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151 Cards in this Set
- Front
- Back
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what are the first generation epilepsy drugs?
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carbamazepine, phenytoin, phenobarbital, valproic acid, clonazepam, ethosuximide
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what drug is only effective against absence seizures?
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ethosuximide
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what are the second generation epilepsy drugs?
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oxcarbazepine, gabapentin, pregabalin, ezogabine, lamotrigine, levetiracetam, topiramate, felbamate
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what are the narrow spectrum epilepsy drugs?
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carbamazepine, phenytoin, phenobarbital, ethosuximide which are 1st gen, and oxcarbazepine, gabapentin, pregabalin, ezogabine which are 2nd gen
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what are the broad spectrum epilepsy drugs?
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valproic acid and clonazepam which are 1st gen, and lamotrigine, levetiracetam, topiramate, felbamate, zonisamide which are 2nd gen
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what NT alterations are responsible for seizures?
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GABA and glutamate, GABA antagonists or glutamate agonists are convulsant
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what type of drugs are anticonvulsant?
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drugs that enhance GABA or inhibiti glutamate
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what is the kindling model?
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low intensity electrical stimulation repeatedly leads to seizure activity
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what is the cause of generalized epilepsy?
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strong genetic component, ion channel mutations
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what channel is involved in absence seizures?
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voltage gated T type Ca2+ channel, cortex activated by these channels, thalamocortical circuit is dysfunctional
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what are some of the genetic mutations in ion channel receptors in epilepsy?
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voltage gated Na channel subunit mutations(promotes depol and neuronal excitability), voltage gated K channel(prolong depol and increases neuronal hyperexcitability
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what other ion channel undergoes a mutation that leads to epilepsy?
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GABA A
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what causes partial seizures?
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focal lesions such as head trauma, stroke, tumors
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what is the most prevalent partial seizure?
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complex partial seizure arising from mesial temporal lobe, sensitive to damage
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what is the most common lesion associated with mesial temporal lobe seizure?
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hippocampal sclerosis
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what occurs in the dentate gyrus?
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high levels of neurogenesis for memory, damage can lead to altered firing
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what are the three major categories for pharmacotherapy?
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1)limit repetitive firing by promoting inactivated state of voltage gated Na channels 2)enhance GABA mediated synaptic inhibition(inhib Cl- ion channel)3)inhibition of voltage activated Ca2+ channels associated with T type Ca2+ currents
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what type of drugs work on simple partial, complex partial and partial with secondary generalized tonic clonic seizures?
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carbamazepine ,phenytoin, valproic acid, lamotrigine, topiramate, zonisamide
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what is the function of benzodiazepines and barbiturates?
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enhance GABA A receptors, enhances Cl- flow, hyperpolarizes the membrane
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what type of seizures do benzodiazepines and barbiturates work on?
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partial and tonic clonic seizures
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at high doses what can benzodiazepines and barbiturates be used for?
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status epilepticus
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what inhibits GABA transport site preventing reuptake back into presynaptic cell?
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Tiagabine
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what are some characteristics of absence seizures?
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presence of thalamic and neocortical discharge of 3/sec generalized spike and wave discharges
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what was the first drug to show anti seizure activity without sedative effects?
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phenytoin
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what is phenytoin effective against?
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partial seizures, at higher doses against tonic clonic seizures but NOT absence
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what is the action of phenytoin at therapeutic doses?
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slows recovery of Na 2+ channels from inactivation
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what is the action of phenytoin at higher doses?
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non selective effects including enhancing GABA
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is phenytoin extensively or weakly bound?
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extensively bound
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what drug competes with phenytoin for protein binding?
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valproate
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what drug's metabolism does phenytoin inhibit?
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warfarin, increase bleeding disorders
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is phenytoin an enzyme inducer or inhibitor
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inducer, can enhance metabolism of oral contraceptives
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what are the A/E of phenytoin?
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cosmetic:facial hair, skin problems, rash(sometimes Stevens Johnson), GINGIVAL HYPERPLASIA(>20%, treat with folic acid), osteoporosis(give vit D), megaloblastic anemia(give folate), mental dullness
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what is the MOA of phenobarbital?
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increase GABA A receptor mediated current, increases durationg of bursts, at higher doses can limit sustained repetitive firing(help status epilepticus)
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what is phenobarbital effective for?
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generalized tonic clonic and partial seizures, NOT effective in absence seizures
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is phenobarbital an inducer or inhibitor?
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inducer, faster metabolism of oral contraceptives
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what are the A/Es of phenobarbital?
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sedation early on, nystagmus and ataxia in excessive doses, cognitive dulling, agitation and confusion in the elderly, significant birth defects in pregnancy, hypoprothrombinemia with hemorrhage in newborns(prophylaxis in mother with vit K), osteoporosis (give vit D), megaloblastic anemia, mental dullness, behavioural toxicity in children
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what is the MOA of carbamazepine?
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limits firing of AP evoked by sustained depol, works by altering the rate of recovery of voltage gated Na channels from inactivation
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what is carbamazepine the primary drug for?
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partial(simple and complex) and generalized tonic clonic seizures
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what should be monitored while on carbamazepine?
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renal and hepatic fxn
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what is another use for carbamazepine?
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bipolar disorder including refractory patients
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is carbamazepine an inducer or inhibitor?
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inducer, increases metabolism of oral contraceptives
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what are the A/E of carbamazepine?
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drowsiness, vertigo, ataxia, blurred vision(should increase dose slowly), acute toxicity(coma, convulsions, resp depression), vomiting, aplastic anemia, agranulocytosis, hypersensitivity rxns
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what is the advantage of oxcarbazepine?
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prodrug that results in less potent enzyme inducer, does not interfere with warfarin, it does reduce steroid oral contraceptives
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what is oxcarbazepine approved for?
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monotherapy or adjunct therapy for partial seizures
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what is the MOA of ethosuximide?
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inhibit clonic seizures, reduces the low threshold of Ca2 currents, T type currents in thalamic neurons, does NOT inhibit sustained repetitive firing or enhance GABA responses
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what is ethosuximide effective for?
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absence seizures but NOT tonic clonic seizures
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what are the A/E of ethosuximide?
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parkinson like symptoms, photophobia, restleness, inability to concentrate and other CNS effects, uticaria, serious skin reactions, leukopenia, thrombocytopenia, aplastic anemia
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what is the MOA of valproic acid?
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inhibits sustained repetitive firing by depol, prolongs recovery of voltage activated Na channels from inactivation, increase GABA CNS levels, reduces T type Ca2 currents
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what type of seizures is valproic acid effective for?
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partial, myoclonic, tonic clonic and absence
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what are the A/E of valproic acid?
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anorexia, nausea, vomiting, sedation, ataxia, tremor, chronic effects in some patients(weight gain, alopecia, rash), can elevate hepatic transaminases
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what are some drug interactions of valproic acid?
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inhibits various liver enzymes, highly bound to albumin so can displace phenytoin, rare adverse interaction between valproate and clonazepam(ABSENCE STATUS EPILEPTICUS)
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what population should valproic acid be avoided?
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pregnant women, can effect cognitive development, should be AVOIDED in women during child bearing years, associated with polycystic ovary system
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what is the MOA of clonazepam?
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a benzodiazepine, increase frequency of GABA A activated Cl channels
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what is clonazepam approved for?
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absence seizures and myoclonic seizures
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what are the A/E of clonazepam?
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drowsiness, lethargy, cognitive effects
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what is the MOA of gabapentin and pregabalin?
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act at Ca2 channel subunit alpha2 delta1, may lead to increase GABA transport
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what type of seizures are gabapentin and pregabalin effective for?
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partial and some generalized seizures
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what other conditions are gabapentin and pregabalin effective for?
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migraine, chronic neuropathic pain, bipolar disorder
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what are the A/Es of gabapentin and pregabalin?
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somnolence, dizziness, ataxia, fatigue
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what is the MOA of ezogabine?
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targets neuron specific voltage gated K channels to dampen neuronal hyperexcitability
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what is ezogabine effective for?
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drug resistant partial seizures
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what is the MOA of lamotrigine?
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blocks sustained repetitive firing and delays recovery from inactivation of Na channels, may also inhibit glutamate release
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what is lamotrigine metabolized by?
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glucuronidation
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what drugs interfere with lamotrigine metabolism?
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valproate inhibits glucuronidation and phenytoin, carbamapezine, phenobarbital reduce the plasma concentration
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what seizures is lamotrigine effective for?
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partial and secondary generalized tonic clonic seizures, generalized tonic clonic seizures and in absence seizures
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what is Lennox Gastaut syndrome?
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multiple seizure types, mental retardation, refractoriness to anti seizure medication
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what is the MOA of Levetriacetam?
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unknown, binds to synaptic vesicle protein, SV2A
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what seizures is levetriacetam effective for?
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partial, generalized tonic clonic and myoclonic
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what are the A/E of levetriacetam?
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well tolerated, some somnolence, asthenia, dizziness, low incidence of thinking/memory problems, may cause mood changes
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what are the drug interactions of levetriacetam?
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none
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what is the MOA of topiramate?
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reduces voltage gated Na currents, activates hyperpolarizing K currents, enhances GABA currents, limits activation of AMPA receptors(glutamate receptors), also inhibits carbonic anhydrase, increases acidity which might suppress seizures
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what is a PK issue with topiramate?
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reduces oral contraceptive plasma levels
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what conditions is topiramate useful for?
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partial and generalized seizures, refractory patients, Lennox Gastaut, migraine prevention
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what is the MOA of topiramate?
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reduces voltage gated Na currents, activates hyperpolarizing K currents, enhances GABA currents, limits activation of AMPA receptors(glutamate receptors), also inhibits carbonic anhydrase, increases acidity which might suppress seizures
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what are some A/E of topiramate?
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somnolence, fatigue, weight loss, nervousness, precipitate renal caliculi, risk of glaucoma, cognitive impairment in 1/3 of the patients
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what is a PK issue with topiramate?
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reduces oral contraceptive plasma levels
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what conditions is topiramate useful for?
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partial and generalized seizures, refractory patients, Lennox Gastaut, migraine prevention
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what is the MOA of felbamate?
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inhibits NMDA responses and potentiates GABA evoked responses
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what is the MOA of topiramate?
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reduces voltage gated Na currents, activates hyperpolarizing K currents, enhances GABA currents, limits activation of AMPA receptors(glutamate receptors), also inhibits carbonic anhydrase, increases acidity which might suppress seizures
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what is the MOA of topiramate?
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reduces voltage gated Na currents, activates hyperpolarizing K currents, enhances GABA currents, limits activation of AMPA receptors(glutamate receptors), also inhibits carbonic anhydrase, increases acidity which might suppress seizures
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what are some A/E of topiramate?
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somnolence, fatigue, weight loss, nervousness, precipitate renal caliculi, risk of glaucoma, cognitive impairment in 1/3 of the patients
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what conditions is felbamate useful for?
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partial and generalized seizures, refractory patients, Lennox Gastaut syndrome
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what is a PK issue with topiramate?
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reduces oral contraceptive plasma levels
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what is a PK issue with topiramate?
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reduces oral contraceptive plasma levels
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what is the MOA of topiramate?
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reduces voltage gated Na currents, activates hyperpolarizing K currents, enhances GABA currents, limits activation of AMPA receptors(glutamate receptors), also inhibits carbonic anhydrase, increases acidity which might suppress seizures
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what conditions is topiramate useful for?
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partial and generalized seizures, refractory patients, Lennox Gastaut, migraine prevention
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what conditions is topiramate useful for?
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partial and generalized seizures, refractory patients, Lennox Gastaut, migraine prevention
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what is the MOA of felbamate?
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inhibits NMDA responses and potentiates GABA evoked responses
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what are the A/Es of felbamate?
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when given in combo with other large doses of other anticonvulsants, rash and potentially lethal toxicities
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what is the MOA of zonisamide?
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inhibits T type Ca2 currents, prolongs the inactivated state of voltage gated Na channels and inhibits brain carbonic anhydrase
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what are some A/E of topiramate?
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somnolence, fatigue, weight loss, nervousness, precipitate renal caliculi, risk of glaucoma, cognitive impairment in 1/3 of the patients
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what conditions is felbamate useful for?
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partial and generalized seizures, refractory patients, Lennox Gastaut syndrome
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what are some A/E of topiramate?
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somnolence, fatigue, weight loss, nervousness, precipitate renal caliculi, risk of glaucoma, cognitive impairment in 1/3 of the patients
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what is a PK issue with topiramate?
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reduces oral contraceptive plasma levels
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what are the A/Es of felbamate?
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when given in combo with other large doses of other anticonvulsants, rash and potentially lethal toxicities
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what is the MOA of felbamate?
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inhibits NMDA responses and potentiates GABA evoked responses
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what is the MOA of felbamate?
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inhibits NMDA responses and potentiates GABA evoked responses
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what conditions is zonisamide useful for?
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partial and generalized tonic clonic seizures, absence seizures, NOT myoclonic seizures
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what conditions is topiramate useful for?
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partial and generalized seizures, refractory patients, Lennox Gastaut, migraine prevention
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what is the MOA of zonisamide?
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inhibits T type Ca2 currents, prolongs the inactivated state of voltage gated Na channels and inhibits brain carbonic anhydrase
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what conditions is felbamate useful for?
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partial and generalized seizures, refractory patients, Lennox Gastaut syndrome
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what conditions is felbamate useful for?
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partial and generalized seizures, refractory patients, Lennox Gastaut syndrome
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what are some A/E of topiramate?
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somnolence, fatigue, weight loss, nervousness, precipitate renal caliculi, risk of glaucoma, cognitive impairment in 1/3 of the patients
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what are the A/E of zonisamide?
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somnolence, anorexia, dizziness, in children-hyperthermia and oligohydrosis , with other antiepileptic drugs-steven johnson, agranulocytosis, aplastic anemia
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what are the A/Es of felbamate?
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when given in combo with other large doses of other anticonvulsants, rash and potentially lethal toxicities
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what conditions is zonisamide useful for?
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partial and generalized tonic clonic seizures, absence seizures, NOT myoclonic seizures
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what is the MOA of topiramate?
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reduces voltage gated Na currents, activates hyperpolarizing K currents, enhances GABA currents, limits activation of AMPA receptors(glutamate receptors), also inhibits carbonic anhydrase, increases acidity which might suppress seizures
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what is the MOA of felbamate?
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inhibits NMDA responses and potentiates GABA evoked responses
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what are the A/Es of felbamate?
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when given in combo with other large doses of other anticonvulsants, rash and potentially lethal toxicities
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what is the MOA of zonisamide?
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inhibits T type Ca2 currents, prolongs the inactivated state of voltage gated Na channels and inhibits brain carbonic anhydrase
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what is the MOA of zonisamide?
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inhibits T type Ca2 currents, prolongs the inactivated state of voltage gated Na channels and inhibits brain carbonic anhydrase
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what are the A/E of zonisamide?
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somnolence, anorexia, dizziness, in children-hyperthermia and oligohydrosis , with other antiepileptic drugs-steven johnson, agranulocytosis, aplastic anemia
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what is a PK issue with topiramate?
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reduces oral contraceptive plasma levels
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what conditions is felbamate useful for?
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partial and generalized seizures, refractory patients, Lennox Gastaut syndrome
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what conditions is topiramate useful for?
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partial and generalized seizures, refractory patients, Lennox Gastaut, migraine prevention
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what conditions is zonisamide useful for?
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partial and generalized tonic clonic seizures, absence seizures, NOT myoclonic seizures
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what conditions is zonisamide useful for?
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partial and generalized tonic clonic seizures, absence seizures, NOT myoclonic seizures
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what are the A/Es of felbamate?
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when given in combo with other large doses of other anticonvulsants, rash and potentially lethal toxicities
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what are some A/E of topiramate?
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somnolence, fatigue, weight loss, nervousness, precipitate renal caliculi, risk of glaucoma, cognitive impairment in 1/3 of the patients
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what are the A/E of zonisamide?
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somnolence, anorexia, dizziness, in children-hyperthermia and oligohydrosis , with other antiepileptic drugs-steven johnson, agranulocytosis, aplastic anemia
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what is the MOA of zonisamide?
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inhibits T type Ca2 currents, prolongs the inactivated state of voltage gated Na channels and inhibits brain carbonic anhydrase
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what are the A/E of zonisamide?
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somnolence, anorexia, dizziness, in children-hyperthermia and oligohydrosis , with other antiepileptic drugs-steven johnson, agranulocytosis, aplastic anemia
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what conditions is zonisamide useful for?
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partial and generalized tonic clonic seizures, absence seizures, NOT myoclonic seizures
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what is the MOA of topiramate?
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reduces voltage gated Na currents, activates hyperpolarizing K currents, enhances GABA currents, limits activation of AMPA receptors(glutamate receptors), also inhibits carbonic anhydrase, increases acidity which might suppress seizures
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what is the MOA of felbamate?
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inhibits NMDA responses and potentiates GABA evoked responses
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what are the A/E of zonisamide?
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somnolence, anorexia, dizziness, in children-hyperthermia and oligohydrosis , with other antiepileptic drugs-steven johnson, agranulocytosis, aplastic anemia
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what is a PK issue with topiramate?
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reduces oral contraceptive plasma levels
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what conditions is felbamate useful for?
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partial and generalized seizures, refractory patients, Lennox Gastaut syndrome
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what conditions is topiramate useful for?
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partial and generalized seizures, refractory patients, Lennox Gastaut, migraine prevention
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what are some A/E of topiramate?
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somnolence, fatigue, weight loss, nervousness, precipitate renal caliculi, risk of glaucoma, cognitive impairment in 1/3 of the patients
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what is the MOA of felbamate?
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inhibits NMDA responses and potentiates GABA evoked responses
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what are the A/Es of felbamate?
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when given in combo with other large doses of other anticonvulsants, rash and potentially lethal toxicities
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what is the MOA of zonisamide?
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inhibits T type Ca2 currents, prolongs the inactivated state of voltage gated Na channels and inhibits brain carbonic anhydrase
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what conditions is felbamate useful for?
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partial and generalized seizures, refractory patients, Lennox Gastaut syndrome
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what are the A/Es of felbamate?
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when given in combo with other large doses of other anticonvulsants, rash and potentially lethal toxicities
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what conditions is zonisamide useful for?
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partial and generalized tonic clonic seizures, absence seizures, NOT myoclonic seizures
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what is the MOA of zonisamide?
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inhibits T type Ca2 currents, prolongs the inactivated state of voltage gated Na channels and inhibits brain carbonic anhydrase
|
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what are the A/E of zonisamide?
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somnolence, anorexia, dizziness, in children-hyperthermia and oligohydrosis , with other antiepileptic drugs-steven johnson, agranulocytosis, aplastic anemia
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what conditions is zonisamide useful for?
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partial and generalized tonic clonic seizures, absence seizures, NOT myoclonic seizures
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what are the A/E of zonisamide?
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somnolence, anorexia, dizziness, in children-hyperthermia and oligohydrosis , with other antiepileptic drugs-steven johnson, agranulocytosis, aplastic anemia
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when do you start treating seizures?
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after two unprovoked seizures, after the first if warranted by EEG discharges, abnormal neuro exam or other structural abnormality responsible for the seizure
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what are the first line drugs for partial seizures?
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carbamazepine, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, topiramate, valproate
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what are the first line drugs for generalized seizures?
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lamotrigine, levetiracetam, topiramate, valproate
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what drugs are useful for absence seizures?
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ethosuximide, valproate, lamotrigine
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what drugs are useful for myoclonic convulsions?
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valproic acid and levetiracetam
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what is status epilepticus?
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prolonged seizure, any type, greater than 30 min, give IV lorazepam, diazepam followed by phenytoin, phenobarbital, attend to HTN, hypoventilation
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how should dosing of these drugs be handled?
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gradual dose titration, improves CNS tolerability and reduces risk of idiosyncratic adverse effects, dose with least amount of sedation as possible
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when can AEDs be discontinued?
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can be considered after 2-4 years of seizure freedom, predictors of recurrence are adolescent onset, focal seizures, underlying neuro disorder, abnormal EEG at time of withdrawal, good outcome for idiopathic epilepsy syndrome of childhood
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what is the long term prognosis?
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excellent for most children with seizures, particularly if cryptogenic(unknown origin), long term mortality increased in childhood onset epilepsy
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what are epileptics more likely to experience?
|
assault
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how does alcohol affect epileptics?
|
the state of alcohol withdrawal aggravates the seizure, start sometime between 6-72 hrs after having 3 or more alcoholic drinks
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