Seizures Flashcards

Refractory SE treatment

Midazolam, propofol, pentobarbital (Long-term neurologic complications; anesthetize to prevent damage)

SE Treatment

Benzos: lorazepam, diazepam; phenytoin, fosphenytoin, phenobarbital, misc meds (IV VPA, Levetiracetam)

Status Epilepticus: Misc

Any seizure type can progress to this; can be refractory; considered a medical emergency (neurological sequela)

Status Epilepticus

>30 minutes of continuous seizure activity; >2 seizures with full recovery of consciousness; Clinical: continuous seizures lasting >5 minutes

VNS

implantable device that send impulses every 5 minutes, reduces seizure frequency about 30%

Teratogenicity

VPA, phenytoin, carbamazepine: Neural tube defects, >90% deliver healthy baby, folic acid supplementation

Special population: Women

Enzyme inducers and hormonal contraceptives: Phenytoin, carbamazepine, phenobarbital

Stopping therapy

Generally lifelong, but possible if: Seizure free for 2-5 years, Normal EEG, Neuro exam, IQ; Single type of seizure

Switching AEDs: Complex

Initiate 2nd agent to therapeutic dose prior to tapering first agent- can take months or years to switch

AED drug interactions: Protein binders

>90% protein bound; phenytoin, VPA; increase in phenytoin displacement leads to increase in phenytoin free levels

AED drug interactions: Enzyme inhibitors

Valproic Acid, Felbamate

AED drug interactions: Enzyme inducers

Phenytoin, carbamazepine, phenobarbital, primidone, felbamate, topiramate; watch oral contraceptives, use secondary contraception

Fosphenytoin: Indications

better infusion tolerance than phenytoin(150mg/min max); less CV depression, can be given IM; dosed in PE, used in status epilepticus

Benzodiazepines: used for seizures

Clonazepam, diazepam, lorazepam, clorazepate

Perampanel: Dis

Enzyme inducers decrease perampanel; perampanel high dose decreases levonorgesterel

Perampanel: Indication

Adjunctive for partial unset with or w/o secondary generalized seizures; primary GTCS

Ezogabine: Adverse effects

CNS related (Dizziness, somnolence, fatigue)

Ezogabine: BBW

Retinal abnormalities/potential vision loss

Ezogabine: Indication

Adjunctive for partial onset seizures not reponding to other therapies

Vigabatrin: BBW

Vision loss- limits use; cannot be prevented with monitoring

Rufinamide: Indication

Adjunctive for seizures associated with Lennox-Gastaut syndrome

Lacosamide: Control Schedule

C-V: abuse potential due to euphoria effect

Lacosamide: Indication

Monotherapy or adjunctive for partial- onset seizures in adults

Pregabalin: Side effects

Dizziness, somnolence, dry mouth, edema, blurred vision, weight gain, angioedema

Levetiracetam: Misc.

Minimal drug interactions; reduce dose in impaired renal function

Levetiracetam: Side effects

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Levetiracetam: Dose

Increase by 1000 mg to a max of 3000 mg/day; BID and QD dosing, formulation dependent

Oxcarbazepine: Misc.

Analogue of caramazepine; no autoinduction, no formation of 10, 11-epoxide

Oxcarbazepine: Side effects

>5%- dizziness, somnolence, diplopia, N/V, ataxia, hyponatremia, osteoporosis

Oxcarbazepine: Dose

Increase by 600mg per week to 1200-2400mg/day

Zonisamide: Side Effects

Somnolence 17%, Dizziness 13%, nephrolithiasis 4%; hypersensitivity to sulfonamides

Zonisamide: Daily Dose

Increase by 100 mg to 400-600 mg/day (taken once daily at bedtime)

Tiagabine: Side effects

Dizziness, nervousness, arthenia, tremor, confusion, increased incidence of seizures; neurocognitive effects

Tiagabine: Daily Dose

Increase to a maintenance dose of 32-56 mg/day

Topiramate: Side effects: Non-dose dependent

Nephrolithiasis, acute glaucoma, weight loss; can offset side effects of phenobarb and others

Topiramate: Side effects: Dose dependent

sedation, ataxia, cognitive(word finding difficulties)

Felbamate: Side effects

Dose dependent: insomnia, N/V, anorexia; Non-dose dependent: aplastic anemia, hepatic failure (Restricted use)

Felbamate: Indications

Mono/adjunctive therapy: SPS, CPS, Lennox-Gastaut Syndrome

Gabapentin: Common use

Neuropathy, fibromyalgia- not great for seizures, but good for neuropathy

Gabapentin: Side effects

sedation, dizziness, ataxia, fatigue, edema, weight gain

Gabapentin: Metabolism

Renal: eliminated as the parent compound

Lamotrigine + Valproate

Valproate is an inhibitor: Taper up for lamotrigine should be more conservative with valproate present

Lamotrigine: Side effects

possibly life-threatening rashes, dizziness, sedation, ataxia, Steven's Johnson Syndrome

Ethosuximide: Therapeutic Range

40-100 mcg/mL

Ethosuximide: Indications

Absence seizures (Now use VPA or lamotrigine)

VPA/Divalproex: Spectrum

Broad: not going to aggrevate another seizure type

N/V, lethargy, tremor, weight gain, alopecia, hepatotoxicity, hematologic toxicities, pancreatitis, osteoporosis, thrombocytopenia (dose dependent- can back off the dose to mitigate this) Limit N/V by using Depakote instead of depakene

VPA/Divalproex Therapeutic Range

50-100 mcg/mL

VPA/Divalproex MOA

Modulates Na Channels

VPA T1/2

Approximately 12 hours

VPA Metabolism

Hepatic

VPA Formulations

Depakene (VPA); Depakote DR/ER: Divalproex NA; Depacon: VPA injection

Valproic Acid: Daily Dose

750-3000 mg (15-30 mg/kg); loading doses

Valproic Acid: Indications

All Seizure Types

Primidone: Therapeutic range

5-20 mcg/mL; draw phenobarbital level at the same time of day because of the active metabolite

Primidone: T1/2

Approximately 12 hours (2-4 days for PB)

Primidone: Metabolism

Hepatic conversion to PB and phenylethylmalonamide (PEMA)

Primidone: MOA

Modulates Na Channels

Primidone: Daily dose

Initial: 125 mg BID increase gradually; Maintenance: 750-1500 mg in divided doses

Primidone: Indications

SPS, CPS, GTCS

Phenobarbital: Withdrawal

Abrupt withdrawal can induce seizures; long taper to avoid this

Phenobarbital: side effects

sedation, possible learning impairment, hyperactivity, osteoporosis (not well tolerated, other meds preferred)

Phenobarbital: Therapeutic range

15-40 mcg/mL

Phenobarbital: Long T1/2

2-4 days

Phenobarbital: MOA

Modulates Na Channels

Phenobarbital: Daily dose

90-240 mg once daily at bedtime

Phenobarbital: indications

SPS, CPS, GTCS

Phenytoin dosing: >12 mcg/mL

increase by 30mg/day

Phenytoin dosing: 7-12 mcg/mL

Increase by 50-60mg/day

Phenytoin dosing: <7mcg/mL

Increase dose by 100mg/day

Gingival hyperplasia, coarsening of facial features, hirsutism, acne, folate deficiency, rash, osteoporosis

Nystagmus, ataxia, cognitive, impairment, lethargy

Phenytoin: Therapeutic range

10-20 mcg/mL (free 1-2)

Phenytoin: MOA

Modulates Na Channels

Phenytoin: Metabolism

Michaelic-Menton Elimination (limited metabolism capacity)

Phenytoin: Formulations

ER caps: 30 & 100mg; chewable: 50 mg; Suspension: 30mg/5mL & 125mg/5mL; Injection: 50mg/mL; Phenytoin Na (92% Phenytoin); Phenytoin acid (100% phenytoin)

Phenytoin: Daily Dose

Usually 200-400 mg (4-6 mg/kg); loading doses

Phenytoin: Indications

SPS, CPS, GTCS

Carbamazepine: Side Effects

Ataxia, diplopia/blurred vision, lethargy, nausea; leukopenia, thrombocytopenia, rash, fluid retention, osteoporosis, hyponatremia; Aplastic Anemia: monitor CBC(Can be fatal); trigeminal neuralgia, bipolar

Carbamazepine: Therapeutic range

4-12 mcg/mL

Carbamazepine: Autoinduction

Resolves in 3-4 weeks

Carbamazepine: Active metabolite

10,11 epoxide

Carbamazepine: Dosing

Initial: 200 mg BID and gradual increase; Maintenance: 15mg/kg(divided doses); tabs, ER tabs/caps, chewable, suspension

Carbamazepine: MOA

modulates Na Channels

Carbamazepine: Indications

SPS, CPS, GTCS

Pharm therapy: Tonic-Clonic: Alternative agents

Levetiracetam, Topiramate, Phenobarb

Pharm therapy: Tonic-Clonic: First line

Phenytoin, Carbamazepine, VPA, Lamotrigine, Oxcarbazepine

Pharm therapy: Myoclonic: Alternative agents

Levetiracetam, Topiramate, Clonazepam

Pharm Therapy: Myoclonic: First line

VPA, Lamotrigine

Pharm Therapy: Absence seizure: Alternative agents

Ethosuximide

Pharm Therapy: Absence seizure: First line

Lamotrigine, VPA

Pharm therapy: Partial seizures: Alternative agents

Topiramate, Zonisamide, Gabapentin, Pregabalin, Phenobarb

Pharm therapy: Partial seizures: First line

Carbamazepine, phenytoin, lamotrigine, VPA, Levetiracetam, Oxcarbazepine

Seizure drug, warnings

Suicidal behavior and ideation: increased risk with any indication;

Seizure med dose titration

Start low, go slow; assess pt according to seizure control and side effects; use total and free blood concentrations as a guideline (some prescribers will reduce dose to stay within guidelines, even if pt doing well)

Seizures: Principles of therapy

Select most appropriate drug from seizure pattern and EEG(some drugs can worsen seizures (CBZ, Ox-CBZ, PB, Primidone, PHT, gabapentin, pregabalin); optimize first drug then add second drug if control is unsatisfactory; awareness of comorbid conditions; reinforce importance of compliance

Seizures Flashcards ionicons-v5-c