Chapter_024

Report
Chapter 24
Drugs for Epilepsy
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Definition of Epilepsy
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Group of disorders characterized by
excessive excitability of neurons in the CNS
Can produce a variety of symptoms ranging
from brief periods of unconsciousness to
violent convulsions
May also cause problems with learning,
memory, and mood
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Seizure: Generation
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Initiated by synchronous, high-frequency
discharge from a group of hyperexcitable
neurons called a focus
Focus may result from
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Congenital defects
Hypoxia at birth
Head trauma
Brain infection
Stroke
Cancer
Genetic disorders
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Seizures: Types
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Partial (focal) seizures
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Simple partial
Complex partial
Secondarily generalized
Generalized seizures
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Tonic-clonic (grand mal)
Absence (petit mal)
Atonic
Myoclonic
Status epilepticus (SE)
Febrile
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Antiepileptic Drugs
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Effects
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Suppress discharge of neurons within a seizure
focus
Suppress propagation of seizure activity from the
focus to other areas of the brain
Mechanisms of action
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Suppression of sodium influx
Suppression of calcium influx
Antagonism of glutamate
Potentiation of GABA
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Mixed Seizures:
Lennox-Gastaut Syndrome
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Severe form of epilepsy that usually develops
during the preschool years
Developmental delay and a mixture of partial
and generalized seizures
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Goal of Treatment
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Reduce seizures to a level that allows the
patient to live as normal a life as possible
Balance the desire for complete seizure
control with the acceptability of side effects
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Epilepsy: Therapeutic Considerations
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Treatment goal and treatment options
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Neurosurgery (best success rate)
Vagal nerve stimulation
Ketogenic diet
Diagnosis and drug selection
Drug evaluation
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Epilepsy: Therapeutic Considerations
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Monitoring plasma drug levels
Promoting patient adherence
Withdrawing antiepileptic drugs
Suicide risk – antiepileptic drugs
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Classification of Antiepileptic Drugs
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Two major categories
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Traditional antiepileptic drugs (AEDs)
• Phenytoin, carbamazepine, valproic acid, and others
Newer AEDs
• Oxcarbazepine, gabapentin, zonisamide, and others
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Phenytoin (Dilantin)
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Partial and tonic-clonic seizures
Mechanism of action: selective inhibition of
sodium channels
Varied oral absorption
Half-life: 8 to 60 hours
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Fig. 24-1. Relationship between dose and plasma level for
phenytoin compared with most other drugs.
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Phenytoin (Dilantin)
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Adverse effects
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Nystagmus
Sedation
Ataxia
Diplopia
 Cognitive impairment
 Gingival hyperplasia
 Skin rash
 Effects in pregnancy
 Cardiovascular effects
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Phenytoin (Dilantin)
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Drug interactions
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Decreases the effects of oral contraceptives,
warfarin, and glucocorticoids
Increases levels of diazepam, isoniazid,
cimetidine, alcohol, and valproic acid
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Carbamazepine (Tegretol)
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Uses
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Epilepsy
Bipolar disorder
Trigeminal and glossopharyngeal neuralgias
Adverse effects
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Neurologic effects: nystagmus, ataxia
Hematologic effects: leukopenia, anemia,
thrombocytopenia
Birth defects
Hypo-osmolarity
Dermatologic effects: rash, photosensitivity
reactions
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Valproic Acid (Depakene,
Depakote, Depacon)
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Uses
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Seizure disorders
Bipolar disorder
Migraine
Adverse effects
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GI effects
Hepatotoxicity: liver failure
Pancreatitis
Teratogenic effects
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Ethosuximide
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Drug of choice for absence seizures
Generally devoid of significant adverse
effects and interactions
Initially may cause drowsiness, dizziness, and
lethargy
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Phenobarbital
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Uses
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Epilepsy (partial and generalized tonic-clonic
seizures)
Promotes sleep and sedation
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Newer Antiepileptic Drugs
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Gabapentin
Lamotrigine
Levetiracetam
Oxcarbazepine
Tiagabine
Topiramate
Zonisamide
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Management of Generalized
Convulsive Status Epilepticus
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Continuous series of tonic-clonic seizures
lasting 20 to 30 minutes
Goals of treatment
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Maintain ventilation
Correct hypoglycemia
Terminate seizures
• IV benzodiazepines (lorazepam or diazepam)
Initiate or continue long-term suppression drugs
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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