Epilepsy or Seizure Flashcards
Precipitating factors for seizure
Hyponatremia, hypocalecemia, hypomagnesemia, hypoglycaemia
Drug abuse, use of TCA, carbapenenms, baclofen
Alcohol withdrawal/intoxication
Benzodiazepine withdrawal
Stroke/TIA
CNS infection, febrile illness
Antimicrobials that can lower seizure threshold
Carbapenems, cephalosporins (cefepime), fluoroquinolones, macrolides, penicillins, isoniazid, linezolid, metronidazole, amphotericin, azoles (fluconazole), anti-malarials (chloroquine), acyclovir, ganciclovir
Analgesics that can lower seizure threshold
Codeine, fentanyl, meperidine, morphine, NSAIDs, tramadol, pentazocine
CNS agents that can lower seizure threshold
Anti-psychotic: Clozapine, haloperidol, lithium, olanzapine, risperidone, phenothiazines, pimozide, thiothixene
Antidepressants: Bupropion, TCAs, SSRIs, MAOIs, doxepin, trazodone, venlafaxine
Others
Cancer agents, digoxin, flecainide, ephedrine, esmolol, propanolol, immunosuppressants (tacrolimus, cyclosporine), sumatriptan, atropine, flumazenil, levodopa, baclofen, etc.
Phenytoin PK, PD, DI-DI, S/E
CYP2C9, 2C19, 3A and UGT inducer
Oral to IV phenytoin requires dose conversion, 100% oral: 92% IV
Absorption is reduced at higher doses, space 2 hours between enteral feeds and phenytoin
Highly albumin bound, affected by low albumin, other drugs and displacement. Most labs measure total phenytoin (unable to detect free phenytoin changes)
Zero-order kinetics, clearance dependent on concentration, larger increases in AUC with increasing doses
Avoid if HLA-B*1502 positive
Dose-related toxic effects: drowsiness, dizziness, nystagmus, ataxia
Phenytoin: hepatotoxicity, TEN, gingivial hyperplasia, hirsutism, osteomalacia
Valproate PK, PD, DI-DI, S/E
2C9, UGT and epoxide hydrolase inhibitor
Highly protein bound, competes with warfarin, phenytoin, NSAIDS
Saturable protein-binding within therapeutic range - decreased protein binding at higher concentration and higher free fraction of drug with low albumin
>Difficult to predict valproate concentrations at higher valproate levels
Dose-related toxic effects: drowsiness, dizziness, nystagmus, ataxia
nausea, vomitting,
Valproate: hepatotoxicity, pancreatitis, alopecia, weight gain
Carbamazepine
CYP3A4 inducer and substrate
Highly protein bound to albumin and alpha-1 acid glycoprotein
Autoinduction occurs 2-3 weeks after dose initiation, gradually increase over few weeks
Require HLA-B1502 testing prior to starting, avoid if HLA-B1502 positive
Dose-related toxic effects: drowsiness, dizziness, nystagmus, ataxia,
Carbamazepine: hepatotoxicity, peripheral neuropathy (may respond to folate supplementation), osteomalacia, hyponatremia
Idiopathic/hypersensitivity adverse events associated with all current ASMS - especially serious
Blood dyscrasias (apalstic anaemia, agranulocytosis),
Lupus-like reaction
Exofiative dermatitis
TEN and SJS
Increased suicidal ideation
Lamotrigine dosing recommendations
If taking concomitant carbamazepine, phenytoin, phenobarbital or primidone - double dose in dose escalation ladder
Maintenance dose: 300-500 mg/day in 2 divided doses
If taking valproate - halve dosing e.g. 25 mg every other day instead of every day
100-200 mg/day if with valproate alone
Normal dose escalation:
Week 1-2 : 25 mg everyday
Week 3-4: 50 mg/day
Week 5 onwards to maintenance: Increase by 50mg/d every 1-2 weeks
225 - 375 mg/day as maintenance dose
Cross-sensitivity across anti-seizure medicines
Aromatic AEDS:
Carbamazepine, Lamotrigine, Oxcarbazepine, Phenytoin, Phenobarbital
Non-aromatic AEDS:
Valproate, Levetiracetam, Gabapentin, Topiramate
Levetiracetam side effects
Low protein binding, renally eliminated
Common: Drowsiness, dizziness, coordination difficulties
Take note: can induce neuropsychiatric side effects such as irritability, aggression.
Lamotrigine PK side effects:
Moderate protein binding, hepatically eliminated (100%)
Common: Dizziness, nausea/vomiting, drowsiness, tremor, weakness
Serious: Rash, SJS/TEN, DRESS. Titrate slowly
DDI - Oral contraceptives will reduce lamotrigine serum concentration and lead to seizure breakthroughs
Topiramate PK and S/E
Less protein bound, renally eliminated and dose dependent DDI
CYP3A4 inducer
Other known S/E:
Glaucoma, hyperammonemia, metabolic acidosis, hyperthermia, paresthesias, renal stones
Anti-seizure meds that are safe for use in pregnancy
Lamotrigine and Levetiracetam
Never valproate (males as well), carbamazepine, topiramate, phenobarbital
Status epilepticus
