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56 Cards in this Set
- Front
- Back
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Epilepsy
Definition |
sudden, transient episodes of abnormal motor, sensory, autonomic or psychic phenomena
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Types of Seizures
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Partial Seizures
Complex partial seizures Generalized Seizures |
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Simple partial seizures
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No loss of consciousness, 20-60 seconds
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Complex partial seizures
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Impaired consciousness, 45-90 seconds
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Generalized Seizures
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Immediate loss of consciousness
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Absence Seizures
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Mild motor activity such as eye blinking
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Tonic-clonic seizures
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Major convulsions, 90 seconds or less
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Goals of Therapy
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-Control or reduce seizure frequency
-Limit side effects and drug-drug interactions -Maintain or restore quality of life |
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Partial Seizures
First Line Agents |
Carbamazepine
Phenytoin Valproic Acid |
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Generalized Tonic-Clonic Seizures
First Line Agents |
Phenytoin
carbamazepine/Oxcarbazepine Valproic Acid |
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Absence Seizures
First Line Agents |
Ethosuximide
Valproic Acid Lamotrigine |
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Myoclonic Seizures
First Line Agents |
Valproic Acid
Alternative Agents Clonazepam Zonisamide |
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Mixed seizures
Myoclonic and tonic-clonic seizures First Line Agents |
Lamotrigine
Valproic Acid |
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Antiseizure Agents
Mechanism of action (general) |
-Elevate seizure threshold
-Limit spread of abnormally discharged neurotransmitters -Stabilize cell membranes |
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Traditional Agents
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-Hydantoins
-Barbiturates: - |
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Miscellaneous Ajents:
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Carbamazepine
Valproic Acid Succinamides Benzodiazepines |
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New” Agents
(Primarily Adjunctive Treatment) |
Felbamate
Gabapentin Lamotrigine Topiramate Tiagabine, Vigabatrin Oxcarbazepine, Pregabalin Levetiracetam, Zonisamide |
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Hydantoins
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-Phenytoin (Dilantin®)
-Fosphenytoin (Cerebyx®) -MOA Limit spread of abnormally discharged NT’s and stabilize cell membranes -Block voltage dependent neuronal sodium channels |
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Hydantoins PK
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Highly protein bound
Absorption affected by particle size Therapeutic range: 10-20 mcg/ml 1-2 mcg/ml free level Liver metabolism (inducer) Michaelis-Menten kinetics |
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Michaelis-Menten Kinetics
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This kinetic model is valid only when the concentration of enzyme is much less than the concentration of substrate (i.e., enzyme concentration is the limiting factor),
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Hydantoins
Adverse Effects |
-Acute Sedation, cognitive impairment, nystagmus, ataxia
-Chronic Peripheral neuropathy, gingival hyperplasia, hirsutism, rash, bone loss -Dose dependent Drowsiness, nystagmus, diplopia, seizures |
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Barbiturates: Phenobarbital
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Trade name Luminal® Sodium
MOA Increases seizure threshold and decreases excitatory NT activity (bind to GABA receptors) -PK 50% protein bound Long half-life Liver metabolism (inducer) Therapeutic range: 15-40 mcg/ml |
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Barbiturates: Phenobarbital
Efficacy/Adverse Effects |
-Efficacy-Partial seizures & generalized tonic-clonic seizures
-Adverse Effects-Sedation, drowsiness,Depression Hepatotoxicity,Rash Hypotension and respiratory depression(IV), Hyperactivity (children) |
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Barbiturates: Primidone
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Trade name-Mysoline®
MOA-Same as phenobarbital PK-Metabolized to 2 active metabolites,Phenobarbital and phenylethylmalonamide (PEMA) AE-Similar to phenobarbital CNS depression, rash |
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Carbamazepine
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Trade names
Carbatrol®, Tegretol®, Tegretol®-XR -MOA-Limits the spread of abnormal NT discharges Blocks voltage dependent sodium channels Efficacy-Partial seizures and tonic-clonic seizures |
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Carbamazepine AE
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AE-Nausea, vomiting, diarrhea
Drowsiness, dizziness, blurred/double vision, lethargy, headache Hematologic effects Thrombocytopenia, anemia, leukopenia |
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Carbamazepine adverse effects
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Adverse Effects
Rash (10%), pruritus Steven-Johnson syndrome and toxic epidermal necrolysis Hyponatremia, fluid retention |
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Valproic Acid
Trade names Mechanism of action |
Trade names
Depacon®, Depakene®, Depakote®DR, Depakote®ER, Depakote Sprinkle® -MOA-Membrane stabilizer Increases GABA levels or inhibits degredation of GABA Blocks voltage-dependent sodium channels |
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Valproic Acid
Efficacy PK |
Efficacy
Partial & generalized seizures PK Highly protein bound Liver metabolism (inhibitor) Therapeutic range: 50-100 mcg/ml |
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Valproic Acid
Adverse Effects |
Adverse Effects
GI,Thrombocytopenia Leukopenia Increase in liver function tests (50%) Increase in ammonia level Pancreatitis CNS-Drowsiness, ataxia, tremor |
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Succinamides
Mechanism of action Efficacy PK |
Ethosuximide (Zarontin®)
MOA-Affects sodium/potassium ATPase and calcium channels Efficacy-Absence seizures PK-No protein binding Liver metabolism & renal excretion |
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Succinamides
adverse effects |
Adverse Effects
Nausea, vomiting Drowsiness, lethargy, hiccups, headaches Parkinsonian movements (chronic therapy) Rash (rare) |
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Benzodiazepines
examples, MOA |
Examples
Clonazepam (Klonopin®), Diazepam (Valium®), Lorazepam (Ativan®) Mechanism of action Enhance GABA activity |
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Benzodiazepines
PK.Adverse Effects |
PK-Liver metabolism
Lorazepam has no active metabolites Adverse Effects-Sedation Tolerance develops to major side effects |
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Felbamate
Mechanism of action PK |
Felbamate (Felbatol®)
MOA-Limits spread of abnormal NT discharge and increases seizure threshold Restricted to: Lennox-Gastaut Syndrome Severe refractory epilepsy PK-No protein binding Elimination: urine |
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Felbamate AE
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Adverse Effects
CNS,GI disturbances weight loss Aplastic anemia and hepatic failure Monitor LFT’s (weekly) and CBC (every other week) |
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Gabapentin
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Gabapentin (Neurontin®)
Mechanism of Action Limits spread and uptake of excitatory NT’s (glutamate) Increases the release of GABA PK 50-60% absorption Renally eliminated |
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Gabapentin AE
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Adverse Effects
CNS Sedation, dizziness, ataxia |
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Lamotrigine
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Lamotrigine (Lamictal®)
Mechanism of Action Limits spread and release of excitatory NT’s (glutamate) by blocking Na channels Efficacy Partial & generalized seizures PK Hepatic & renal |
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Lamotrigine AE
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Adverse Effects
Diplopia, ataxia, fatigue, somnolence Rash Especially with high doses and/or concomitant Valproic Acid therapy Steven-Johnson syndrome (rare) Improves mood |
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Topiramate
MOA |
Topiramate (Topamax®)
Mechanism of Action Potentiates GABA Antagonizes glutamate Blocks sodium channels Modulates calcium channels |
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Topiramate
Adverse effects |
Adverse effects
Parasthesias, cognitive dysfunction, Weight loss GI,Kidney stones, Acute myopia and glaucoma |
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Tiagabine(Gabitril®)
Mechanism of Action Efficacy, PK |
Tiagabine
MOA,Inhibits GABA uptake by presynaptic neurons-prolonging GABA effect Efficacy Partial seizures PK, Highly protein bound (96%) Liver metabolism |
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Tiagabine AE
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Adverse Effects
Dizziness, sedation, HA, mild memory impairment,Depression GI |
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Oxcarbazepine(Trileptal®)
MOA Efficacy |
MOA-Similar to Carbamazepine
Limits spread of abnormally discharged NT’s through voltage dependent sodium channels Efficacy-Partial seizures |
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Oxcarbazepine AE
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CNS
Ataxia, nervousness, headache, dizziness, vertigo GI,Hyponatremia in Elderly and those receiving high doses |
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Levetiracetam
MOA, efficacy, PK |
MOA-Unknown,
Efficacy-Partial seizures PK-Protein binding <10% Renally eliminated |
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Levetiracetam AE
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Adverse Effects
CNS Fatigue, altered behavior/coordination, anxiety Infection |
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Zonisamide (Zonegran®)
Mechanism of Action Efficacy |
MOA-Inhibits sodium and calcium channels
Efficacy-Partial seizures Contraindicated in patients with allergy to sulfonamides |
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Zonisamide AE
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Somnolence, dizziness, ataxia, difficulty concentrating, confusion
Nausea, anorexia Hematologic effects Anemia and leukocytopenia |
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Pregabalin
MOA, Efficacy |
Lyrica®
MOA-Inhibits excitatory NT release Efficacy-Partial seizures Adverse Effects CNS,Xerostomia |
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Vigabatrin
MOA Efficacy, T1 |
Sabril®,MOA-Increases GABA levels
Efficacy-Partial & generalized seizures (may exacerbate absence) Half-life: 5-8 hours |
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Vigabatrin AE
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Fatigue
Headache Dizziness, drowsiness Agitation |
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Antiepileptic Drug Interactions
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-Carbamazepine and Lamotrigine
-Phenytoin and Topiramate -Phenytoin and Oxcarbazepine -Lamotrigine and Valproic Acid -Phenytoin and Valproic Acid -Carbamazepine and Valproic Acid -Felbamate and Valproic Acid |
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Teratogenicity
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Phenytoin
Carbamazepine Valproic Acid Phenobarbital |
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Pregnancy
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Increases seizures in 35% of epileptic women
Older agents are category D Newer agents are category C Monitor drug levels Replete folic acid and vitamin K |
