Epilepsy NN

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EPILEPSY


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What is Epilepsy?

Epilepsy is a seizure disorder resulting fromsudden bursts of electrical energy in the brain.

These electrical discharges produce seizureswhich vary from one person to another infrequency and form.

Sometimes the electrical signal only reachespart of the brain where a part of the body, like

an arm or a leg may move on its own. If thesignal goes through all of the brain, the personmay shake all over, fall and loseconsciousness.


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Etiology

Identifiable Causes of Epilepsy in Children:

Brain injury to the fetus during pregnancy

Birth traumalack of oxygen

Head trauma, e.g., car accident Brain tumor and stroke

Infection e.g., meningitis

Poisoning from substance abuse orenvironmental contaminants, e.g., leadpoisoning.


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Characteristics

The characteristics and frequency of seizures vary

greatly.

Some known characteristics are:

Uncontrolled movements such as shaking of arms orlegs

Loss of consciousness

Falling

Staring into space (absences) mostly in children

Appearing dazed, confused


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Types of Seizures

There are many different kinds of seizures.

Two main types are: partial and generalized.

Simple partial seizure

sudden jerky movements

distortion in sight or smell

sudden sense of fear, stomach discomfort, dizziness

sensations above are called an aura

Strategy: Reassure the person


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Partial seizures continued

Complex partial seizure loses awareness

appears dazed and confused

random walking, head turning and pulling at clothes

person does not remember these behaviours after theseizure

2/3 of people have this type of seizure

Strategy: do not restrain the person stay with theperson until he/she is out danger.


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Generalized seizures

Generalized seizures affect the whole body.They are generalized absence or tonic-clonic.

Generalized absence seizure

staring into space eyes may roll forward

5 to 15 second lapses of consciousness

person does not recall this lapse

occur in childhood and disappear in adolescence

Strategy: Talk gently to the person, be comforting as itmay take time for the person to become re-oriented.


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Generalized seizures

continuedTonic-clonic seizure (grand mal)

occurs in two phases

Tonic phase: loses consciousness and falls

Clonic phase: muscles stiffen, body jerks and twitches bladder control may be lost

consciousness returns slowly

Strategy: Require First Aid Treatment plus immediate

medical attention if the seizure lasts more than 5minutes.


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Incidence of Seizure Types

Based on informationfrom:

Epilepsy -

A Comprehensive

Textbook,

1997


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Evidence for the

Pathophysiology of SeizuresIncreased EAA

Increased ExcitatoryAmino Acid Transmission

Increased sensitivity toEAA

Progressive increase inglutamate release duringkindling

Increased glutamate andaspartate at start ofseizure

Upregulation of NMDAreceptors in kindled rats

Decreased GABA

Decreased binding ofGABA and

benzodiazepines Decreased Cl- currents

in response to GABA

Decreased glutamate

decarboxylase activity(synthesizes GABA)

Interfere with GABAcauses seizures


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Strategies in Treatment

Stabilize membrane and preventdepolarization by action on ion

channels

Increase GABAergic transmission

Decrease EAA transmission


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Classification of Anticonvulsants

Action on Ion

Channels

Enhance GABA

Transmission

Inhibit EAA

TransmissionNa+:

Phenytoin,

Carbamazepine,

LamotrigineTopiramate

Valproic acid

Ca++:

Ethosuximide

Valproic acid

Benzodiazepines

(diazepam, clonazepam)

Barbiturates

(phenobarbital)Valproic acid

Gabapentin

Vigabatrin

Topiramate

Felbamate

Felbamate

Topiramate

Na+:

For general tonic-clonic

and partial seizures

Ca++:

For Absence seizures

Most effective in

myoclonic but also in

tonic-clonic and partial

Clonazepam: for Absence


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Classification of Anticonvulsants

Classical

Phenytoin

Phenobarbital Primidone

Carbamazepine

Ethosuximide

Valproic Acid

Trimethadione

Newer Lamotrigine

Felbamate

Topiramate

Gabapentin

Tiagabine

Vigabatrin

Oxycarbazepine Levetiracetam

Fosphenytoin

Others


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Phenytoin

Phenobarbital Carbamazepine

Ethosuximide Trimethadione

Valproic Acid

R1

R2

R3

X


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Phenytoin or Diphenylhydantoin

Limited water solubility not given i.m.

Slow, incomplete and variable absorption.

Extensive binding to plasma protein. Metabolized by hepatic ER by hydroxylation.

Chance for drug interactions.

Therapeutic plasma concentration: 10-20 g/ml


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Phenytoin Toxicity and

Adverse EventsAcute Toxicity

High i.v. rate: cardiac arrhythmias hypotension; CNS depression.


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Fosphenytoin

A Prodrug. Given i.v. or i.m. and rapidlyconverted to phenytoin in the body.

Avoids local complications associated withphenytoin: vein irritation, tissue damage,pain and burning at site, muscle necrosiswith i.m. injection, need for large fluidvolumes.

Otherwise similar toxicities to phenytoin.


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Other Na Channel Blockers

Carbamazepine:

Serious hematological toxicity: aplastic anemia.

Antidiuretic effect (anti ADH). Lamotrigine: possible other mechanisms.

Effective in Absence seizures and has

antidepressant effects in bipolar depression. No

chronic associated effects.


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Inhibitors of Calcium Channels

Ethosuximide Drug of choice forAbsence. Blocks Ca++

currents (T-currents) in the thalamus.

Not effective in other seizure types GI complaints most common

CNS effects: drowsiness lethargy


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Enhancers of GABA

Transmission

Phenobarbital The only barbiturate with selective anticonvulsant

effect.

Bind at site on GABA receptor and duration of

opening of Cl channel. Ca-dependent release of neurotransmitters at high

doses.

Inducer of microsomal enzymes drug interactions.

Toxic effects: sedation (early; tolerance develops);nystagmus & ataxia at higher dose; osteomalacia,folate deficiency and vit. K deficiency.


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Benzodiazepines Sedative - hypnotic- anxiolytic drugs.

Bind to another site on GABA receptor. Othermechanisms may contribute. frequency of opening

of Cl channel. Clonazepam and clorazepate for long term treatment

of some epilepsies.

Diazepam and lorazepam: for control of status

epilepticus. Disadvantage: short acting. Toxicities: chronic: lethargy drowsiness.

in status epilepticus: iv administration: respiratoryand cardiovascular depression. Phenytoin and PBalso used.

Enhancers of GABA

Transmission


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GABA-A ReceptorBinding Sites

Cl-


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Gabapentin: Developed as GABAanalogue. Mechanism: Increases release

of GABA by unknown mechanism. Vigabatrin: Irreversible inhibitor of GABA

transaminase. Potential to causepsychiatric disorders (depression and

psychosis).

Tiagabine: decreases GABA uptake byneuronal and extraneuronal tissues.

Enhancers of GABA Transmission


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Valproic Acid

Effective in multiple seizure types.

Blocks Na and Ca channels. Inhibits GABA

transaminase. Increases GABA synthesis. Toxicity: most serious: fulminant hepatitis. More

common if antiepileptic polytherapy in children

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