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38 Cards in this Set
- Front
- Back
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Define seizure, epilepsy, focus and convulsion.
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seizure: self-sustaining episode of neuronal hyperactivity epilepsy: chronic neurologic disease characterized by spontaneous recurring seizures focus: the site of origination of a seizure convulsion: a violent involuntary muscular contraction, or a series of suck contractions producing jerking movements |
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List some causes of isolated seizures.
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stroke, head trauma, CNS infections, metabolic probs, hypoxia, tramadol, buproprion, theophylline, TCAs, amphetamines, cocaine, imipenem, lithium, large doses of beta lactams
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Describe the pathophysiology of epilepsy.
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excessive excitatory neurotransmitter (glutamate) activity and lack of inhibitory neurotransmitter (GABA) activity -all seizures involve a sudden electrical disturbance of the cerebral cortex: a group of neurons fires rapidly and repetitively for seconds to minutes |
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Differentiate between partial, generalized, unclassified and status epilepticus seizures.
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partial: seizures begin locally; results in asymmetrical, unilateral seizures; can be simple (no LOC), complex (LOC) or secondarily generalized (partial progressing to ton/clon) generalized: bilaterally symmetrical and without local onset (absence, myoclonic, tonic-clonic, atonic, infantile spasms) unclassified: doesn't fit into one class status epilepticus: prolonged partial or generalized seizures without recovery between attacks |
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Name the traditional antiseizure drugs.
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phenobarbital phenytoin primidone ethosuximide diazepam carbamazepine valproic acid |
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Name the newer antiseizure drugs.
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felbamate gabapentin lamotrogine topiramate tiagabine levetiracetam oxcarbazepine zonisamide pregabalin lacosamide rufinamide vigabatrin ezogabine brivaracetam perampanel |
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What are the principles of therapy for seizure disorders?
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-control seizures with minimal side effects -select drug most appropriate -titrate dose to desired response -monotherapy preferred -consider discontinuing antiseizure drug if possibel -traditional drugs should be first choice |
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Name the first-line drugs of choice for partial seizures.
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carbamazepine phenytoin lamotrigine valproic acid oxcarbazepine |
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Name some alternative drug choices for partial seizures.
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gabapentin topiramate levetiracetam zonisamide tiagabine phenobarbital felbamate |
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Name the first-line drugs of choice for absence seizures.
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valproic acid ethosuximide |
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Name the alternative drugs for absence seizures.
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lamotrigine
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Name the first-line drugs for myoclonic seizures.
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valproic acid clonazepam |
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Name the alternative drugs for myoclonic seizures.
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lamotrigine topiramate levetiracetam |
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Name the first-line drugs for tonic-clonic seizures.
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phenytion carbamazepine valproic acid |
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Name the alternative drugs for tonic-clonic seizures.
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lamotrigine topiramate phenobarbital oxcarbazepine |
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What is the MOA for antiseizure drugs (overall)?
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-affecting ion channels (Na and Ca): prolongation of the refractory period = suppression of rapid repetitive firing in isolated neurons -augmenting inhibitory neurotransmission (GABA) -modulating excitatory neurotransmission (glutamate and aspartate) |
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Discuss the pharmacokinetics of antiseizure drugs (overall).
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absorption: usually good, bioavailabiltity 80-100% protein binding: significant for phenytoin, valproic acid and tiagabine cleared or metabolized chiefly by hepatic mechanisms (long half lives) |
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Phenytoin
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indications: "broad spectrum" MOA: reduces spread of seizure by blocking Na channels, alters neurotransmitter concentrations (GABA), may also reduce Ca influx (inhibits release of neurotransmitters) pharmacokinetics: oral good, IM not so much, highly protein bound, metabolized in liver, elimination is dose-dependent (zero-order kinetics at higher doses) dosing and admin: oral and IV, fosphenytoin is a prodrug that has increased water solubility allowing for rapid IV admin, therapeutic blood levels 10-20mcg/ml, give loading dose for status epilepticus, titrate dose individually drug-drug interactions: enteral feeding decreases absorption, displaced from protein by other highly bound drugs, induces hepatic enzymes adverse effects: dose related - nystagmus, ataxia, cognitive impairment, lethargy, seizures, coma (>20); not dose related - gingival hyperplasia, hirsutism, folic acid defic, peripheral neuropathy, hypersensitivity rxn |
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Phenobarbital/Primidone
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indications: generalized (except absence) and partial; DOC for neonatal seizures MOA: increase seizure threshold and limit spread (potentate GABA, fast Na channel inactivation), block excitatory responses via glutamate dosing and admin: phenobarb ok oral and IV, primidone is metabolized to phenobarb drug interactions: potent liver enzyme inducer pharmacokinetics: rapid and complete absorption, widely distributed, metabolized in liver, long half life adverse effects: fatigue, sedation, cognitive impairment, ataxia, slurred speech, nystagmus, paradoxical hyperactivity in children, tolerance develops to CNS probs, rare - rashes, osteomalacia, porphyria |
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Carbamazepine
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indications: gen tonic-clonic, partial and complex partial; also used for trigeminal neuralgia and some psych stuff MOA: unknown but effects similar to phenytoin (fast Na channel inactivation) dosing and admin: oral only, start low and titrate up, induces its own metabolism (aka autoinduction, results in increased dose and frequency with chronic therapy) adverse effects: diplopia, blurred vision, nystagmus, ataxia, dz, ha, thrombocytopenia, anemia, leukopenia, rashes, rarely - hepatitis, osteomalacia, cardiac conduction defects |
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Ethosuximide
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indications: DOC for generalized absence seizures MOA: unknown but does elevate seizure threshold, modulates Ca channels adverse effects: drowsiness, lethargy, dz, ha, hiccups, N/V |
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Valproic acid, Divalproex sodium
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MOA: suppresses propagation of a seizure (affects Na channels, direct membrane-stabilizing effects, may affect K channels), may also have GABAergic effects dosing and admin: or and iv adverse effects: sedation, impaired concentration, lethargy, ataxia, GI common, hepatotoxicity, thrombocytopenia, weight gain |
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Felbamate
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indication: refractory seizures and children with Lennox-Gastaut syndrome MOA: unknown, NMDA receptor blockade, inhibits glutamate adverse effects: aplastic anemia, liver failure, many interactions with other antiseizure drugs |
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Gabapentin
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indications: partial sz, chronic pain syndromes MOA: unknown, elevates human brain GABA levels, does not act on GABA receptors, modulate Ca channels dosing and admin: oral only pharmacokinetics: excreted unchanged by kidney, no sig interactions with other antisz drugs adverse effects: sedation, dz, HA, ataxia, weight gain, GI upset |
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Lamotrigine
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indications: adjunct and monotherapy for partial seizures, adjunct for tonic-clonic sz, adjunct for Lennox-Gastaut syndrome, bipolar d/o MOA: Na channel blockade, may also involve Ca channels adverse effects: sedation, ataxia, blurred vision, rashes (stevens-johnson) drug interactions: phenobarb, phenytoin and carbamazepine increase metabolism by 50%; valproic acid decreases metab by 50% |
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Topiramate
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indications: adjunct and monotherapy of partial or tonic-clonic sz, adjunct for Lennox-Gastaut syndrome, migraine prophylaxis MOA: block Na channels, potentiates GABA (on a whole new site), depresses excitatory neurotrans adverse effects: sedation, confusion, tremor, ataxia, HA, fatigue, memory probs, attention probs, nephrolithiasis, anorexia and weight loss drug-interactions: affected by other drugs that induce hepatic enzymes |
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Tiagabine
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indication: adjunctive for partial MOA: inhibits GABA reuptake adverse effects: confusion, dz, GI upset, anorexia, fatigue drug interactions: phenobarb, phenytoin, carbamazepine increase clearance |
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Oxcarbazepine
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indications: monotherapy or adjunctive therapy for partial seizures MOA: similar to carbamazepine (its an analogue of carba: prodrug) Fast Na channel inactivation adverse effects: better tolerated than carbamazepine, dizziness, drowsiness, HA, tiredness, ataxia, hyponatremia also: no autoinduction props or hepatic enzyme induction |
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Levetiracetam
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indications: adjunctive tx for partial, tonic-clonic and myoclonic sz MOA: not sure but does not involve inhibitory or excitatory neuropathways adverse effects: somnolence, asthenia, coordination difficulties, dz **adjust dose for renal dysfxn** |
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Pregabalin
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indications: adjunct for partial; neuropathic pain MOA: GABA analog adverse effects: edema, weight gain, constipation, ataxia, dz, HA, somnolence, fatigue, blurred vision, jaundice, hypersensitivity rxn, angioedema, increased CK level |
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Zonisamide
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indications: adjunctive tx of partial seizures MOA: modulates Na and Ca channels adverse effects: nausea, dz, drowsiness, nystagmus, anemia, leukopenia, kidney stones, Sulfa derivative |
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Lacosamide
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indications: adjunctive for tx of partial sz MOA: enhances slow activation of Na channels = stabilizing hyperexcitable neuronal membranes and inhibiting repetitive neuronal firing adverse effects: dz, ataxia, hypersensitivity rxn, diplopia |
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Vigabatrin
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indications: adjunctive tx for complex partial and monotherapy for infantile spams MOA: increases GABA by inhibiting GABA-transaminase adverse effects: peripheral field defects asso with retinal dysfxn (BBW) |
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Rufinamide
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indications: adjunct for Lennox-Gastaut syndrome MOA: unknown, may prolong the inactive state of Na channels adverse effects: shortened QT, ataxia, dz, somnolence, blurred vision, hypersensitivity rxn |
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What is the FDA alert associated with all antiseizure drugs?
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they must carry a warning regarding the risks of suicidal thoughts and actions
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Acetazolamide
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a miscellaneous antiseizure drug - a carbonic anhydrase inhibitor diuretic MOA: unknown tolerance to its antisz effect develops rapidly useful as adjunct |
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ACTH
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standard therapy for infantile spasms
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How do you treat status epilepticus?
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IV diazepam or lorazepam
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