This document discusses the management of seizures. It covers the approach to evaluating a patient with seizures, including common diagnostic tests. It then classifies traditional and newer antiepileptic drugs, describing their mechanisms of action and uses in treating different seizure disorders. The document discusses in detail several commonly used antiepileptic drugs, including phenytoin, carbamazepine, phenobarbital, vigabatrin, lamotrigine, felbamate, gabapentin, pregabalin, topiramate, and valproic acid. It also addresses status epilepticus, drug interactions, teratogenic effects, surgical treatment options, and newer drugs in development.

1. MANAGEMENT OF SEIZURESDR.PRAVEEN NAGULA

2. 1.APPROACH TO A CASE OF A SEIZURE2.ANTIEPILEPTIC DRUG CLASSIFICATION3.MECHANISM OF ACTION AT RECEPTORS4.DRUGS IN EACH SEIZURE DISORDER5.INDIVIDUAL DRUG DESCRIPTION 6.STATUS EPILEPTICUS7.SPECIFIC SCENARIOS8.CONCLUSION

3. Approach to a case of seizure

4. Investigations1.EEG2.CT scan3.MRI 4.ROUTINE INVESTIGATIONS- serum electrolytes,blood glucose levels,ABG.5.LUMBAR PUCTURE

5. FOUR PARTS1.Use of anti epileptic drugs2.Surgical excision of epileptic foci3.Removal of causative and precipitating factors4.Regulation of physical and mental activity

7. Course of a case of EPILEPSY

9. TRADITIONAL AEDs1.BROMIDES2.PHENOBARBITAL3.PHENYTOIN4.CARBAMAZEPINE5.BENZODIAZEPINES6.ETHOSUXIMIDE7.PRIMIDONE8.VALPROIC ACID

10. NEWER ANTIEPILEPTICs1.OXCARBAZEPINE2.PREGABALIN3.GABAPENTIN4.TOPIRAMATE5.LAMOTIRIGINE6.LEVETIRACETAM7.TIAGABINE8.FELBAMATE9.ZONISAMIDE10.FOSPHENYTOIN

11. EXCITATORY GLUTAMATERGIC SYNAPSEPHENYTOINCARBAMAZEPINELAMOTRIGINEETHOSUXIMIDELAMOTRIGINEGABAPENTINPREGABALINLACOSAMIDERETIGABINEGLUTAMATELEVETIRACETAMFELBAMATEPHENOBARBITALTOPIRAMATELAMOTRIGINE

12. INHIBITORY GABA ergic SYNAPSEGABA-TVIGABATRINGAT -1 TIAGABINEGABA A BENZODIAZEPINES

13. Choice of AEDs by type of adult seizure disorder

14. COMBINATION of AEDs for REFRACTORY seizures

15. PHENYTOINOldest non sedative antiseizure drugMore soluble parenteral drug is fosphenytoinM.O.A- blocks sustained high frequency repetitive firing of action potentials –Na channels – at therapuetic concentrations Inhibits release of serotonin,NEPromotes uptake of dopamineInhibits MAO activityStabilization of membraneReduces calcium permeability

16. Accumulates in liver,brain,muslce fat.Elimination is dose dependent.T1/2 -24 hoursWhen oral therapy is started -300mg/day regardless of the body weight.Increased the dose by 25-30 mg in adultsDrug interactions – sulfonamides displace phenytoinHigh affinity for Thyroid binding globulinConc. is with use of phenobarbitone,carbamazepine concentration of phenytoin –isoniazidToxicity – nystagmus,diplopia,ataxia,sedationGingival hyperplasia,hirusitismCoarsening of facial featuresMild peripheral neuropathy OsteomalcaiaCausal relation to hodgkin’ s lymphoma agranulocytosis

17. PHENYTOIN METABOLISM

18. CARBAMAZEPINEClosely related to IMIPRAMINEM.O.A –similar to phenytoin – blocks Na channelsPotentiates post synaptic action of GABAInhibits uptake ,release of NEUses – focal seizures,GTCS,trigeminalneuralgia,BPDNot sedativeINDUCES MICROSOMAL enzymesValproic acid  its levels, Phenytoin ,phenobarbitone –  levelsOnly oral form.15-25mg/kg/d – children 1gm/day -adults

19. CARBAMAZEPINE metabolism

20. PhenobarbitalOldest of the available antiseizure drugs –sedativeDOC in seizures of infantsM.O.A –exact is unknownEnhancement of inhibitory processes,dimintion of excitatory transmissionNa channel blocking at high dosesGABAa receptor actionMay worsen absence ,atonic ,infantile spasmsIn febrile seizures <15ug/ml -ineffective

21. VIGABATRINIrreversible inhibitor of GABA T (degrades GABA)Increases GABA at synaptic sitesInhibits GABA transporterFOCAL seizures,WEST syndromeT1/2 -6-8 hrs 500mg bid2-3 g/dayToxicity -drowsiness,dizziness,weight gain

22. LamotrigineSimilar to phenytoin in action Absence attacks in children –voltage gated Ca channelsAdd on treatmentLinear kineticsT1/2 -24 hrs

23. FelbamateM.O.A –not knownThird line drug because of aplasticanemia,hepatitisNMDA receptor blockade via glycine binding siteIncreases phenytoinlevels,valproateDecreases carbamazepineLennox gestaut syndrome

24. Gabapentin,PregabalinGABAPENTIN –analog of GABASpasmolytic,antiseizure drugDoes not act on GABA receptorsAdjunctive drugsNot metabolisedNot bound to plasma proteinsExcreted via renal

25. TopiramateSubstituted monosaccharideM.O.A –phenytoinPotentiates GABA action200- 600 mg/ daTIAGABINE –inhibitor of GABA uptakeLEVETIRACETAM – analog of piracetam ,M.O.A unknown,notmetabolised by cytochrome P450Linear kinetcis

26. EthosuximidePure petit mal drugReduces T TYPE CALCIUM CURRENTS in thalamusInhibits na k ATPaseDepresses cerebral metabolic rateInhibits GABAaminotransferaseNot protein boundDecrease the dose with valproic acid

27. Valproic acidSodium salt,or free acidFatty carboxylic acidBranching,unsaturation – increases lipophilictyEffective agianst absence seizuresEffective in myoclonic seizuresHepatotoxicity90% bound to plasmaproteinsSedation with phenobarbital useBipolar disorders,migraine prophylaxis

28. Benzodiazepines6 Lorazepam –long acting than dioazepamDiazpeam –short acitng,GTCS,respiratory depressionClobazam – 1.,5 benzodiazepineNitrazepamClobazateAcetazomaide –mild acidosis in brain,rapidtolernace

29. Drug interactions

30. Teratogenic effectsValproic acid

31. Surgical treatment

32. STATUS EPILEPTICUS

33. Classification of STATUS EPILEPTICUS

34. AEDs In Pregnancy

35. Doses

37. NEWER drugs in pipeline

41. answers

42. REFERENCES1.KATZUNG’S 11 th Ed PHARMACOLOGY2.LIPPINCOTT ‘S PHARMACOLOGY3.MEDICINE UPDATE 20094.HARRISON’S PRINCIPLES OF INTERNAL MEDICINE 17 th Ed5.ADAM and VICTOR’S NEUROLOGY,9 th Ed6.www.medscape.com7.www.ilae.org8.www.netterimages.com

43. THANK YOU