Anticonvulsants

Question 1

Basic likely cause of seizure.

Answer 1

An imbalance between inhibitory (mainly GABA) and excitatory (mainly Glutamate) force.

Question 2

What is the basic physiological aim of an anticonvulsant.
And examples of these drugs.

Answer 2

Either to potentiate the inhibitory (GABA) system:
- e.g. imepitoin, BZD, barbiturates, phenobarbitones etc.
Or antagonise excitatory system (Glutamate):
- e.g. ketamine.

Question 3

1. What are anticonvulsants with short half lives used for?
   Give examples.
2. What are anti-epileptics with longer half lives used for?
   Give examples.

Answer 3

1. Stopping seizures.
   - Rapid onset of action.
   - short acting.
   - emergency management.
   - e.g. Diazepam, midazolam, propofol.
2. For longer term control of seizures (prevention).
   - slow onset of action.
   - long acting.
   - long term management.
   - e.g. Phenobarbitone, Imepitoin, Levetiracetam, KBr.

Question 4

3 general possibilities for seizure cause?

Answer 4

Known trigger.
Epilepsy (structural or idiopathic).
Status or clusters.

Question 5

Should I start long-term tx w/ anticonvulsants?

Answer 5

Monitoring appropriate for:
- known toxic trigger.
- long interictal period (frequency low at 1 seizure per >3 months).
- single seizure.
Treatment indicated:
- underlying structural or metabolic cause (until fixed).
- cluster seizures or status epilepticus.
- if >1 seizure per month.
- if seizures are increasing in frequency.

Question 6

Main goals of epilepsy management?

Answer 6

Reduce seizure frequency.
- by 50% or more.
- aim for <1 seizure per month or per 3 months.
Reduce severity.
Acceptable side effects.
Acceptable costs.
Practical management e.g. time commitment etc.

Question 7

1. First choice drugs for epilepsy management in dogs?
2. Second choice drugs for epilepsy management in dogs?

Answer 7

1. Phenobarbitone.
2. Imepitoin (dogs w/o cluster seizures and w/ long inter-ictal period).
   Potassium bromide (dogs only, if liver dysfunction).

Question 8

1. First choice drugs for epilepsy management in cats?
2. Second choice drugs for epilepsy management in cats?
3. What drug cannot be used in cats for epilepsy management?

Answer 8

1. Phenobarbitone.
2. Levetiracetam.
   Imepitoin.
3. Potassium bromide - toxic!

Question 9

1. Dose related side effects of phenobarbitone?
2. Idiosyncratic reactions to phenobarbitone?
3. Dose related side effects of Imepitoin?

Answer 9

1. PUPD, sedation, ataxia, polyphagia.
2. Dermatitis, liver failure, cytopenias, pseudolymphoma.
3. PUPD, sedation, ataxia.

Question 10

1. Dose related side effects of potassium bromide?
2. Idiosyncratic reactions to potassium bromide?

Answer 10

1. PUPD, sedation, ataxia, v+.
2. Pancreatitis, pneumonitis (cats).

Question 11

1. Owner communication regarding side effects.
2. Action to take when idiosyncratic reaction/s occur/s?

Answer 11

1. Inform that side effects often reduce or go when a steady state is reached so give it time.
2. Discontinue on drug.

Question 14

1. When is the steady state reached w/ phenobarbitone?
2. When is the steady state reached w/ Imepitoin?
3. When is the steady state reached w/ potassium brome?

Answer 14

1. 2-3w.
2. 2-3d.
3. 2-3m.

Question 15

1. Metabolism of phenobarbitone?
2. Metabolism of Imepitoin?
3. Metabolism of potassium bromide?

Answer 15

1. Liver.
2. Liver.
3. Kidneys.

Question 16

Lab changes related to phenobarbitone administration in dogs?

Answer 16

Elevated:
- ALT and ALP.
- cholesterol.
- triglycerides.
WITH NO CLINICAL CONSEQUENCES USUALLY.
CONTINUE TO MONITOR!

Question 17

Lab changes suggestive of phenobarbitone-induced hepatotoxicity effects?

Answer 17

Albumin decreased.
Bilirubin.
AST and GGT elevated.
Abnormal bile acid stimulations.
DISCONTINUE DRUG IN THESE INSTANCES!

Question 18

Drug monitoring w/ serum levels and bloodwork checks.

Answer 18

Test at expected steady state for that drug:
- at 3w for PB.
- at 2-3m for KBr.
Test if seizure control lost.
Test if signs of toxicity arise.
Test q6-12months.
IMPORTANT OWNER COMMUNICATES AND MONITORS CORRECTLY!
- Recommended to keep a seizure calendar e.g. recommend RVC Pet Epilepsy Tracker.

Question 19

When do I add a second anticonvulsant?

Answer 19

Improper seizure control despite appropriate use of first line drug.
If increasing first line drug leads to unacceptable side effects.
If increasing first line drug means reaching a possible toxic blood level.
ALWAYS USE ONE DRUG IF POSSIBLE!

Question 20

Alternative antiepileptic options.

Answer 20

Add second line drug:
- KBr in dogs.
- Levetiracetam in cats.
Third line drugs:
- Levetiracetam in dogs.
- Zonisamide.
Fourth line drugs:
- Gabapentin? Pregablin? Felbamate? Topiramate?

Question 21

Ensuring owners’ compliance in managing the epileptic patient.

Answer 21

Diary/drug planner.
Use fewer drugs where possible.
Regular rechecks.
Provide adequate drug supply.
Set and manage the expectations of the owner.
- seizures will not be completely resolved in most patients.

Question 22

Main principles to manage seizures as emergencies?

Answer 22

Don’t panic.
Stepwise approach using guidelines.
Use a short acting drug first.
Check vital parameters.
Protect patient.
Try to get IV access.
Check blood glucose.
Give anticonvulsants:
- IV – diazepam, midazolam (can give CRI).
- rectally – diazepam.
- intranasally? – midazolam.
- Can repeat doses of all these 3x.
- DO NOT GIVE DIAZEPAM IM.

Question 23

Acute seizures management - recurrent seizures.

Answer 23

Use anti-epileptic which is longer acting.
- PB loading dose IV.
- Levetiracetam.
Consider CRI:
- Ketamine.
- Propofol.