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56 Cards in this Set

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Epilepsy
Definition
sudden, transient episodes of abnormal motor, sensory, autonomic or psychic phenomena
Types of Seizures
Partial Seizures
Complex partial seizures
Generalized Seizures
Simple partial seizures
No loss of consciousness, 20-60 seconds
Complex partial seizures
Impaired consciousness, 45-90 seconds
Generalized Seizures
Immediate loss of consciousness
Absence Seizures
Mild motor activity such as eye blinking
Tonic-clonic seizures
Major convulsions, 90 seconds or less
Goals of Therapy
-Control or reduce seizure frequency
-Limit side effects and drug-drug interactions
-Maintain or restore quality of life
Partial Seizures
First Line Agents
Carbamazepine
Phenytoin
Valproic Acid
Generalized Tonic-Clonic Seizures
First Line Agents
Phenytoin
carbamazepine/Oxcarbazepine
Valproic Acid
Absence Seizures
First Line Agents
Ethosuximide
Valproic Acid
Lamotrigine
Myoclonic Seizures
First Line Agents
Valproic Acid
Alternative Agents
Clonazepam
Zonisamide
Mixed seizures
Myoclonic and tonic-clonic seizures
First Line Agents
Lamotrigine
Valproic Acid
Antiseizure Agents
Mechanism of action (general)
-Elevate seizure threshold
-Limit spread of abnormally discharged
neurotransmitters
-Stabilize cell membranes
Traditional Agents
-Hydantoins
-Barbiturates:
-
Miscellaneous Ajents:
Carbamazepine
Valproic Acid
Succinamides
Benzodiazepines
New” Agents
(Primarily Adjunctive Treatment)
Felbamate
Gabapentin
Lamotrigine
Topiramate
Tiagabine, Vigabatrin
Oxcarbazepine, Pregabalin
Levetiracetam, Zonisamide
Hydantoins
-Phenytoin (Dilantin®)
-Fosphenytoin (Cerebyx®)
-MOA Limit spread of abnormally discharged NT’s and stabilize cell membranes
-Block voltage dependent neuronal sodium channels
Hydantoins PK
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
Michaelis-Menten Kinetics
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),
Hydantoins
Adverse Effects
-Acute Sedation, cognitive impairment, nystagmus, ataxia
-Chronic Peripheral neuropathy, gingival hyperplasia, hirsutism, rash, bone loss
-Dose dependent Drowsiness, nystagmus, diplopia, seizures
Barbiturates: Phenobarbital
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
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)
Barbiturates: Primidone
Trade name-Mysoline®
MOA-Same as phenobarbital
PK-Metabolized to 2 active metabolites,Phenobarbital and phenylethylmalonamide (PEMA)
AE-Similar to phenobarbital
CNS depression, rash
Carbamazepine
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
Carbamazepine AE
AE-Nausea, vomiting, diarrhea
Drowsiness, dizziness, blurred/double vision, lethargy, headache
Hematologic effects
Thrombocytopenia, anemia, leukopenia
Carbamazepine adverse effects
Adverse Effects
Rash (10%), pruritus
Steven-Johnson syndrome and toxic epidermal necrolysis
Hyponatremia, fluid retention
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
Valproic Acid
Efficacy
PK
Efficacy
Partial & generalized seizures
PK
Highly protein bound
Liver metabolism (inhibitor)
Therapeutic range: 50-100 mcg/ml
Valproic Acid
Adverse Effects
Adverse Effects
GI,Thrombocytopenia
Leukopenia
Increase in liver function tests (50%)
Increase in ammonia level
Pancreatitis
CNS-Drowsiness, ataxia, tremor
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
Succinamides
adverse effects
Adverse Effects
Nausea, vomiting
Drowsiness, lethargy, hiccups, headaches
Parkinsonian movements (chronic therapy)
Rash (rare)
Benzodiazepines
examples, MOA
Examples
Clonazepam (Klonopin®), Diazepam (Valium®), Lorazepam (Ativan®)
Mechanism of action
Enhance GABA activity
Benzodiazepines
PK.Adverse Effects
PK-Liver metabolism
Lorazepam has no active metabolites
Adverse Effects-Sedation
Tolerance develops to major side effects
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
Felbamate AE
Adverse Effects
CNS,GI disturbances
weight loss
Aplastic anemia and hepatic failure
Monitor LFT’s (weekly) and CBC (every other week)
Gabapentin
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
Gabapentin AE
Adverse Effects
CNS
Sedation, dizziness, ataxia
Lamotrigine
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
Lamotrigine AE
Adverse Effects
Diplopia, ataxia, fatigue, somnolence
Rash
Especially with high doses and/or concomitant Valproic Acid therapy
Steven-Johnson syndrome (rare)
Improves mood
Topiramate
MOA
Topiramate (Topamax®)
Mechanism of Action
Potentiates GABA
Antagonizes glutamate
Blocks sodium channels
Modulates calcium channels
Topiramate
Adverse effects
Adverse effects
Parasthesias, cognitive dysfunction, Weight loss
GI,Kidney stones,
Acute myopia and glaucoma
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
Tiagabine AE
Adverse Effects
Dizziness, sedation, HA, mild memory impairment,Depression
GI
Oxcarbazepine(Trileptal®)
MOA Efficacy
MOA-Similar to Carbamazepine
Limits spread of abnormally discharged NT’s through voltage dependent sodium channels
Efficacy-Partial seizures
Oxcarbazepine AE
CNS
Ataxia, nervousness, headache, dizziness, vertigo
GI,Hyponatremia in
Elderly and those receiving high doses
Levetiracetam
MOA, efficacy, PK
MOA-Unknown,
Efficacy-Partial seizures
PK-Protein binding <10%
Renally eliminated
Levetiracetam AE
Adverse Effects
CNS
Fatigue, altered behavior/coordination, anxiety
Infection
Zonisamide (Zonegran®)
Mechanism of Action
Efficacy
MOA-Inhibits sodium and calcium channels
Efficacy-Partial seizures
Contraindicated in patients with allergy to sulfonamides
Zonisamide AE
Somnolence, dizziness, ataxia, difficulty concentrating, confusion
Nausea, anorexia
Hematologic effects
Anemia and leukocytopenia
Pregabalin
MOA, Efficacy
Lyrica®
MOA-Inhibits excitatory NT release
Efficacy-Partial seizures
Adverse Effects
CNS,Xerostomia
Vigabatrin
MOA Efficacy, T1
Sabril®,MOA-Increases GABA levels
Efficacy-Partial & generalized seizures (may exacerbate absence)
Half-life: 5-8 hours
Vigabatrin AE
Fatigue
Headache
Dizziness, drowsiness
Agitation
Antiepileptic Drug Interactions
-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
Teratogenicity
Phenytoin
Carbamazepine
Valproic Acid
Phenobarbital
Pregnancy
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