1. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 24 Drugs for Epilepsy

2. 2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Definition of Epilepsy  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

3. 3Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Seizure: Generation  Initiated by synchronous, high-frequency discharge from a group of hyperexcitable neurons called a focus  Focus may result from  Congenital defects  Hypoxia at birth  Head trauma  Brain infection  Stroke  Cancer  Genetic disorders

4. 4Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Seizures: Types  Partial (focal) seizures  Simple partial  Complex partial  Secondarily generalized  Generalized seizures  Tonic-clonic (grand mal)  Absence (petit mal)  Atonic  Myoclonic  Status epilepticus (SE)  Febrile

5. 5Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Antiepileptic Drugs  Effects  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  Suppression of sodium influx  Suppression of calcium influx  Antagonism of glutamate  Potentiation of GABA

6. 6Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Mixed Seizures: Lennox-Gastaut Syndrome  Severe form of epilepsy that usually develops during the preschool years  Developmental delay and a mixture of partial and generalized seizures

7. 7Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Goal of Treatment  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

8. 8Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Epilepsy: Therapeutic Considerations  Treatment goal and treatment options  Neurosurgery (best success rate)  Vagal nerve stimulation  Ketogenic diet  Diagnosis and drug selection  Drug evaluation

9. 9Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Epilepsy: Therapeutic Considerations  Monitoring plasma drug levels  Promoting patient adherence  Withdrawing antiepileptic drugs  Suicide risk – antiepileptic drugs

10. 10Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Classification of Antiepileptic Drugs  Two major categories  Traditional antiepileptic drugs (AEDs) Phenytoin, carbamazepine, valproic acid, and others Phenytoin, carbamazepine, valproic acid, and others  Newer AEDs Oxcarbazepine, gabapentin, zonisamide, and others Oxcarbazepine, gabapentin, zonisamide, and others

11. 11Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Phenytoin (Dilantin)  Partial and tonic-clonic seizures  Mechanism of action: selective inhibition of sodium channels  Varied oral absorption  Half-life: 8 to 60 hours

12. 12Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Fig. 24-1. Relationship between dose and plasma level for phenytoin compared with most other drugs.

13. 13Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Phenytoin (Dilantin)  Adverse effects  Nystagmus  Sedation  Ataxia  Diplopia  Cognitive impairment  Gingival hyperplasia  Skin rash  Effects in pregnancy  Cardiovascular effects

14. 14Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Phenytoin (Dilantin)  Drug interactions  Decreases the effects of oral contraceptives, warfarin, and glucocorticoids  Increases levels of diazepam, isoniazid, cimetidine, alcohol, and valproic acid

15. 15Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Carbamazepine (Tegretol)  Uses  Epilepsy  Bipolar disorder  Trigeminal and glossopharyngeal neuralgias  Adverse effects  Neurologic effects: nystagmus, ataxia  Hematologic effects: leukopenia, anemia, thrombocytopenia  Birth defects  Hypo-osmolarity  Dermatologic effects: rash, photosensitivity reactions

16. 16Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Valproic Acid (Depakene, Depakote, Depacon)  Uses  Seizure disorders  Bipolar disorder  Migraine  Adverse effects  GI effects  Hepatotoxicity: liver failure  Pancreatitis  Teratogenic effects

17. 17Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Ethosuximide  Drug of choice for absence seizures  Generally devoid of significant adverse effects and interactions  Initially may cause drowsiness, dizziness, and lethargy

18. 18Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Phenobarbital  Uses  Epilepsy (partial and generalized tonic-clonic seizures)  Promotes sleep and sedation

19. 19Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Newer Antiepileptic Drugs  Gabapentin  Lamotrigine  Levetiracetam  Oxcarbazepine  Tiagabine  Topiramate  Zonisamide

20. 20Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Management of Generalized Convulsive Status Epilepticus  Continuous series of tonic-clonic seizures lasting 20 to 30 minutes  Goals of treatment  Maintain ventilation  Correct hypoglycemia  Terminate seizures IV benzodiazepines (lorazepam or diazepam) IV benzodiazepines (lorazepam or diazepam)  Initiate or continue long-term suppression drugs