Antiepileptics

Question 1

What constitutes lower risk vs higher risk of recurrent seizures?

Answer 1

Lower risk:

• only had single seizure
• normal EEG
• normal brain scan

Higher risk:

• previous (undiagnosed) seizures
• epileptiform EEG
• abnormal brain scan

Question 2

What is the pathophysiology of epilepsy?

Answer 2

Abnormal hypersynchronous discharge from a mass of CNS neurons

Question 3

What are the different types of epilepsy?

Answer 3

1. Generalized seizures (affecting whole brain):
   - tonic clonic (grand mal)
   - absence (petit mal)
   - myoclonic
   - atonic
2. Partial seizures:
   - simple (consciousness not impaired)
   - complex (consciousness impaired)
3. Status epilepticus - potentially life threatening, keep having multiple seizures

Question 4

What is EEG?

Answer 4

Electroencephalogram

Question 5

What is the rationale of Antiepileptics treatment?

Answer 5

In epilepsy, there is an imbalance between excitation and inhibition. Hence, reduce excitation or increase inhibition.

• decrease membrane excitability by altering sodium and calcium conductance during action potentials
• enhance effects of inhibitory GABA neurotransmitters

Question 6

MOA of Phenytoin?

What type of seizure is phenytoin used for?

What is needed when using phenytoin?

Can phenytoin be used in pregnancy?

Answer 6

• blockade of voltage dependent sodium channels
• suitable for all types of seizures except absence seizures
• relatively narrow therapeutic range
• saturation kinetics -> non linear relationship between dose and plasma concentration
• need titration and monitoring
• teratogenic

Question 7

What is carbamazepine’s MOA?

Answer 7

Blockade of voltage dependent sodium channels

Question 8

What type of seizures is carbamazepine used for?

Answer 8

All types of seizures except absence seizures

Question 9

Drug interaction of carbamazepine?

Answer 9

It is a CYP450 inducer. Half-

Ife shortens with repeated doses. Accelerates elimination of other drugs

Question 10

What is an important adverse effect of carbamazepine?

Answer 10

Aplastic anaemia (bone marrow cannot produce blood cells)

Question 11

What is the MOA of valproate?

Answer 11

Blockade of voltage dependent sodium and calcium channels

Inhibits GABA transaminase -> increases GABA

Question 12

What types of seizures is valproate used for?

Answer 12

All types of seizures, including absence seizures

Question 13

Drug interactions of valproate?

Answer 13

Strongly bound to plasma proteins, displaces other Antiepileptics

Question 14

What are some general adverse effects of Antiepileptics?

Answer 14

Dose related side effects:
drowsiness, confusion, nystagmus, ataxia,
slurred speech, nausea, unusual behavior, mental changes, coma

Non dose related:
hirsutism, acne, gingival hyperplasia, folate
deficiency, osteomalacia, hypersensitivity reactions (including Stevens-Johnson syndrome)

Question 15

What are the benzodiazepines used as Antiepileptics?

Answer 15

Clonazepam (intermediate acting) is used for seziures
Lorazepam (intermediate acting) is used for status epilepticus
Diazepam (long acting) is used for seizures and status epilepticus

Question 16

What is the treatment strategy for epilepsy?

Which Antiepileptic deug should be chosen initially?

Answer 16

• patients should be commenced on monotherapy initially. If develops adverse reaction or if initial monotherapy is unsuccessful, monotherapy using another drug should be tried ( DO NOT ADD ON)
• all Antiepileptics have similar efficacy in newly diagnosed epilepsy -> can use medicine doctor most familiar with
• carbamazepine, phenytoin and sodium valproate are first line for newly diagnosed partial and generalized tonic clonic seizures
• if absence seizures, only can use valproate

Use lowest dose which controls seizures

Question 17

When are Antiepileptics drug level tested?

Answer 17

When there is a clinical indication:

• assessment of compliance
• possible Antiepileptics drug toxicity
• titration of phenytoin dose due to saturation kinetics

Otherwise, routine checking of drug level is not necessary, not cost effective.

Question 18

What factors cause increased risk for breakthrough seizures?

Answer 18

• non compliance
• drug interaction lowering blood level of Antiepileptic
• alcohol abuse
• sleep deprivation
• concurrent illness