1. Chapter 16: Anticonvulsants Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.

2. 2 Chapter 16 Outline  Anticonvulsants  Epilepsy Generalized seizures Generalized seizures Partial (focal) seizures Partial (focal) seizures  Drug therapy of patients with epilepsy General adverse reactions to anticonvulsant agents General adverse reactions to anticonvulsant agents Carbamazepine Carbamazepine Valproate Valproate Phenobarbital Phenobarbital Phenytoin Phenytoin Miscellaneous anticonvulsant agents Miscellaneous anticonvulsant agents New anticonvulsant agents New anticonvulsant agentscont’d…

3. 3Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Chapter 16 Outline  Dental treatment of the patient with epilepsy  Nonseizure uses of anticonvulsants Neurologic pain Neurologic pain Psychiatric use Psychiatric use

4. 4Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Epilepsy  Haveles (pp. 213-214)  A group of disorders involving a chronic stereotyped recurrent attack of involuntary behavior or experience or changes in neurologic function caused by electrical activity in the brain that can be recorded via an electroencephalogram (EEG)  Can be localized or generalized cont’d…

5. 5Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Epilepsy  Each episode is termed a seizure  The seizure can be accompanied by motor activity such as convulsions or by other neurologic changes  Seizure disorders are estimated to affect approximately 1% of the population  Many etiologies: infection, trauma, toxicity to exogenous agents, genetic or birth influences, circulatory disturbances, metabolic or nutritional alterations, neoplasms, hereditary factors, fevers, and degenerative diseases  Most patients have idiopathic epilepsy; the cause is unknown cont’d…

6. 6Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Epilepsy  Haveles (pp. 213-214) (Fig. 16-1; Box 16-1)  The International Classification of Epileptic Seizures divides seizures into two major groups and a miscellaneous group  The two major groups are partial and generalized seizures Partial seizures are divided into simple and complex attacks Partial seizures are divided into simple and complex attacks The most common generalized seizures are tonic-clonic and absence seizures The most common generalized seizures are tonic-clonic and absence seizurescont’d…

7. 7Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Generalized Seizures  Haveles (p. 213)  Consciousness is lost in both absence and tonic-clonic seizures  Little movement occurs in absence seizures; major movement of large muscle groups occurs in tonic-clonic seizures  The patient may experience an aura before the onset of the seizure  May be characterized by numbness, nausea, or unusual sensitivity to light, odor, or sound

8. 8Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Absence Seizures (Petit Mal)  Haveles (p. 214)  Symptoms of absence seizures include a brief loss of consciousness with characteristic EEG waves and little movement  Absence seizures usually begin during childhood and disappear during middle age  The patient is usually unaware that these seizures are occurring, and body tone is not lost  No aura or postictal state occurs

9. 9Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Tonic-Clonic Seizures  Haveles (p. 214)  Generalized tonic-clonic seizures include longer periods of loss of consciousness and major motor activity of the large muscles of the body  The seizure begins by the body becoming rigid and the patient falling to the floor  Tonic rigidity is followed by clonic jerking of the face, limbs, and body  Finally, the patient becomes limp and comatose  Consciousness gradually returns with postictal confusion, headache, and drowsiness

10. 10Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Status Epilepticus  Haveles (p. 214)  Status epilepticus seizures are continuous tonic- clonic seizures that last longer than 30 minutes or recur before the end of the postictal period of the previous seizure  Status epilepticus seizures represent an emergency situation  Rapid therapy is required, especially if the seizure activity has produced hypoxia  Parenteral benzodiazepines, such as diazepam, are the drugs of choice to control this type of seizure

11. 11Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Partial (Focal) Epilepsies  Haveles (pp. 213-214)  Partial epilepsies involve activation of only part of the brain, and the location of the activity determines the clinical manifestations  The attack is called an elementary (simple) partial attack when consciousness is not impaired  The attack is termed a complex partial attack when consciousness is impaired Complex seizures are also called psychomotor or temporal-lobe seizures Complex seizures are also called psychomotor or temporal-lobe seizures

12. 12Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Drug Therapy of Patients with Epilepsy  Haveles (p. 215) (Fig. 16-2; Box 16-2)  Drug therapy has variable efficacy, from complete control of all seizures to reducing the frequency of seizures  Anticonvulsant agents may be used singly or in combination  These agents are central nervous system (CNS) depressants that attempt to prevent epileptic seizures without causing excessive drowsiness  These agents prevent the spread of abnormal electric discharges in the brain

13. 13Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. General Adverse Reactions to Anticonvulsant Agents  Haveles (pp. 215-217)  Anticonvulsants have a narrow therapeutic index  Most anticonvulsants stimulate liver microsomal enzymes that metabolize themselves, other anticonvulsants, and other drugs that the patient may be taking  The metabolism of anticonvulsants can saturate the liver microsomal enzymes  At some point, when the enzymes become saturated, the metabolism converts to zero-order kinetics, and the drug level can increase abruptly

14. 14Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Central Nervous System Depression  Haveles (pp. 215-216)  Depressed CNS function is a common side effect of the anticonvulsant agents  Tolerance often develops to these effects, whereas the anticonvulsant effect persists  Behavior alterations are reported to include both hyperactivity and sedation

15. 15Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Gastrointestinal Distress  Haveles (p. 216)  Gastrointestinal (GI) distress, including anorexia, nausea, and vomiting, can occur with most anticonvulsants  Effects can be minimized by taking the drug with food

16. 16Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Drug Interactions  Haveles (pp. 216-217)  The most important drug interaction involves stimulation of the hepatic microsomal enzymes  Inducing these enzymes results in a reduction in the blood level of the affected drugs  Drug interactions with anticonvulsants are more significant than with other drug groups because of their narrow therapeutic indexes cont’d…

17. 17Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Drug Interactions  Haveles (p. 217)  Idiosyncratic reactions  Dermatologic side effects: rash, Stevens-Johnson syndrome, exfoliative dermatitis, and erythema multiforme  Drug-induced systemic lupus erythematosus and hematologic effects have been reported  Teratogenicity/growth  Several interactions have been implicated in production of fetal anomalies  Associated with alteration in growth  Withdrawal  Abrupt withdrawal can precipitate seizures  Other interactions  Suppression of antidiuretic hormone

18. 18Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Carbamazepine  Haveles (pp. 217-218 )  Related to tricyclic antidepressants  Used in the treatment of trigeminal neuralgia; also indicated in treatment of bipolar depression

19. 19Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Pharmacologic Effects of Carbamazepine  An anticonvulsant, anticholinergic, antidepressant, sedative, and muscle relaxant  Blocks sodium channels, which blocks the propagation of nerve impulses

20. 20Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Adverse Reactions of Carbamazepine  Haveles (p. 217)  CNS effects  Can produce dizziness, vertigo, drowsiness, fatigue, ataxia, confusion, headache, nystagmus, and visual (diplopia) and speech disturbances  GI effects  Side effects include nausea, vomiting, and gastric distress  Hematologic effects  Fatal blood dyscrasias have been reported cont’d…

21. 21Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Adverse Reactions of Carbamazepine  Haveles (p. 217)  Dermatologic effects  Rashes, urticaria, photosensitivity reactions, and altered skin pigmentation can occur  Oral effects  Dry mouth, glossitis, and stomatitis can sometimes be seen in patients taking carbamazepine  Other effects  Cardiovascular side effects include congestive heart failure and alterations in blood pressure  Abnormal liver function tests and cholestatic jaundice have been reported

22. 22Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Drug Interactions of Carbamazepine  Haveles (pp. 217-218) (Box 16-3)  Carbamazepine can induce liver microsomal enzymes  It can decrease the effect of doxycycline, warfarin, theophylline, and oral contraceptives  Effects may be increased by erythromycin, isoniazid, propoxyphene, and calcium channel blockers

23. 23Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Valproate  Haveles (p. 218)  Valproates are a group of anticonvulsants that are not structurally related to any other agents  The mechanism of action may be its effect on sodium and potassium channels, a reduction in aspartate levels, or an increase in the inhibitory neurotransmitter γ-aminobutyric acid (GABA)

24. 24Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Adverse Reactions of Valproate  Haveles (p. 218)  GI effects: the most frequent side effects are indigestion, nausea, and vomiting  CNS effects: sedation and drowsiness have been reported  Hepatotoxicity: the idiosyncratic toxicity of valproate  Bleeding: bleeding time may be prolonged  Teratogenicity: may increase birth defects

25. 25Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Drug Interactions of Valproate  Haveles (p. 218) (Box 16-4)  Other drugs that are CNS depressants can have an additive CNS depressant effect when used with valproate  Valproate inhibits the metabolism of phenobarbital, producing excessive sedation  It also has been associated with drug interactions with phenytoin, resulting in decreased valproate action and increased phenytoin action  It can affect bleeding

26. 26Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Phenobarbital  Haveles (p. 218)  The most common barbiturate used in treatment of epilepsy  Used to treat tonic-clonic and partial seizures  Sedation is the most common side effect  Skin reactions occur in 1% to 3% of patients

27. 27Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Phenytoin  Haveles (pp. 218-220)  Used to treat both tonic-clonic and partial seizures with complex symptoms  Has been used to treat trigeminal neuralgia  Also has quinidine-like antiarrhythmic properties

28. 28Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Adverse Reactions of Phenytoin  Haveles (p. 219)  GI effects  Reactions are not uncommon  CNS effects  Mental confusion, nystagmus, ataxia, slurred speech, blurred vision, diplopia, amblyopia, dizziness, and insomnia  Dermatologic effects  Skin reactions range from rash to exfoliative dermatitis, lupus erythematosus, or Stevens-Johnson syndrome  Some patients have hypertrichosis on the trunk and face cont’d…

29. 29Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Adverse Reactions of Phenytoin  Haveles (p. 219) (Fig. 6-3)  Vitamin deficiency  Deficiency may involve vitamin D and folate  Osteomalacia may result from interference with vitamin D metabolism  Teratogenicity/growth  Maternal ingestion of phenytoin is associated with fetal hydantoin syndrome  Includes craniofacial anomalies, microcephaly, nail or digit hypoplasia, limb defects, growth deficiency, and mental retardation cont’d…

30. 30Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Adverse Reactions of Phenytoin  Haveles (pp. 219-220)  Gingival enlargement  Occurs in approximately 50% of all chronic users  Symptoms  Often begin as a painless enlargement of the gingival margin  With time, the interproximal papillae become involved and finally coalesce to cover even the occlusal surfaces of the teeth  The better the patient’s oral hygiene is, the less likely the lesions are to occur or the less severe they will be cont’d…

31. 31Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Adverse Reactions of Phenytoin  Haveles (p. 220) (Box 16-5)  Etiology  The cause of phenytoin gingival enlargement is unknown  Management: some possible alternatives include the following:  Choose another antiepileptic drug  Discontinue phenytoin  Improve oral hygiene  Consider gingivectomy  Consider other drugs

32. 32Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Miscellaneous Anticonvulsant Agents  Haveles (p. 220)  Ethosuximide  The drug of choice for the treatment of absence seizures  Its mechanism of action may involve inhibiting the T- type calcium channels  GI adverse effects: anorexia, gastric upset, cramps, pain, diarrhea, and nausea and vomiting  CNS adverse effects: drowsiness, hyperactivity, headache, and hiccups cont’d…

33. 33Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Miscellaneous Anticonvulsant Agents  Haveles (p. 220)  Benzodiazepines  Clonazepam is used as an adjunct to treat absence seizures not responsive to ethosuximide  Drowsiness and ataxia occur often  Behavioral disturbances and adverse neurologic effects can occur  Other side effects reported relate to the GI tract and to the dermatologic and hematologic systems

34. 34Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. New Anticonvulsant Agents  Haveles (p. 220) (Table 16-2)  Felbamate  A newer anticonvulsant that has been associated with serious toxicities  Aplastic anemia and acute hepatic failure have been reported  This agent should be reserved for use only if the seizures are refractory to other anticonvulsant agents cont’d…

35. 35Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. New Anticonvulsant Agents  Haveles (p. 221) (Table 16-2)  Gabapentin  Effective as an adjunct against partial and generalized tonic-clonic seizures  Its mechanism of action is unknown  CNS effects: somnolence, dizziness, tremor, and ataxia  Gastric complaints: dyspepsia, nausea, and vomiting  One major advantage over the other anticonvulsants is that it is not metabolized

36. 36Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Dental Treatment of the Patient with Epilepsy  Haveles (p. 221)  The dental team should not treat a patient who has a history of seizure disorders without reviewing the management of the patient with epilepsy, including the procedures for handling a patient experiencing tonic-clonic seizures  Management should include moving the patient to the floor if possible, tilting the patient’s head to one side to prevent aspiration, and removing objects from the patient’s mouth before the seizure to prevent fractured teeth

37. 37Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Nonseizure Uses of Anticonvulsants  Haveles (p. 221)  Neurologic Pain  Several anticonvulsants are used to manage chronic pain syndromes  Psychiatric Use  Carbamazepine, valproic acid, clonazepam, and gabapentin have been used in the treatment of certain mental disorders  They can be used to “level out” (stabilize) the mood in patients with bipolar disorder