Epilepsy

Question 1

List some DDx for a presenting seizure?

Answer 1

Seizure causes:

• CVA (ischaemic or haemorrhagic)
• Infective: meningitis, encephalitis, brain abscess
• Malignancy: primary brain tumour, mets
• Metabolic: hypo/hyperglycaemia, hyponatraemia, hypocalcaemia, hypomagnesia
• Toxicity: ETOH/Benzo withdrawal, drug intoxication, uraemia

Seizure mimics:

• Syncope
• CVA (TIA)
• Psychiatric disorders
• Delirium
• Sleep disorders

Question 2

What are the 1st line drugs for epilepsy?

Answer 2

• For focal/partial seizures: Carbamezepine
• For complex/generalised seizures: Sodium Valproate (2nd line Carbamezepine, 3rd line phenytoin)
• For absent seizures: Ethosuximide

Question 3

Describe the MAO of Carbamezapine?

Answer 3

Carbamezapine (Tegretol)
Indicated: partial seizures (1st line), generalised seizures (2nd line), bipolar, neuropathic pain

MAO: Na channel blocker

• > binds to Na channels in inactivated state -> extends inactivated phase
• > inhibits neuron depolarisation -> decreased glutamate release
• > decreased cell excitability (reduced inward current needed for AP)
• > reduced seizure risk

Use-dependent blockage: preferentially blocks cells firing repetitively

Question 4

Describe the SE of Carbamezapine?

Answer 4

Type A: due to primary drug effect, dose dependent, predictable

• Visual (occur first): blurred vision/diplopia, nystagmus
• CNS: dizzy, drowsy, coma, headache, ataxia, lethargy
• GIT: nausea, vomiting, diarrhoea, increased liver enzymes
• Cardiac: arrhythmia (prolonged QRS, ventricular arrhythmia, hypotention)- Na channel blockade
• Hyponatraemia
• Fluid retention

Type B: idiosyncratic, not dose-dependent, not predictable
- Haem: agranulocytosis, aplastic anaemia, thrombocytopenia
- Skin: Steven-Johnson’s syndrome, toxic epidermal necrolysis
CBZ overdose: proconvulsant effect (antagonised adenosine receptors)

Question 5

Describe the drug interactions of Carbamezapine?

Answer 5

Induced the CYP450 enzymes
-> accelerates metabolism of some drugs -> reducing efficacy
E.g. OCP, Warfarin, corticosteroids, phenytoin, some abx

Question 6

How is Carbamezapine excreted?

Answer 6

Metabolised in liver (by CYP450)

Question 7

What are the driving restrictions of epileptics?

Answer 7

Australian Roads Guidelines suggest pt should be able to drive if:

1. He has no residual damage from his seizures, and they do not impact his driving
2. Other neurological causes are ruled out
3. Has not had a seizure for one year

Question 8

What is the mechanism of diplopia in Carbamezapine use?

Answer 8

MA:

• > Na+ channel blockade (cranial nerves and internuclear pathways)
• > impaired extra-ocular muscles

Note: susceptible if just started Rx or dose too high (occular symptoms occur first)