A group of chronic CNS disorders characterized by recurrent seizures. Seizures are sudden, transitory, and uncontrolled episodes of brain dysfunction resulting from abnormal discharge of neuronal cells with associated motor, sensory or behavioral changes.

1. EPILEPSY AND ANTIEPILEPTIC DRUGS By Imran Shafiq Malik

6. Causes for Acute Seizures

8. Neuronal Substrates of Epilepsy The Brain The Synapse The Ion Channels/Receptors ions

9. Cellular and Synaptic Mechanisms of Epileptic Seizures (From Brody et al., 1997)

10. Abnormal Excitation Excitation Inhibition GABA glutamate, aspartate

11. Restoring Balance Reduce excitation Increase inhibition Excitation Inhibition

13. Epilepsy Classification Tonic- clonic Tonic Myoclonic Atonic Infantile spasms Absence Simple Partial Epilepsy Partial Epilepsy Generalized Epilepsy Simple Partial Epilepsy Secondary Generalized

17. Scheme of Seizure Spread Simple (Focal) Partial Seizures Contralateral spread

19. Scheme of Seizure Spread Complex Partial Seizures Complex Secondarily Generalized Partial Seizures

26. Scheme of Seizure Spread Generalized Tonic-Clonic Seizures Both hemispheres are involved from outset

27. Neuronal Correlates of Paroxysmal Discharges Generalized Seizures

28. Neuronal Correlates of Paroxysmal Discharges

31. Scheme of Seizure Spread Primary Generalized Absence Seizures Thalamocortial relays are believed to act on a hyperexcitable cortex

32. Neuronal Correlates of Paroxysmal Discharges Generalized Absence Seizures

33. Scheme of Seizure Spread

36. Pattern of AED Use AED #1 AED #2 Failure of initial monotherapy Alternative monotherapy Adjunctive therapy as bridge to alternative monotherapy

46. Pharmacokinetic Parameters

56. CLONAZEPAM (RIVOTRIL) Dosage And Administration The dosage of Rivotril must be individually adjusted according to the patient's clinical response, tolerance of the drug and the patient's age Age group Initial dose Maintenance dose Infant &children upto 10 years (or over to 30kg body weight) 0.01-0.03mg/kg/day 0.05-0.1mg/kg/day For children over 10years Or over 30kg 1.2mg/day 1.5-3mg/day For Adults 1-2mg/day 2-4mg/day

57. Management Of Epilepsy Other types

61. COMPETITIVE DRUGS Used To Treat Epilepsy

99. Safety issues with old and new AED’s Phenytoin Aplastic anemia,hepatic failure,Stevens-Johnson syndrome Carbamazepine Aplastic anemia, hepatic failure, Stevens-Johnson syndrome Valproic acid Hepatic failure, pancreatitis, thrombocytopenia Gabapentin None known Lamotrigine Rash, Steven’s –Johnson Topiramate Renal calculi, open angle glaucoma, hypohydrosis, hepatic failure? Tiagabine Spike-wave stupor Levetiracetam None known Oxcarbazepine Rash Zonisamide Renal calculi, rash, hypohydrosis, aplastic anemia?

100. AED Partial GTCC Lennox-Gastaut JME Absence Valproic acid + + + + + Zonisamide + + ? ?+ ? Lamotrigine + + + ? + Topiramate + + + ?+ ? Levetiracetam + + ? ?+ ? Ethosuximide - - - - + Phenytoin + + - - - Carbamazepine + + - - - Oxcarbazepine + + - - - Gabapentin + + - - - Tiagabine + + - - -

112. Table 2. Proposed Mechanisms of Antiepileptic Drug Action ↓ Na+ ↓Ca+ ↓K+ ↑ Inh. ↓Excitatory channels channels channels transmission transmission ________________________________________________________________________________ Established AED’s PHT +++ CBZ +++ ESM +++ PB + +++ + BZD’s +++ VPA + + ++ + New AED’s LTG +++ + OXC +++ + + ZNS ++ ++ VGB +++ TGB +++ GBP + + ++ FBM ++ ++ ++ ++ TPM ++ ++ ++ ++ LEV + + + ________________________________________________________________________________ +++ primary action, ++ possible action, + probable action. From P. Kwan et al. (2001) Pharmacology and therapeutics 90:21-34. [Data from Upton (1994), Schachter (1995), McDonald and Kelly (1995), Meldrum (1996), Coulter (1997), and White (1999).]