Epilepsy II Flashcards

Question

How to reduce occurrence and severity of dose-plasma concentration-related adverse effects?

Answer 1

- Initiating therapy at a low dose, and slowly increasing the dose. - Avoiding large dosage changes - Restricting therapy to one drug only (if clinically feasible) - Adjusting the administration schedule >> Administration of largest dose at bedtime >> Dividing a daily dose into smaller doses given more frequently >> Use of sustained-release formulations >> Reducing the total daily dose

Answer 2

Rare (<0.1%) - Blood dyscrasia (aplastic anemia, granulocytosis) (phenytoin and carbamazepine) - Hepatotoxicity (first generation ASMs: phenytoin, valproate, carbamazepine) - Pancreatitis (sodium valproate) - Lupus-like reaction - Dermatitis - Stevens-Johnson syndrome (carbamazepine, phenytoin and lamotrignine)

Answer 3

- Neurological >> Encephalopathy: phenytoin, phenobarbitone >> Peripheral neuropathy: phenytoin, carbamazepine and phenobarbitone - Gastrointestinal >> Sodium valproate (increased weight gain), topiramate (weight loss) - Hematological: Blood dyscrasias, megaloblastic anemia - Neonatal congenital defects >> Associated with phenytoin, phenobarbitone and topiramate >> Valproate – cognition - Suicidal ideation >> All of the key drugs, except phenytoin >>No changes to therapy without first discussing with physician >> Requires close monitoring of symptoms

Answer 4

- Rash is a common side effect - Could be Stevens-Johnson syndrome, or just a macropapular rash. - can be caused by: carbamazepine, phenytoin, lamotrigine - Risk management strategies: 1. Pharmacogenetic testing: carbamazepine >> Strong association between carriage of HLA-B 1502 and risk of carbamazepine-induced SJS. >> Relevant for Han Chinese and other Asian ethnic groups. 2. Follow dosing guidelines: lamotrigine 3. Identify potential cross-sensitivity reactions (ASMs with aromatic rings)

Answer 5

- mechanisms by which ASMs induce skin reactions is unclear. - main hypotheses: ASMs with an aromatic ring can form an arene-oxide intermediate - become immunogenic through interactions with proteins or cellular macromolecules - in the event if an individual is allergic to an aromatic ASM, he may switch to a non-ringed ASM, or continue with the ringed ASM if symptoms are deemed mild, and epilepsy severe, subject to close monitoring.

Answer 6

Common side effects: somnolence, dizziness, asthenia, coordination difficulties, headache Other known side effects: irritability, aggression

Answer 7

1. To establish an individual’s therapeutic range • “Reference range” may not be effective for all due to interindividual variability. • Plasma ASM levels correlate much better with clinical effects than dose. 2. To assess lack of efficacy • Some individuals may be fast metabolizers, may have adherence issues. • Need to decide if choice of drug and dosing is right for a particular patient in achieving long-term seizure control. • Doses tend to be prophylactic, seizures occur at irregular intervals. 3. Assess for potential toxicity • Concentration-dependent adverse effects, slow metabolizers, renal or hepatic impairment 4. To assess loss of efficacy (breakthrough seizures) • Drug interactions, changes in physiology or formulation

Answer 8

- Receive counselling on importance of early discussion on family planning - Cannot prescribe teratogenic drugs - Use of oral contraceptives >> Potent enzyme inducers may render OC ineffective, alternative methods required. >> For patients on lamotrigine, OC may lower lamotrigine concentrations, resulting in breakthrough seizures.

Answer 9

- Women with epilepsy should be referred to specialist care for pre-conception counselling. - Taking ASM is not an absolute contraindication to breastfeeding - All breastfeeding women on ASM should be encouraged to breastfeed, and receive support from healthcare professionals.

Answer 10

o Drug discontinuation can be considered after a minimum of two years without a seizure. o Longer for patients who are at increased risk of seizure recurrence. o Discuss with family members and caregivers o Drug tapering schedule should be individualized. o Patients are considered free from epilepsy if: they have not experienced seizure for 10 years, and have remained off-medicine for 5 OR if they suffered from age-dependent epilepsy syndrome and are now past the given age.

Answer 11

o Constant state of epilepsy o Need to act within 5 mins, else seizure will be prolonged, need to act within 30 mins, else there will be long-term consequences to the seizures.

Answer 12

1. First 5 mins: stabilize the seizure, time the seizure onset, check vital signs etc. Collect finger stick glucose (hypoglycemia may cause seizure) 2. 5-20 mins: prescribe benzodiazepine as the initial therapy of choice - IV diazepam, midazolam, lorazepam, if not: rectal diazepam, IV phenobarbital 3. 20-40 mins: - Phenytoin, valproate, or levetiracetam 4. 40-60 mins (if patient is still seizing): - No clear guidelines on what to use, but can give anesthetic agents like thiopental, midazolam, propofol.