers/anti-scizophrenics)
ACP (acepromazine)
Chlorpromazine
Haloperidol (parrots feather plucking, lots of side effects)
Risperidone
How do antipsychotics work?
Block DA receptors (and newer compounds may also have 5HT antag)
Are antipyschotics used regularly in animals?
No because of side effects
Although still used a bit in Europe
What are the side effects of antipsychotics?
^PRL (-> milk production)
Seizures
Sedatino and anticholinergic effects
Extra-pyramidal symptoms eg. muscle tremor (due to blocking of DA receptors in basal nuclei, controlling motor function) - seen more in high potency neuroleptics eg. haloperidol
Give some examples of low potency antipsychotics
Chlorpromazine, acepromazine
- low specificity, hence many side effects
Give some examples of high potency antipsychotics
Haloperidol, azaperone (eg. Suicalm, give to pigs before mixing)
- more specific
- less sedation but greater risk of extra-pyramidal effects
Give some examples of atypical neuroleptics/antipsychotics
Clozapine, ripseridone
- newer, potentially better, less side effects
Is ACP recommended for tranquillising anxious animals?
NO - provides motor sedation but no anxiolytic effect
Give some examples of anticonvulsants
RARELY USED (Antiepileptics)
- Phenobarbitone (Epiphen)
- Phenytoin (Epanutin)
- Primidone (Mysolene)
- Carbamazepine (Tegretol)
When may carbamazepine be used?
Peripheral sensory neuropathy/ectopic firing
eg. Burmese cats with facial pain where scratching -> neuralgia
- erratic absorption so best administered with food
What types of partial seizures are possible?
Anywhere in the brain eg. visual (fly snapping)
Motor/central brain (absent seizure)
Amygdala/limbic system (sudden emotional response/jump up)
Which drug is advocated for use with motor partial seizures? What must be wary of?
Phenobarbitone
(used to be used more widely but effect due to sedation only)
- regular blood monitoring to check hepatotoxicity
What is the action of Phenytoin?
Reduces spread of focal seizures
- used extensively in humans
How does the pharmacokinetics of phenytoin differ in cats and dogs?
Dogs - metabolised very rapidly, high and frequent dosing needed
Cats - metabolised slowly, problems with toxicity
What is the effect of progestagens?
Anti-testosterone, secondary sedative effect - non-specific
Are progestagens advocated? What are the side effects?
NO common and severe side effects - ^apetetie, weight gain - hyperglyceamia - diabetes - lethargy - poor cognitive function - mammry hyperplasia - adencarcinoma (mammary) - endometrial hyperplasia - pyometra - aspermatogensis - adrenocroticol supression - bone marrow suppression -retinal detachment
Are progestagens licensed?
Yes unfortunately
- dogs
- also advocated for use in cats
- sometimes used to test for effect of castration
- > beware secondary sedative effect which may mean castration doesnt have same impact
- testosterone driven tumours may shrink with progestagen use - if this proves true then castration will hope treat tumour
Give 4 treatments of age related changes
- selegeline
- A antag
- Xanthine derivative
- Dietary intervention
Give a common drug combination
Benzodiazepenes and TCAs to manage acute episodes in dogs
What does polypharmacy increase the risk of?
Side effects and problems with long term use
What should be carried out throughout pharmacological treatment?
Blood monitoring (prior to starting medication swell to check for normal levels)
Can off label drugs be used?
Yes providing informed consent is given
