Anticonvulsants, behaviour, euthanasia drugs

Question 1

What are anticonvulsants and how do they work

Answer 1

Drugs to prevent seizures
Action: suppress the spread of abnormal electric impulses from the seizure focus to other areas of the cerebral cortex
All CNS depressants

Question 2

3 classes of anticonvulsants

Answer 2

Maintenance anticonvulsants - to treat idiopathic epilepsy
Adjuncts = add-ons; when seizure control is required
Drugs for emergency use and status epilepticus
Diazepam, injectable phenobarbital, propofol

Question 3

Goal of maintenance anticonvulsants

Answer 3

Decrease frequency of seizures (does not eliminate)
Decrease length and severity of individual seizures
Prevent having more than 1 per day

Question 4

How is phenobarbital used as an anticonvulsant

Answer 4

Barbiturate class anticonvulsant
Commonly used. For life
Usually oral form
Controlled drug
Can’t miss doses ( given q12hrs)
Requires therapeutic drug monitoring

Question 5

Adverse effects of phenobarbital

Answer 5

Adverse effects with acute use
- Acute sedation/ataxia, PUPD, polyphagia
Adverse effects with chronic use
- Hepatotoxicity
- Causes induction of cytochrome P450
- Leads to increased metabolism of phenobarbital (and potentially other medications the patient is on) therefore may need to increase dose over time to achieve same effect i.e. seizure control

Question 6

Phenobarbital blood testing is done because

Answer 6

Measuring actual level of phenobarbital in the blood to ensure the levels are within therapeutic range
Too low- ineffective
Too high- toxic range

Question 7

When to do phenobarbital blood testing

Answer 7

First testing done approx. 2 weeks after starting on phenobarbital once steady state is reached (~5 t1/2)
Has a very long half life (1.5-3.5 days), so timing of testing compared to individual dose not important

Question 8

Potassium bromide as an anticonvulsant

Answer 8

Compounded chemical (KBr). No “DIN”
Maintenance control drug for epilepsy
Can be used on own, or added on as an adjunct when PB is not enough to control seizures
Commonly used in dogs; “For life”
Can’t miss doses (given q12hrs)
Levels need to checked periodically
Cannot give with high salt diet

Question 9

Why cant you give sodium bromide with a high salt diet

Answer 9

Body will keep the Cl- and excrete Br-

Question 10

Side effects of potassium bromide

Answer 10

Sedation, PU/PD, Polyphagia (or sometimes inappetance)

Question 11

Blood testing for potassium bromide

Answer 11

Again very long half life (~24 hours) so testing should be done after steady state has been reached, but timing relative to dose is not important

Question 12

What are some uncommon anticonvulsants

Answer 12

May be used in combination with PB and/or KBr or used on their own in certain situations
Not commonly used due to cost/availability
- Levetiracetam (Keppra)
- Zonisamide
- Gabapentin

Question 13

When and how to use emergency anticonvulsant drugs

Answer 13

Treating seizures at home
Treating Status Epilepticus (seizure activity continuing for more than 5 minutes)
Need to stop this quickly
After ~30min get severe damage to the brain
After ~60min usually results in death

Question 14

Diazepam as an emergency anticonvulsant work by

Answer 14

Benzodiazepine class tranquilizer - works by increasing GABA (inhibitory neurotransmitter)

Question 15

How to use diazepam as an emergency anticonvulsant

Answer 15

Emergency at home drug:
- “To be used in the event of a seizure,…very severe, lasting more than 5 min, in the event of more than 1 seizure within a 24 h period”
- Owners administers rectally – orally ineffective and risk of aspiration
- Give up to 2 doses 15 minutes apart
Emergency in-clinic
- CRI or repeated IV bolus

Question 16

How to store diazepam

Answer 16

Store in dark; never in plastic; never mix with other drugs.
Therefore owner should not have preloaded in a syringe.
Controlled drug

Question 17

Injectable phenobarbital as an emergency anticolvulsant

Answer 17

Oral tablets usually used for maintenance
Injectable given IV for emergence use in clinic

Question 18

Propofol used as an anticonvulsent

Answer 18

For refractory seizures/status epilepticus (that aren’t responding to other drugs) can use injectable propofol to anesthetize patient
Initial IV bolus, followed by a CRI
Will usually stop seizure activity and maintain under anesthetic until seizure activity passes (usually continue for 6-12 hours; maximum 48 hours)
Considerable monitoring/care required

Question 19

What are the three main categories of behaviour modifying drugs

Answer 19

Antipsychotic Drugs-basically tranquilizers
Antidepressant Drugs- tricyclic antidepressants(TCAs), selective serotonin reuptake inhibitors (SSRIs) and monoamineoxidase inhibitors (MAOIs)
Anxiolytic Drugs– decrease anxiety or fear

Question 20

What is a common antipsychotic drug

Answer 20

Acepromazine

Question 21

Acepromazine as a antipsychotic drug works by and when to use

Answer 21

Blocks dopamine and the stimulation ofdopamine receptors in the brain that are related to emotion
blocks ALL behavior, good and bad, therefore some of the animal’s good traits are lost as well
causes hypotension
not recommended for treatment of aggression, as this is an “ instinctual behavior” and the animal may actually compensate for the feeling of sedation or loss of awareness by becoming more aggressive

Question 22

What are some antidepressants for animals and how do they work

Answer 22

Tricyclic antidepressants
clomipramine Clomicalm®
amitriptyline Elavil®
These drugs work by decreasing the reuptake of serotonin and norepinephrine from the synaptic cleft, allowing them to accumulate there and prolong their stimulatory activity which modifies “mood”

Question 23

Use of tricyclic antidepressants

Answer 23

Separation anxiety
Inappropriate urination and spraying in cats
Psychogenic licking in cats
Excessive feather plucking in birds
Aggression in dogs
Note– it may take several weeks for the drug to produce their intended effect and therefore can be frustrating for owners

Question 24

Selective serotonin reuptake inhibitors (SSRIs) are derived from and work by

Answer 24

Derived from TCAs BUT ARE MORE SELECTIVE FOR ONLY BLOCKING SEROTONIN REUPTAKE (and not norepinephrine) ….prolong the effects of serotonin
Fluoxetine (Prozac ®= Reconsile®= the veterinary version)
Note- like the TCAs, several weeks may be needed to see beneficial behavioral changes and shouldn’t stop meds abruptly

Question 25

When to sue fluoxetine

Answer 25

Studies show that lack of serotonin increases aggression. Therefore, since fluoxetine prolongs serotonin effects, this drug has been useful for: Dog to people aggression Dog to dog aggression Anxiety Obsessive compulsive disorders

Question 26

Monoamine oxidase inhibitors (MAOIs) as a behavioural drug works by

Answer 26

Inhibit the enzyme monoamine oxidase (whose purpose is to break down serotonin, dopamine, and norepinephrine) Selegiline (Anipryl®) – veterinary product used to treat pituitary dependent Cushings and Canine Cognitive Dysfunction = old dog senility

Question 27

How does trazodone HCL work

Answer 27

Antidepressant drug Increases serotonin levels in brain Used in dogs for anxiety disorders/fears (storm phobia, vet visits, fireworks, other situational anxiety, etc) Rapid onset of action, therefore can be used on an “as needed” basis Recommended 1-2 hours prior to stressful event

Question 28

Side effects of trazodone

Answer 28

Considered relatively safe; side effects uncommon When they are seen, side effects include food seeking behavior, sedation, nausea and diarrhea Serotonin syndrome – serotonin levels get too high in the brain Very uncommon Usually only a concern if also taking other drugs that increase serotonin levels

Question 29

How do anxiolytic drugs work

Answer 29

These are tranquilizers belonging to the benzodiazepine group E.g. diazepam (Valium®) – at low doses, the animal will become relaxed and less excitable Interfere with the pets ability to learn or be trained Drug tolerance can develop Drug misuse (i.e. owners taking it for themselves) is a concern Not used in cats due to unpredictable drug induced hepatopathy

Question 30

Gabapentin as a behavioural drug works by and is used when

Answer 30

In vet med, traditionally used to control neuropathic pain and/or seizures Also has started to be used with increasing frequency as an anti-anxiety medication in cats This is ELDU and research is limited at this point However anectodal evidence suggests it is fairly effective at reducing anxiety

Question 31

Zylkene as a behavioural drug is used when

Answer 31

Can be used in combination with Trazodone (dogs) or Gabapentin (cats) prior to coming to the vet to decrease stress associated with vet visits Used in horses for travel stress, box stall rest… For overall anxiety reduction, requires long term use

Question 32

What are some common pheromones used for behavioural issues

Answer 32

Feliway – cats - Facial pheromone analogue (original) - Mammary gland pheromone (multicat) Adaptil – dogs - Pheromone produced by mother dog to calm puppies Confidence EQ – equine appeasing pheromone - Equine maternal pheromone

Question 33

Pentobarbital is used when

Answer 33

A euthanasia drug Controlled drug Euthanasia solutions may not be sterile or completely free of other contaminants therefore do not use as anesthetic Administered overdose of a barbituate anesthetic Standard protocol to color blue for recognition; “Blue juice” Examples: Euthanyl® (240 mg/ml) Euthanyl Forte (540 mg/ml), Euthansol®, Dorminol®, Somnotol®

Question 34

What are some routes of administration for pentobarbital

Answer 34

IV – preferred; place an IV catheter (extravascular drug burns) faster onset through Stage 1 and 2 IP – larger dose, takes a long time (up to 20 min in a cat) IC – only humane if unconscious (can be under GA)

Question 35

What are some common euthanasia drugs

Answer 35

Pentobarbital T-61 Potassium Chloride or magnesium sulfate

Question 36

T-61 contains what

Answer 36

“For smooth euthanasia of dogs. Each mL of T-61 contains: 200 mg embutramide which produces a strong narcotic action and concurrently paralyses the respiratory centre 50 mg mebozonium iodide which produces a curariform paralytic action on striated skeletal and respiratory muscles and rapidly induces circulatory collapse and 5 mg tetracaine hydrochloride, in aqueous solution with dimethylformamide as preservative.”

Question 37

How does T-61 work

Answer 37

Essentially paralyses respiratory muscles inducing circulatory collapse and suffocation. This takes longer than pentobarital which acts centrally.

Question 38

When and why use T-61

Answer 38

Only considered humane for euthanizing animals when used in combination with other drugs i.e. pentobarbital and/or very heavy sedation/anesthesia. Horses - Can help decrease the viscosity of pentobarbital. Not a control drug therefore no recordkeeping required. Route of administration – IV injection only Only labelled in dogs but used in several other species.

Question 39

When and how to use potassium chloride of magnesium sulfate and a euthanasia drug

Answer 39

In the event that Pentobarbital is not available both of these are available commercially or can be compounded. Recent (2021/2022) shortage of pentobarbital lead to alternate methods being used, especially in shelter settings/lab animals, etc. Only acceptable to use in an unconscious patient Route of administration – IV injection only Can see increased muscle contraction/fasciculations after death which can be traumatic for owners.