Treating seizures

Question 1

What do we consider epilepsy and its tx?

Answer 1

at least 2 unprovoked epileptic seizures over 24h apart
antiepileptic drugs

Question 2

What is different about reactive seizures and their tx?

Answer 2

occurs as response to transient disturbance in function
reversible when cause is rectified
tx the underlying cause

Question 3

What are the mechanisms of action of antiepileptic drugs?

Answer 3

enhancement of inhibitory signalling via facilitation of GABA

reduction of excitatory signaling

modulation of membrane cation conductance

Question 4

How does gaba inhibit in the cns?

Answer 4

binds to 2 types of reveptors

GABAa-R: opens chloride ion channel causing influx into neuron hyperpolarising the neuronal membrane and reduces likelihood of action potential occuring

GABAb-R: increases potassium conductance which reduced neuronal hyperexcitability

Question 5

What drugs bind to GABAa-R?

Answer 5

barbiturates and benzodiazepines

Question 6

When should you start treating seizures?

Answer 6

cluster seizures
status epilepticus
severe post-ictal signs
worsening frequency or severity
2+ seizures in 6 months
underlying structural lesion

Question 7

What are the goals of treating seizures?

Answer 7

reduce frequency or eliminate seizures
reduce seizure severity
minimise seizure-related morbidity and mortality
avoid adverse effects

Question 8

What do we consider when choosing the drug to tx seizures?

Answer 8

efficacy: how well will it control the seizures
balanced with
tolerability: what adverse effects could it cause since its long term tx

balancing eliminating seizures with quality of life of ptx

Question 9

What are the 4 common drugs used to tx seizures?

Answer 9

phenobarbital (most evidence of effective)
imepitoin (most evidence of effective)
potassium bromide (somewhat effective)
levetiracetam

Question 10

Which of the seizure tx drugs are most safe/cause minimal side effects?

Answer 10

most safe: levetiracetam
then imepitoin
then phenobarbital
then potassium bromide

Question 11

What is an important characteristic of anticonvulsant medications?

Answer 11

need rapid and effective transport across the BBB

Question 12

What is first line tx for seizures in an otherwise healthy dog?

Answer 12

phenobarbital
or imepitoin (limited supplies, not licensed for clustur seizures)

Question 13

What is second line tx for seizures?

Answer 13

potassium bromide
when phenobarbital is at max therapeutic concentration but seizure control not sufficient or if phenobarbital is contraindicated

Question 14

What is phenobarbital?

Answer 14

GABA receptor agonist
very effective anticonvulsant

Question 15

What are the likely side effects of phenobarbital and when is it contraindicated?

Answer 15

contraindicated: hepatic dysfunction
poor liver function may = higher serum concentration
potent inducer of cytochrome p450 enzyme activity in liver
risk of withdrawal seizure if sudden stop tx

Question 16

How do we manage and monitor the use of phenobarbital in seizure ptx?

Answer 16

assess ham, biochem and BAST before tx

check serum levels 14 days after start, after dose changem if poor seizure control
check serum levels 3-6 months when stable

ensure safe and effective concentration in blood, guides decisions of dose changes

Question 17

What are the acute adverse effects of phenobarbital?

Answer 17

sedation, ataxia, resolve in a week
neutropaenia, anaemia, thrombocytopaenia: STOP TX
acute hepatotoxicity, rapid elevation of ALT and bile acids: STOP TX
superficial necrolytic dermatitis
=/- pancreatitis, dyskinesia, anxiety

Question 18

What are the chronic adverse effects of phenobarbital?

Answer 18

polyuria
polydipsia
polyphagia
elevation of ALKP and ALT
low T4 +/- high TSH
chronic hepatotoxicity

Question 19

What is imepitoin?

Answer 19

low affinity partial agonist of benzodiazepine site of GABAa-R
licensed for idiopathic epilepsy

Question 20

What makes imepitoin safer than phenobarbital?

Answer 20

reduced side effects
less sedation and ataxia
less polyuria, polydipsia, polyphagia
not contraindicated in hepatic compromise
1-2 days steady state

Question 21

When is potassium bromide used as seizure tx?

Answer 21

as add-on tx once phenobarbital and/or imepitoin are at max dose but seizure control inadequate

Br ions cause neuronal membrane hyperpolarisation

Question 22

What are the side effects of potassium bromide?

Answer 22

sedation, ataxia, weakness
polyuria, polydipsia, polyphagia
GI mucosal irritation: vomiting, diarrhoea (divide daily dose and admin with food)
necrotising pancreatitis: STOP TX

Question 23

When does potassium bromide reach steady concentration?

Answer 23

120 days after start if tx/ dose change

Question 24

What are the side effects of using potassium bromide?

Answer 24

excreted unchanged in urine
used with caution in animals with renal disease: reduced excretion

high diet chloride increase KBr excretion

Question 25

What are reasons for seizure treatment failure?

Answer 25

poor compliance
incorrect dose
change in patient body weight
incorrect dx
patient develops tolerance to drug
refractory seizures that don’t respond to medications

Question 26

What are add-on drugs for refractory seizures?

Answer 26

Usually: levetiracetam

gabapentin, pregabalin, zonisamide, felbamate

Question 27

What is the action of levetiracetam?

Answer 27

reduces excitatory neurotransmitter release, possibly neuroprotective
rapid onset of action
can be used as pulse therapy in dogs with cluster seizures

Question 28

What should we inform/warn clients about seizure tx?

Answer 28

only 15-30% of idiopathtic epileptic dogs achieve seizure freedom with tx
only 2/3 of dogs respond to AEDs
majority of dogs = lifelong commitment = expensive
AED use is associated with adverse side effects

Question 29

When do we discontinue AEDs?

Answer 29

if life threatening adverse effects
if seizure remission achieved (none for 1-2 years) slow decrease *could come back worse

Question 30

What is the first line tx for seizures in cats?

Answer 30

phenobarbital
10-14 days steady state
transdermal also possible

Question 31

What are the main side effects of phenobarbital in cats?

Answer 31

sedation
polyphagia
ataxia
elevated ALT and ALKP
paraparesis

Question 32

What are the main side effects of levetiracetam in cats?

Answer 32

hypersalivation
sedation
anorexia
ataxia
eliminated via kidneys: reduce dose if compromise

Question 33

What are the effects of imepitoin and potassium bromide in cats?

Answer 33

imepitoin: not licensed, early studies shown safe
potassium bromide: contraindicated, causes allergic pneumonitis

Question 34

How can diet help manage IE?

Answer 34

could help improve seizure control and behavioural changes associated with epilepsy

medium chain triglyceride supplemented diet!
or MCT in oil based supplement

Question 35

What is status epilepticus?

Answer 35

greater than 5 min of continuous epileptic seizures
OR
2 or more seizures between which there is incomplete recovery of consciousness

Question 36

Why is status epilepticus an emergency?

Answer 36

increased autonomic discharge = hypertension, tachycardia, cardiac arrhythmias
gets worse with more CS
if left untreated: multiple organ failure!

Question 37

How do we approach status epilepticus in ER?

Answer 37

ABC
IV access
diazepam IV
evaluated electrolytes/blood glucose + correct abnormalities

longer acting AED: phenobarbital
evaluate temp and start cooling if over 40
IVFT, oxygen, supportive care

if continued seizure: CRI of midazolam, medetomidine or propofol

Question 38

What are benzodiazepines?

Answer 38

first line drugs in emergency setting
potent rapid onset
15-20n min effect

diazepam, midazolam