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23 Cards in this Set
- Front
- Back
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Therapeutic
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•Seizure frequency
•Serum drug concentration (if routinely measured): CBZs, phenytoin, valproate, ethosuximade •Quality of life |
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Toxicity
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•Seizure frequency
•Serum drug concentration* •Suicidal ideation/depression •Medication side effects (dizziness, drowsiness, and somnolence) |
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QoL
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•Quality of life in epilepsy patient weighted
•QOLIE-10-P: screening •QOLIE-31-P: more comprehensive QOLIE-AD-48 (adolescent) •Seizure Severity Questionnaire (SSQ)-in conjuction with QOLIE |
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Sucidality
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Two times the risk of suicidal vs. placebo
–Seen as early as 1 week after starting AED –Observed at any time during treatment –No specific subgroup to which the risk could be attributed But it may happen independent of AEDs |
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General Monitoring
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•Adherence
–Avoid abruptly stopping •Dosing regimen –Serum concentrations (if routinely measured) –Instructions to avoid adverse effects (i.e. take topiramate with plenty of water to avoid kidney stones or take phenobarbital at bedtime to minimize sedation). •Side effects (SE) –Concentration dependent –Idiosyncratic –Chronic –Suicidality/depression •Drug interactions |
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CBZs
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-Carbamazepine is a substrate of CYP3A4 and induces CYP1A2, CYP2C9, and CYP3A4.
-Autoinduction begins 3-5 days after starting therapy |
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CBZs Monitoring
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•Therapeutic–Epilepsy: 4-12 mg/L, Neuralgias: 2-7 mg/L
-Serum levels ideally obtained after the autoinduction period is complete -Mild leukopenia is common and not a reason to discontinue therapy |
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Phenytoin SEs
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Concentration dependent: Nystagmus
Idiosyncratic: Lupus Chronic: Gingival hyperplasia (50%), Hypertrichosis (werewolf syndrome) |
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Phenytoin Kinetics
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A: overall slow, F=20-90%, chewable & Susp > caps > Kapseals
D: 90% albumin bounded, lipid soluble (obese: >Vd, larger loading dose) M: linear at low dose -> saturation -> non-linear -> small increase -> larger [ ] changes Metabolised by & Autoinduce: CYP2C9, CYP2C19 |
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Hypoalbuminemia Phenytoin formula
ESRD Elderly nursing home/critically ill trauma |
Cobserved=Cnormal / (0.2 x Alb) + 0.1
Cobserved=Cnormal / (0.1 x Alb) + 0.1 Cobserved=Cnormal / (0.25 x Alb) + 0.1 |
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Phenytoin DD interaction
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Increase Phenytoin Levels:
•Amiodarone Decrease Phenytoin Levels: •Alcohol (chronic) •Antacids Phenytoin decrease levels of: •Carbamazepine •Warfarin •Digoxin |
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Phenytoin Monitoring
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Therapeutic
–Total: 10-20 mcg/mL –Free: 1-2 mcg/mL When switching between the phenytoin sodium salt and acid forms Serum levels obtained 7-10 days after dose change. Toxic –Nausea/vomiting –Nystagmus –CNS depression •Sedation •Inability to concentrate •Confusion •Coma Other •Infusion rate •Rash •CBC •BMD •Suicidality/depression |
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Valproate SEs
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[ ] dependent: N&V, Tremor, elderly decreased cl -> somnolence
Idiosyncratic: Hepatic failure, Pancreatitis Chronic: Alopecia, Behaviour changes (anxiety, mood swings, depression, and disturbed thinking), Hyperammonemia (lethargy, vomiting, and acute mental status changes) |
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Valproate Kinetics
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A: 90-100%, 90-95% protein-bound
M: CYP2C9 inhibitor E: free fraction increase, clearance also increase (clearance decrease in elderly) |
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Valproate Monitoring
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Therapeutic
–Epilepsy: 50-100 mcg/mL (High dose 80-150 mcg/mL) –Bipolar Mania: 50-125 mcg/mL Frequency/timing –Troughs before morning dose (Diurnal fluctuation) –3-5 days after dose change or starting therapy Other •Liver function tests: hepatotoxicity •CBC (platelets): thrombocytopenia •Amylase: rarely progress to pancreatitis •Ammonia: hyperammonia (confusion/unexplained lethergy) •Suicidality/depression |
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Ethosuximide SEs
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Uses: Absence seizure
Concentration dependent •Nausea •Vomiting Chronic •Headache: esp. children •Behavior changes: esp. children •Suicidality/depression |
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Ethosuximide Kinetics
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A: nearly complete
D: not protein bound, not distributed into fat (Vd=70% IBW) M: CYP3A4 substrate, t1/2: 60hrs (adult), 30hrs (child) |
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Ethosuximide Monitoring
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Therapeutic
–40-100 mcg/mL, may go up to 150mcg/ml (full-remission) –Seizure frequency Frequency –Initially: steady state •Children: 6 days •Adults: 12 days –Maintenance: • Every 4-6 months Other •CBC: Blood dyscrasias •Liver function tests •Nausea/vomiting: may divide daily dose to min N&V |
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Phenobarbital SEs
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Treat seizures with hynoptic and sedative effect
Concentration Dependent •Sedation (>5 mcg/mL) •Impaired cognition (>19 mcg/mL) •Ataxia (35-80 mcg/mL) •Potential coma (>65 mcg/mL) •Coma without reflexes (>80 mcg/mL) Idiosyncratic •Blood Dyscrasias •Rash Chronic •Behavior changes •Sedation •Intellectual blunting •Folate deficiency (52%) •Vitamin D deficiency (10%) -> ?Osteoporosis BMD •Liver damage (<1%) |
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Phenobarbital Kinetics
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•Inducer:
–CYP3A4, 2D6, 2C, 1A2 •Decreases levels of: – blockers –Calcium channel blockers –Warfarin –Other antiepileptic drugs –Theophylline –Digoxin –Corticosteroids |
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Phenobarbital Monitoring
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Serum Concentrations
–Therapeutic: 10-40 mcg/mL –Toxic: >40 mcg/mL –Frequency: •Initial 3-4 days •Confirmation: 3-4 weeks –Primidone: 5-12 mcg/mL Other –CBC –Liver function –Suicidality –Depression |
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Epilepsy & elderly
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2x recurrence risk
Age prolongs post-ictal (event: seizure, stoke, headache); Longer periods of confusion, tiredness •Seizures can often present as confusion, agitation, altered awareness, or lost sense of time. •Elderly patients with seizures are also at risk for increased risk for the side effects of antiepileptic medications and falls. |
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Monitoring epilepsy
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Discontinuation of therapy
•Assess risks and benefits –Seizure recurrence, QoL –Side effects of medications •Normal neurologic exam •Single type of seizure •Seizure free for >4 years |
