Treating Seizures

Question 1

What are the three mechanism of actions of anti epileptic drugs?

Answer 1

i. Enhancement of inhibitory signalling via facilitation of GABA
ii. Reduction of excitatory signalling
iii. Modulation of membrane cation conductance

Question 2

What is GABA? How does this relate to seizure treatment?

Answer 2

γ -Aminobutyric acid- its the the main inhibitory neurotransmitter in the CNS

Question 3

How do GABAA receptors work to reduce seizures?

Answer 3

Medication binds to the receptor in the neuron- causing chloride influx into the neuron, this hyperpolarises the neuronal membrane & reduces the likelihood of an action potential occurring

Question 4

What is the result of medication binding to a GABAB receptor?

Answer 4

Increases potassium conductance

Question 5

What are the indications for the prescription of Anti Epileptic drugs? (5)

Answer 5

Cluster seizures (2 or more seizures within 24 hours)
Status epilepticus
Severe post-ictal signs
Worsening frequency or severity of seizures
2+ seizures within 6 months

Question 6

What does Anti Epileptic treatment aim to do? (3)

Answer 6

• Reduce or eliminate seizures
• Reduce seizure severity
• Minimise seizure-related morbidity & mortality

Question 7

In order of highest tolerability and stability, give the four main AED’s?

Answer 7

Levetiracetam > Imepitoin > Phenobarbital > Potassium Bromide

Question 8

When is Phenobarbital contraindicated?

Answer 8

• Not licensed for clustered seizures
• In hepatic disease (its hepatically metabolised)

Question 9

What is the mechanism of action of Phenobarbital?

Answer 9

Acts as a GABA receptor agonist

Question 10

What is the time taken for Phenobarbital to reach a steady state/ concentration in the body?

Answer 10

10-14 days.. so check serum levels 14 days after starting treatment or after a dose change

Question 11

What are some acute adverse effects of Phenobarbital? (4)

Answer 11

Sedation & Ataxia (resolves in 7 days)
Neutropenia & Anaemia
Acute hepatoxicity
Superficial necrolytic dermatitis

Question 12

What are some chronic adverse effects of Phenobarbital?

Answer 12

Polyuria/ Polydipsia
Low T4 & high TSH
Chronic Hepatoxicity

Question 13

What type of epilepsy is Imepitoin used for?

Answer 13

Idiopathic epilepsy

Question 14

What are the benefits to using Imepitoin when compared to Phenobarbital?

Answer 14

Reduced side effects compared to phenobarbital
Not contraindicated in hepatic compromised patients

Question 15

In what way do we use potassium bromide as an AED?

Answer 15

used as an add on therapy- once phenobarbital and/or imepitoin are at maximum dose but seizure control remains inadequate

Question 16

What are some possible side effects of Potassium Bromide? (4)

Answer 16

Sedation
Polyuria, polydipsia
Can cause GI mucosal irritation e.g. Vomiting, diarrhoea- this can be mitigated by dividing the daily dose and administering it with food
Can also cause necrotising pancreatitis

Question 17

What time does it take for Potassium Bromide to reach a steady state in the body?

Answer 17

120 days- so assess serum concentration 120 days after initiation of treatment

Question 18

Give an example of an add on drug used for refractory seizures?

Answer 18

Levetiracetam

Question 19

How does Levetiracetam work?

Answer 19

Reduces excitatory neurotransmitter release so possibly neuroprotective

Question 20

How would we use Levetiracetam to treat cluster seizures?

Answer 20

Pulse therapy- start administration after a seizure, and continue until 72 hours of seizure freedom has been achieved, then stop

Question 21

When would we discontinue or reduce the use of AEDs?

Answer 21

If patient has had nso seizures for 1-2 years- decrease dose by ~20 % every 4 weeks to minimize risk of withdrawal seizures and status epilepticus

Question 22

What is recommended as the first line treatment for seizures in cats and how is administered and why?

Answer 22

Phenobarbital-
Transdermal is a preferable route of administration even though oral is possible- think orally medicating a cat everyday- no thanks!

Question 23

How does dietary management aid in the treatment of Seizures?

Answer 23

Potentially improves behavioural changes associated with epilepsy such as anxiety- supplement with a medium chain triglyceride e.g. Purina Neurocare

Question 24

What is Status Epilepticus?

Answer 24

greater than 5 minutes of continuous epileptic seizures or two or more seizures between which there is incomplete recovery of consciousness

Question 25

Why is Status Epilepticus such an emergency?

Answer 25

Increased autonomic discharge leads to hypertension, tachycardia, cardiac arrhythmias
Then to hyperthermia, lactic acidosis, hyperkalemia which ultimately progresses to hypotension, hypoxemia, hypoglycaemia as energy demand exceeds supply

… Leading to ORGAN FAILURE

Question 26

How do we approach treating Status Epilepticus?

Answer 26

Administer Diazepam & correct electrolyte abnormalities > Administer long acting AED such as Phenobarbital and start cooling the body temperature > If continued seizure activity then consider Propofol or Medetomidine

Question 27

What is the first line drug to treat Status Epilepticus and why?

Answer 27

Benzodiazepine-
Potent, rapid onset with 15-20 minutes duration of effect
Can be administered rectally if no IV access or via intranasal administration