Antiepileptic

Question 1

what are the circumstances where single seizure is provoked but may not necessarily be epilepsy? (What could trigger single seizure?)

Answer 1

• alcohol
• hypoglycaemia
• pyrexia
• sleep deprivation

Question 2

2 different risk profiles of recurrent seizures

Answer 2

1. lower risk (30-50%)
   - single seizure
   - normal EEG
   - normal brain scan
2. higher risk (80%)
   - previous (undiagnosed) seizures)
   - epileptiform EEG
   - abnormal brain scan

Question 3

How do we diagnose someone w epilepsy?

Answer 3

based on:
- clinical Hx and examination

• blood test (liver function, blood chemistry)
• EEG,
• brain scan (CT/MRI)

to determine risk of recurrent seizures

Question 4

epilepsy is

Answer 4

recurrent seizures

Question 5

pathophysiology for seizures to occur

Answer 5

• neuronal depolarisation (firing) depends on membrane potential
• excessive synchronous depolarization, usually starting from defined regions (“foci”) and spreading to other regions
• unbalanced excitatory and inhibitory receptor/ ion channel function –> favouring DEPOLARIZATION –> dysregulated discharge

–> causes seizure

Question 6

causes of epilepsy

Answer 6

• congenital or hereditary
• brain injury, scarring, tumor
• infections: meningitis or encephalitis
• blood glucose alteration
• metabolic disorder e.g. adrenal insufficiency leading to hyponatremia

Question 7

what can be the differential diagnosis other than epilepsy

Answer 7

• patient can present w loss of awareness (present like seizure but wasn’t seizures)
• -> hypoglycaemia, panic attacks
• -> transient cardiac arrhythmia/ ischaemic attacks
• patient present w abnormal movement
• -> movement disorders
• -> tremor
• -> drop attacks

Question 8

3 categories of seizures

Answer 8

1. generalised seizures
   - -> tonic clonic (grand mal)
   - -> absence (petit mal)
   - -> myoclonic (muscle jerking)
   - -> atonic (paralytic; sudden loss of muscle strength)
2. partial seizures
   - -> simple (consciousness not impaired)
   - -> complex (consciousness impaired)
3. status epilepticus (never resolves)

Question 9

difference between generalised and partial seizure based on EEG?

Answer 9

generalised: multi-foci (frontal, ocular, temporal)
partial: 1 or 2 out of the 3 foci mentioned

Question 10

what can antiepileptic drug do (2 ways)

Answer 10

1. decrease membrane excitability by altering Na+ and Ca2+ conductance during action potential
2. enhance effect of inhibitory GABA neurotransmitters

Question 11

MOA of phenytoin

Answer 11

• block voltage-dependent Na+ channels

Question 12

Phenytoin can be used in what type of seizures

Answer 12

all types EXCEPT absence seizures

Question 13

PK of phenytoin

Answer 13

• narrow therapeutic range (plasma conc 40-100um)
• saturation kinetics bet dose and plasma conc –> thus need titration and monitoring
• -> non-linear relationship bet dose and steady state plasma conc

Question 14

Adverse effect/ danger of phenytoin

Answer 14

teratogenic - toxic for developing foetus

Question 15

MOA of carbamazepine

Answer 15

• blockade of voltage-dependent Na+ channels

Question 16

Carbamazepine can be used in what type of seizures and what are the exceptions?

Answer 16

• all types of seizure EXCEPT for absence seizures

Question 17

PK of Carbamazepine

Answer 17

cyp450 inducer and cyp450 metabolite, thus HALF LIVE shortens with repeated doses

AND

increases the elimination of other drugs

Question 18

SE/Adv effect/ Caution of Carbamazepine

Answer 18

aplastic anemia (2 per million per year)

Question 19

MOA of Valproate

Answer 19

• blockage of voltage-dependent Na+ and Ca2+ channels

- inhibits GABA transaminase –> increases GABA

Question 20

Valproate use in what type of seizures

Answer 20

for all type of seizures, including absence seizures

Question 21

PK of valproate

Answer 21

strongly bound to plasma proteins, displaces other antiepileptics

Question 22

what are the dose-related SE of anti-epileptics

Answer 22

Dose-related SE: drowsiness, confusion, slurred speech, nausea, unusual behaviour, mental changes, coma, nystagmus, ataxia

Question 23

what are the non-dose related SE of anti-epileptics

Answer 23

• hirsutism, acne, gingival hyperplasia, folate deficiency, osteomalacia, hypersensitivity rxn (SJS)

Question 24

BZDs use as an anti-epileptic MOA

Answer 24

enhances effects of inhibitory GABA neurotransmitters

GABA acts on the GABAa receptors CL- channels –> potentiates influx of CL- ions leading to hyperpolarisation –> neurons not firing

Question 25

Names of the BZDs and their DOA for anti-epileptic purposes

Answer 25

• diazepam (long-acting)
• clonazepam (intermediate acting)
• lorazepam (intermediate-acting) (more for status epilepticus)

Question 26

BZDs use in anti-epileptic is what line

Answer 26

last line of therapy

Question 27

what factors need to be considered before the initial choosing of an antiepileptic drug

Answer 27

• seizure type
• epilpsy syndrome
• co-medication (esp cyp450)
• comorbidity
• lifestyle/preferences

Question 28

how should anti-epileptic therapy start

Answer 28

• MONOtherapy first
• if patient have adverse rxn to the initial monotx,
• monotherapy of ANOTHER drug should be tried

Question 29

which anti-epileptic drug is first line?

Answer 29

• carbamazepine
• phenytoin
• sodium valproate

for partial and generalised tonic clonic seizures

Question 30

when do we test the anti-epileptic drug levels in a patient

Answer 30

• check for compliance in patient w refractory epilepsy (definition: medicine isn’t bringing your seizures under control)
• sx of drug toxicity
• titration of initial phenytoin dose

But routine checking w/o a clear indication is not required

Question 31

reasons for increase risk for breakthrough seizures

Answer 31

• non-compliance
• interactions w antiepileptic med; lowering the blood lvls of antiepileptic drug
• alcohol abuse
• sleep deprivation
• concurrent illness