Partial seizures
start in 1 side of brain (can spread across)
Simple partial seizure
No LOC
Complex partial seizure
LOC
Genearlized seizures
Starts in both parts of brain and leads to LOC
Status epilepticus
> 5 minutes or > or = to 2 or more seizures without regaining consciousness in between
Pregnancy Category D
Carbamazepine, Clonazepam, Phenobarb/Primidone, Phenytoin/Fosphenytoin, Topiramate, VPA (VPA is D for seizures and X if for migraine prophylaxis)
Preganancy Category C
Lyrica, Neurontin, Lamictal, Keppra
Most common AEs of AEDs
CNS depression
Inducers
Carbamazepine, Oxcarbazepine, Fospehnytoin/Phenytoin, Phenobarb/Primidone, Topiramate
With inducers you need to add…
Vitamin D and Ca+2
DI with inducers
Use a non-hormonal birth control
Drugs that lower seizure threshold
Antipsychotics, antivirals, bupropion, carbapenems (imipenem), cephalosporins, FQs, Lindane, Li+2 and theophylline (in toxicity), Meperidine, Metoclopramide, Penicillins, Tramadol, Natural products (primrose oil, gingko, melatonin, dendrobium)
Medguide required with AEDs stating….
Increased risk of suicidality
Dosing requirements
Upward titration and tapering off
DOC for status epilepticus
IV Ativan (midazolam IM alternative) follwed by phenytoin (max 50 mg/min) or fosphenytoin (max 150 mg/min)
Keppra, Keppra XR generic
Levetiracetam
Keppra indicated for…
adjunctive therapy for all types except absence seizures
AEs of Keppra
Somnolnce, dizziness, weakness, infection (must report signs)
Tx for partial seizures (including secondarily generalized)
Carbamazepine, Lamictal, Keppra, Oxcarbazepine
Tx for primary generalized tonic-clonic
Lamictal, Keppra, Valproate
Tx for absence seizures (which are often outgrown)
Ethosuximide, Valproate
Tx for atypical absence seizures, myoclonic, atonic
Ethosuximide, Keppra, Lamictal, VPA
Minimal DIs
Lamictal, Lyrica, Gabapentin, Lacosamide
Lamictal generic
Lamotrigine
Lamictal indicated for…
adjunctive therapy for all types except absence seizures, also bipolar
Lamictal has chewable formulation
and ODT
Lamictal MOA
excitation (glutamate and aspartate)
Lamictal AEs
N/V, insomnia, somnolence, rash (SJS/TEN), headache
Lamictal formulations
3 different kinds (orange for those not taking interacting meds), blue for those on VPA (due to VPA inc { }s of lamictal), and green (for those taking inducers) - different type
VPA DI with Lamictal
VPA increases Lamictal 2x = inc SJS risk
Tegretol, Tegretol XR, Carbatrol, Epitol generic
Carbamazepine
Carbamazepine MOA
NA blocker (similar to TCAs)
Tegretol indications
Trigeminal neuralgia, bipolar (Equetro), and partial seizures
TR of Tegretol
4-12 mcg/mL
AEs of Tegretol
SIADH (inc water retention, same sodium, dilutional hyponatremia), hypothyroidism, SJS/TEN (ALL ASIANS MUST BE TESTED FOR ALLELE HLA-B*1502), aplastic anemia, agranulocytosis, photosensitivity, ataxia, dry mouth due to anticholinergic effects
Carbamazepine is an inducer/inhibitor…
inducer (AUTOINDUCER - even decreases concentrations of itself)
Trileptal, Oxtellar XR generic
Oxcarbazepine
Oxcarbazepine indications
partial seizures
Cross-sensitivity with
Carbamazepine (25-30%)
Oxcarbazepine AEs
hyponatremia, SJS/TEN (Asians CAN be tested for HLA-B*1502), nystagmus/vision disturbances
Oxcarbazepine reduced in…
renal impairment CrCl <30
Depakene, Depacon, Stavzor generic
Valproate/Valproic Acid
Depakote, Depakote ER, Depakote Sprinkle generic
Divalproex
TR of VPA
50-100 mcg/mL
VPA/Depakote Boxed warnings
Hepatic failure (mostly in children
AEs of VPA/Depakote
Hyperammonemia, tremor, PCOS, alopecia, anorexia, weight gain
Dose related: thrombocytopenia (monitor platelets), diplopia and blurred vision occur with toxic doses
VPA pregnancy category
D for seizures, X for migraine prophylaxis
VPA MOA
increase GABA (Ca and Na blocker)
Dilantin, Dilantin Infatabs, Phenytek generic
Phenytoin
Phenytoin/Fosphenytoin MOA
fast Na channels –> stabilizing neuronal membrane
Fosphenytoin is dosed in…
Pehnytoin equivalents (PE) - 1:1
Phenytoin follows ________ kinetics
Michaelis-Mentin kinetics (saturable kinetics), sometimes small doses lead to a greatly increased plasma [ ]
Low albumin (<3.5) can affect which AEDs?
VPA/Divalproex and Phenytoin/Fosphenytoin
Prodrug of Phenytoin
Fosphenytoin
IV Phenytoin is a vesicant and can lead to
purple glove syndrome
Max rate of IV phenytoin infusion
50 mg/min
Max rate of fosphenytoin infusion
150 mg/min
AEs of Phenytoin/Fosphenytoin
SJS/TEN (should screen Asian patients for HLA-B*1502)
Dose-related: nystagmus, ataxia, dizziness, confusion, blurred vision, displopia, slurred speach
Chronic use: skin thickening, gingival hyperplasia, coarsening of facial features (uglifying drug)
Phenytoin/Fosphenytoin are inducers/inhibitors
INDUCERS
IV Phenytoin can only be mixed with
NS (requires a filter and is stable for 4 hours)
IV: PO of Phenytoin
1:1
If albumin is low must correct PHT
corrected PHT = (PHT measured)/((0.2xalb) +1)
Enteral feedings must be separated by…
1-2 hours prior or 1-2 hours after phenytoin
Topamax generic
Topiramate
Topamax MOA
enhances GABA (inhibitory)
Warnings of Topamax
metabolic acidosis, oligohydrosis (reduced perspiration/hyperthermia), nephrolithiasis (kidney stones), hyperammonemia, visual problems (reversible)
AEs of Topamax
paresthesias, weight loss, anorexia, mood changes
Indications of Topamax
adjunctive for seizures, migraine prophylaxis
Must titrate Topamax due to
CNS effects
Pregnancy category of Topamax
D - cleft palate/lip
Lyrica generic
Pregabalin
AEs of Pregabalin
Fluid retention
MOA of Pregabalin
excitatory neurons (glutamate and aspartate) through Ca chanells
Pregabalin indications
Adjunctive therapy for partial seizures and neuropathic pain
AEs of Pregabalin
Weight gain, ataxia, diplopia, blurred vision, dry mouth, mild euphoria
Neurontin generic
Gabapentin
Neurontin indications
Postherptic neuralgia, RLS, seizures
AEs of Gabapentin
Diplopia, weight gain/edema, dry mouth, blurred vision
Gabapentin off-label uses
fibromyalgia, pain, headache, peripheral neuropathy, drug abuse, alcohol withdrawal
DIs with Pregabalin/Gabapentin
None significant - but use caution with glitazones and pregabalin due to additive edema
Phenobarbital/Primidone are what class
Barbiturate
Things barbiturates have in common with opioids and benzos
Physical dependence, tolerance, and addictive potential
TR of Phenobarbital/Primidone
20-40 mcg/mL
Do not give Phenobarb injection by
SC administration
Paradoxical reactions of Phenobarbital/Primidone
hyperactive/aggressive behavior (with acute pain or in PEDs)
Primidone is a prodrug of
Phenobarbital and Phenylethylmalonamide (PEMA) - both are active metabolites
AEs of Phenobarbital/Primidone
Physiological dependence, tolerance, and hangover effects
Also SJS/TEN
Phenobarbital/Primidone are inducers/inhibitors
INDUCERS
VPA is an inducer/inhibitor
INHIBITOR
Ethosuximide brand name
Zarontin
Ethosuximide AEs
Very well tolerated (GI -N/V/ weight loss/abdominal pain) and hiccups)
Ethosuximide DOC for
absence seizures
Lacosamide brand name
Vimpat
Warnings of Lacosamide
Increased PR interval - arrhythmias - use caution in CV patients and monitor ECG at baseline and at SS
Clobazam brand
Onfi
Clobazam class
Benzo
Clobazam indication
Lennox-Gastaut syndrome
Ezogabine brand
Potiga
Potiga used for
Refractory partial seziures
Potiga BBW
retinal abnormalitis (vision loss - 33% after 4 yr tx)
Felbamate brand
Felbatol
Felbatol indication
Refractory seizures
BBW of Felbatol
Hepatic failure and aplastic anemia (must sign informed consent to take)
Perampanel brand
Fycompa
Fycompa BBW
neuropsych events
Vigabatrin brand
Sabril
Sabril indications
Refractory seizures
Sabril BBW
permanent vision loss (30% of patients)
Zonisamide brand
Zonegran
CI of Zonegran
Hypersensitivity to sulfonamides
AEs of Zonegran
oligohydrosis, nephrolithiasis
Teratogenic AEDs
Carbamazepine, Phenytoin, Clonazepma, Topiramate, Phenobarbital, VPA
Hepatotoxicity AEDs
Carbamazepine, Felbamate, Phenobarb/Primidone, Phenytoin, VPA
Decreases efficacy of oral contraceptives with these AEDs
Carbamazepine, Clobazam, Oxcarbazepine, Perampanel, Phenobarb, Phenytoin, Primidone, Topiramate
Fatal pancreatits AEDs
VPA
Aplastic anemia AEDs
Carbamazepine (and agranulocytosis), Felbamate
SJS AEDs
Carbamazepine, Lamictal, Oxcarbazepine, Phenobarb, Tigabine, Zonisamide, Phenytoin/Fosphenytoin
Oligohydrosis AEDs (inability to sweat, risk of heat stroke, and highest risk in children)
Topiramate, Zonisamide
Nephrolithiasis (kidney stones) AEDs
Topiramate, Zonisamide
Weight gain AEDs
VPA, Gabapentin, Pregabalin
Weight loss AEDs
Felbamate, Ethosuximide, Topiramate, Zonisamide
Hyponatremia AEDs
Carbamazepin, Oxcarbazepine (more common)