Behavioural Pharmacology

Question 1

NAme 4 Neurotransmitters we target with behavioural drug use

Answer 1

1. Serotonin
2. Dopamine
3. Noradrenaline
4. GABA

Note too little or too much of ANY NT can have major side effects

Question 2

MOA serotonin

Answer 2

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.

Question 3

MOA dopamine

Answer 3

Major role in reward and pleasure (involved in compulsions/stereotypies)

Helps regulate emotional responses

Question 4

MOA GABA

Answer 4

The major inhibitory neurotransmitter in the body

Question 5

MOA Noradrenaline

Answer 5

Helps form connections in the brain, hence important for learning

Facilitates function of other NTs such as dopamine and acetylcholine
Sympathetic NT

Question 6

NAme the 5 psychoactive drugs in the UK

Answer 6

1. Tricyclic antidepressants (TCAs)
2. Specific serotonin reuptake inhibitors (SSRIs)
3. Monoamine oxidase inhibitors (MAOIs)
   MAO-A and MAO-B
4. Benzodiazepines (BZDs)
5. Betablockers

Question 7

MOA Tricyclic antidepressants (TCAs)

Answer 7

Block the serotonin and noradrenaline receptor transporters, thereby inhibiting reuptake and increasing concentration in the synapse = enhances function

Question 8

What TCAs are used to treat

Answer 8

Mainly anxiety disorders, also chronic pain

Question 9

Side effects of TCAs

Answer 9

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.

Question 10

Examples TCAs

Answer 10

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

Question 11

MOA Specific serotonin reuptake inhibitors (SSRIs)

Side effects

Answer 11

• 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.

Question 12

Example of SSRI

Answer 12

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

Question 13

MOA Monoamine oxidase inhibitors (MAOIs)

MAO-A and MAO-B

Answer 13

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

Question 14

Side effects of MAOIs

Answer 14

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

Question 15

example MAOIs

Answer 15

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

Question 16

Benzodiazepines (BZDs) MOA

Answer 16

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

Question 17

What are BZDs used for?

Answer 17

to manage exposure to expected, unavoidable fear-inducing stimuli, and those that occur without prior warning e.g. a dog attack

Question 18

Side effects BZDs

Answer 18

• 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

Question 19

e.g BZDs

Answer 19

alprazolam is often used in canine behaviour patients
No BZDs are licensed

Amnesia good e.g. fireworks

Question 20

Use Betablockers

Answer 20

anxiety/anticipation scenarios, to reduce the physiological signs of negative emotional states involving panic and stress
Negative inotrope = dec HR
Propanolol most commonly used

Question 21

What drug do we use in low doses whose main role is management of mild fears, mostly sedation

Answer 21

Alpha 2 agonists

Has an anxiolytic effect

Question 22

Example of alpha 2 agonist used in behavioural pharmacology

Answer 22

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

Question 23

Which two Anti epileptic drugs have applications in behavioural pharmacology?

Answer 23

Topiramate and Imeptoin (Pexion®, Boehringer Ingelheim)

Question 24

MOA Topiramate

Answer 24

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

Question 25

MOA Imeptoin (Pexion®, Boehringer Ingelheim)

Answer 25

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

Question 26

Talk about serotonin syndrome

Answer 26

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!

Question 27

List non pharmacological agents but pheromones

Answer 27

These are used in most practises rather than prescribing drugs!

1. Adaptil
2. Feliway Classic
3. Feliway Friends
4. Feliscratch

Question 28

Effects of adaptil and feliway classic

Answer 28

1. 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
2. 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

Question 29

Affects of Feliway friends and feli scratch

Answer 29

3. 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
4. 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