Goodman &Gilman's: The Pharmacological Basis of Therapeutics, 13e >Pharmacotherapy of the

Epilepsies
Laurence L. Brunton, Randa Hilal-Dandan, Björn C. Knollmann+
Drug Facts for Your Personal Formulary: Antiseizure Agents

Drugs Therapeutic Uses (Seizure Types) Clinical Pharmacology and Tips

Sodium Channel Modulators • Enhance fast inactivation

•Once-daily dosing only available with extended-release

Focal formulation
•Aware •Intravenous use with fosphenytoin
Phenytoin •With impaired awareness •Nonlinear pharmacokinetics
•May interfere with drugs metabolized by CYP2C9/19
Generalized •Induces CYPs (e.g., CYP3A4)
•Tonic-clonic •Side effects: gingival hyperplasia, facial coarsening;
hypersensitivity (rare)

Focal
•Aware
•Induces CYP enzymes (e.g., CYP2C, CYP3A) and UGT
•With impaired awareness
Carbamazepine •Active metabolite (10,11-epoxide)
•Focal to bilateral tonic-clonic
•Side effects: drowsiness, vertigo, ataxia, blurred vision, increased
seizure frequency
Generalized
•Tonic-clonic

Focal
Eslicarbazepine
•Aware
•With impaired awareness

Focal
•Aware
•Reduced half-life in the presence of phenytoin, carbamazepine, or
•With impaired awareness
Lamotrigine phenobarbital
•Increased concentration in the presence of valproate
Generalized
•Also used in Lennox-Gastaut syndrome
•Absence
•Tonic-clonic

•Prodrug, metabolized to eslicarbazepine

Focal •Short half-life
Oxcarbazepine
•Aware •Less-potent enzyme induction (vs. carbamazepine)
•With impaired awareness •Side effects: lower incidence of hypersensitivity reactions (vs.
carbamazepine)

Focal
Rufinamide Can be used in Lennox-Gastaut syndrome
•Aware
•With impaired awareness

Sodium Channel Modulators • Enhance slow inactivation

 Focal
Lacosamide
•Aware
•With impaired awareness

Calcium Channel Blockers • Block T-type calcium channels

•Side effects: gastrointestinal complaints, drowsiness, lethargy,

Ethosuximide Generalized
dizziness, headache, hypersensitivity/skin reactions
•Absence
•Titration can reduce side-effect occurrence

Focal
Zonisamide
•Aware •Side effects: somnolence, ataxia, anorexia, fatigue
•With impaired awareness

Calcium Channel Modulators • α2δ ligands

Focal
Gabapentin
•Aware •Side effects: somnolence, dizziness, ataxia, fatigue
•With impaired awareness

Focal •Side effects: dizziness, somnolence

Pregabalin
•Aware •Linear pharmacokinetics
•With impaired awareness •Low potential for drug-drug interactions

GABA-Enhancing Drugs • GABAA receptor allosteric modulators (benzodiazepines, barbiturates)

Generalized •Side effects: drowsiness, lethargy, behavioral disturbances

Clonazepam
•Absence •Abrupt withdrawal can facilitate seizures
•Myoclonic •Tolerance to antiseizure effects

Lennox-Gastaut syndrome
•N-Desmethyl-clobazam, clobazam’s active metabolite, is
•Generalized
Clobazam increased in patients with poor CYP2C19 metabolism
•Atonic
•Side effects: somnolence, sedation
•Tonic
•Tapered withdrawal recommended
•Myoclonic

•Short duration of action

Diazepam Status epilepticus •Side effects: drowsiness, lethargy, behavioral disturbances
•Abrupt withdrawal can facilitate seizures
•Tolerance to antiseizure effects

Focal
•Induces CYPs (e.g., CYP3A4) and UGT
•Focal to bilateral tonic-clonic
Phenobarbital •Side effects: sedation, nystagmus, ataxia; irritability and
hyperactivity (children); agitation and confusion (elderly); allergy,
Generalized
hypersensitivity (rare)
•Tonic-clonic
 Focal
•Focal to bilateral tonic-clonic
Primidone •Induces CYP enzymes (e.g., CYP3A4)
•Not commonly used
Generalized
•Tonic-clonic

GABA-Enhancing Drugs • GABA uptake/GABA transaminase inhibitors

Focal
Tiagabine •Metabolized by CYP3A
•Aware
•Side effects: dizziness, somnolence, tremor
•With impaired awareness

Stiripentol Generalized •Used in Dravet syndrome

•Tonic-clonic (Dravet syndrome) •Inhibits CYP3A4/2C19

•Used in infantile spasms, especially when caused by tuberous

Vigabatrin Focal sclerosis
•With impaired awareness •Side effects: can cause progressive and bilateral vision loss

Glutamate Receptor Antagonists • AMPA receptor antagonists

Focal •Metabolized by CYP3A

Perampanel
•Aware •Side effects: anxiety, confusion, imbalance, visual disturbance,
•With impaired awareness aggressive behavior, suicidal thoughts

Potassium Channel Modulators • KCNQ2-5–positive allosteric modulator

•Side effects: blue pigmentation of skin and lips, dizziness,

Focal somnolence, fatigue, vertigo, tremor, attention disruption, memory
Ezogabine
•Aware impairment, retinal abnormalities, urinary retention, QT
•With impaired awareness prolongation (rare)

Synaptic Vesicle 2A Modulators

Focal

•Aware
•Side effects: somnolence, asthenia, ataxia, dizziness, mood
Levetiracetam •With impaired awareness
changes
Generalized

•Myoclonic
•Tonic-clonic

Focal
Brivaracetam
•Aware
•With impaired awareness

Mixed Mechanisms of Action

 Focal
•Aware
Topiramate •With impaired awareness •Used in Lennox-Gastaut syndrome
•Side effects: somnolence, fatigue, cognitive impairment
Generalized
•Tonic-clonic

Focal
•Aware
•With impaired awareness
•Focal to bilateral tonic-clonic •Side effects: transient gastrointestinal symptoms, sedation, ataxia,
Valproate
tremor, hepatitis (rare)
Generalized •Inhibits CYP2C9, UGT
•Absence
•Myoclonic
•Tonic-clonic

Date of download: 12/18/22 from AccessPharmacy: accesspharmacy.mhmedical.com, Copyright © McGraw Hill. All rights reserved.