Antiepileptic Medications - Part 2

Newer antiepileptics (approved after 1990) are used in the treatment of a variety of epilepsy syndromes.  Drug choice varies based on type of epilepsy and choice of individual agent is complex.  Many antiepileptics can be used for a variety of seizure disorders; however, certain drugs are only indicated in specific seizure disorders.  Antiepileptic choice must also take into account the patient's other medical conditions and age to determine the most appropriate medication.

Class Drugs

• Eslicarbazepine

• Ezogabine

• Felbamate

• Fosphenytoin

• Gabapentin

• Lacosamide

• Lamotrigine

• Levetiracetam

• Oxcarbazepine

• Perampanel

• Pregabalin

• Rufinamide

• Tiagabine

• Topiramate

• Vigabatrin

• Zonisamide

Class Mechanism of Action

• See each drug

Class Application

Treatment of seizures

Other applications apply to individual drugs

Class Adverse Effects

• See each drug

• Drug interactions are the norm and not the exception

• Pregnancy concerns

Many drugs cause birth defects or developmental problems such as neural tube defects, cognitive defects, and behavioral abnormalities

• Pregnancy planning is important

• Many drugs increase the metabolism of oral contraceptives

Phenytoin

• Phenobarbital

• Carbamazepine

• Topiramate

• Oxcarbazepine

• Rufinamide

Drug Table

Drug Name	Application	Comments	Image
Eslicarbazepine	Partial-onset seizures	Mechanism; Voltage gated sodium channel blocker; Adverse Effects; Dizziness; Somnolence; Diplopia; Headache; Rash; Psychiatric effects; Hyponatremia	"Elsa" "Car" "Pine tree"
Ezogabine	Seizures	Mechanism; -Likely opens potassium channels; -Stabilizes membranes; Adverse Effects; ; Urinary retention; QT prolongation; Blue skin discoloration; Retinal abnormalities	"Ego Mower" "Pine tree"
Felbamate	Reserved for refractory epilepsy due to side-effect profile	Mechanism; -Blocks voltage gated sodium channels; -Calcium channel blocker; -Potentiates GABA; Competitive antagonist at NMDA receptor; Adverse Effects; ; Hepatic failure; Aplastic anemia	"Regis Philbin"
Fosphenytoin	Focal seizures; Tonic-clonic seizures; Status epilepticus	IV/IM formulation, does not cause tissue necrosis locally when administered; Mechanism; -Converted to phenytoin rapidly in blood; -Blocks Na channels in inactive state, slowing recovery; Adverse Effects; -Rapid saturation kinetics; Small changes in dose can increase free drug levels quickly; -CNS depression; cerebellum and vestibular system most affected; -Nystagmus; -Ataxia; -Gingival hyperplasia; -Peripheral neuropathy; -Osteoporosis; -Stevens-Johnson syndrome	"Phosphorus" "Fence" "Toe"
Gabapentin	Adjunct for focal seizures; Post-herpetic neuralgia	Mechanism; -Similar to GABA but does not work on GABA system; -Mechanism unknown; Adverse Effects; Caution in renal disease as eliminated by kidneys	"Gabby" "Pen" "Tin"
Lacosamide	Adjunct for focal seizures	Mechanism; Likely stabilizes neurons by inhibiting repetitive firing via the voltage-gated sodium channels; Adverse Effects; -Dizziness; -Headache; -Fatigue	"Tacos"
Lamotrigine	Generalized, focal, and absence seizures; Bipolar disorder	Mechanism; -Blocks Na channels; -Blocks high voltage calcium channels; Adverse Effects; ; -Caution in combination with valproate; Valproate leads to decreased lamotrigine clearance; -Stevens-Johnson syndrome; -Diplopia	"Limo" "Tricycle" "Jeans"
Levetiracetam	Generalized tonic-clonic; Focal onset seizures; Myoclonic seizures	Mechanism; Binds synaptic vesicle protein SV2A, modulating neurotransmitter release; Adverse Effects; ; Mood alterations	"Level" "Tear" "Ace"
Oxcarbazepine	Partial onset seizures	Mechanism; -Blocks Na channels; -Converted to 10-monohydroxy (MHD), which gives activity; Adverse Effects; ; Hyponatremia; Diplopia	"Ox" "Car" "Pine tree"
Perampanel	Partial onset seizures in age 12 and older	Mechanism; Alpha-3-hydroxy-5-methyl-4-isoxazolepropionic acid antagonist (reduces excitatory activity); Adverse Effects; ; Behavioral reactions; Falls; Gait disturbance	"Pear" "Amp" "Electrical Panel"
Pregabalin	Focal onset seizures; Diabetic neuropathy; Post-herpetic neuralgia; Fibromyalgia	Mechanism; Binds the alpha-2-delta subunit of voltage-gated calcium channels, reducing calcium influx and release of excitatory neurotransmitters (same target as gabapentin); Adverse Effects; ; -Renal elimination, caution in renal dysfunction; -Weight gain; -Peripheral edema; -Ataxia	"Prego" "Ball in"
Rufinamide	Adjunct in Lennox-Gastaut syndrome in those older than 4 years	Mechanism; Possibly prolongs inactive state of sodium channels; Adverse Effects; ; -Short QT interval; -Do not give to patients with familial short QT; -Food increases absorption	"Rough-In"
Tiagabine	Adjunct for partial-onset seizures	Mechanism; -Blocks GABA uptake in presynaptic neurons, increasing levels and thereby increasing general inhibition; Adverse Effects; ; Can cause seizures in those without epilepsy	"Tia Gabbing"
Topiramate	Partial epilepsy; Generalized epilepsy; Migraine prophylaxis	Mechanism; -Blocks voltage-dependent sodium channels; -Reduces high-voltage calcium currents; -Carbonic anhydrase inhibitor; Adverse Effects; ; Kidney stones; Glaucoma; Hyperthermia; Paresthesias; Cognitive complaints	"Toe" "Pirate"
Vigabatrin	Lennox-Gastaut Syndrome	Mechanism; Increases GABA levels by irreversibly inhibiting GABA-T, which metabolizes GABA; Adverse Effects; Visual field loss	"Vigoro" "Bat"
Zonisamide	Focal epilepsy	Mechanism; -Blocks voltage gated sodium channels; -Blocks T-type calcium currents; Adverse Effects; ; -Kidney stones; -Oligohydrosis; Contraindications:; -Sulfonamide hypersensitivity; -Carbonic anhydrase inhibitor hypersensitivity	"Zone" "Midas"