Treatment

Question 1

Phenytoin?

Answer 1

Phenytoin can be used for tonic-clonic, focal seizures & status epilepticus.Causes a voltage-dependent block of VgNa+ channels on the neuronal cell membrane, promoting the efflux of sodium ions from neurons and stabilising the threshold against hyperexcitability.For tonic-clonic seizures, loading dose of 3–4 mg/kg daily, then 200–500 mg dailyTherapeutic plasma concentration of 10-20 μg/L – narrow therapeutic index.The most notable signs of toxicity associated with the intravenous use of this drug are cardiovascular collapse and/or CNS depression.The rate of administration is very important; it should not exceed 50 mg per minute in adults, and 1 to 3 mg/kg/min

Question 2

Common side effects of anticonvulsants?

Answer 2

Gastrointestinal (nausea and vomiting, weight gain)
* Hyperammonaemia (nausea, vomiting, ataxia) – ammonia levels must be monitored
* Haemopoietic (leucopenia, thrombocytopaenia)
* CNS (suicidal ideation)
* Reduce fertility
* Increase risk of reproductive endocrine disorder & cause polycystic ovary syndrome

Question 3

Ethosuximide, Lamotrigine & Levetiracetam may cause:

Answer 3

• DRESS: drug reaction with eosinophilia and systemic symptoms (hypersensitivity causing inflammation of organs and may be fatal)
• SJS: Stevens-Johnsons syndrome (complex immune-mediated hypersensitivity where flu-like symptoms and blistering rash are experienced)

Question 4

Interactions?

Answer 4

Common across all anticonvulsants
3A4 inhibitors (e.g. erythromycin) increase plasma levels & 3A4 inducers (e.g. phenytoin, rifampicin) decrease plasma levels.
Lithium may cause CNS toxicity.
Antipsychotics lower seizure threshold

Question 5

Specific
* Carbamazepine - interactions

Answer 5

o Decrease plasma levels of corticosteroids, CCBs, warfarin, valproate, oral contraceptives (CYP3A4 inducer)

Question 6

Sodium valproate

Answer 6

o Drugs that elevate levels of glucuronosyltransferases (e.g. phenytoin,
carbamazepine, rifampicin) may increase the metabolism of valproate
o Aspirin inhibits metabolism
o Carbapenem antibiotics cause significant reduction in plasma conc therefore loss
of seizure control
Valproate decreases efficacy of diazepam and phenytoin (by displacing from albumin binding sites and inhibiting metabolism)

Question 7

Phenytoin kinetics

Answer 7

What are the kinetics of phenytoin? Most drugs undergo first-order kinetics; when a
constant proportion of the drug is eliminated per unit time. Rate of elimination is proportional to the amount of drug in the body. Phenytoin undergoes zero-order kinetics; it has a constant rate of elimination. If the dose is doubled, there is a disproportionate rise in serum-phenytoin. Because phenytoin undergoes zero-order kinetics, rate of elimination = rate of administration