Chapter 16:Anticonvulsants DH206: Pharmacology Lisa Mayo, RDH, BSDH Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.

Seizure Types for Review  Drugs most commonly used for both Gen & Partial Seizures 1)Barbiurates (Phenobarbital) 2)Phenytoin(Dilantin) 3)Carbamazepine (Tegretol) 4)Valproic acid (Depakene) 5)Primidone (Mysoline) 6)Levetiracetam (Keppra) 7)Topiramate (Topomax) 8)Zonisamide (Zonegram)  Drugs most commonly use for Partial Seizures 1)Felbamate (Felbatol) 2)Gabapentin (Neurontin) 3)Tiagabine (Gabitril) 4)Lamotrigine (Lamictal)

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Seizure Types for Review  Drugs most commonly used for Absence Seizures (petit mal) 1)Ethosuximide (Zarontin) 2)Trimethadione (Tridione) 3)Benzodiazepines: Diazepam(Valium), Clonazepam(Klonopin), Lorazepam(Ativan)  Drugs most commonly use for Status Epilepticus 1)Lorazepam(Ativan) 2)Diazepam(Valium) 3)Phenytoin (Dilantin)

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Seizure Types for Review Drugs most commonly used for Epileptic Seizures  Absence Seizures 1)Ethosuximide (Zarotin) 2)Valproic acid (Depakene) 3)Lamotigine (Lamictal)  Gen Tonic-Clonic Seizures 1)Phenytoin(Dilantin) 2)Valproic acid (Depakene) 3)Carbamazepine (Tegretol) 4)Lamotigine (Lamictal) & Topiramate(Topomax) used on kids a lot (newer drugs)  Partial Seizures 1)Phenytoin(Dilantin) 2)Valproic acid (Depakene) 3)Carbamazepine (Tegretol) 4)Lamotigine (Lamictal) & Topiramate(Topomax)

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Outline 1.Seizure Types 2.Epilepsy 3.First-generation drug 4.Second-generation drugs

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Seizure Types for Review Generalized SeizuresPartial Seizures BrainAffects both hemispheresAffects 1 hemisphere TypesAbsence (last <20sec) Tonic-Clonic (last 1-2min) Simple Complex ConsciousnessLoses consciousnessDoes NOT lose consciousness

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Epilepsy – Common CNS disorder: 1:200 people – Repeated reoccurrence of seizures – Multiple etiologies

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Anti-Epileptic Drug Therapy Treatment or control of seizures depends on types of seizures the patient experiences – Drugs for tonic-clonic not always effective for absence There are specific 1 st -line drugs One of the MOST important complications of drugs ↑ congenital defects Drugs used for seizures also are used in tx of: 1)Anxiety disorders 2)Bipolar 3)Migraine 4)Neuropathic pain

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. First-Generation Drugs FIRST GENERATION DRUGS SEZIURES USED TO TX ACTION Phenobarbital(Luminal)All except AbsenceEnhance GABA Phenytoin(Dilantin)All except AbsenceBlock Na channels Carbamazepine(Tegretol)All seizuresBlock Na channels Oxcarbazepine(Trileptal)All seizuresBlock Na channels Valproic Acid(Depakene)All seizuresBlock Na channels Enhance GABA Ethosuximide(Zarotin)Absence (generalized)Block Ca channels Clonazepam(Klonopin)Myoclonic in kidsBenzo: Enhance GABA Lorazepam(Ativan)Status epilepticusBenzo: Enhance GABA

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Phenobarbital(Luminal) – 1 st anti-epileptic drug developed – Use declining with newer drugs on the market – GABA Phenytoin(Dilantin) – 1 st line drug for all seizures EXCEPT absence – Widely used – 1 st non-sedating drug – Narrow therapeutic index – Adverse reactions: gingival enlargement, tetratogenic (pregnancy category D), vitamin deficiency (D&Folate) First Generation Drugs

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Carbamazepine(Tegretol) – Also used for bipolar, trigeminal neuralgia – Adverse effects: severe blood disorders which can lead to gingival bleeding & agranulocytosis – Blood lab tests needed for dental tx! – Metabolized by P450 enzyme system – drug interactions Erythromycin, Clarithromycin, Doxycycline Birth control CCB Warfarin Oxcarbazepine(Trileptal) – Similar to Tegretol with less side effects First Generation Drugs

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Valproic Acid(Depakene) – Many adverse effects Xerostomia Inhibit platelet aggregation GI Weight gain, hair loss Drowsiness, behavior changes, tremors 3 BLACK BOX WARNINGS 1)Severe, fatal hepatoxic rxns <2yrs 2)Tetratogenic: Pregnancy category D (neural tube defects) 3)Life-threatening pancreatitis First Generation Drugs

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. First Generation Drugs Ethosuximide (Zarontin) – Adverse effects Leukopenia ( ↓ WBC) GI Anorexia, dizziness, confusion Hiccups

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Second-Generation Drugs  Newer drugs  Less side effects because more specific sites of action SECOND GENERATION DRUGS Levetiracetam(Keppra) Tiagabine(Gabitril) Lamotrigine(Lamictal) Gabapentin(Neurotin) Pregabalin(Lyrica) Felbamate(Felbatol) Topiramate(Topamax) Zonisamide(Zonegran)

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Second-Generation Drugs Felbamate(Felbatol) Gabapentin(Neurontin)

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Felbamate(Felbatol) Action: Block Na & Ca channels Drug used when patient unresponsive to other anticonvulsants Use ONLY when benefits would outweigh the adverse effects Gabapentin(Neurotin) Only used for partial seizures (change this info in book, p.220) Action: Blocks Ca channels (change this info in book, p.220) One major advantage over the other anticonvulsants: does not affect hepatic microsomal enzymes, little drug interactions **Please update your book (p.220) with this info, book info not wrong- just outdated, we now know more about this drug then we used to 3 years ago** Second-Generation Drugs

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. All of the following drugs are anticonvulsants EXCEPT which one? a.Gabapentin(Neurontin) b.Carbamazepine(Tegretol) c.Phenytoin(Dilantin) d.Nifedipine(Procardia) e.Diazepam(Valium) f.Valproic acid(Depakene) NBQ

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. All of the following drugs are anticonvulsants EXCEPT which one? a.Gabapentin(Neurontin) b.Carbamazepine(Tegretol) c.Phenytoin(Dilantin) d.Nifedipine(Procardia)CCB e.Diazepam(Valium) f.Valproic acid(Depakene) NBQ

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Which of the following anti-epileptic drugs decreases doxycycline levels? a.Primidone b.Levetiracetam c.Phenytoin(Dilantin) d.Valproic acid(Depakene) NBQ

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Which of the following anti-epileptic drugs decreases doxycycline levels? a.Primidone b.Levetiracetam c.Phenytoin(Dilantin) d.Valproic acid(Depakene) NBQ

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Which of the following anti-epileptic drugs increases incidence of gingival enlargement? a.Phenobarbital b.Lamotrigine c.Carmazepine d.Phenytoin e.Depakene f.Ethosuximide NBQ

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Which of the following anti-epileptic drugs increases incidence of gingival enlargement? a.Phenobarbital b.Lamotrigine c.Carmazepine d.Phenytoin e.Depakene f.Ethosuximide NBQ

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Which of the following anti-epileptic drugs can also be used in the treatment of trigeminal neuralgia? a.Phenobarbital b.Lamotrigine c.Carmazepine d.Phenytoin e.Tegretol f.Primidone NBQ

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Which of the following anti-epileptic drugs can also be used in the treatment of trigeminal neuralgia? a.Phenobarbital b.Lamotrigine c.Carmazepine d.Phenytoin e.Tegretol f.Primidone NBQ