Components of the presentation

Introduction Drugs of choice for different seizure types Combination therapy Common side effects of antiepileptics

Introduction
What is a seizure?
Sudden change in motor activity or behavior due to abnormal electrical activity in the brain

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

Commonly Used AEDs

Carbamazepine Sodium Valproate Ethosuximide Phenytoin sodium Clonazepam

Classification
Seizure
Generalized Partial Tonic Simple Atonic Complex Clonic Unclassified

Tonic clonic

Partial to 2ry generalized

myoclonic

Abscence

Drug choice for Different seizure types

Tonic Atonic Clonic TC MyoC Absence
Typical Atypical
Simple/ Complex partial

Partial to 2ry Gen

CBZ Na Val ESX Ph Na CLZ LMG Top + + + + + + + +

+ + + + + + + + + + + + + + + + + + + +

+ + + + + ESX = Ethosuximide LMG = Lamotrigine

+ + + + +

CBZ = Carbamazepine Ph Na = Phenytoin sodium Top = Topiramide

Na Val = Sodium valproate CLZ = Clonazepam

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 = 1 5 years = 5 10 years = 10 15 years = 100 200 400 0.4 200 mg 400 mg 600 mg 1g

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 initially, 500 mg daily, increased by 250 mg at intervals of 4 7 days to usual dose of 1 1.5 g daily

child over 6 years

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 low therapeutic 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 20 30 mg/kg daily) - max. 35 mg/kg daily

By intravenous injection (over 3 5 minutes) or by 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 4 8 mg/kg daily (max. 300 mg daily) intravenous injection
Plasma concentration for optimum response 10 20 mg/litre (40 80 micromol/litre)

 Clonazepam -all forms of epilepsy(2nd line drug) myoclonus; status epilepticus -Dose :
child up to 1 year 1 5 years
initially 250 micrograms increased according to response over 2 4 weeks usual maintenance dose of 0.5 1 mg initially 250 micrograms increased as above to 1 3 mg initially 500 micrograms increased as above to 3 6 mg

5 12 years

Infantalie Spasms - Vigabatrin Neonatal seizures Phenobarbitone Phenytoin Na

 How monotherapy is uaually given

Combination therapy
Indication When monotherapy with several alternative drugs have failed. Problemenhances toxicity and drug interactions

 Can Carbamazepine and Na Valproate be given as combination therapy?

Yes
-Due to
- minimum interactions - action of the 2 drugs varies

 Dangerous combination !!!! = Carbamazepine + Phenytoin Sodium Reason: - Carbamazapine is a hepatic enzyme inducer - causes increse in phenytoin plasma concentration(low therapeutic index) - so phenytoin toxicity occurs

Common side effects of AEDs

Carbamazepine
Common Side-effects
nausea and vomiting, dizziness, drowsiness, headache, ataxia, confusion visual disturbances (especially diplopia and often associated with peak plasma concentrations) 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 and aplastic 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

 Cautions in Mx of carbmazepine

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

recommends blood counts and hepatic and renal function tests

If Leucopenia which is severe, progressive or associated with clinical symptoms 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 bleeding develop.

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

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

monitor liver function before therapy and during first 6 months especially in patients most at risk
Liver toxicity 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 bleeding before starting avoid abrupt withdrawal Monitor renal functions Advise:
Blood or hepatic disorders Pancreatitis
Patients or their carers should be told how to recognise signs and symptoms of blood or liver disorders and advised to seek immediate medical attention if symptoms develop

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

Ethosuximide
Side-effects Frequent:
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

Cautions avoid abrupt withdrawal hepatic impairment renal impairment Blood disorders

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 hepatoxicity, peripheral neuropathy blood disorders (including megaloblastic anaemia (may be treated with folic acid)

rarely

with excessive dosage nystagmus, diplopia, slurred speech, ataxia, confusion, and hyperglycaemia Cautions
avoid abrupt withdrawal recommends blood counts

Clonazepam
Side-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

Thank you