Antiepileptic Drugs – Flashcards
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Felbamate
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-Reserved for refractory in partial and general seizures -Consent form needed -Contraindicated in hepatic disease and blood dyscrasias
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Gabapentin
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no drug-drug interactions
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Lacosamide
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-Schedule V -no drug-drug interactions
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Lamotrigine
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no comments
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*Levetiracetam
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-Used off label -No drug-drug interaction b/c does not go through liver
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Oxcarbazepine
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-structurally related to carbamaepine BUT can be effect in patients who have failed carbamazepine -This is a pro-drug: converts to an active metabolite -No auto-induction like carbamazepine
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Phenobarbital
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-Schedule IV medication -Contraindicated in severe hepatic dysfunction, dyspnea or airway obstruction, porphyria
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Pregabaline
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Schedule V medication
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Primidone
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metabolized by phenobarbital
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Rufinamide
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-Adjuntive therapy for Lennox-Gastaut Syndrome -Contraindication in patiets with familial short QT syndrome -May precipitate status epilepticus -May increase # of other types of seizures
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Tiagabine
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Gabitril
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Topiramate
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weak carbonic anhydrase inhibitor
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Valproic Acid
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-Divalproex is converted to the active moiety in the GI -Several dosage forms
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Vigabatrin
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-Rarely used due to vision loss -re-approved for use in US -may increase seizure activity
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Zonisamide
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Cross reaction with sulfonamides hypersensitivities
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What is the difference between a seizure and epilepsy?
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Time Seizure: a group of cortical neurons that discharge abnormally in synchrony Epilepsy: at least 2 unprovoked seizures separated by 24 hours
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Potential causes of seizures/epilepsy?
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-Abrupt withdrawal of some CNS medications -alcohol withdrawal -acute neurological illnesses -traumatic brain injury -systemic toxic conditions -fever
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Which antiepileptic drugs are considered partial and are used as first-line?
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-Carbamazepine -Lamotrigine -Oxcarbazepine -Phenytoin -Valproic Acid
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Which antiepileptic drugs are considered generalized tonic-clonic and are used as first-line
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-lamotrigine -topiramate -valproic acid
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Which antiepileptic drugs are considered for absence and are used as first-line
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-Ethosuximide -Lamotrigine -Valproic Acid
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Which antiepileptic drugs are considered for Lennox-Gastaut and are used as first-line
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-Lamotrigine -Topiramate -Valproic Acid
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Which anitepileptic drug is used first-line for all types of seizures?
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Valproic Acid
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Which antiepileptic drugs are considered alternative in partial seizure types?
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-Ezogbine -Gabapentin -Lacosamide -Levitiracetam -Phenobarbital -Pregabalin -Primidone -Tiagabine -Topiramate -Zonisamide
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Which antiepileptic drugs are considered alternative in generalized tonic-clonic seizure types?
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-carbamazepine -Levetiracetam -Oxcarbazepine -Phenobarbital -Phenytoin
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Which antiepileptic drugs are considered alternative in Lennox-Gastaut types?
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Rufinamide
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Which antiepileptic drugs are considered refractory in partial seizure types?
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-Felbamate -Vigabatrin
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Which antiepileptic drugs are considered refractory in generalized tonic-clonic seizure types?
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-Felbamate
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Describe the classification of a partial seizure.
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Affect one hemisphere and is aymmetric motor manifestation. Two types: Simple partial seizure has no loss of consciousness and Complex: impairment of consciousness
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Describe generalized seizures.
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-Involvement of both hemispheres -motor manifestations are bilateral -loss of consciousness
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Describe status epilepticus.
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-Recurrent seizures without intervening period of consciousness before the next seizure OR -Seizure lasting longer than 30 minutes whether or not consciousness is impaired
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What are the consequences of Seizures?
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long term seizures are life threatening
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What is the general approach to mono-therapy? when to consider poly therapy?
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Titrate the drug to effectiveness or side effects. If it does not work do the same when changing medication or seizures can be induced; dirrent MOA
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Drug used in first line status epilepticus?
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benzodiazepines
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Most commonly prescribe drug for epilepsy.
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Carbamazepine: -which is structurally related to tricyclic antidepressants (if a patient is allergic don't prescribe); -Auto induction -Active metabolite which adds to toxicity and efficacy
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Often used monotherapy because it does not go through the liver? no drug interactions.
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Levetiracetam
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What are the 4 main mechanisms of action?
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-Enhance GABA inhibitory transmission -Diminution of excitation transmission -Modification of ionic conductance (Na or Ca) -K+ channel opener
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Which drugs work on the glutamate receptors? Which receptors?
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Felbamate: AMPA and NMDA Topiramate: AMPA, kainate, Na+ channels and enhance GABA current
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Which drugs work on the GABA receptors? Which one?
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--Benzodiazepines: GABA increase frequency of channel openings -Phenobarbital/Primidone (Barbituates): prolong channel opening -Tiagabine: Inhibit GABA reuptake -Vigabatrin: inhibit GABA-T which is responsible for GABA degradation GABA (A) is a chloride channel and mediates fast inhibitory transmission
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Drugs which prolong the inactivation of Na+ channels?
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-Phenytoin/Fosphenytoin, Carbamazepine and Rufinamide -Oxcarbazapine -Zonisamide -Lamotrigine -Lacosomide -Valproate
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Drugs which work to open K+ channels?
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-Ezogabine
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Drugs which work to open Ca++ channels?
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-Ethosuximide -Gabapentin and Pregabalin
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Drugs which regulate neurotransmitter release? SV2A
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levetiracetam
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Blocks NMDA and potentiates GABA (A)
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Felbamate
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Broad sprectum, blocks glutamte binding on AMPA, kainate receptors, Na+ channels, and potentiates effects of GABA
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Topiramate
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Enhances GABA (A)
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-Benzodiazepines -Phenobarbital -Primidone
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Blocks GABA reuptake?
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Tiagabine
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Irreversibly inhibits GABA-transaminase?
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Vigabatrin
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Blocks high-frequency firing of neurons through action Na+ channels?
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-Phenytoin -Fosphenytoin -Carbamazepine -Rufinamide
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Blocks Na + and K+ channels
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Oxcarbazepine
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Blocks Na+ and Ca2+ channels?
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Zonisamide
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Blocks Na+ channels and Ca2+ channels and inhibit glutamate release?
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lamotrigine
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Blocks Na+ channels and Blocks CRMP-2?
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Lacosamide
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BlockValprs Na+ channels and blocks NMDA receptors and increase GABA
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Valproate
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Enhances K+ channels?
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Ezogabine
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Reduces Ca2+ currents (T-type)?
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Ethosuximide
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Decreases glutamate transmission by actin on Ca2+ channels? May modifiy GABA release?
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-Gabapentin -Pregabalin
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Action on synaptic protein SV2A to modify the release of GABA and glutamate?
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Levitiracetam
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Broad-spectrum AEDs?
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-Felbamate -Topiramate -Lamatrigine -Valproate
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Which mechanism of action is implicated in absence seizures?
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Ca2+ currents (T-type)
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What is the concern with Phenytoin dosing?
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It has non-linear kinetics because metabolism of the drug become saturated in the body; toxicity to the patient; PROBLEM Saturation happens at therapeutic doses
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Drug that induces it's own metabolism: autoinduction?
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carbamazepine
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Two drugs in which absorption decreases as the dose increases? Best way to deal with this problem is to give the drug more frequently.
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Gabapentin and rufinamide
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What consideration must be monitored when dosing phenytoin?
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Protein binding! low albumin (hypoalbumin anemia) levels. total albumin level are measured as total don't know how much is bound or unbound; patient can become toxic: correction calculations are make to predict the true amount
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How are this drugs cleared? What is the benefit of dual clearance?
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hepatic and renal; hope for compensation by one organ (switching)
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What is the black box warning for carbamazepine?
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-Rash toxic epidermal necrolysis -Blood dyscrasias
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What is the black box warning for felbamate?
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Aplastic anemia
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What is the black box warning for lamotrigine?
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Rash toxic Epidermal necrolysis
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What is the black box warning for phenytoin?
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Hypotension based on administration rate
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What is the black box warning for valproic acid?
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-Hepatic failure -Pancreatitis -Teratogenic
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What is the black box warning for vigabatrin?
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Vision loss
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Drugs that are strong inducers of CYP and increase drug interaction?
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-Carbamazeipine -Oxcarbazepine -Phenobarbital -Phenytoin inducers cause the drug to be metabolized more quickly
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Drugs that are strong inhibitor of CYP and increase drug interaction?
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Valproic Acid (inhibit enzyme and make a person toxic)
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No Drug-Drug interactions?
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-Gabapentin -Levitiracetam -Locosamide
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Therapeutic concentration of carbamzepine, phenytoin, valproic acid and phenobarbital.
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-Carbamazepine :4-14 -Phenobarbital: 10-40 -Valproic Acid: 50-150 -Phenytoin 10-20 (total) 1-2 (free)
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What is the treatment for status epilepticus?
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-First try benzodiazepam (2 times) -Second try Phenytoin (IV faster) -Third try phenobarbital
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What is the definition of an absence seizure?
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brief (usually less than 20 seconds), generalized epileptic seizures of sudden onset and termination. They have 2 essential components: clinically the impairment of consciousness (absence)
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Phenytoin
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-Fosphenytoin is the prodrug of phenytoin and converted to phenytoin in 7-15 min -less hypotension -No extravasation -Can administer faster: 150 mg PE/min -phenytoin 1mg=fosphenytoin 1 P.E.
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Pregabalin
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-Schedule V medication
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Primidone
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-metabolized to phenobarbital
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Rufinamide
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-Adjunctive therapy for Lennox-Gastaut Syndrome -Contraindicated in patients with familial QT syndrome -May precipitate status epilepticus -May increase # of other types of seizures
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Tiagabine
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no comment
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Topiramate
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weak carbonic anhydrase inhibitor
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Valproic Acid, Valproate sodium, Divalproex sodium
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All are valproic acid and have multiple dosage forms
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Vigabatrin
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-Rarely used due to vision loss -Recently re-approved for use in US -Available under SHARE -Increases seizure activity
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Zonisamide
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Cross reaction with sulfonamides hypersensitivies
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