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

Chapter 16:Chapter 16:

AnticonvulsantsAnticonvulsants

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.

22Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.

Chapter 16 OutlineChapter 16 Outline

AnticonvulsantsAnticonvulsants EpilepsyEpilepsy

• Generalized seizuresGeneralized seizures• Partial (focal) seizuresPartial (focal) seizures

Drug therapy of patients with epilepsyDrug therapy of patients with epilepsy• General adverse reactions to anticonvulsant agentsGeneral adverse reactions to anticonvulsant agents• CarbamazepineCarbamazepine• ValproateValproate• PhenobarbitalPhenobarbital• PhenytoinPhenytoin• Miscellaneous anticonvulsant agentsMiscellaneous anticonvulsant agents• New anticonvulsant agentsNew anticonvulsant agents

cont’d…cont’d…


Chapter 16 OutlineChapter 16 Outline

Dental treatment of the patient with epilepsyDental treatment of the patient with epilepsy Nonseizure uses of anticonvulsantsNonseizure uses of anticonvulsants

• Neurologic painNeurologic pain

• Psychiatric usePsychiatric use


EpilepsyEpilepsy

Haveles (pp. 213-214)Haveles (pp. 213-214) A group of disorders involving a chronic A group of disorders involving a chronic

stereotyped recurrent attack of involuntary stereotyped recurrent attack of involuntary behavior or experience or changes in behavior or experience or changes in neurologic function caused by electrical neurologic function caused by electrical activity in the brain that can be recorded via activity in the brain that can be recorded via an electroencephalogram (EEG)an electroencephalogram (EEG) Can be localized or generalizedCan be localized or generalized



EpilepsyEpilepsy

Each episode is termed a Each episode is termed a seizureseizure The seizure can be accompanied by motor activity such The seizure can be accompanied by motor activity such

as convulsions or by other neurologic changesas convulsions or by other neurologic changes Seizure disorders are estimated to affect Seizure disorders are estimated to affect

approximately 1% of the populationapproximately 1% of the population Many etiologies: infection, trauma, toxicity to exogenous Many etiologies: infection, trauma, toxicity to exogenous

agents, genetic or birth influences, circulatory agents, genetic or birth influences, circulatory disturbances, metabolic or nutritional alterations, disturbances, metabolic or nutritional alterations, neoplasms, hereditary factors, fevers, and degenerative neoplasms, hereditary factors, fevers, and degenerative diseasesdiseases

Most patients have idiopathic epilepsy; the cause is Most patients have idiopathic epilepsy; the cause is unknownunknown



EpilepsyEpilepsy

Haveles (pp. 213-214) (Fig. 16-1; Box 16-1)Haveles (pp. 213-214) (Fig. 16-1; Box 16-1) The International Classification of Epileptic The International Classification of Epileptic

Seizures divides seizures into two major Seizures divides seizures into two major groups and a miscellaneous groupgroups and a miscellaneous group The two major groups are partial and generalized The two major groups are partial and generalized

seizuresseizures• Partial seizures are divided into simple and complex Partial seizures are divided into simple and complex

attacksattacks

• The most common generalized seizures are tonic-clonic The most common generalized seizures are tonic-clonic and absence seizures and absence seizures



Generalized SeizuresGeneralized Seizures

Haveles (p. 213)Haveles (p. 213) Consciousness is lost in both absence and Consciousness is lost in both absence and

tonic-clonic seizurestonic-clonic seizures Little movement occurs in absence seizures; major Little movement occurs in absence seizures; major

movement of large muscle groups occurs in tonic-movement of large muscle groups occurs in tonic-clonic seizuresclonic seizures

The patient may experience an aura before The patient may experience an aura before the onset of the seizurethe onset of the seizure May be characterized by numbness, nausea, or May be characterized by numbness, nausea, or

unusual sensitivity to light, odor, or soundunusual sensitivity to light, odor, or sound


Absence Seizures (Petit Mal)Absence Seizures (Petit Mal)

Haveles (p. 214)Haveles (p. 214) Symptoms of absence seizures include a Symptoms of absence seizures include a

brief loss of consciousness with characteristic brief loss of consciousness with characteristic EEG waves and little movementEEG waves and little movement Absence seizures usually begin during childhood Absence seizures usually begin during childhood

and disappear during middle ageand disappear during middle age The patient is usually unaware that these seizures The patient is usually unaware that these seizures

are occurring, and body tone is not lostare occurring, and body tone is not lost No aura or postictal state occursNo aura or postictal state occurs


Tonic-Clonic SeizuresTonic-Clonic Seizures

Haveles (p. 214)Haveles (p. 214) Generalized tonic-clonic seizures include Generalized tonic-clonic seizures include

longer periods of loss of consciousness and longer periods of loss of consciousness and major motor activity of the large muscles of the major motor activity of the large muscles of the bodybody The seizure begins by the body becoming rigid and The seizure begins by the body becoming rigid and

the patient falling to the floorthe patient falling to the floor Tonic rigidity is followed by clonic jerking of the Tonic rigidity is followed by clonic jerking of the

face, limbs, and bodyface, limbs, and body Finally, the patient becomes limp and comatoseFinally, the patient becomes limp and comatose Consciousness gradually returns with postictal Consciousness gradually returns with postictal

confusion, headache, and drowsinessconfusion, headache, and drowsiness


Status EpilepticusStatus Epilepticus

Haveles (p. 214)Haveles (p. 214) Status epilepticus seizures are continuous tonic-Status epilepticus seizures are continuous tonic-

clonic seizures that last longer than 30 minutes or clonic seizures that last longer than 30 minutes or recur before the end of the postictal period of the recur before the end of the postictal period of the previous seizureprevious seizure Status epilepticus seizures represent an emergency Status epilepticus seizures represent an emergency

situationsituation Rapid therapy is required, especially if the seizure Rapid therapy is required, especially if the seizure

activity has produced hypoxiaactivity has produced hypoxia Parenteral benzodiazepines, such as diazepam, are the Parenteral benzodiazepines, such as diazepam, are the

drugs of choice to control this type of seizuredrugs of choice to control this type of seizure


Partial (Focal) EpilepsiesPartial (Focal) Epilepsies

Haveles (pp. 213-214)Haveles (pp. 213-214) Partial epilepsies involve activation of only Partial epilepsies involve activation of only

part of the brain, and the location of the part of the brain, and the location of the activity determines the clinical manifestationsactivity determines the clinical manifestations The attack is called an elementary (simple) partial The attack is called an elementary (simple) partial

attack when consciousness is not impairedattack when consciousness is not impaired The attack is termed a complex partial attack The attack is termed a complex partial attack

when consciousness is impairedwhen consciousness is impaired• Complex seizures are also called psychomotor or Complex seizures are also called psychomotor or

temporal-lobe seizurestemporal-lobe seizures


Drug Therapy of Patients with Drug Therapy of Patients with EpilepsyEpilepsy

Haveles (p. 215) (Fig. 16-2; Box 16-2)Haveles (p. 215) (Fig. 16-2; Box 16-2) Drug therapy has variable efficacy, from Drug therapy has variable efficacy, from

complete control of all seizures to reducing complete control of all seizures to reducing the frequency of seizuresthe frequency of seizures Anticonvulsant agents may be used singly or in Anticonvulsant agents may be used singly or in

combinationcombination These agents are central nervous system (CNS) These agents are central nervous system (CNS)

depressants that attempt to prevent epileptic depressants that attempt to prevent epileptic seizures without causing excessive drowsinessseizures without causing excessive drowsiness

These agents prevent the spread of abnormal These agents prevent the spread of abnormal electric discharges in the brainelectric discharges in the brain


General Adverse Reactions to General Adverse Reactions to Anticonvulsant AgentsAnticonvulsant Agents

Haveles (pp. 215-217)Haveles (pp. 215-217) Anticonvulsants have a narrow therapeutic indexAnticonvulsants have a narrow therapeutic index Most anticonvulsants stimulate liver microsomal Most anticonvulsants stimulate liver microsomal

enzymes that metabolize themselves, other enzymes that metabolize themselves, other anticonvulsants, and other drugs that the patient anticonvulsants, and other drugs that the patient may be takingmay be taking

The metabolism of anticonvulsants can saturate The metabolism of anticonvulsants can saturate the liver microsomal enzymesthe liver microsomal enzymes At some point, when the enzymes become saturated, At some point, when the enzymes become saturated,

the metabolism converts to zero-order kinetics, and the the metabolism converts to zero-order kinetics, and the drug level can increase abruptlydrug level can increase abruptly


Central Nervous System Central Nervous System DepressionDepression

Haveles (pp. 215-216)Haveles (pp. 215-216) Depressed CNS function is a common side Depressed CNS function is a common side

effect of the anticonvulsant agentseffect of the anticonvulsant agents Tolerance often develops to these effects, Tolerance often develops to these effects,

whereas the anticonvulsant effect persistswhereas the anticonvulsant effect persists Behavior alterations are reported to include both Behavior alterations are reported to include both

hyperactivity and sedationhyperactivity and sedation


Gastrointestinal DistressGastrointestinal Distress

Haveles (p. 216)Haveles (p. 216) Gastrointestinal (GI) distress, including Gastrointestinal (GI) distress, including

anorexia, nausea, and vomiting, can occur anorexia, nausea, and vomiting, can occur with most anticonvulsantswith most anticonvulsants Effects can be minimized by taking the drug with Effects can be minimized by taking the drug with

foodfood


Drug InteractionsDrug Interactions

Haveles (pp. 216-217)Haveles (pp. 216-217) The most important drug interaction involves The most important drug interaction involves

stimulation of the hepatic microsomal enzymesstimulation of the hepatic microsomal enzymes Inducing these enzymes results in a reduction in Inducing these enzymes results in a reduction in

the blood level of the affected drugsthe blood level of the affected drugs Drug interactions with anticonvulsants are Drug interactions with anticonvulsants are

more significant than with other drug groups more significant than with other drug groups because of their narrow therapeutic indexesbecause of their narrow therapeutic indexes



Drug InteractionsDrug Interactions Haveles (p. 217)Haveles (p. 217)

Idiosyncratic reactionsIdiosyncratic reactions Dermatologic side effects: rash, Stevens-Johnson Dermatologic side effects: rash, Stevens-Johnson

syndrome, exfoliative dermatitis, and erythema multiformesyndrome, exfoliative dermatitis, and erythema multiforme Drug-induced systemic lupus erythematosus and Drug-induced systemic lupus erythematosus and

hematologic effects have been reported hematologic effects have been reported Teratogenicity/growthTeratogenicity/growth

Several interactions have been implicated in production of Several interactions have been implicated in production of fetal anomaliesfetal anomalies

Associated with alteration in growthAssociated with alteration in growth WithdrawalWithdrawal

Abrupt withdrawal can precipitate seizuresAbrupt withdrawal can precipitate seizures Other interactionsOther interactions

Suppression of antidiuretic hormoneSuppression of antidiuretic hormone


CarbamazepineCarbamazepine

Haveles (pp. 217-218 )Haveles (pp. 217-218 ) Related to tricyclic antidepressantsRelated to tricyclic antidepressants

Used in the treatment of trigeminal neuralgia; also Used in the treatment of trigeminal neuralgia; also indicated in treatment of bipolar depressionindicated in treatment of bipolar depression


Pharmacologic Effects of Pharmacologic Effects of CarbamazepineCarbamazepine

An anticonvulsant, anticholinergic, An anticonvulsant, anticholinergic, antidepressant, sedative, and muscle antidepressant, sedative, and muscle relaxantrelaxant

Blocks sodium channels, which blocks the Blocks sodium channels, which blocks the propagation of nerve impulsespropagation of nerve impulses


Adverse Reactions of Adverse Reactions of CarbamazepineCarbamazepine

Haveles (p. 217)Haveles (p. 217) CNS effects CNS effects

Can produce dizziness, vertigo, drowsiness, fatigue, Can produce dizziness, vertigo, drowsiness, fatigue, ataxia, confusion, headache, nystagmus, and visual ataxia, confusion, headache, nystagmus, and visual (diplopia) and speech disturbances(diplopia) and speech disturbances

GI effectsGI effects Side effects include nausea, vomiting, and gastric Side effects include nausea, vomiting, and gastric

distressdistress Hematologic effectsHematologic effects

Fatal blood dyscrasias have been reported Fatal blood dyscrasias have been reported cont’d…cont’d…


Adverse Reactions of Adverse Reactions of CarbamazepineCarbamazepine

Haveles (p. 217)Haveles (p. 217) Dermatologic effectsDermatologic effects

Rashes, urticaria, photosensitivity reactions, and Rashes, urticaria, photosensitivity reactions, and altered skin pigmentation can occuraltered skin pigmentation can occur

Oral effectsOral effects Dry mouth, glossitis, and stomatitis can sometimes Dry mouth, glossitis, and stomatitis can sometimes

be seen in patients taking carbamazepinebe seen in patients taking carbamazepine Other effectsOther effects

Cardiovascular side effects include congestive heart Cardiovascular side effects include congestive heart failure and alterations in blood pressurefailure and alterations in blood pressure

Abnormal liver function tests and cholestatic Abnormal liver function tests and cholestatic jaundice have been reportedjaundice have been reported


Drug Interactions of Drug Interactions of CarbamazepineCarbamazepine

Haveles (pp. 217-218) (Box 16-3)Haveles (pp. 217-218) (Box 16-3) Carbamazepine can induce liver microsomal Carbamazepine can induce liver microsomal

enzymesenzymes It can decrease the effect of doxycycline, warfarin, It can decrease the effect of doxycycline, warfarin,

theophylline, and oral contraceptivestheophylline, and oral contraceptives Effects may be increased by erythromycin, Effects may be increased by erythromycin,

isoniazid, propoxyphene, and calcium channel isoniazid, propoxyphene, and calcium channel blockersblockers


ValproateValproate

Haveles (p. 218)Haveles (p. 218) Valproates are a group of anticonvulsants Valproates are a group of anticonvulsants

that are not structurally related to any other that are not structurally related to any other agentsagents The mechanism of action may be its effect on The mechanism of action may be its effect on

sodium and potassium channels, a reduction in sodium and potassium channels, a reduction in aspartate levels, or an increase in the inhibitory aspartate levels, or an increase in the inhibitory neurotransmitter neurotransmitter γγ-aminobutyric acid (GABA)-aminobutyric acid (GABA)


Adverse Reactions of ValproateAdverse Reactions of Valproate

Haveles (p. 218)Haveles (p. 218) GI effects: the most frequent side effects are GI effects: the most frequent side effects are

indigestion, nausea, and vomitingindigestion, nausea, and vomiting CNS effects: sedation and drowsiness have CNS effects: sedation and drowsiness have

been reportedbeen reported Hepatotoxicity: the idiosyncratic toxicity of Hepatotoxicity: the idiosyncratic toxicity of

valproatevalproate Bleeding: bleeding time may be prolongedBleeding: bleeding time may be prolonged Teratogenicity: may increase birth defectsTeratogenicity: may increase birth defects


Drug Interactions of ValproateDrug Interactions of Valproate

Haveles (p. 218) (Box 16-4)Haveles (p. 218) (Box 16-4) Other drugs that are CNS depressants can Other drugs that are CNS depressants can

have an additive CNS depressant effect when have an additive CNS depressant effect when used with valproateused with valproate Valproate inhibits the metabolism of phenobarbital, Valproate inhibits the metabolism of phenobarbital,

producing excessive sedationproducing excessive sedation It also has been associated with drug interactions It also has been associated with drug interactions

with phenytoin, resulting in decreased valproate with phenytoin, resulting in decreased valproate action and increased phenytoin actionaction and increased phenytoin action

It can affect bleedingIt can affect bleeding


PhenobarbitalPhenobarbital

Haveles (p. 218)Haveles (p. 218) The most common barbiturate used in The most common barbiturate used in

treatment of epilepsytreatment of epilepsy Used to treat tonic-clonic and partial seizuresUsed to treat tonic-clonic and partial seizures Sedation is the most common side effectSedation is the most common side effect Skin reactions occur in 1% to 3% of patientsSkin reactions occur in 1% to 3% of patients


PhenytoinPhenytoin

Haveles (pp. 218-220)Haveles (pp. 218-220) Used to treat both tonic-clonic and partial Used to treat both tonic-clonic and partial

seizures with complex symptomsseizures with complex symptoms Has been used to treat trigeminal neuralgiaHas been used to treat trigeminal neuralgia Also has quinidine-like antiarrhythmic propertiesAlso has quinidine-like antiarrhythmic properties


Adverse Reactions of PhenytoinAdverse Reactions of Phenytoin

Haveles (p. 219)Haveles (p. 219) GI effectsGI effects

Reactions are not uncommonReactions are not uncommon CNS effectsCNS effects

Mental confusion, nystagmus, ataxia, slurred speech, Mental confusion, nystagmus, ataxia, slurred speech, blurred vision, diplopia, amblyopia, dizziness, and blurred vision, diplopia, amblyopia, dizziness, and insomniainsomnia

Dermatologic effectsDermatologic effects Skin reactions range from rash to exfoliative dermatitis, Skin reactions range from rash to exfoliative dermatitis,

lupus erythematosus, or Stevens-Johnson syndromelupus erythematosus, or Stevens-Johnson syndrome Some patients have hypertrichosis on the trunk and faceSome patients have hypertrichosis on the trunk and face




Haveles (p. 219) (Fig. 6-3)Haveles (p. 219) (Fig. 6-3) Vitamin deficiencyVitamin deficiency

Deficiency may involve vitamin D and folateDeficiency may involve vitamin D and folate Osteomalacia may result from interference with Osteomalacia may result from interference with

vitamin D metabolismvitamin D metabolism Teratogenicity/growthTeratogenicity/growth

Maternal ingestion of phenytoin is associated with Maternal ingestion of phenytoin is associated with fetal hydantoin syndromefetal hydantoin syndrome

Includes craniofacial anomalies, microcephaly, nail Includes craniofacial anomalies, microcephaly, nail or digit hypoplasia, limb defects, growth or digit hypoplasia, limb defects, growth deficiency, and mental retardationdeficiency, and mental retardation



Adverse Reactions of PhenytoinAdverse Reactions of Phenytoin Haveles (pp. 219-220)Haveles (pp. 219-220)

Gingival enlargementGingival enlargement Occurs in approximately 50% of all chronic usersOccurs in approximately 50% of all chronic users

SymptomsSymptoms Often begin as a painless enlargement of the gingival Often begin as a painless enlargement of the gingival

marginmargin With time, the interproximal papillae become involved With time, the interproximal papillae become involved

and finally coalesce to cover even the occlusal and finally coalesce to cover even the occlusal surfaces of the teethsurfaces of the teeth

The better the patient’s oral hygiene is, the less likely The better the patient’s oral hygiene is, the less likely the lesions are to occur or the less severe they will bethe lesions are to occur or the less severe they will be




Haveles (p. 220) (Box 16-5)Haveles (p. 220) (Box 16-5) EtiologyEtiology

The cause of phenytoin gingival enlargement is The cause of phenytoin gingival enlargement is unknownunknown

Management: some possible alternatives Management: some possible alternatives include the following:include the following: Choose another antiepileptic drugChoose another antiepileptic drug Discontinue phenytoinDiscontinue phenytoin Improve oral hygieneImprove oral hygiene Consider gingivectomyConsider gingivectomy Consider other drugsConsider other drugs


Miscellaneous Anticonvulsant Miscellaneous Anticonvulsant AgentsAgents

Haveles (p. 220)Haveles (p. 220) EthosuximideEthosuximide

The drug of choice for the treatment of absence The drug of choice for the treatment of absence seizuresseizures

Its mechanism of action may involve inhibiting the T-Its mechanism of action may involve inhibiting the T-type calcium channelstype calcium channels

GI adverse effects: anorexia, gastric upset, cramps, GI adverse effects: anorexia, gastric upset, cramps, pain, diarrhea, and nausea and vomitingpain, diarrhea, and nausea and vomiting

CNS adverse effects: drowsiness, hyperactivity, CNS adverse effects: drowsiness, hyperactivity, headache, and hiccupsheadache, and hiccups



Miscellaneous Anticonvulsant Miscellaneous Anticonvulsant AgentsAgents

Haveles (p. 220)Haveles (p. 220) BenzodiazepinesBenzodiazepines Clonazepam is used as an adjunct to treat Clonazepam is used as an adjunct to treat

absence seizures not responsive to absence seizures not responsive to ethosuximideethosuximide Drowsiness and ataxia occur oftenDrowsiness and ataxia occur often Behavioral disturbances and adverse neurologic Behavioral disturbances and adverse neurologic

effects can occur effects can occur Other side effects reported relate to the GI tract and Other side effects reported relate to the GI tract and

to the dermatologic and hematologic systemsto the dermatologic and hematologic systems


New Anticonvulsant AgentsNew Anticonvulsant Agents

Haveles (p. 220) (Table 16-2)Haveles (p. 220) (Table 16-2) FelbamateFelbamate

A newer anticonvulsant that has been associated A newer anticonvulsant that has been associated with serious toxicitieswith serious toxicities

Aplastic anemia and acute hepatic failure have Aplastic anemia and acute hepatic failure have been reportedbeen reported

This agent should be reserved for use only if the This agent should be reserved for use only if the seizures are refractory to other anticonvulsant seizures are refractory to other anticonvulsant agentsagents



New Anticonvulsant AgentsNew Anticonvulsant Agents

Haveles (p. 221) (Table 16-2)Haveles (p. 221) (Table 16-2) GabapentinGabapentin

Effective as an adjunct against partial and Effective as an adjunct against partial and generalized tonic-clonic seizuresgeneralized tonic-clonic seizures

Its mechanism of action is unknownIts mechanism of action is unknown CNS effects: somnolence, dizziness, tremor, and CNS effects: somnolence, dizziness, tremor, and

ataxiaataxia Gastric complaints: dyspepsia, nausea, and Gastric complaints: dyspepsia, nausea, and

vomitingvomiting One major advantage over the other One major advantage over the other

anticonvulsants is that it is not metabolizedanticonvulsants is that it is not metabolized


Dental Treatment of the Patient Dental Treatment of the Patient with Epilepsywith Epilepsy

Haveles (p. 221)Haveles (p. 221) The dental team should not treat a patient who The dental team should not treat a patient who

has a history of seizure disorders without has a history of seizure disorders without reviewing the management of the patient with reviewing the management of the patient with epilepsy, including the procedures for handling a epilepsy, including the procedures for handling a patient experiencing tonic-clonic seizurespatient experiencing tonic-clonic seizures Management should include moving the patient to the Management should include moving the patient to the

floor if possible, tilting the patient’s head to one side floor if possible, tilting the patient’s head to one side to prevent aspiration, and removing objects from the to prevent aspiration, and removing objects from the patient’s mouth before the seizure to prevent patient’s mouth before the seizure to prevent fractured teethfractured teeth


Nonseizure Uses of Nonseizure Uses of AnticonvulsantsAnticonvulsants

Haveles (p. 221)Haveles (p. 221) Neurologic PainNeurologic Pain

Several anticonvulsants are used to manage Several anticonvulsants are used to manage chronic pain syndromeschronic pain syndromes

Psychiatric UsePsychiatric Use Carbamazepine, valproic acid, clonazepam, and Carbamazepine, valproic acid, clonazepam, and

gabapentin have been used in the treatment of gabapentin have been used in the treatment of certain mental disorderscertain mental disorders

They can be used to “level out” (stabilize) the They can be used to “level out” (stabilize) the mood in patients with bipolar disordermood in patients with bipolar disorder

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

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