1 Clinically important adverse drug reactions of AEDs Gitanjali-39:

2 Five commonest ADRs with AEDs Ataxia Dizziness Fatigue Nausea Somnolence Gitanjali-49:

3 Predictable Dose Dependent Reactions Sedation – phenobarbitone, primidone, benzodiazepines (all drugs to some extent) Nystagmus, ataxia, incoordination, dysarthria (cerebellar signs) – phenytoin, primidone, carbamazepine Gitanjali-41:

4 Nystagmus Gitanjali-42:

5 Nystagmus Gitanjali-50:

6 Unpredictable idiosyncratic reactions Aplastic anaemia, hepatotoxicity - Felbamate Stevens Johnsons syndrome - Lamotrigine Hepatotoxicity - Valproate Bone marrow suppression - Carbamazepine Gitanjali-42:

7 Hepatic necrosis Gitanjali-49:

8 Gitanjali-43:

9 Gitanjali-44:

10 Gitanjali-45:

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12 Aplastic anaemia Gitanjali-49:

13 Chronic toxicity Sexual dysfunction, Dupuytren’s contracture – Phenobarbitone, primidone Coarse facies, gingival hyperplasia, hypertrichosis, megaloblastic anaemia, folate defieciency - Phenytoin Weight gain, polycystic ovary disease - Valproate Bradykinesia, parkinsonian syndrome - Ethosuximide Gitanjali-46:

14 Dupuytren’s contracture Gitanjali-49:

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17 Gingival hyperplasia Gitanjali-49:

18 Gum Hyperplasia - phenytoin

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20 Megaloblastic anemia Blood smear Gitanjali-49:

21 Megaloblasts in marrow Gitanjali-49:

22 Delayed toxicity Neural tube defects (1% risk) - Valproate, Carbamazepine Increased risk of cleft lip and palate, cardiac anomalies, CNS anomalies – all drugs Fetal hydantoin syndrome - phenytoin Gitanjali-47:

23 Antiepileptic Therapy & Pregnancy Antiepileptic medication should not be discontinued in pregnant epileptic women, for whom medication is necessary for prevention of major seizures. 4-6% of infants of mothers with epilepsy have malformations Most teratogenic – Valproate, phenytoin Spina bifida, neural tube defect – Valproate, carbamazepine Incidence of malformations greatest with phenytoin plus phenobarbitone compared to Phenobarbitone alone Phenytoin, Phenobarbitone, Primidone - Deficiency of vitamin K dependent clotting factor in newborn Folate supplementation 0.4mg/day

24 Cleft lip and palate Gitanjali-49:

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26

27 Proconvulsant effects of AEDs Carbamazepine can induce Juvenile Myoclonic Epilepsy. Phenobarbitone can induce tonic seizures in children with Lennox Gastaut syndrome, can aggravate absence seizures. Ethosuximide worsens atonic seizures in children with juvenile myoclonic epilepsy. Gitanjali-49:

28 COMMONLY USED ANTIEPILEPTICS DURING PREGNANCY AND THEIR POTENTIAL TOXIC EFFECTS DrugPotential fetal /neonatal effects 1. CarbamazepineFacial dysmorphism, neural tube defects, hypoplasia of distal phalanges 2. PhenobarbitalNeonatal withdrawal, neonatal coagulopathy 3. PhenytoinFacial clefting hypoplasia of distal phalanges, hypertelorism, neonatal coagulopathy 4. PrimidoneNeonatal withdrawal, neonatal coagulopathy 5. Valproic acidFacial dysmorphism, neural tube defects

29 Side effects of newer AEDs DrugCommon S.E.Rare S.E. FelbamateAnorexia, nausea, insomnia, headache Aplastic anemia, Hepatic failure FosphenytoinParaesthesia, pruritus, ataxia, nystagmus Severe rash, Steven Johnson’s Syndrome (SJS). GabapentinDrowsiness, fatigue, dizziness, nausea, ataxia None known LamotrigineRash, tremor, dizziness, nausea, headache, weight gain Severe rash, SJS. Gitanjali-49:

30 Cost of Common AEDs Rs./tab Rs/day Carbamazepine - 200mg Phenytoin - 100mg Phenobarbitone - 30mg Sodium valproate - 200mg Clonazepam - 0.5mg Clobazam - 5mg Lamotrigine - 25mg Gitanjali-49: