Transcript EPILEPSY

ANTICONVULSANTS

SAMUEL AGUAZIM (MD) 1

What is a Epilepsy?

Epilepsy

is a chronic disorder characterized by recurrent episodes in which the brain is subject to abnormal excessive discharges (

seizures

) synchronized throughout a population of neurons.

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EPILEPSY

PRIMARY or IDIOPATHIC SECONDARY

• • • • • KNOWN CAUSES: HEAD INJURY TUMORS MENINGITIS HYPOGLYCEMIA DRUG WITH DRAWAL 3

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• • • • The two main categories of seizures include

Partial seizures

– no loss of consciousness and

Generalized seizures

– loss of consciousness • A partial seizure can evolve to a generalized seizure. 5

Partial Seizures

The site of origin is a

localized or discreet area in one hemisphere of the brain

. • • • • Symptoms depend on the site of neuronal discharge The two most common types of partial seizure are Simple partial and Complex partial. 6

Simple Partial

• • • These produce symptoms associated with the area of abnormal neural activity in the brain confined to

single locus

: The electrical discharge

does not

spread Can occur at any age • motor signs, sensory symptoms, autonomic signs and symptoms • There is no impairment of consciousness in simple partial seizures. 7

Complex Partial

• • • • Impairment of consciousness, characteristic of complex partial seizures (CPS)

Results in the inability to respond to or carry out simple commands or to execute willed movement, and a lack of awareness of one’s surroundings and events.

Exhibit complex sensory hallucinations, mental distortion and motor dysfunction Experience initial seizures before age of 20 yrs 8

Generalized Seizures

At the onset,

seizure activity occurs simultaneously in large areas of the brain, often in both hemispheres

.

• • Begin locally and rapidly spread to both the hemispheres.

Loss of consciousness • • Seizures can be convulsive or non-convulsive.

The two most common types are

tonic-clonic (grand mal) and Absence (Petit mal).

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• • • •

Tonic-clonic (grand mal). Most common

There is loss of consciousness during the seizure.

The tonic phase

, consisting of increased muscle tone (rigidity), is followed by

The Clonic phase

, which involves jerking of the extremities.

Followed by confusion and exhaustion. 10

• • • • Absence (petit mal) This type occurs years most often in children, usually beginning between the ages of 5 and 12 and often stopping spontaneously in the teens.

The loss of consciousness is so brief that the child usually does not even change position

.

Typically described as a blank stare and often misinterpreted as daydreaming.

Most absence seizures last 10 seconds or less. 11

Myoclonic seizures are rapid, brief contractions of bodily muscles, sudden jerks or clumsiness. •

Infantile Spasms a.k.a West Syndrome

sudden spasm or bending (flexion) of the body either at the waist or neck . 12

Status Epilepticus was defined as between the seizures 30 minutes of continuous seizure activity or a series of seizures without return to full consciousness • Febrile seizures are convulsions brought on by a fever in infants or small children. 13

CLASSIFICATION Seizures

• • PARTIAL / FOCAL • SIMPLE • COMPLEX GENERALIZED • GRAND MAL ( tonic clonic) • PETIT MAL ( Absence) • MYOCLONIC • • FEBRILE STATUS EPILEPTICUS 14

ANTIEPILEPTIC DRUGS

• • • • • • • • • • •

PHENYTOIN CARBAMAZEPINE VALPROIC ACID ETHOSUXIMIDE BENZODIAZEPINES BARBITURATES LAMOTRIGINE - NEWER AGENTS GABAPENTIN - NEWER AGENTS TIAGABINE - NEWER AGENTS TOPIRAMATE - NEWER AGENTS VIGABATRIN - NEWER AGENTS

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BARBITURATES

- PHENOBARBITAL PRIMIDONE •

BENZODAIZEPINES

- DIAZEPAM CLONAZEPAM, CLORAZEPATE 16

ANTI EPILEPTIC DRUGS MECH

• INHIBIT ELECTRICAL DISCHARGE • INHIBIT SPREAD OF DISCHARGE 17

PHENYTOIN

• • MECH: DECREASES Na INFLUX STABILIZES CELL MEMBRANE • • DECREASES INFLUX OF Ca DECREASES FIRING RATE 18

ACTION :

• • • • • •

DECREASES PROPAGATION OF ABNORMAL IMPULSES

USES:

First line treatment for tonic-clonic seizures First line prophylaxis for status epilepticus Treatment for simple and complex seizures.

Drug of choice for initial therapy in adults 19

• DROWSINESS – LITTLE HYPNOSIS – NO • • • KINETICS : ROUTE – ORAL, IV – ST. EPILEPTICUS MET : LIVER, EASILY SATURATED EXCRETION : URINE.

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• • • • • • • • • • • •

PHENYTOIN - SE

Side effects of phenytoin include: CNS Depression Gingival hyperplasia Hirsutism

Osteomalacia from decreased vitamin D Megaloblastic anemia from decreased folate (decreased GI absorption from inhibition of conjugases)

Aplastic anemia Stevens-Johnson syndrome Nystagmus Yellow-browning of skin

Neuropathy (vertigo, ataxia, headache)

SLE-like syndrome

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TERATOGENIC EFFECT

FETAL HYDANTOIN SYNDROME

IF GIVEN IN PREGNANCY

• • • •

CLEFT LIP, CLEFT PALATE

GROWTH RETARDATION LOW IQ CONGENITAL HEART DISEASES 23

Phenytoin's teratogenic effects usually result in cleft lip and palate.

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CARBAMAZEPINE

• • •

MECH : BLOCKS Na CHANNELS USED MAINLY All partial, grand mal epilepsy Drug of choice in Trigeminal neuralgia

ORAL ROUTE

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SE : MC : GIT

• • • • • • •

Chronic use can cause : STUPOR, RESP DEPRESSION, COMA APLASTIC ANEMIA, THROMBOCYTOPENIA, AGRANULOCYTOSIS, LIVER FAILURE Steven-Johnson syndrome Teratogenicity Cleft lip and palate Spina bifida

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Steven-Johnson syndrome

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Carbamazepine's teratogenic effects usually result in cleft lip, cleft palate, and spina bifida.

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• •

BARBITURATES

PHENOBARBITAL PRIMIDONE

• • • • • • • •

MECH May be due to GABA activation USES ; FEBRILE CONVULSIONS, CAN ALSO BE USED FOR SIMPLE & GRAND MAL EPILEPSY Not effective in complex partial Induced CYP450 SE : SEDATION, ATAXIA, NYSTAGMUS, VERTIGO CHR: PSYCHOSIS.

Rebound seizures occur on discontinuance

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• • • •

PRIMIDONE

Also effective in complex partial

SE

Same as phenobarbital 30

BENZODIAZEPINES

DIAZEPAM, CLONAZEPAM, CLORAZEPATE

SAFEST DRUGS OF ALL THE ANTIEPILETPTIC DRUGS

• •

Diazepam Slow I. V. – Status Epilepticus SE : Resp depression, CVS depression with i.v. administration of high doses

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• •

CLONAZEPAM, CLORAZEPATE For Chronic treatment

• • •

DIAZEPAM, LORAZEPAM For acute conditions Status EPI Lorazepam longer duration than diazepam

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VALPROIC ACID(Divalproex)

• • • • • • MECH : GABA action increased Blocks Na Channels Broad spectrum antiepileptic drug

Inhibitor of CYP45O

USES : MYOCLONIC SEIZURES and Bipolar disorder Absent seizures – 2 nd drug of choice. (hepatotoxicity) • • SE : hepatotoxicity GIT , TREMOR, ATAXIA,SEDATION THROMBOCYTOPENIA • CI :

LIVER FAILURE

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ETHOSUXIMIDE ( zarontin)

Mech: Reduces propagation of abnormal electrical activity in the brain by inhibiting Calcium channels •

USES: Drug of choice for ABSENCE SEIZURES

• • • • • • •

SE:

MC : GIT distress CONFUSION, LACK OF CONCENTRATION STEVEN JOHNSON SYNDROME.( skin reaction) Headache, Itching Fatigue 34

Adjunct Antiepileptic drugs

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LAMOTRIGINE ( lamictal)

• • • • • • Broad spectrum IHIBITS GLUTAMATE, ASPARTATE

Blocks Na channels and high voltage ca channels

Prevents firing 36

Lennox-Gastaut syndrome (LGS

), or childhood epileptic encephalopathy, is a pediatric epilepsy syndrome characterized by

multiple seizure types; mental retardation or regression

; and abnormal findings on electroencephalography (EEG).

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GABAPENTIN.( neurontin)

• • • • Analogue of GABA Mech – Not known May interfere with ca channels Can be used for Simple and partial seizures ,

peripheral neuropathy and Postherpetic neuralgia

SE;

Sedation, Ataxia,

Drowsiness, ataxia, fatigue

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• • • •

TIAGABINE

Blocks GABA uptake into presynaptic neurons More GABA for receptor binding Exe: BILE ( Major), small amt in Urine It is effective in decreasing the number of seizures in patients with partial onset epilepsy .

• SE: Drowsiness, ataxia, tremor, GI upset dizziness 39

• • • • • • • • •

TOPIRAMATE

Many actions, Broad spectrum Blocks Na channels Increases GABA activity Block Ca channels Prevent Phosporylation of proteins Has shown reduction in seizures in refractory cases when used with other Anti-epileptic drugs.

Can be used

tonic-clonic, simple and complex

seizures as well as for migraine prophylaxis.

.

Exe: Urine SE: Drowsiness, ataxia, Nephrolithiasis , taste alteration, confusion 40

• • •

VIGABATRIN

• • • Inhibit enzyme GABA transaminase Increases the GABA levels Can be used for Partial, General tonic clonic seizures & sometimes for Infantile spasms Exe: Urine Adv: very less drug interactions SE: Aggression, Alopecia, Skin rash, drowsiness.

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