Management of seizures

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Management of seizures

  1. 1. MANAGEMENT OF SEIZURES<br />DR.PRAVEEN NAGULA<br />
  2. 2. 1.APPROACH TO A CASE OF A SEIZURE<br />2.ANTIEPILEPTIC DRUG CLASSIFICATION<br />3.MECHANISM OF ACTION AT RECEPTORS<br />4.DRUGS IN EACH SEIZURE DISORDER<br />5.INDIVIDUAL DRUG DESCRIPTION <br />6.STATUS EPILEPTICUS<br />7.SPECIFIC SCENARIOS<br />8.CONCLUSION<br />
  3. 3. Approach to a case of seizure<br />
  4. 4. Investigations<br />1.EEG<br />2.CT scan<br />3.MRI <br />4.ROUTINE INVESTIGATIONS- serum electrolytes,blood glucose levels,ABG.<br />5.LUMBAR PUCTURE<br />
  5. 5. FOUR PARTS<br />1.Use of anti epileptic drugs<br />2.Surgical excision of epileptic foci<br />3.Removal of causative and precipitating factors<br />4.Regulation of physical and mental activity<br />
  6. 6.
  7. 7. Course of a case of EPILEPSY<br />
  8. 8.
  9. 9. TRADITIONAL AEDs<br />1.BROMIDES<br />2.PHENOBARBITAL<br />3.PHENYTOIN<br />4.CARBAMAZEPINE<br />5.BENZODIAZEPINES<br />6.ETHOSUXIMIDE<br />7.PRIMIDONE<br />8.VALPROIC ACID<br />
  10. 10. NEWER ANTIEPILEPTICs<br />1.OXCARBAZEPINE<br />2.PREGABALIN<br />3.GABAPENTIN<br />4.TOPIRAMATE<br />5.LAMOTIRIGINE<br />6.LEVETIRACETAM<br />7.TIAGABINE<br />8.FELBAMATE<br />9.ZONISAMIDE<br />10.FOSPHENYTOIN<br />
  11. 11. EXCITATORY GLUTAMATERGIC SYNAPSE<br />PHENYTOIN<br />CARBAMAZEPINE<br />LAMOTRIGINE<br />ETHOSUXIMIDE<br />LAMOTRIGINE<br />GABAPENTIN<br />PREGABALIN<br />LACOSAMIDE<br />RETIGABINE<br />GLUTAMATE<br />LEVETIRACETAM<br />FELBAMATE<br />PHENOBARBITAL<br />TOPIRAMATE<br />LAMOTRIGINE<br />
  12. 12. INHIBITORY GABA ergic SYNAPSE<br />GABA-T<br />VIGABATRIN<br />GAT -1 <br />TIAGABINE<br />GABA A <br />BENZODIAZEPINES<br />
  13. 13. Choice of AEDs by type of adult seizure disorder<br />
  14. 14. COMBINATION of AEDs for REFRACTORY seizures<br />
  15. 15. PHENYTOIN<br />Oldest non sedative antiseizure drug<br />More soluble parenteral drug is fosphenytoin<br />M.O.A- blocks sustained high frequency repetitive firing of action potentials –Na channels – at therapuetic concentrations <br />Inhibits release of serotonin,NE<br />Promotes uptake of dopamine<br />Inhibits MAO activity<br />Stabilization of membrane<br />Reduces calcium permeability <br />
  16. 16. Accumulates in liver,brain,muslce fat.<br />Elimination is dose dependent.<br />T1/2 -24 hours<br />When oral therapy is started -300mg/day regardless of the body weight.Increased the dose by 25-30 mg in adults<br />Drug interactions – sulfonamides displace phenytoin<br />High affinity for Thyroid binding globulin<br />Conc. is with use of phenobarbitone,carbamazepine<br /> concentration of phenytoin –isoniazid<br />Toxicity – nystagmus,diplopia,ataxia,sedation<br />Gingival hyperplasia,hirusitism<br />Coarsening of facial features<br />Mild peripheral neuropathy Osteomalcaia<br />Causal relation to hodgkin’ s lymphoma agranulocytosis<br />
  17. 17. PHENYTOIN METABOLISM<br />
  18. 18. CARBAMAZEPINE<br />Closely related to IMIPRAMINE<br />M.O.A –similar to phenytoin – blocks Na channels<br />Potentiates post synaptic action of GABA<br />Inhibits uptake ,release of NE<br />Uses – focal seizures,GTCS,trigeminalneuralgia,BPD<br />Not sedative<br />INDUCES MICROSOMAL enzymes<br />Valproic acid  its levels, Phenytoin ,phenobarbitone –  levels<br />Only oral form.<br />15-25mg/kg/d – children 1gm/day -adults<br />
  19. 19. CARBAMAZEPINE metabolism<br />
  20. 20. Phenobarbital<br />Oldest of the available antiseizure drugs –sedative<br />DOC in seizures of infants<br />M.O.A –exact is unknown<br />Enhancement of inhibitory processes,dimintion of excitatory transmission<br />Na channel blocking at high doses<br />GABAa receptor action<br />May worsen absence ,atonic ,infantile spasms<br />In febrile seizures <15ug/ml -ineffective<br />
  21. 21. VIGABATRIN<br />Irreversible inhibitor of GABA T (degrades GABA)<br />Increases GABA at synaptic sites<br />Inhibits GABA transporter<br />FOCAL seizures,WEST syndrome<br />T1/2 -6-8 hrs <br />500mg bid<br />2-3 g/day<br />Toxicity -drowsiness,dizziness,weight gain <br />
  22. 22. Lamotrigine<br />Similar to phenytoin in action <br />Absence attacks in children –voltage gated Ca channels<br />Add on treatment<br />Linear kinetics<br />T1/2 -24 hrs<br />
  23. 23. Felbamate<br />M.O.A –not known<br />Third line drug because of aplasticanemia,hepatitis<br />NMDA receptor blockade via glycine binding site<br />Increases phenytoinlevels,valproate<br />Decreases carbamazepine<br />Lennox gestaut syndrome<br />
  24. 24. Gabapentin,Pregabalin<br />GABAPENTIN –analog of GABA<br />Spasmolytic,antiseizure drug<br />Does not act on GABA receptors<br />Adjunctive drugs<br />Not metabolised<br />Not bound to plasma proteins<br />Excreted via renal<br />
  25. 25. Topiramate<br />Substituted monosaccharide<br />M.O.A –phenytoin<br />Potentiates GABA action<br />200- 600 mg/ da<br />TIAGABINE –inhibitor of GABA uptake<br />LEVETIRACETAM – analog of piracetam ,M.O.A unknown,notmetabolised by cytochrome P450<br />Linear kinetcis<br />
  26. 26. Ethosuximide<br />Pure petit mal drug<br />Reduces T TYPE CALCIUM CURRENTS in thalamus<br />Inhibits na k ATPase<br />Depresses cerebral metabolic rate<br />Inhibits GABAaminotransferase<br />Not protein bound<br />Decrease the dose with valproic acid<br />
  27. 27. Valproic acid<br />Sodium salt,or free acid<br />Fatty carboxylic acid<br />Branching,unsaturation – increases lipophilicty<br />Effective agianst absence seizures<br />Effective in myoclonic seizures<br />Hepatotoxicity<br />90% bound to plasmaproteins<br />Sedation with phenobarbital use<br />Bipolar disorders,migraine prophylaxis<br />
  28. 28. Benzodiazepines<br />6 <br />Lorazepam –long acting than dioazepam<br />Diazpeam –short acitng,GTCS,respiratory depression<br />Clobazam – 1.,5 benzodiazepine<br />Nitrazepam<br />Clobazate<br />Acetazomaide –mild acidosis in brain,rapidtolernace<br />
  29. 29. Drug interactions<br />
  30. 30. Teratogenic effects<br />Valproic acid<br />
  31. 31. Surgical treatment<br />
  32. 32. STATUS EPILEPTICUS<br />
  33. 33. Classification of STATUS EPILEPTICUS<br />
  34. 34. AEDs In Pregnancy<br />
  35. 35. Doses<br />
  36. 36.
  37. 37. NEWER drugs in pipeline<br />
  38. 38.
  39. 39.
  40. 40.
  41. 41. answers<br />
  42. 42. REFERENCES<br />1.KATZUNG’S 11 th Ed PHARMACOLOGY<br />2.LIPPINCOTT ‘S PHARMACOLOGY<br />3.MEDICINE UPDATE 2009<br />4.HARRISON’S PRINCIPLES OF INTERNAL MEDICINE 17 th Ed<br />5.ADAM and VICTOR’S NEUROLOGY,9 th Ed<br />6.www.medscape.com<br />7.www.ilae.org<br />8.www.netterimages.com<br />
  43. 43. THANK YOU<br />

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