Behavioural Pharmacology Flashcards
NAme 4 Neurotransmitters we target with behavioural drug use
- Serotonin
- Dopamine
- Noradrenaline
- GABA
Note too little or too much of ANY NT can have major side effects
MOA serotonin
NB several different receptors, so various roles.
Involved with regulation of mood, appetite and arousal, and may have a role in pain inhibition.
Lots of serotonin in the amygdala so possibly plays a role in reducing fear and aggression.
Stimulation of one receptor type (2C) may contribute to depression/anxiety, rather than reduce it.
MOA dopamine
Major role in reward and pleasure (involved in compulsions/stereotypies)
Helps regulate emotional responses
MOA GABA
The major inhibitory neurotransmitter in the body
MOA Noradrenaline
Helps form connections in the brain, hence important for learning
Facilitates function of other NTs such as dopamine and acetylcholine
Sympathetic NT
NAme the 5 psychoactive drugs in the UK
- Tricyclic antidepressants (TCAs)
- Specific serotonin reuptake inhibitors (SSRIs)
- Monoamine oxidase inhibitors (MAOIs)
MAO-A and MAO-B - Benzodiazepines (BZDs)
- Betablockers
MOA Tricyclic antidepressants (TCAs)
Block the serotonin and noradrenaline receptor transporters, thereby inhibiting reuptake and increasing concentration in the synapse = enhances function
What TCAs are used to treat
Mainly anxiety disorders, also chronic pain
Side effects of TCAs
Not very selective- block lots of receptors
Prolonged use also downregulates post-synaptic 5-HT and NA receptors.
Also block Na+ and Ca2+ channels so be careful giving to animals with cardiac disease
Parasympathetic issues, constipation.
Examples TCAs
Clomipramine is licenced TCA in animals
- For dogs with separation anxiety. Make sure definitely sep anxiety before admin.
- Other unlicensed anxiolytic products may be more appropriate for some
Pharmacokinetics:
- Extensive first pass hepatic metabolism
- Highly plasma protein bound
- Hepatically metabolised (cytochrome P450) by same system phenobarbitome antiepileptic – monitor lvier
- Mainly excreted in bile
- Off licence for any other anxiety disorder than separation
MOA Specific serotonin reuptake inhibitors (SSRIs)
Side effects
- similar to TCAs, inhibit reuptake serotinin
Side effects - Chronic use downregulates post synaptic serotonin receptors – dose inc as time
Much less binding of muscarinic, histaminic and adrenergic receptors than TCAs hence likely fewer side effects.
Example of SSRI
Main drug – Fluoxetine (Prozac). Not authorised for use in animals in UK
Pharmacokinetics of fluoxetine:
• First pass hepatic metabolism after oral administration
- Highly plasma protein bound
- Extensively hepatically metabolised.
- Mainly excreted in urine
- Long elimination half-life (4-6 days in chronic use in humans) and takes 6-8 weeks to reach maximum efficacy
MOA Monoamine oxidase inhibitors (MAOIs)
MAO-A and MAO-B
Both MAO-A and B involved in serotonin, noradrenaline and dopamine breakdown.
Inhibition of MAOIs = inc these NTs time in CNS
There are two types: MAO-A and MAO-B. Different species have different ratios of MAO-A and B in various tissues, meaning drugs which affect these enzymes can have very different effects
Side effects of MAOIs
Systemic side effects are common
several other neuroactive mechanisms of action, beyond inhibition of MAO.
Note: only MAO-B inhibitors are utilised in veterinary behavioural medicine
example MAOIs
Selegiline (Selgian®, Ceva)
- MAO-B inhibitor authorised for use in emotional disorders in dogs in the UK
- main indication in first opinion practice is for treatment of canine cognitive dysfunction (CCDS).
- Selegiline increases free radical scavenging, enhances nerve growth factor synthesis and protects the CNS from ischaemic damage, all of which are particularly relevant to treatment of CCDS
- Inc dopamine in system treatment of fear associated with low self-confidence
Benzodiazepines (BZDs) MOA
facilitate the action of GABA – activate GABA Cl- channel
Their main effects in modulating behaviour derive from their activity in the hypothalamus and limbic system, and these drugs can be useful due to their anxiolytic and sedative actions
What are BZDs used for?
to manage exposure to expected, unavoidable fear-inducing stimuli, and those that occur without prior warning e.g. a dog attack
Side effects BZDs
- Amnesia- less appropriate for long term behavioural management.
- Physical addiction
- Rebound phenomenon = undesirable behaviour returns suddenly and more severely than before treatment
- sometimes result in paradoxical excitement and a test dose should be given before prescribing these drugs as part of behavioural management
- BZDs (particularly diazepam) should usually be avoided in cats, due to their potential to induce fatal hepatic necrosis
e.g BZDs
alprazolam is often used in canine behaviour patients
No BZDs are licensed
Amnesia good e.g. fireworks
Use Betablockers
anxiety/anticipation scenarios, to reduce the physiological signs of negative emotional states involving panic and stress
Negative inotrope = dec HR
Propanolol most commonly used
What drug do we use in low doses whose main role is management of mild fears, mostly sedation
Alpha 2 agonists
Has an anxiolytic effect
Example of alpha 2 agonist used in behavioural pharmacology
Dexmedetomidine (Dexdomitor®, Vetoquinol) is the drug most likely to be used, and has been shown to be effective when administered as an oromucosal gel (Korpivaara et al, 2017), although this is an unlicensed route.
= Oral gel applied to mucous membranes (oromucosal gel Sileo is licensed. Makes calmer doesn’t sedate as dose so small. Good for something like fireworks
Gabapentin – blocks release glutamate by binding presynaptic Ca2+ channels. Reduced glutamate in amygdala thought to reduce anxiety. E.g. travelling or vet
Which two Anti epileptic drugs have applications in behavioural pharmacology?
Topiramate and Imeptoin (Pexion®, Boehringer Ingelheim)
MOA Topiramate
Main MOA is potentiating GABA activity
o Also may reduce glutamate mediated excitation, enhance Na++ channel inactivation and reduce current through Ca+ channels.
o Renal excretion
unauthorised for veterinary use, but may be of use in managing compulsive behaviours
MOA Imeptoin (Pexion®, Boehringer Ingelheim)
imepitoin acts as a partial agonist at the benzodiazepine site of the GABA receptor, thereby potentiating the action of GABA. This drug may also act on Ca++ channels to reduce their activity.
o Oral administration, with improved bioavailability if given on an empty stomach
It has been recently shown to have a potential role in rapid reduction of fear and anxiety in dogs (McPeake & Mills, 2017) and has been primarily used where noise-related negative emotional reactions are reported.
o Some hepatic metabolism, and excretion of metabolites and unchanged imepitoin in faeces
o Can be used as single agent or add-on to phenobarbitone.
o Not recommended or licensed for cluster seizures, although some new evidence that may have more efficacy than originally thought
Talk about serotonin syndrome
Serotonin toxicity
can be fatal so foods, herbal remedies and other drugs that contain serotonin precursors shouldn’t be used in combination with these behavioural pharmacology drugs.
Clinical signs include cognitive deficits (confusion, agitation) autonomic effects (hyperthermia, tachycardia) and somatic effects such as muscle twitching or tremor
Owners may give herbal remedy st johns wort so make clear cant give this!
List non pharmacological agents but pheromones
These are used in most practises rather than prescribing drugs!
- Adaptil
- Feliway Classic
- Feliway Friends
- Feliscratch
Effects of adaptil and feliway classic
- Adaptil= subtle effect, calming and reassuring dogs - synthetic version of the dog appeasing pheromone which is found in sebaceous glands along the mammary chain of the dam
- Feliway Classic® - synthetic version of the F3 fraction of the feline facial pheromone; a pheromone which is thought to increase the perception that the environment is safe by identifying known objects. It can have a significant effect in reducing problems associated with stress and anxiety
Affects of Feliway friends and feli scratch
- Feliway Friends® - synthetic version of the feline appeasing pheromone, which is found in sebaceous glands along the mammary chain of the dam. reducing the signs of social tension in multicat households through increasing the personal safety of each cat, and thereby increasing the level of tolerance between them
- Feliscratch® - replica of the interdigital pheromone which cats use to mark territory. This should be applied to areas where you want the cat to scratch, as it will attract cats both by virtue of the interdigital marker and because it contains catnip
