Anti-Seizure Drug

Name MOA Effects Pharmacokinetics Uses Side Effects Interactions

Common Suppress Oral Resistance = ↑drug Rifampin
Characteristics repetitive action Good absorption transporters at BBB + hepatic metabolism
potentials in Good bioavailability ↓plasma level
epileptic foci Hepatic Metabolism Teratogenic
(mostly)
Low plasma protein Weight Gain or Loss
binding (mostly) Hyponatremia
Osteoporosis
N/V
Sedation
Ataxia
Rash

OD = Resp Depression

Withdrawal
Antiabsence easier WD

Cyclic Ureides
Phenytoin X Voltage gated Na channels No effect on Rapid Onset DOC Generalized Fetal Hydantoin Carbamazepine
(Rate dependent) Infantile spasm Extended Release Tonic-Clonic Syndrome (growth Sulfonamide
↑inactivated state of Na ch Absence Seizure (Grand Mal) retardation, Valproic Acid
↑refractory period of neuron First pass metabolism Seizures microencephaly, Competitive binding
varies craniofacial ↑free phenytoin in
Nonlinear metabolism First Choice Partial abnormalities) – plasma
Mod-HD: zero order Seizures Epoxide metabolite
elimination Rifampin
Some efficacy in Nystagmus Phenobarbital
97% binds to plasma Clonic, Myoclonic, Diplopia + hepatic metabolism
proteins Atonic Sedation ↓phenytoin
Gingival Hyperplasia
NEVER IM Migraine Hirsutism INH
(tissue damage, Acne Cimetidine
necrosis) Coarse facial features - metabolism
Anemias ↑phenytoin
IV Status Epilepticus – Peripheral Neuropathy
prolonged Tx ↓DTR in LE
 Osteoporosis
Cardiotoxic

Opioid Withdrawal
symptoms in
methadone programs

↓Folic Acid, Thyroxine,

Vitamin K

↑hepatic metabolism
(↓Carbamazepine,
Clonazepam,
Lamotrigine)

↓metabolism
(↑ Phenobarbital,
Warfarin)

Fosphenytoin Prodrug Parenteral Status Epilepticus –

IM/IV prolonged Tx
Water soluble
Active metabolite
Phenobarbital + inhibition of GABAA Long T 1/2 Generalized Tonic- Sedation
(Barbiturate) (↑duration of Cl opening) Clonic (Grand Mal) Cognitive Dysfunction
Seizures Tolerance
HD Infants – Primary Dependence
X Voltage gated Na channels Adults – Alternate ↑hepatic metabolism
(Rate dependent)
↑inactivated state of Na ch Alternative for
↑refractory period of neuron Partial Seizures

Glutamate antagonist Status Epilepticus –

children
Primidone + inhibition of GABAA Active metabolite
(Barbiturate) (↑duration of Cl opening)
Ethosuximide X T type Ca channels (low Long T ½ DOC Absence GIT Distress (BDS to
threshold) Adults =60h Seizures reduce this)
Site = thalamic neurons Children = 30h (uncomplicated) Lethargy
(pacemakers for rhythmic Minimal sedation Headache
cortical discharge) Behavioral Changes

C/I = Partial, Tonic

Clonic Seizures

Tricyclics
Carbamazepine X Voltage gated Na channels Active metabolite DOC Generalized Common Competitive binding
(Rate dependent) Tonic-Clonic Diplopia most common ↑free Phenytoin in
↑inactivated state of Na ch (Grand Mal) Ataxia most common plasma
↑refractory period of neuron Seizures GIT Distress
Sedation (HD) Phenytoin
DOC Partial + hepatic metabolism
Seizures (complex) Water retention
Hyponatremia Propoxyphene
Bipolar Disorder Rash Valproic Acid
Antidepressant Agitation in children - metabolism

DOC Trigeminal Rare

Neuralgia SJS
Blood dyscrasias

Craniofacial
abnormalities
Spina Bifida
Cognitive Dysfunction

↑hepatic metabolism
(↓Clonazepam,
Lamotrigine,
Valproic Acid)
Oxcarbazepine DOC Partial Hyponatremia LESS DRUG
Seizures INTERACTIONS
Benzodiazepines + inhibition of GABAA Plasma protein binding Sedation
(↑freq of Cl opening) Tolerance
Dependence
Diazepam IV Status Epilepticus –
(Valium) short term
Clonazepam Alternative for Phenytoin
Absence Seizures + hepatic metabolism

HD
Myoclonic Seizure
Lorazepam IV Status Epilepticus –
short term

GABA Eliminated mostly Dizziness No Drug Interactions

Derivatives unchanged by KIDNEY Sedation
Gabapentin X T type Ca channels (low Neuropathic Pain Ataxia
threshold) - α1 & 2 Postherpetic Nystagmus
Site = thalamic neurons Neuralgia
(pacemakers for rhythmic
cortical discharge) Migraine

Structural analogue of GABA Adjunct therapy in

but does not activate Partial and
receptors directly Secondarily
Generalized (adults
+ children)
Monotherapy
Pregabalin X T type Ca channels (low Neuropathic Pain Ataxia
threshold) Fibromyalgia Nystagmus
Site = thalamic neurons
(pacemakers for rhythmic Adjunct for Partial
cortical discharge) and Secondarily
Generalized
Vigabatrin Irreversible X GABA-T Weight Gain
(GABA-T terminates action of Visual field defects
GABA) long term, irreversible
Valproic Acid + GABA inhibition Plasma protein binding DOC Primary Drowsiness Competitive binding
Generalized Tonic- Nausea
X T type Ca channels (low Toxic active metabolite Clonic (Grand Mal) Tremor dose related ↓metabolism of
threshold) Seizures Alopecia transient Carbamazepine
Site = thalamic neurons Weight gain
(pacemakers for rhythmic Alternative for PCOS
cortical discharge) Partial Seizures Menstrual disturbance
Bone Loss
↑K channel permeability DOC Absence Ankle Swelling
Neuronal membrane Seizures
hyperpolarization concomitant grand Fatal Hepatotoxicity
mal or myoclonic children <2y, multiple
HD seizures drugs
X Voltage gated Na channels Minimal sedation C/I = Liver Disease
(Rate dependent)
↑inactivated state of Na ch DOC Juvenile NTDs (Spina Bifida)
↑refractory period of neuron Myoclonic Epilepsy
(usually monoTx) Competes for plasma
HD protein binding sites
Irreversible X GABA-T Photosensitive ↑free Phenytoin
(GABA-T terminates action of Epilepsy
GABA) ↓ metabolism
First Line MANIA (↑ Carbamazepine,
Ethosuximide
Phenytoin
Phenobarbital
Lamotrigine)
Lamotrigine X Voltage gated Na channels SLIDES say C/I Elimination = Generalized Tonic- Skin Rashes Phenytoin
(Rate dependent) in Myoclonic Hepatic Glucoronidation Clonic (Grand Mal) + hepatic metabolism
↑inactivated state of Na ch Seizures and Seizures Steven Johnson or TEN
↑refractory period of neuron KAPLAN says Lennox Gastaut life threatening
Adjunctive Tx children higher risk
X synaptic release of for Myoclonic Absence Seizures
Glutamate Seizures Dizziness
Simple and Ataxia
Complex Partial Nausea
Adults – monoTx
>2y – adjunctive Tx C/I = Myoclonic Seizure

Adjunctive for
Myoclonic Seizure

Bipolar Disorder
Levetiracetam Eliminated mostly Absence Seizures Dizziness No Drug Interactions
unchanged by KIDNEY Sedation
Backup for Weakness
Myoclonic Seizure Irritability
Hallucinations
Psychosis
Tiagabine X GAT-1 (GABA Transporter) Plasma protein binding Abd Pain No Drug Interactions
↑action of GABA Nausea
Hepatic + Renal Dizziness
Tremor
Asthenia
Topiramate + GABA inhibition Hepatic + Renal Generalized Tonic- Drowsiness
Clonic (Grand Mal) Dizziness
X Na channels Seizures Ataxia
Psychomotor Slowing
X Glutamate receptors Alternative for Memory Impairment
Partial Seizures Paresthesia
Weight Loss
Backup for Acute Myopia
Myoclonic Seizure

Migraine
Zonisamide X Voltage gated Na channels Hepatic + Renal Absence Seizures Severe Skin Rash
(Rate dependent) SJS
↑inactivated state of Na ch Backup for Dizziness
↑refractory period of neuron Myoclonic Seizure Confusion
Agitation
Diarrhea
Weight loss
Felbamate X Glutamate NMDA Broad Spectrum Severe Refractory Acute Hepatic Failure
receptors (competitive) Seizure States
+ GABA inhibition Lennox-Gastaut Aplastic Anemia
X Voltage dependent Na Syndrome
channels
X Ca channels Alternative for
Partial Seizures

Adjunctive for
Myoclonic Seizure
• Treatment failure cause = lack of compliance
• Partial Seizures
o Carbamazepine, Phenytoin
o Valproic acid, Lamotrigine, Gabapentin, BZD, Barbiturates
o Adjunct: Tiagabine, Topiramate, Levetiracetam, Zonisamide
• Tonic Clonic/Grand Mal Seizures
o Carbamazepine, Phenytoin
o Valproic acid, Lamotrigine, Gabapentin, BZD, Barbiturates
o Adjunct: Topiramate, Zonisamide
• Absence/Petit Mal Seizures
o Ethosuximide
o Valproic Acid (concomitant tonic clonic)
o Clonazepam
o Adjunct: Lamotrigine, BZD
• Myoclonic
o Valproic Acid
o Clonazepam
o Adjunct: Levetiracetam
• Status Epilepticus
o IV Diazepam or Lorazepam
o IV Fosphenytoin/Phenytoin/Phenobarbital