Antiepileptics

Question 1

Seizure Vs Epilepsey

Answer 1

Seizure: paroxysmal event caused by avoidable circumstance (E.g. alc, hypoglycemia).

Epilepsy: Chronic event

Question 2

Factors that affect the risk of recurring seizures from Epilepsy (IMPT!!)

Answer 2

Lower risks:

• Single seizure
• Normal EEG
• Normal Brain scan

Higher risk:
- Previous undiagnosed seizures
- Epileptiform EEG
- Abnormal brain scan
(basically opposite of lower risk)

Question 3

Possible causes of Epilepsy

Answer 3

1. Congenital/Hereditary
2. Brain injury/scarring/tumour (esp. those affecting brain structure)
3. Brain Infections (e.g. meningitis)
4. Blood glucose alterations (e.g. hypogly)
5. Metabolic disorders (e.g. adrenal insufficiency leading to hyponatremia)

Question 4

Three main classifications of epilepsy and their sub-categories if any

Answer 4

1. Generalised:
   - Tonic Clonic (dramatic)
   - Absence (“zoning out”)
   - Myoclonic (brief repetitive movements)
   - Atonic (brief movements without muscle tone)
2. Partial
   - Simple
   - Complex (impaired consciousness)
3. Status Epilepticus (long seizures without recovery time)

Question 5

The main rationale of Antiepileptics

Answer 5

• Seizures are caused by firing of neurons, involving Na & Ca ions
• Antiepileptics decrease membrane excitability by altering Na and Ca conductance during action potential
• They can also enhance effects of inhibitory GABA neurotransmitters

Question 6

Drugs that only blocks voltage-dependent Na+ channels

Answer 6

1) Phenytoin

2) Carbamazepine

Question 7

Disadvantages of Phenytoin

Answer 7

1) Teratogenic: unsuitable in pregnancy
2) Narrow-therapeutic range with non-linear PK requiring titration and monitoring
3) Not suitable for absence seizures

Question 8

Can Carbamazepine be used for all types of seizures?

Answer 8

No, Carbamazepine cannot be used for absence seizures

Question 9

Rare but significant fatal adverse effect of Carbamazepine

Answer 9

Aplastic anemia

Question 10

What enzyme does Carbamazepine upregulates, leading to DDI?

Answer 10

CYP450

Question 11

MoA of Valproate

Answer 11

1) Blocks BOTH Na and Ca voltage-dependent channels

2) Inhibits GABA transaminase, hence increasing GABA levels in synaptic space

Question 12

Valproate can potentially interact with other drugs. Why is this so?

Answer 12

Valproate is strongly bound to plasma proteins and can displace drugs which are also bound to proteins such as other antiepileptics

Question 13

What kind of seizure(s) is Valproate suitable for?

Answer 13

All types of absence

Question 14

General Dose-related SE of antiepileptics?

Answer 14

1. Drowsiness
2. Confusion
3. Nystagmus
4. Ataxia
5. Slurred speech
6. Nausea
7. Unusual Behaviour
8. Mental Changes
9. Coma

(i.e. a lot of CNS SE)

Question 15

General Non-dose related SE of antiepileptics?

Answer 15

1. Hypersensitivity rxn like SJS

2. Others: hirsutism, acne, gingival hyperplasia, folate deficiency, osteomalacia

Question 16

BZDs can be used as Antiepileptics. However, why are they not the first-line drugs? What are they usually used for?

Answer 16

High potential for abuse, and causes death in overdose

Usual uses:
- Sedative, hypnotic

Question 17

MoA of BZDs that confers them antiepileptic properties

Answer 17

• Binds to GABA receptors, enhancing action of the endogenous GABA
• Leads to greater entry of chloride ions
• Cells are now hyperpolarised and harder to excite
• Hence neurons cease to fire

Question 18

There are short-acting, intermediate-acting and long-acting BZDs. Which BZD(s) is/are most suitable as antiepileptics and why?

Answer 18

Intermediate and long-acting

• Epilepsy is chronic conditions
• Important in refractory seizures and in status epilepticus as emergency use
• Duration for short-acting BZD is insufficient, and frequent use leads to addiction

Question 19

Considerations when initiating antiepileptic drug

Answer 19

1. Individualised according to seizure type, epilepsy syndrome, other meds, comorbidities, lifestyle and preferences
2. Initiate monotherapy. If AE is encountered, or monotherapy is unsuccessful, try another monotherapy using another drug
3. Initiate with lowest therapeutic dose

Question 20

Antiepileptics that are considered first line treatments for newly diagnosed partial and generalised tonic clonic seizures (according to MOH guidelines)

Answer 20

Carbamazepine, Phenytoin, Valproate

• No specific preferences as they have similar effectiveness

Question 21

When must the drug levels of antiepileptics be tested?

Answer 21

1. Assessing compliance for refractory epilepsy
2. Assessing sx for possible antiepileptic drug toxicity
3. Titrating phenytoin dose

Question 22

If patient is well-controlled, must the testing of antiepileptic drug levels continue?

Answer 22

No. Routine assessment w/o clear clinical indication is not cost-effective

Question 23

Factors that increse the risk for breakthrough seizures (i.e. seizure episode in epileptic patients)

Answer 23

1. Non-compliance to antiepileptics
2. Interactions with antiepileptics causing lower concentration of antiepileptics
3. Alc abuse
4. Sleep deprivation
5. Concurrent illness