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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