Anti Epileptic Drugs Presentation

8/3/2019 Anti Epileptic Drugs Presentation

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Components of the presentation

Introduction

Drugs of choice for different seizure types

Combination therapy

Common side effects of antiepileptics


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Introduction

What is a seizure?

Sudden change in motor activity or behavior due

to abnormal electrical activity in the brain


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Mechanism of action of the

antiepileptic drugs

Prevents abnormal electrical activity of brain

by:

Block sodium channels of cerebral neurons Eg: Carbamazepine, phenytoin, Lamotrigine

Enhancing GABA mediated synaptic inhibition

Eg: Sodium valproate, Vigabatrin, Phenobarbitone,

Bensodiazepines Blocking Calcium channels

Eg: Ethosuximide


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Commonly Used AEDs

Carbamazepine

Sodium Valproate

Ethosuximide

Phenytoin sodium

Clonazepam


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Classification

Seizure

Generalized

Tonic

Atonic

Clonic

Tonic clonic

myoclonic

Abscence

Partial

Simple

Complex

Partial to 2ry generalized

Unclassified


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Drug choice for Different seizure types

Tonic Atonic Clonic TC MyoC Absence Simple/Complex

partial

Partial

to

2ry GenTypical Atypical

CBZ + + +

Na Val + + + + + + + + +

ESX + + +

Ph Na + + + + + + + + +

CLZ + + +

LMG + + + + + +

Top + + + + +

CBZ = Carbamazepine Na Val = Sodium valproate ESX = Ethosuximide

Ph Na = Phenytoin sodium CLZ = Clonazepam LMG = Lamotrigine

Top = Topiramide


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Summery

Carbamazepine- partial and secondary generalized tonic-clonic seizures

trigeminal neuralgia

may exacerbate absence and myoclonic seizures

Dose By mouth

For child - daily in divided doses, up to 1 year = 100200 mg 15 years = 200400 mg

510 years = 400600 mg

1015 years = 0.41 g

Ethosuximide

For typical & atypical absence seizures Dose

child up to 6 years initially 250 mg daily

increased gradually to usual dose of 20 mg/kg daily - max. 1 g daily

child over 6 years initially, 500 mg daily,

increased by 250 mg at intervals of 47 days to usual dose of 11.5 g daily


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Summery cont..

Sodium Valproate & Phenytoin sodium

For all forms of epilepsy Sodium valproate is usually given for generalized seizures

Use of phenytoin is relatively limited due to lowtherapeutic index

Na valproate Dose : By mouth- preferably after food

child body-weight up to 20 kg 20mg/kg daily in divided doses (up to 40mg/kg under monitoring)

child under 12 years body-weight over 20 kg initially 400 mg daily in divided doses increased according to response (usual range 2030 mg/kg daily) - max. 35 mg/kg daily

By intravenous injection (over 35 minutes) orby intravenous infusion, same as current dose by oral route

Phenytoin sodium Dose: Child = initially 5 mg/kg daily in 2 divided doses, usual dose range 48 mg/kg daily (max.

300 mg daily)

intravenous injection

Plasma concentration for optimum response 1020 mg/litre (4080 micromol/litre)


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Clonazepam

-all forms of epilepsy(2nd line drug)

myoclonus; status epilepticus

-Dose : child up to 1 year

initially 250 micrograms increased according to response over 24 weeks usual maintenance dose of 0.51 mg

15 years initially 250 micrograms increased as above to 13 mg

512 years initially 500 micrograms increased as above to 36 mg

Infantalie Spasms - Vigabatrin

Neonatal seizures PhenobarbitonePhenytoin Na


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How monotherapy is uaually given


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Combination therapy

Indication

When monotherapy with several alternative

drugs have failed.

Problem-

enhances toxicity and drug interactions


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Can Carbamazepine and Na Valproate be

given as combination therapy?

Yes

-Due to

- minimum interactions

- action of the 2 drugs varies


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Dangerous combination !!!!

= Carbamazepine + Phenytoin Sodium

Reason:

- Carbamazapine is a hepatic enzymeinducer

- causes increse in phenytoin plasma

concentration(low therapeutic index)

- so phenytoin toxicity occurs


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Common side effects of AEDs


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Carbamazepine

Common Side-effects nausea and vomiting, dizziness, drowsiness, headache, ataxia, confusion

visual disturbances (especially diplopia and often associated with peak plasmaconcentrations)

constipation or diarrhoea, anorexia

mild transient generalised erythematous rash may occur in a large number of patients(withdraw if worsens or is accompanied by other symptoms)

leucopenia and other blood disorders (including thrombocytopenia, agranulocytosis andaplastic anaemia)

Other side-effects:

cholestatic jaundice, hepatitis acute renal failure Stevens-Johnson syndrome - toxic epidermal necrolysis, alopecia lymph node enlargement cardiac conduction disturbances depression impotence (and impaired fertility), gynaecomastia, galactorrhoea


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Cautionsin Mx ofcarbmazepine hepatic impairment renal impairment cardiac disease skin reactions history of haematological reactions to other drugs

recommends blood counts and hepatic and renal functiontests

If Leucopenia which is severe, progressive or associated with clinicalsymptoms requires withdrawal (if necessary under cover of suitable alternative)

avoid abrupt withdrawal

Advise : Patients or their carers should be told how to recognise signs of

blood, liver, or skin disorders advise to seek immediate medical attention if symptoms such

as fever, sore throat, rash, mouth ulcers, bruising, or bleedingdevelop.


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Sodium Valproate

Side-effects Frequent

nausea, gastric irritation, diarrhoea; weight gain hyperammonaemia, thrombocytopenia transient hair loss (regrowth may be curly)

less frequently Increased alertness, aggression, hyperactivity, behavioural disturbances Ataxia, tremor, and vasculitis

rarely hepatic dysfunction

withdraw treatment immediately if persistent vomiting and abdominal pain, anorexia,jaundice, oedema, malaise, drowsiness, or loss of seizure control

lethargy, drowsiness, confusion anaemia, leucopenia, pancytopenia, hearing loss

very rarely pancreatitis


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Management:

Contra-indications active liver disease, family history of severe hepatic dysfunction

monitor liver function before therapy and during first 6 months especiallyin patients most at risk Livertoxicity Raised liver enzymes during valproate treatment are usually transient But patients should be reassessed clinically and liver function (including

prothrombin time) monitored until return to normal Discontinue if abnormally prolonged prothrombin time (particularly in

association with other relevant abnormalities). Liver dysfunction (including fatal hepatic failure -especially in children < 3

years ) usually in first 6 months and usually involving multiple antiepileptic therapy.

measure full blood count and ensure no undue potential for bleedingbefore starting

avoid abrupt withdrawal Monitor renal functions

Advise: Blood or hepaticdisorders

Patients or their carers should be told how to recognise signs and symptoms of blood orliver disorders and advised to seek immediate medical attention if symptoms develop

Pancreatitis Patients or their carers should be told how to recognise signs and symptoms of

pancreatitis and advised to seek immediate medical attention if symptoms such as

abdominal pain, nausea and vomiting develop; discontinue if pancreatitis is diagnosed


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Ethosuximide

Side-effectsFrequent:

gastro-intestinal disturbances (including nausea, vomiting,diarrhoea, abdominal pain, anorexia, weight loss)

less frequently: headache, fatigue, drowsiness, dizziness hiccup, ataxia irritability, impaired concentration

rarely: tongue swelling gingival hypertrophy blood disorders such as leucopenia, agranulocytosis,

pancytopenia, and aplastic anaemia


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Cautions

avoid abrupt withdrawal

hepatic impairment renal impairment

Blood disorders


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Phenytoin Sodium

Side-effects

Frequent: nausea, vomiting, constipation Insomnia, transient nervousness, tremor, paraesthesia dizziness, headache, anorexiaz gingival hypertrophy and tenderness rash (discontinue; if mild re-introduce cautiously but discontinue

immediately if recurrence) acne, hirsutism, coarse facies

rarely hepatoxicity, peripheral neuropathy blood disorders (including megaloblastic anaemia (may be treated

with folic acid)

with excessive dosage nystagmus, diplopia, slurred speech,

ataxia, confusion, and hyperglycaemia

Cautions avoid abrupt withdrawal recommends blood counts


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ClonazepamSide-effects

Frequent: drowsiness, fatigue, dizziness muscle hypotonia, co-ordination disturbances poor concentration, restlessness, confusion, amnesia

dependence, and withdrawal salivary or bronchial hypersecretion in infants and small

children

rarely

gastro-intestinal symptoms respiratory depression urinary incontinence reversible hair loss


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Thank you

Anti Epileptic Drugs Presentation

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