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INTRODUCTIONINTRODUCTION
Is a family of different recurrent seizure Is a family of different recurrent seizure disorders characterized by sudden, excessive disorders characterized by sudden, excessive and synchronous discharge of cerebral and synchronous discharge of cerebral neurons.neurons.
This results in abnormal movements or This results in abnormal movements or perception that are of short duration and perception that are of short duration and tend to recur.tend to recur.
The site of electric discharge determines the The site of electric discharge determines the symptoms that are produced. symptoms that are produced.
The goal of drug management is restoration of The goal of drug management is restoration of normal patterns of electrical activitynormal patterns of electrical activity
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TYPES OF EPILEPSYTYPES OF EPILEPSY
PRIMARY or IDIOPATHICPRIMARY or IDIOPATHIC
SECONDARYSECONDARY
KNOWN CAUSES:KNOWN CAUSES: HEAD INJURY HEAD INJURY TUMORSTUMORS MENINGITISMENINGITIS HYPOGLYCEMIAHYPOGLYCEMIA DRUG WITH DRAWALDRUG WITH DRAWAL
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CLASSIFICATIONCLASSIFICATION Seizures Seizures
PARTIAL / FOCALPARTIAL / FOCAL• SIMPLESIMPLE• COMPLEXCOMPLEX
GENERALIZEDGENERALIZED• GRAND MAL ( tonic clonic)GRAND MAL ( tonic clonic)• PETIT MAL ( Absence)PETIT MAL ( Absence)• MYOCLONICMYOCLONIC• FEBRILE FEBRILE • STATUS EPILEPTICUSSTATUS EPILEPTICUS
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The two main categories of seizures The two main categories of seizures includeinclude
Partial seizures – Partial seizures – no loss of consciousnessno loss of consciousness
and and Generalized seizures – Generalized seizures – loss of consciousness loss of consciousness
A partial seizure can evolve to a A partial seizure can evolve to a generalized tonic-clonic seizure. generalized tonic-clonic seizure.
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Partial SeizuresPartial Seizures Symptoms depend on the site of neuronal Symptoms depend on the site of neuronal dischargedischarge
The two most common types of partial The two most common types of partial seizure are seizure are
Simple partial and Simple partial and Complex partial. Complex partial.
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Simple PartialSimple Partial These produce symptoms associated with the These produce symptoms associated with the
area of abnormal neural activity in the brain area of abnormal neural activity in the brain confined to confined to single locussingle locus: :
The electrical discharge The electrical discharge does notdoes not spread spread
Can occur at any ageCan occur at any age
There is There is no impairment of consciousness in no impairment of consciousness in simple partial seizures. simple partial seizures.
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Complex PartialComplex Partial
Impairment(altered) of consciousness, Impairment(altered) of consciousness, characteristic of complex partial seizures characteristic of complex partial seizures (CPS)(CPS)
results in the inability to respond to or results in the inability to respond to or carry out simple commands or to execute carry out simple commands or to execute willed movement, and a lack of awareness willed movement, and a lack of awareness of one’s surroundings and events, of one’s surroundings and events, hallucination. hallucination.
Experience initial seizure before age of 20 Experience initial seizure before age of 20 yrsyrs
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Generalized SeizuresGeneralized Seizures Begin locally and rapidly spread to both the Begin locally and rapidly spread to both the
hemispheres.hemispheres.
Loss of consciousnessLoss of consciousness
Seizures can be convulsive or nonconvulsive.Seizures can be convulsive or nonconvulsive. The two most common types are The two most common types are tonic-tonic-
clonic (grand mal) andclonic (grand mal) and Absence (Petit mal). Absence (Petit mal).
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Tonic-clonic (grand mal). Tonic-clonic (grand mal). Most Most commoncommon
There is loss of consciousness during There is loss of consciousness during the seizurethe seizure. .
The tonic phase, consisting of The tonic phase, consisting of continuous muscle contraction (rigidity), continuous muscle contraction (rigidity), is followed by the clonic phase, which is followed by the clonic phase, which involves jerking of the extremities.involves jerking of the extremities.
Followed by confusion and exhaustion Followed by confusion and exhaustion post-ictally . post-ictally .
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Absence (petit mal) Absence (petit mal) This type occurs This type occurs most most often in children, usually beginning between often in children, usually beginning between the ages of 3 to 5 years the ages of 3 to 5 years lasting until puberty. lasting until puberty.
This seizure involves a brief, abrupt and self-This seizure involves a brief, abrupt and self-limiting loss of consciousness last 10 seconds limiting loss of consciousness last 10 seconds or less. or less.
The patient stares and exhibits rapid eye-The patient stares and exhibits rapid eye-blinking which lasts for 3 to 5 secsblinking which lasts for 3 to 5 secs
There is no postictal state, but the person There is no postictal state, but the person usually lacks awareness of what occurs during usually lacks awareness of what occurs during the seizure. the seizure.
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Myoclonic seizuresMyoclonic seizures are are rapid, brief rapid, brief contractions of bodily muscles, contractions of bodily muscles, sudden jerks or clumsiness. sudden jerks or clumsiness.
Infantile SpasmsInfantile Spasms sudden spasm or sudden spasm or bending (flexion) of the body either bending (flexion) of the body either at the waist or neck. at the waist or neck.
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Status EpilepticusStatus Epilepticus is defined as is defined as 30 30 minutes of continuous seizure activity or minutes of continuous seizure activity or a series of seizures without return to full a series of seizures without return to full consciousness between the seizuresconsciousness between the seizures
Febrile seizuresFebrile seizures are are convulsions convulsions brought on by a fever in infants or small brought on by a fever in infants or small children. children.
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ANTIEPILEPTIC DRUGSANTIEPILEPTIC DRUGS PHENYTOINPHENYTOIN CARBAMAZEPINECARBAMAZEPINE VALPROIC ACIDVALPROIC ACID ETHOSUXIMIDEETHOSUXIMIDE BENZODIAZEPINESBENZODIAZEPINES BARBITURATESBARBITURATES LAMOTRIGINE - NEWER AGENTSLAMOTRIGINE - NEWER AGENTS GABAPENTIN - NEWER AGENTSGABAPENTIN - NEWER AGENTS TIAGABINE - NEWER AGENTS TIAGABINE - NEWER AGENTS TOPIRAMATE - NEWER AGENTSTOPIRAMATE - NEWER AGENTS VIGABATRIN - NEWER AGENTSVIGABATRIN - NEWER AGENTS
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ANTI EPILEPTIC DRUGS -ANTI EPILEPTIC DRUGS -MECHMECH
Preventing the influx of Na⁺ through fast Na Preventing the influx of Na⁺ through fast Na channels: channels: carbamazepine, phenytoincarbamazepine, phenytoinFacilitation of the effect of GABA resulting in Facilitation of the effect of GABA resulting in hyperpolarization: hyperpolarization: barbiturate & benzodiazepinebarbiturate & benzodiazepine↓ ↓ presynaptic calcium influx through the T-type presynaptic calcium influx through the T-type calcium channel: calcium channel: ethosuximide, valproic acid, ethosuximide, valproic acid, phenytoinphenytoin↓ ↓ excitatory effect of glutamic acid:excitatory effect of glutamic acid: Lamotrigine, Lamotrigine, topiramate & felbamatetopiramate & felbamate
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PHENYTOINPHENYTOIN
MECH: MECH: DECREASES Na INFLUXDECREASES Na INFLUX
DECREASES INFLUX OF CaDECREASES INFLUX OF Ca
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USESUSES: MAINLY in : MAINLY in PartialPartial generalized generalized status epilepticusstatus epilepticus
OTHERS: treatment of arrhythmiaOTHERS: treatment of arrhythmia
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Undergoes zero-order kinetics of Undergoes zero-order kinetics of eliminationelimination
An inducer of cyt P450An inducer of cyt P450
KINETICS :KINETICS : ROUTEROUTE – ORAL, IV – ST. EPILEPTICUS – ORAL, IV – ST. EPILEPTICUS MET MET : LIVER via cyt P450 : LIVER via cyt P450 EXCRETIONEXCRETION : URINE. : URINE.
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Drug interactions: Phenytoin Drug interactions: Phenytoin
Induces P 450 Induces P 450 :: ↓ ↓ effectiveness ofeffectiveness of : OCP, ANTI : OCP, ANTI
COAGULANT, QUINIDINE.COAGULANT, QUINIDINE.
DRUGS INCREASING PHENYTOIN DRUGS INCREASING PHENYTOIN LEVELS:LEVELS:
INH, CIMETIDINE, SULFONAMIDESINH, CIMETIDINE, SULFONAMIDES
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PHENYTOIN - SEPHENYTOIN - SE CNS depressionCNS depression: causing sedation & : causing sedation &
drowsinessdrowsiness NYSTAGMUS, ATAXIANYSTAGMUS, ATAXIA
GINGIVAL HYPERPLASIAGINGIVAL HYPERPLASIA FACIAL FEATURES – COARSEFACIAL FEATURES – COARSE
Inhibition of ADH and INSULIN releaseInhibition of ADH and INSULIN release
MEGALOBLASTIC ANEMIAMEGALOBLASTIC ANEMIA
Aplastic anemia Aplastic anemia
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FETAL HYDANTOIN SYNDROME FETAL HYDANTOIN SYNDROME IF GIVEN IN PREGNANCYIF GIVEN IN PREGNANCY
CLEFT LIP, CLEFT PALATECLEFT LIP, CLEFT PALATE GROWTH RETARDATIONGROWTH RETARDATION LOW IQLOW IQ CONGENITAL HEART DEFECTCONGENITAL HEART DEFECT
TERATOGENIC EFFECTTERATOGENIC EFFECT
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CARBAMAZEPINECARBAMAZEPINE MECH MECH : BLOCKS Na CHANNELS: BLOCKS Na CHANNELS USED MAINLY -All partial, grand USED MAINLY -All partial, grand
mal epilepsymal epilepsy Drug of choice for Trigeminal Drug of choice for Trigeminal
neuralgia and manianeuralgia and mania
ORAL ROUTEORAL ROUTE
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SE :SE : CNS depression CNS depression resulting in sedation resulting in sedation
and drowsinessand drowsiness Megaloblastic anemiaMegaloblastic anemia Aplastic anemiaAplastic anemia Exfoliative dermatitisExfoliative dermatitis ↑↑ADH secretion ADH secretion causing dilutional causing dilutional
hyponatremiahyponatremia
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DRUG DRUG INTERACTIONSINTERACTIONS
Induces cyt P450Induces cyt P450Increase in metabolism of other drugs, Increase in metabolism of other drugs, ↓ing ↓ing
their effectivenesstheir effectiveness OCPOCP ORAL ANTI COAGULANTSORAL ANTI COAGULANTS PHENYTOINPHENYTOIN INH (Isoniazid)INH (Isoniazid) CIMETIDINECIMETIDINE STEROIDSSTEROIDS
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BARBITURATESBARBITURATES PHENOBARBITALPHENOBARBITAL PRIMIDONEPRIMIDONE
MECH OF ACTIONMECH OF ACTION due to Facilitation of the effect of due to Facilitation of the effect of
GABA GABA USES ; USES ; FEBRILE CONVULSIONS, FEBRILE CONVULSIONS, CAN ALSO BE CAN ALSO BE
USED FOR USED FOR SIMPLE PARTIAL SIMPLE PARTIAL & & GRAND MAL GRAND MAL EPILEPSYEPILEPSY
Not effective in complex partial Not effective in complex partial
SE : SEDATION, ATAXIA, NYSTAGMUS, SE : SEDATION, ATAXIA, NYSTAGMUS, VERTIGO, VERTIGO, morbiliform rashmorbiliform rash
Rebound seizures occur on discontinuanceRebound seizures occur on discontinuance DOC: for seizure in pregnancy DOC: for seizure in pregnancy
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PRIMIDONEPRIMIDONE Metabolized to phenobarbitalMetabolized to phenobarbital effective in complex partialeffective in complex partial Mechanism of action & side Mechanism of action & side
effect:effect: Same as phenobarbitalSame as phenobarbital
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BENZODIAZEPINESBENZODIAZEPINES
DIAZEPAM, LORAZEPAM, DIAZEPAM, LORAZEPAM, CLONAZEPAM, CLORAZEPATECLONAZEPAM, CLORAZEPATE
Diazepam, lorazepam - Slow I. V. – Diazepam, lorazepam - Slow I. V. – Status Epilepticus Status Epilepticus
SE : Resp depression, CVS depression SE : Resp depression, CVS depression with i.v. administration of high doseswith i.v. administration of high doses
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CLONAZEPAM, CLORAZEPATECLONAZEPAM, CLORAZEPATE For Chronic treatmentFor Chronic treatment
DIAZEPAM, LORAZEPAMDIAZEPAM, LORAZEPAM For acute conditions of Status For acute conditions of Status
EpilepticusEpilepticus Lorazepam longer duration than Lorazepam longer duration than
diazepamdiazepam
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VALPROIC ACID(Divalproex)VALPROIC ACID(Divalproex)
MOA : enhances the effect of GABA MOA : enhances the effect of GABA Blocks Na ChannelsBlocks Na Channels
USES : USES : MYOCLONIC SEIZURESMYOCLONIC SEIZURES Absent seizures – 2Absent seizures – 2ndnd drug of choice. drug of choice. maniamania
SE : SE : GIT , TREMOR, ATAXIA,SEDATIONGIT , TREMOR, ATAXIA,SEDATION THROMBOCYTOPENIA, THROMBOCYTOPENIA, hepatotoxichepatotoxic
CI : LIVER FAILURE CI : LIVER FAILURE
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ETHOSUXIMIDEETHOSUXIMIDE Mech: Reduces propagation of abnormal Mech: Reduces propagation of abnormal
electrical activity in the brain by electrical activity in the brain by inhibiting inhibiting T-type Calcium channels T-type Calcium channels
USES: ABSENCE SEIZURESUSES: ABSENCE SEIZURES
SE:SE: MC : GITMC : GIT CONFUSION, CONFUSION, LACK OF CONCENTRATIONLACK OF CONCENTRATION STEVEN JOHNSON SYNDROME.STEVEN JOHNSON SYNDROME. APLASTIC ANEMIA , APLASTIC ANEMIA , THROMBOCYTOPENIA.THROMBOCYTOPENIA.
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LAMOTRIGINE LAMOTRIGINE
Broad spectrumBroad spectrum IHIBITS GLUTAMATE, ASPARTATEIHIBITS GLUTAMATE, ASPARTATE Blocks Na channels and high voltage ca Blocks Na channels and high voltage ca
channelschannels Can be used for partial and GTCS. Can be used for partial and GTCS. Lennox-Gastaut syndromeLennox-Gastaut syndrome
SE : RASH, Drowsiness, ataxia, confusion, SE : RASH, Drowsiness, ataxia, confusion, blood dyscrasiasblood dyscrasias
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GABAPENTIN.GABAPENTIN.
Analogue of GABAAnalogue of GABA Mech – Not knownMech – Not known May interfere with ca channelsMay interfere with ca channels Can be used for partial seizures Can be used for partial seizures
SE; Drowsiness, ataxia..SE; Drowsiness, ataxia..
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TIAGABINETIAGABINE
Blocks GABA uptake into presynaptic Blocks GABA uptake into presynaptic neurons neurons
Making GABA available for receptor Making GABA available for receptor binding, thereby enhancing the effect binding, thereby enhancing the effect of GABAof GABA
Exe: BILE ( Major), small amt in UrineExe: BILE ( Major), small amt in Urine Can be used for Can be used for Partial and GTCS Partial and GTCS
Seizures in refractory patientsSeizures in refractory patients SE: Drowsiness, ataxia, tremor,SE: Drowsiness, ataxia, tremor, GI upset dizziness GI upset dizziness
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TOPIRAMATETOPIRAMATE Many actions, Broad spectrumMany actions, Broad spectrum Blocks Na channelsBlocks Na channels Increases GABA activityIncreases GABA activity Block T-type Ca channelsBlock T-type Ca channels
Can be used for Partial and GTCSCan be used for Partial and GTCS
Exe: UrineExe: Urine
SE: Drowsiness, ataxia, SE: Drowsiness, ataxia, NephrolithiasisNephrolithiasis,, taste alteration, confusiontaste alteration, confusion
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VIGABATRINVIGABATRIN
Inhibit enzyme GABA transaminaseInhibit enzyme GABA transaminase Increases GABA levelsIncreases GABA levels Can be used for Partial, GTCS & Can be used for Partial, GTCS &
sometimes for sometimes for Infantile spasmsInfantile spasms Exe: UrineExe: Urine Adv: very less drug interactionsAdv: very less drug interactions SE: Aggression, Alopecia, Skin rash, SE: Aggression, Alopecia, Skin rash,
drowsiness.drowsiness.