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62 Cards in this Set
- Front
- Back
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Def: Seizure
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transiet episode of brain dysfunction resulting from rhythmic, synchronous nueronal firing
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Def. Epilepsy
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group of chronic disorders characterized by recurrent seizures. It's the 2nd most common nuerological disorder.
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Mech of Action of antiseizure drugs
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decrease excitation, enhance inhibition, modify neuronal excitability of ion channel that mediate neuronal firing/rhythmicity
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Mech of Action: Decrease in Excitation
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excitation decreased by decreasing Glutamate.
(phenobarbital): modulate GABAa-R, decreasees glutamatergic transmission, commonly used in infants*// Topiramate: Inhibit AMPA/KA receptors >> no glutamate binding.// Felbamate: binds NMDA-R to block glutamate binding.// Lamotrigine: inhibits release of Glu from presynaptic membrane.// |
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Mech of Action: Enhance Inhibition via GABA transmission
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ex: Topiramate, Felbamate://
Valproate: induces GAD, converting more Glu to GABA. Also, inhibits GABA-T decreasing GABA breakdown.// Tiagabine: block GAT-1, decreaing reuptake of GABA from the synapse into the neuron and glial cell.// Pheobarbital/Levetiracetam: positive effect on GABAa-R. // |
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Mech of aCtion: Alter ion channel activity
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Decrease Sodium influx: oxcarbazepine, phenytoin, valproate, topiramate, zonisamide.//
Enhance K efflux: Oxcarbazepine, topiramate. They prolong AP so few APs per unit time.// Decrease Ca influx: Ethosuximide, valproate, zonisamide, Gabapentin, levetiracetam, oxcarbazepine. |
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Types of Seizures
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There are Partial seizures (localized onset) and generalized seizures that have no localized onset. Partial subtypes include simple partial, complex partial, partial seizure secondarily generalized.
Generalized subtypes include Tonic-clonic (grand mal) and abse'nce (petit mal). |
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Partial Seizures: Simple Partial
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Conciousness is PRESERVED. Sensory 'auras' or limited unilateral motor convulsions. 20-60 sec duration
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Partial Seizures: Complex Partial
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IMPAIRED CONCIOUSNESS: automatisms common, post-ictal confusion and or lethargy. Most common refractory seizure in adults. 30 sec to 2 min duration.
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Partial Seizures: Partial seizure secondarily generalized
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it's a partial seizure that progresses to generalized tonic-clonic seizure. 1-2 min duration.
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Generalized seizure: Tonic-Clonic (grand mal)
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loss of conciousness, major convulsions, tonic spasm of the body followed by clonic jerking, prolonged ictal stupor. 1-2 min duration.
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Generalized seizures: Abse'nce (petit mal)
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abrupt interruption of conciousness associated with starring and cessation of ongoing activities. Symmetrical automatism and or mild jerking common. LACK OF POST ICTAL ABNORMALITIES.
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How would you differentiate between complex partial seizures and Absence (petit mal)?
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Absence lack post-ictal abnormalities.
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What does post-ictal mean?
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It means after the seizure. So individual with complex partial seizure would be confused afterwards but Absence, once the seizure is gone, the person does not show confusion.
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Frontline drugs for Partial Seizures?
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Carbamazepine, phenytoin, oxcarbazepine, lamotrigine, valproate
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frontline drugs for Tonic-clonic seizures?
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valporate, phenytoin, carbamazepine
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frontline drugs for absence (petit mal)?
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ethosuximide, valproate
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Phenytoin
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inhibits Na channel, part of frontline drugs for all seizures.//
NONLINEAR relationship between dose and [plasma], so small increase in dose >> large [plasma] increase.// adverse: gingival hyperplasia, hisutism, coarsed facial features, may interfere with thyroid function test. |
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Carbamazepine
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related to tricyclic depressants, Na ch blocker.//
induces own hepatic metabolism. // adverse: LIVER DAMAGE, liver function test REQUIRED BY FDA. |
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Oxcarbazepine
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safer than carbamazepine, **blocks Na and Ca channels, enhance K eflux**//
Less hepatic induction than carbamazepine.// Adverse: hypnatremia, STEVEN JOHNSON SYNDROME, decreases T4.// |
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Phenobarbital
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a barbiturate, modulates GABAa-R and decreases glutamatergic transmission.//
COMMONLY USED IN INFANTS, NOT IN OTHER POPULATIONS.// |
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Gabapentin
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amino acid ANALOG of GABA. decreases Ca influx by binding alpha-2-delta subunit of VG Ca channel.//
EXCRETED UNCHANGED, NO Rx INTERRACTIONS. adverse effects: periph edema, behav. and thoughts changes in 3-12 yo. adverse effects similar to high dose diazepam.// |
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Tiagabine
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GAT-1 inhibitor//
highly bound to plasma protein.// adverse: Seizures, non-convulsive status epilepticus in non-epileptic patients*** |
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Levetiracetam
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inhibits delayed rectifier K channel, inhibits Ca channel, inhibit neg modulation of GABAa-R by Zn and beta-carboline.//
adverse: irritability, hallucination, psychosis. // |
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Felbatamate
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inhibit NMDA, enhance GABA transmission.//
ONLY IN MEDICALLY REFRACTORY PTS.// adverse: HEPATIC FAILURE. liver function test REQUIRED BY FDA. |
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frontline drugs for Tonic-clonic seizures?
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valporate, phenytoin, carbamazepine
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Note to self
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previous drugs are for partial and general Tonic-clonic only. The next card is for Absence seizures ONLY.
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Ethosuximide: In absence only!!!
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inhibit T type Ca channel. //
adverse: bloody dyscrasias, skin rxn, photophobia, parkinson's like sx. |
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frontline drugs for absence (petit mal)?
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ethosuximide, valproate
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Valproic acid/sodium valproate
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Inhibits Na ch, Ca ch and GABA-transaminase; stim GABA synth enzyme GAD, hyperpolarizes membrane.//
IDIOSYNCRATIC HEPATOTOXICITY. liver fxn test required by FDA |
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Phenytoin
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inhibits Na channel, part of frontline drugs for all seizures.//
NONLINEAR relationship between dose and [plasma], so small increase in dose >> large [plasma] increase.// adverse: gingival hyperplasia, hisutism, coarsed facial features, may interfere with thyroid function test. |
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Carbamazepine
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related to tricyclic depressants, Na ch blocker.//
induces own hepatic metabolism. // adverse: LIVER DAMAGE, liver function test REQUIRED BY FDA. |
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Lamotrigine
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ADULTS ONLY. inhibits Na ch, Glu release. ONLY INDICATED FOR LENNOX-GASTAUT SYNDROME IN PT < 16 YRS OF AGE.//
Adv: Steven-Johnson Syndrome esp. if switched from Valproate.** |
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Oxcarbazepine
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safer than carbamazepine, **blocks Na and Ca channels, enhance K eflux**//
Less hepatic induction than carbamazepine.// Adverse: hypnatremia, STEVEN JOHNSON SYNDROME, decreases T4.// |
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Why does the risk of Steven-Johnson syndrome go up with Lamotrigine if the pt was previously on valproate?
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Sodium Valproate (Valproic acid) inhibits p450, so this could lead to increase [lamotrigine] in plasma >>> toxicity.
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Phenobarbital
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a barbiturate, modulates GABAa-R and decreases glutamatergic transmission.//
COMMONLY USED IN INFANTS, NOT IN OTHER POPULATIONS.// |
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Gabapentin
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amino acid ANALOG of GABA. decreases Ca influx by binding alpha-2-delta subunit of VG Ca channel.//
EXCRETED UNCHANGED, NO Rx INTERRACTIONS. adverse effects: periph edema, behav. and thoughts changes in 3-12 yo. adverse effects similar to high dose diazepam.// |
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Tiagabine
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GAT-1 inhibitor//
highly bound to plasma protein.// adverse: Seizures, non-convulsive status epilepticus in non-epileptic patients*** |
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Levetiracetam
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inhibits delayed rectifier K channel, inhibits Ca channel, inhibit neg modulation of GABAa-R by Zn and beta-carboline.//
adverse: irritability, hallucination, psychosis. // |
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Felbatamate
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inhibit NMDA, enhance GABA transmission.//
ONLY IN MEDICALLY REFRACTORY PTS.// adverse: HEPATIC FAILURE. liver function test REQUIRED BY FDA. |
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Note to self
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previous drugs are for partial and general Tonic-clonic only. The next card is for Absence seizures ONLY.
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Ethosuximide: In absence only!!!
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inhibit T type Ca channel. //
adverse: bloody dyscrasias, skin rxn, photophobia, parkinson's like sx. |
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Valproic acid/sodium valproate
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Inhibits Na ch, Ca ch and GABA-transaminase; stim GABA synth enzyme GAD, hyperpolarizes membrane.//
IDIOSYNCRATIC HEPATOTOXICITY. liver fxn test required by FDA |
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Lamotrigine
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ADULTS ONLY. inhibits Na ch, Glu release. ONLY INDICATED FOR LENNOX-GASTAUT SYNDROME IN PT < 16 YRS OF AGE.//
Adv: Steven-Johnson Syndrome esp. if switched from Valproate.** |
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Why does the risk of Steven-Johnson syndrome go up with Lamotrigine if the pt was previously on valproate?
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Sodium Valproate (Valproic acid) inhibits p450, so this could lead to increase [lamotrigine] in plasma >>> toxicity.
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Topiramate
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inhibits Na ch, enhance GABA transmission, activate K ch, AMPA/ KA-R antagonist, carbonic anhydrase inhibitor.//
adv: metabolic acidosis, renal calculi, weight loss |
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Zonisamide
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inhibits Na, and Ca channels; weak carbonic anhydrase inhibitor. //
adv effect: sulfonamide derivite drug so possible allergic rxn, |
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Vigabatrin
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IRREVERSIBLE inhibitor of GABA degradation enzyme, GABA-T (Transaminase).
Adverse: Long use may cause permanent visual field deficits, psychosis in pts with preexisting mental disorders. |
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Drug Interractions: Which Rx has interraction with almost all of the antiseizure drugs?
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oral contraceptives
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Which antiseizure drugs have the most interractions?
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Carbamazapine, Phenobarbital, Phenytoin. These induce hepatic enzymes.
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Which antiseizure drugs inhibits hepatic enzymes?
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Valproic Acid
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Which antiseizure drugs have no known Rx interractions?
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Gabapentin (aa analog of GABA), Levetiracetam
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What aniseizure drug should NEVER be used off-label?
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Tiagabine because it could cause seizures in non-epileptic patients.
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Status Epilepticus Def.
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continuous prolong seizure >5-10 min, or multiple seizures in rapid succession.//
Most common is generalized tonic-clonic status epilepticus, which is life threatening emergency.// Use IV meds in these patients. |
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What drugs to use in Status Epilepticus?
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IV Lorazepam, IV or rectal Diazepam. Also, iv Fosphenytoin//
In Absence SE, NO barbiturates, substitute valproate for fosphenytoin. |
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What's Fosphenytoin?
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This is a more water soluble form of phenytoin useful for IV or IM injections.
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Def. Infantile Spasm
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epleptic syndrom characterized by myoclonic spasms. First attack before 1 yo in 90% pts.//
Refractory to usual antiseizure drugs.// Use corticotropin, prednisone.// |
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Febrile Seizures, def.?
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NOT a form of epilepsy. brought on by fever in infants and children.//
No Meds. Prophylactic rectal diazepam if prone to febrile seizures.// |
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Best way to manage Epilepsy with treatment?
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Early dx, treatment with single drug for at least 2 years.
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Antiseizure Rx and Pregnancy
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many antiseizure drugs would reduce the effectiveness of oral contraceptives >>> unintended pregancy.
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Drugs with teratogenic effects?
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Valproate**, phenytoin, carbamazepine, phenobarbital
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So what to do with pregnant pts?
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consider either discontinuation prior and during the pregnancy if withdrawal does not posses serious threat to the pt. OR monotherapy with lowest effective dose.//
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