Epilepsy/Seizures Flashcards by Jimmy Hayden

Most common diagnostic test to diagnose epilepsy

Electroencephalogram (EEG)
Records electrical activity in the brain
CT and MRI can identify some conditions that can provoke seizures, including brain tumors and damage from a stroke

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Three main types of seizures

Focal seizures - one side of the brain, can spread to the other side
Generalized seizures - start on both sides
Unknown onset seizures - location unknown, occurred unwitnessed or occurs during the night

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Two different types of focal seizures

Focal aware seizures = no loss of consciousness (formerly known as simple partial seizure)
Focal seizure with impaired awareness = loss of consciousness (formerly known as complex partial seizure)

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Define absence seizure

Seizure with non-motor symptoms

Presents as staring spells

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Define status epilepticus (SE)

seizure lasting beyond 5 minutes

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When can long term damage occur with an untreated seizure?

After 30 minutes

However treatment should begin after 5 minutes

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Non-IV options for initial management of seizure?

Initial management = benzos

Can give IM midazolam
Diazepam rectal gel (Diastat, or Diastat AcuDial for patients who are at risk for long-lasting seizures)
Intranasal or buccal midazolam

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Status epilepticus treatment algorithm (table p 963)

0-5 minutes: Stabilization phase (start EEG, check BG, treat with D25/D50 or raisins (jk), check AED levels, check elecrolytes, may need O2)

5-20 minutes: Initial treatment phase [if seizure continues past 5 mins: give BZD (IV midazolam Versed, IV lorazepam Ativan, rectal diazepam Diastat)]

20-40 minutes: Second treatment phase (Give regular AED option; IV fosphenytoin, valproic acid, levetiracetam. Can consider phenobarbital if other options unavailable]

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Drugs that can lower the seizure threshold (there’s a lot)

Antipsychotics
Antivirals
Bupropion
Carbapenems (especially imipenem with higher doses/renal impairment)
Cephalosporins
Lithium
Lindane
Mefloquine
Meperidine (chronic dosing, poor renal fx)
Metoclopramide
PCNs
Quinolones
Alcohol withdrawal
Infection and fever (esp in children)
Theophylline
Tramadol
Varenicline

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Non-drug treatment of refractory seizures

Ketogenic diet

High fat, low protein, low carb

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Class effect of anti-epileptic drugs

CNS depression
(Dizziness, confusion, sedation, ataxia, coordination difficulties)
Can also cause bone loss and increase fracture risk (after 2 yrs), so supplement with calcium and vitamin D

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Drugs that can cause hypohidrosis in children

Hypohidrosis = lack of sweating
Topiramate and zonisamide
Limit sun exposure

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AED that can cause drug induced rash in children

Lamotrigine

Rash can be fatal

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Enzyme inducing AEDs

Cabamazepine
Oxcarbamazepine
Phenytoin
Fosphenytoin
Phenobartbital
Primidone
Topiramate
Valproic acid can also inc lamotrigine levels (inc risk of fatal rash)

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AED use in pregnancy (long ass card im sorry)

Older AEDs (clonazepam, phenobarbital, primidone, phenytoin, fosphenytoin, carbamazepine, and valproic acid) have known teratogenic risk
Valproic acid has the highest risk
Newer agents risk profile not well defined but most have some degree of risk

Women of childbearing age on AEDs should get folate supplementation
Note AEDs can reduce efficacy of oral contraceptives!

Drug levels should be monitored more closely because they may need increased doses as AED levels can decrease during pregnancy however drug levels can INCREASE postpartum requiring lower doses

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Required AED monitoring for all AED’s, and which ones require blood monitoring?

Seizure frequency (to ensure efficacy)
Mental status (to minimize adverse effects)

Blood levels: phenytoin (trough 10-20 mcg/mL, free 1-2.5 mcg/mL), valproic acid (50-100 mcg/mL total), carbamazepine (4-12 mcg/mL), phenobarbital (20-40 mcg/mL, 15-40 mcg/mL for children)

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Phenytoin kinetics

Michaelis-Mentin, or saturable kinetics

Can saturate enzymes so small increases in dose can cause large increases in drug level

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Corrected phenytoin - when do we use it and whats the formula?

Low albumin (< 3.5 g/dL) and CrCL > 10 mL/min

Correction = total/[(0.2 x albumin) + 0.1]

FREE LEVELS do NOT require any correction

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Medguide warnings for all AEDs

Warnings: suicide risk, monitor mood
Teratogenicity: contraception may be needed
Rash, hypersensitivity reactions can be severe

Drug of choice for absence seizures?

Ethosuximide (Zarontin)

Seizures occur due to imbalances in what neurotransmitters? How do AEDs work to fix this imbalance?

Too much excitatory (ie glutamate)
Too little inhibitory (GABA)
So AED’s work by either increasing GABA or decreasing glutamate

Blocking Na channels decreases neuronal firing rates
Blocking calcium channels slows down or stops transmission of the electrical signal

Levetiracetam brand, MOA, dose forms, dose, side effects

Keppra
Calcium channel blocker and increases GABA
Tablet, solution, and injection (IV:PO is 1:1)
500 mg BID or 1000 mg daily (XR)
Decrease dose for CrCL less than 80
Side effects: Psychiatric (psychotic symptoms), irritability, weakness, etc

Lamotrigine brand, MOA, dose forms, dose, side effects

Lamictal
Na channel blocker
Titrate dose 25 mg daily x 2 weeks
50 mg daily x 2 weeks
Increase by 50 mg daily every 1-2 weeks to therapeutic dose
Dose forms: tablet, chewable, ODT
Side effects: Can cause serious skin reactions (SJS/TENS)

Describe starter kit for lamictal

Orange = standard starting dose

Blue = lower starting dose (use if taking valproic acid)

Green = higher starting dose (use if taking enzyme inducer (ie phenytoin, carbamazepine, phenobarbital, primidone) and not taking valproic acid)

Carbamazepine brand, MOA, dose forms, dose, side effects, monitoring

Tegretol (Equetro is brand for bipolar disorder) Chewable tablet, chewable suspension (???), injection MOA Na channel blocker Dosing 200 mg BID or divided QID for suspension (mx 1600 mg/day) For IV: total daily dose is 70% or oral dose, divided every 6 hours Side effects: Skin reactions (esp if positive HLA-B*1502 allele), aplastic anemia, agranulocytosis, HYPOnatremia, fetal harm, Monitor CBC and platelets prior to and during therapy, monitor carbamazepine levels (goal 4-12 mcg/mL) within 3-4 days and after 4 weeks (autoinduction)!!

Which AED autoinduces its own metabolism

Carbamazepine

Drug interactions carbamazepine

Strong inducer of MANY enzymes and P-gp, and is a major substrate of 3A4 Need non-hormonal contraception as it can decrease levels of hormonal contraceptives

Oxcarbazepine brand, MOA, dose forms, dose, side effects, monitoring

Trileptal Na and Ca channel blocker Tablet, suspension, extended release tab (Oxtellar) Dose 300 mg BID or 600 mg QD XR Lower dose for CrCL < 30 mL/min SJS/TENS if pos for HLA-B*1502, HYPOnatremia, monitor serum Na levels during first 3 months

Conversion carbamazepine to oxcarbazepine

Oxcarbazepine is 1.2-1.5x the carbamazepine dose

Drugs that may have inc rash due to pos HLA-B*1502

Carbamazepine, oxcarbazepine

Phenobarbital brand, MOA, dose forms, dose, side effects, monitoring

No brand, note: C-IV Tablet, solution, elixir, injection Habit forming, may cause respiratory depression, fetal harm Physiological dependence, tolerance, hangover effect Want goal level 20-40 mcg/mL (adults) or 15-40 mcg/mL (children)

Drug interactions phenobarbital

Strong inducer of most CYP enzymes and P-gp | Use non-hormonal contraception

Phenytoin brand, MOA, dose forms, dose, side effects, monitoring

Dilantin Capsule, chewable, suspension, injection (IV only) Na channel blocker (underlined in book) Weight based dose 15-20 mg/kg IV:PO 1:1 Boxed warning do not exceed 50 mg/min (can cause hypotension, cardiac arrhythmias)

Fosphenytoin brand, MOA, dose forms, dose, side effects, monitoring

Cerebyx Injection only Prodrug of phenytoin Dosed in phenytoin equivalents (PE): 1 mg PE = 1 mg phenytoin, fosphenytoin 1.5 mg = 1 mg PE Do not exceed 150 mg PE/min (can cause hypotension, cardiac arrhythmias) Warnings: fetal harm, blood dyscrasias Can cause nystagmus, ataxia, diplopia/blurred vision, gingival hyperplasia, hair growth, hepatotoxicity (all underlined) Monitor levels: trough 10-20 mcg/mL (total) or 1-2.5 mcg/mL (free) and monitor LFT's

Drug interactions phenytoin

Strong inducer of several CYP enzymes and P-gp need non-hormonal contraception Also has high protein binding

Topiramate brand, MOA, dose forms, dose, side effects, monitoring

Topamax Oral only MOA Na channel blocker Titrated dose, increase every week by 25 mg until up to 100 mg then can increase by 100 mg every week until therapeutic effect Decrease dose when CrCL < 70 Warnings can cause metabolic acidosis, oligohidrosis (reduced perspiration), nephrolithiasis (kidney stones), and hyperammonemia, fetal harm Side effects: weight loss (Qsymia is wt loss formulation) Monitor bicarbonate, intraocular pressure

Non-hormonal contraception is recommended with which AED's

``` Topiramate Phenytoin/fosphenytoin carbamazepine oxcarbamazepine phenobarbital ``` Pretty much all of them except lamotrigine, lacosamide, and valproic acid lol

Lacosamide brand, MOA, dose forms, dose, side effects, monitoring

Vimpat (C-V) Tablet, solution, injection Na channel? MOA not in book Prolongs PR interval, inc risk of arrhythmias Take ECG at baseline No underlined side effects, just worry about heart

Valproic acid brand, MOA, dose forms, dose, side effects, monitoring

Depakene, Depacon Also divalproex (Depakote) - tablet only (and sprinkles) Capsule, syrup (Depakene), IV (depacon) MOA Increases GABA Weight based dosing Boxed warning for hepatic failure, neural tube defects (fetal harm) Warnings hyperammonemia, dose-related thrombocytopenia Side effects weight gain Monitor LFTs at baseline, q 6 mo Platelets Levels: 50-100 mcg/mL (total level)

What is Aptiom

Major active metabolite of oxcarbazepine Brand name eslicarbazepine Monitor sodium levels like oxcarbazepine; has same warnings and side effects

Side effects Zarontin

N/V, abdominal pain, weight loss, hiccups | Ethosuximide - used in absence seizures

What is felbatol

Felbamate, comes as a tablet or suspension | Boxed warnings for hepatic failure, aplastic anemia

What is Mysoline

Primidone, the prodrug of phenobarbital

What is Sabril

Vigabatrin | Boxed warning for permanent vision loss in 30% of patients wtf

What is Zonegran

Zonisamide Contraindications in patients w hypersensitivity to sulfonamides Side effects similar to topiramate; including oligohydrosis/hyperthermia (esp in children) and risk of nephrolithiasis