Miscellaneous Quiz / Seizure Drugs

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Can you name the Seizure Drugs?

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Tiagabine class
Class MOA: State dependent Na+ channel blockade, prolongs inactivated state (and thus refractory period), Ca++ mediated neurotransmitter release.
Inhibitory GABAergic interneurons that communicate between cortical neurons - can be overcome during seizure
Drug Use: First line for absence (petit mal)--only use
Drug Use: Similar to carbamazepine (less potent)
Drug SE: skin rash, sedation, & behavioral changes
Drug MOA: Alters GABA metabolism, decrease Ca entry presynaptically?
Fosphenytoin class
Drug MOA: Inteferes w/ synaptic vesicle PRO (SV2A)
Drug SE: Significant toxicity issue, aplastic anemia & hepatitis (=3rd line)
Drug MOA: inhibition of Carbonic Anhydrase
Drug P-kinetics: Oral absorption, completely absorbed (peaks after 3-7 hrs) partitions in H2O compartments. No PRO binding; [plasma] = [CSF]. Metabolized in liver by hydroxylation
Drug P-kinetics: stops seizures, IV or rectally for SE. Chronic oral use ineffective b/c of tolerance.
Drug interactions: Valproate doubles half life, decreased by CYP inducing drugs & oral contraceptives
Drug SE: Mostly during first 4 wks (dose-related; give drug slowly) = somnolence, fatigue, dizziness, significant psychomotor & cognitive slowing, paresthesia, increased IOP, nervo
Drug Use: First line for generalized tonic-clonic, partial, and absence seizure (Ethosuximide preferred b/c of drug's hepatotoxicity), atypical absence, myoclonic seizures
Clonazepam class
Drug SE: Sedation, hemeralopia, mild metabolic acidosis, idiosyncratic derm reactions, reversible nephrotic syndrome
Drug MOA: Inhibits GABA transaminase (results in more GABA release)
Drug P-kinetics: Metabolized to PEMA & phenobarbital (steady state after 20 days)
Drug use: similar to phenobarbital
Drug P-kinetics: Similar to phenytoin. Saturable to nirvanol, the active metabolite
Drug interactions: does not effect levels of other seizure drugs
Drug Use: limited use because of rapid tolerance: epileptic women during menses
Lorazepam class
Drug interactions: Little effect to other antiseizure drugs
Drug SE: Similar to carbamazepine (perhaps less tox). Fewer hypersensitivy reactions.
Excitatory glutaminergic projection neurons that communicate in & out of cortex, layers III, IV, and V - synchronous firing is responsible for seizures
Trimethadione class
Drug SE: Significant toxicity. Neurologic: dizziness, HA, diplopia, nausea, somnolence ataxia. Sytemic: hypersensitivity, skin rash (1-2% life threatening in children--SJS)
Drug MOA: Similar to phenytoin. Blocks Na+ channels, inhibits repetive firing in cells; decreases synaptic transmission. Also inhibition of catecholamine uptake. Effective against
Drug Use: Adjunctive for partial & genralized tonic-clonic seizures, certain myoclonias, febrile seizures & infantile spasms
Drug interactions: Birth control pills are less effective
Drug use: Third line for refractory partial seizures, but does have effectiveness Lennox Gastaut syndrome
Drugs P-kinetics: Oral. Absorbtion: intestines - complete, 3-12 h depending on formulation. Usually dissolved in propylene glycol which can be cardiotoxic; IM - unpredictable, prec
Drug Use: adjunctive therapy for partial-onset seizures (w or w/o generalization)
Drug P-kinetics: oral, good bioavailability
Drugs Use: First choice for most partial seizures & used commonly for generalized tonic-clonic seizures (either primary or secondary), used in combo for status epilepticus. Not for
Drug SE: Drowsiness, cognitive impairment
Ethotoin class
Ethosuximide class
Drug SE: N/v & GI complaints (common & dose related - start drug gradually), abd pain, heartburn (gradual start, temporary reduction helps). common elevation in hepatic enzymes; he
Drug P-kinetics: IV for SE; can be more effective & durable than diazepam.
Drug Use: adjunctive therapy for partial seizures
HintAnswer
Drug MOA: Inhibits GABA uptake (GAT-1 transporter isotype)
Drug interactions: Inc. plasma phenytoin & valproic acid but dec. carbamazepine levels
Drug Use: First line for generalized tonic-clonic siezures, atypical absence, myoclonic, atonic, effects against Lennox-Gastaut and West's syndrome. Used in the preventative mgmt o
Chlorazepate class
Drug Use: Similar to phenytoin
Drugs effects: increase GABAergic transmission
Drug P-kinetics: Not metabolized renal excretion, short half life
Valproic acid class
Acetazolamide class
Drug SE: minor: nervousness, dizziness, tremor, difficulty concentrating & depression. Discontinue if psychosis confusion, or somnolence occurs. Rash common
Drug SE: Acute: stupor or coma, hyperirritability, convulsions, & resp depression. Chronic: drowsiness, vertigo, ataxia, diplopia, & blurred vision. Hematologic disorders (aplastic
Drug P-kinetics: Similar to phenytoin. Used in pts hypersensitive to phenytoin. Saturable metb
Lamotrigine class
Congeners of phenytoin
Drug SE: Somnolence, asthenia & dizziness. Rare: anemia, leukopenia
Drug effects: inc. CO2, decreasing the depolarizing action of bicarbonate ions (moving through GABA receptor ion channels)
Gabapentin class
Zonisamide class
Drug interactions: No hepatic enzyme induction. Drug interactions are negligible
Drug MOA: Inhibits gCa++, Na+/K+ atpase & inhibits GABA aminotransferase
Drug SE: Idiosyncratic reactions (rash, agranulocytosis, hepatitis) more frequent.
Levetiracetam class
Drug SE: Relatively safe but marked sedation
Drugs P-kinetics cont: Metabolism: liver (CYP2C9/10 and CYP2C19) para-hydroxylation, then glucuronidation, metabolites are inactive, excreted in urine. DOSE DEPENDENT (saturable) a
Drug Contraindications: Hepatic cirrhosis
Drug effects: Na+ & Ca++ channel conductance
Drug MOA: Similar to phenytoin w/ active metabolite = phenobarbital & PEMA
Vigabatrin class
Drugs that decrease seizure threshold
Drug SE: Drowsiness, dizziness and wt. Gain, less common: psychosis & confusion & visual field defects, animal studies: intramyelinic edema
Drug MOA: Similar to ethosuximide effects on gCa++
Drug interactions: Less hepatic enzyme induction than carbamazepine --> fewer drug interactions.
Drug SE: Hypokalemia, hyperchloremic metabolic acidosis, phosphatemia -> increased pH in urine may cause Ca-PO4 stones, hyperammonemia in cirrhotics
Drug MOA: Similar to carbemazepine
Drug MOA: NMDA receptor blockade
Drug Use: mgmt of epilepsy pts w/ porphyria
Pregabalin class
Drugs P-kinetics cont: Therapeutic plasma level 10 - 20 ug/mL. Toxic level > 20 ug/mL. Oral dosage: typical starting dose 300mg/d; frequently insufficient to reach therapeutic plas
Drug effects: Reduces low threshhold (T-type) Ca++ currents in thalamic neurons, responsible for generating rhythmic cortical discharge in absence attack. Reduces thalamic firing
Drug P-kinetics: Good oral absorption, not PRO bound, liver metabolized
Drug SE: Similar to phenobarbital
Drug P-kinetics: Mainly excreted in urine
Drug interactions: Valproic acid decreases ethosuximide clearance
Drug Use: Febrile seizures (Benzodiezepine first), second line for simple partial, grand mal & as adjunct for SE
HintAnswer
Drug effects: Raises threshold for firine of repetitive thalamic firing
Drug P-kinetics: Good oral absorption, taking w/ meals delays absorption & decreases toxicity. Fully ionized (anion is active) and PRO bound. Half-life 9-18 h; dose dependent clear
Drug P-kinetics: Good oral absorption, plasma protein bound (not displaced by other drugs), induces microsomal enzymes, active metabolites
Drug MOA: Several, inc. GABA transmission, effects Na channel opening
Drug P-kinetics: Administer slowly and inc. dose
Drug Use: Current 1st line drug for partial seizures (with others), except not used in SE. Established efficacy on mania, mood stabilization, bipolar disorder (lithium alternative)
Drug Use: First line for generalized tonic-clonic seizures or monotherapy for partial seizures in adults, myclonic siezures, atypical absence, Lennox Gastaut. Alternative therapy f
Drug Use: Adjunct therapy for partial seizures, also effective for neuropathic pain tx (indicated to tx postherpetic neualgia), also mgmt of migraine HA
Drugs Use: Continuous seizure activity: gran-mal, status epilepticus. Febrile seizures. Or alternative therapies for absence and atypical absence, myoclonic and atonic seizues. Use
Drug P-kinetics: Oral, well absorbed, duration 8-12h, secreted by kidney. Effectiveness declines in 2-3 days.
Drug P-kinetics: Activity is not correlated w/ plasma half life, eliminated via kidneys
Primidone class
Class Drug Interactions: PRO binding: displaced by other drugs (e.g. sulfonamides), leading to increased [free]; hypoalbuminemia-raising dose to maintain total drug concentration m
Drug MOA: Similar to phenytoin, also inhibition of Ca channels, & glutaminergic receptors
Mephobarbital class
Classes/Drugs effects: Decreased repetitive neuronal firing
Mephenytoin class
Drug SE: Less toxic and less side effects than phenytoin.
Drug SE: Somnolence, dizziness, ataxia, HA, & tremor
Drug MOA: Probably effects Na channels, Kainate & AMPA receptor inhibition, potentiates GABA inhibitory effects
Drug interactions: CYP inducers (e.g. phenobarbital and phenytoin) may increase metabolism; and enzyme inhibitors (erythromycin, isoniazid, cimetidine, fluoxetine) inhibit metaboli
Drugs SE: Neurologic: Nystagmus (early); Ataxia and diplopia (adjust dose); incoordination; confusion; sedation (at high plasma levels); gingival hyperplasia and hirsutism (very co
Phenobarbital class
Drug P-kinetics: Rapidly absorbed, glucuronidated, 55% protein bound
Drug MOA: inhances inactivation of Na channels, blocks neurotrophic factor intracellular cascades (collapsin-response mediatior protein, CRMP-2)
Drug P-kinetics: adjunct drug for complex partial seizures (drowsiness and lethargy common -- raise doses slowly).
Drug SE: Gastric distress, transient lethargy, rare skin rash & more marrow suppression (periodic monitoring necessary)
Oxcarbazepine class
Drugs MOA: Allosteric activator of GABA mediated Cl- conductance
Carbamazepine class
Topiramate class
Drug Use: Partial seizures & West's syndrome, infantile spasm (w/ corticotropin)
Drug SE: dizziness, HA, nausea, and diplopia
Phenytoin class
Drug P-kinetics: long acting; one of the best for absence seizures, works for myoclonic seizures; prominent sedative effect; start with low doses -- raise over weeks)
Drug Use: Third line for absence seizures behind succinimides
Drug P-kinetics: Glucuronide is the active metabolite (10-hydroxycarbamazepine)
Drug Use: Similar to phenytoin but less efficacious
Felbamate class
Drug inteeractions: Displaces phenytoin from plasma proteins, inhibits metabolism of many drugs (phenobarbital [can cause stupor or coma], phenytoin & carbamazepine).
Drug MOA: Blocks sustained repetitive firing - inhibits Na+ currents and increases GABA levels in the brain. Increase membrane K+ conductance (high levels)
Diazepam class

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