Anticonvulsants Flashcards
Seizure
The clinical manifestation of an abnormal hypersynchronized discharge in a population of
cortical excitatory neurons
Epilepsy
A tendency toward recurrent seizures unprovoked by acute systemic or neurologic insults
Focal classifications
simple partial
complex partial
secondarily generalized
Generalized classifications
absense myoclonic clonic tonic tonic clonic
An antiepileptic drug (AED) is a drug which
decreases the frequency and/or severity of
seizures in people with epilepsy
Antiepileptic Drug (AED) - treates
Treats the symptom of seizures, not the underlying epileptic condition
Antiepileptic Drug (AED) - does not
Does not prevent the development of epilepsy in individuals who have acquired a risk for seizures (e.g., after head trauma, stroke, tumor)
Antiepileptic Drug (AED) goal of therapy
Goal of therapy is to maximize quality of life by eliminating seizures (or diminish seizure
frequency) while minimizing adverse drug effects
• AEDs have wanted and unwanted effects on target organ
Excitation (too much)
- Ionic: inward Na+ and Ca++ currents
* Neurotransmitter: glutamate, aspartate
nhibition (too little)
Ionic: inward CI-
, outward K+ currents
• Neurotransmitter: GABA
Ion Channel
Modulators
(reduce neuron
excitability - Traget molecule
Partial, secondary
(2ndary)generalized or
generalized tonicclonic
Ion Channel
Modulators
(reduce neuron
excitability - Drugs
Ethosuximide, gabapentin, pregabalin Retigabin Carbamazepine, eslicarbazepine, lamotrigine, oxycarbazepine, phenytoin, zonisamide, lacosamide, fosphenytoin, Rufinamide
Ion Channel
Modulators
(reduce neuron
excitability - Seizure type
Calcium ion channel
Potassium ion channel
Sodium ion channel
Enhancers of GABAergic transmission (enhancer inhibitory transmission) - Target molecule
Emergency treatment Partial, 2nd line add on Refractory complex adjunctive Partial, 2ndary T-C
Enhancers of GABAergic transmission (enhancer inhibitory transmission) - Drugs
Clobazam, Clonazepam, Diazepam,midazolam phenobarbital, primidone Tiagabine Vigabatrin Gabapentin, Pregabalin,
Enhancers of GABAergic transmission (enhancer inhibitory transmission) - Seizure Type
GABAA receptor agonists
GABA Reuptake inhibitor
GABA Transaminase inhibitor
Potential GABA
Glutamate
modulators
(direct and
indirect) - Target Molecule
AMPA receptor
NMDA receptor
Glutamate modulators (direct and indirect) - Drugs
Perampanel
Glutamate modulators (direct and indirect) - Seizure Type
Partial onset, 2ndary
generalized
Multiple modes
of action
- Target Molecule
Na ion, GABAA receptors, NMDA
Na ion, AMPA/kainite,GABAA
Na ion, GABA turnover, NMDA
Multiple modes
of action
- Drugs
Felbamate
Topiramate
Valproate
Multiple modes
of action
- Seizure Type
Multiple*
Multiple
Wide range of seizures
Unknown- Targt molecule
Human synaptic vessel protein
(SV2A)?
Unknown Drugs
Levetiracetam
Unknown - Seizure types
Juvenile myoclonic,
generalized adjunct
Hydantoins - Drugs
First-line treatment for tonic-clonic and partial complex seizures
Hydantoins - Seizure type
Stabilizes neuronal membranes and decreases seizure activity by increasing influx of sodium ions across
cell membranes in the motor cortex
Hydantoins - Adr
Nystagmus, dizziness, pruritus, paresthesia, headache, somnolence, ataxia, confusion
Cardiovascular effects: hypotension, tachycardia
Gastrointestinal (GI) effects: n/v, anorexia, constipation, dry mouth, gingival hyperplasia
Genitourinary effects: urinary retention, urine discoloration
Hydantoins - Monitoring
Liver, renal baseline and periodic, TSH, OTC meds: ibuprofen, Antacids
Hydantoins - interacions
CYP2C9 enzyme system
Levels will increase with cimetidine, diazepam, acute alcohol intake, valproic acid, allopurinol
Decreases effects with barbiturates, antacids, calcium, chronic alcohol use
Causes the decreased effect of: carbamazepine, estrogens, acetaminophen, corticosteroids,
levadopa, sulfonylureas, cardiac glycosides
Carbamazepines - Seizure Type
Partial seizures, secondarily generalized seizures, and tonic-clonic seizures
Carbamazepines - Moa
Depresses neuron transmission in the nucleus ventralis anterior of the thalamus
Has ability to induce its own metabolism
Carbamazepines - ADR
Black Box warning for causing blood dyscrasias
Depression of bone marrow
Liver damage, impairs thyroid function
Drowsiness, dizziness, blurred vision, n/v, dry mouth, diplopia, headache (HA)
Carbamazepines Monitoring
Genetic testing of Asians; Baseline laboratory values: complete blood count, chemical panel, hepatic
panel, TSH level
Carbamazepines - Interactions
nduces metabolism of many CYP450 substrates
Drug levels increase with concurrent use of propoxyphene (Darvocet), cimetidine, erythromycin,
clarithromycin, verapamil, hydantoins, grapefruit/juice
Decreases plasma levels of several drugs: beta blockers, warfarin, doxycycline, succinimides, haloperidol
Succinimides - Seizure Type
Absence seizures in children and adults
Succinimides - MOA
Suppresses seizures by delaying calcium influx into neurons
Decreases nerve impulses and transmission in the motor cortex
Succinimides - ADR
GI most common; CNS: somnolence, fatigue, ataxia
Agranulcytosis, aplastic anemia, granulocytopenia
Succinimides - Monitoring
CBC with differential. Liver, renal, MH
Succinimides - Interactinos
Many: amphetamine, other AEDs, MAOIs, stimulants, TCAs
Lamotrigine - Seizure Type
Adjunctive treatment of primary generalized tonic-clonic seizures and partial seizures in adults and
children older than 2 years of age
Concurrent use with valproic acid, phenytoin
Lamotrigine - MOA
Selectively binds sodium channels, stabilizing presynaptic neuronal membranes and inhibiting
glutamate release
Lamotrigine - ADR
GI – mostly n/v, constipation; CV – chest pain, peripheral edema; CNS – somnolence, fatigue, dizziness,
anxiety insomnia, headache, amblyopia, nystagmus; dermatological – rashes
Lamotrigine - Monitoring
Renal, liver
Lamotrigine - Interactions
Levels decreased by barbiturates, estrogens, phenytoin, mefloquine
Levels increased by alcohol, carbamazepine, CNS depressants, valproic acid
Rufinamide - Seizure Type
Adjunctive treatment for Lennox-Gastaut syndrome (LGS)
Rufinamide - MOA
Modulates the activity of sodium channels
Rufinamide - ADR
ADRs: dizziness, fatigue, headache, increased suicide risk, DRESS (drug rash with eosinophilia and
systemic symptoms)
Contraindicated in familial short QT syndrome
Rufinamide - Monitoring
Drug levels might be helpful, concentrations differ markedly in patients on comparable doses
Rufinamide - Interactions
Interactions: carbamazepine, phenobarbital, valproate
cytochrome P450 enzyme inducers, such as phenobarbital, primidone, phenytoin, and carbamazepine,
increase the clearance of rufinamide
