Madushani Silva MBBS North Colombo Teaching Hospital Ragama Seizure is a convulsion or transient abnormal event resulting from a paroxysmal discharge of cerebral neurons sudden brief attack of altered consciousness ID: 1048203
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1. DRUGS USED IN EPILEPSYDr. Madushani Silva(MBBS)North Colombo Teaching Hospital – Ragama
2. Seizure – is a convulsion or transient abnormal event resulting from a paroxysmal discharge of cerebral neurons (sudden brief attack of altered consciousness)Epilepsy – is the continuing tendency to have seizures, even if a long interval separates attacksEpilepsy
3. Intracranial causesGenetic predispositionDevelopmental – hamartomas, neuronal migration abnormalitiesTumourVascular (infarct or haemorrhage)Arteriovenous malformationTrauma & surgery – depressed fracture, penetrating traumaInfection – abscess, encephalitisNeuronal degenerative disorders – Alzheimer’s diseaseCauses
4. Extracranial causesAnoxiaHypoglycaemiaDrugs – phenothiazines, monoamine oxidase inhibitors, tricyclic antidepressants, lidocaine, nalidixic acid Drug withdrawal – anticonvulsant drugs (phenobarbitol), benzodiazepines Chronic alcohol abuse & alcohol withdrawalMetabolic – hypocalcaemia, hyponatraemia, porphyria (abnormal Hb metabolism)Inborn errors of metabolism
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7. Spread of electrical activity between neurons is normally restricted & synchronous discharge of neurons takes place in restricted groups producing normal EEG rhythmsDuring a seizure, large groups of neurons are activated repetitively, unrestrictedly & hypersynchronously.Inhibitory synaptic activity between neurons fails. This produces high voltage spike-&-wave EEG activity, the electrophysiological hallmark of epilepsy Mechanism
8. Brain becomes epileptogenic either because neurones have a predisposition to be hyperexcitable (in congenital abnormalities) or because the cells acquire this hyperexcitable tendency (trauma, brain neoplasms)Each individual has seizure thresholdSome chemicals induce seizure in everyone (pentylenetetrazol, a toxic gas)
9. Generalized seizure – B/L abnormal electrical activity, with B/L motor manifestations & impaired consciousnessPartial (focal) seizure Simple – without loss of consciousnessComplex – with loss of awarenessUnclassified seizureClassification
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13. First AidKeep calmLet the seizure run its courseMove away objects that can harm the patientDon’t try to force anything into the mouthDon’t give anything to drinkDon’t try to stop the seizure physicallyRoll person onto a side, with head turned to one sideGet help if last more than 10 minutes
14. A prolonged seizure - longer than 3 minutes - or repeated seizures outside hospital are best treated with rectal diazepam (10 mg), or intravenous diazepam Status epilepticus This medical emergency means continuous seizures without recovery of consciousness
15. Aim of treatmentAim is to obtain freedom from fits80% can be controlled with monotherapyIf freedom from seizure not possible, aim for best control with minimal side effects
16. Principles of treatmentDecide if the patient needs to be treatedStart with an appropriate first line anti epileptic drugUse single first line drugStart with low dose, and increase dose slowly until seizure control or toxicity
17. Principles of treatmentIf first drug not effective or not tolerated switch to another drug Use 2 drugs when monotherapy failsStress importance of compliance
18. Drugs use in EpilepsyCarbamazepineEthosuximide GabapentinLamotriginePhenobarbitalPhenytoin
19. TiagabineTopiramateValproateVigabatrin Benzodiazepines
20. Anti epileptic drugsFirst line drugsPhenytoinPhenobarbitoneCarbamazepineSodium valproateSecond LineClonazepan, clobazamTopiramate, lamotrigine
21. Choice of drugsGeneralized – phenytoin, valproateMyoclonic – valproate, clonazepamAbsence – valproate, ethosuximidePartial - carbamazepine, valproate, phenytoin
22. Type 1st line drug2nd line drugsPartial &/or secondary GTCSCarbamazepineLamotrigineTopiramateGabapentinSodium valporateTiagabine Primary GTCSSodium valporateLamotrigineTopiramateCarbamazepineAbsenceEthosuximideSodium valporateMyoclonicSodium valporateLamotrigine
23. Immediate hospital admissionImmediate diazepam 10-20mg IV, if immediate IV access impossible PR diazepam or paraldehydeAdminister O2Monitor ECG, BP, routine bloods (include alcohol, Ca, Mg, drug screen, anticonvulsant levels)Exclude hypoglycaemia – IV glucose if presentIV thiamine 250mg – if nutrition poor or alcohol abuse suspectedManagement of status epilepticus
24. AnticonvulsantsIV lorazepam 4mg at 3mg/minReinstate previous anticonvulsant drugsIf seizure continue – IV phenytoin 15mg/kg (if pt hasn’t had phenytoin recently)If status continue – IV phenobarbitol 10mg/kg Despite above measures if status persist > 90min, use thiopental anaesthesia with assisted ventilationEEG monitoringCT scan – underlying pathologyMx of unwanted effects of drugs
25. CarbamazepineHas a wider therapeutic indexCarbamazepine stabilizes the inactivated state of sodium channels, meaning that fewer of these channels are available to subsequently open, making brain cells less excitable (less likely to fire)
26. SE include nausea, vomiting, drowsiness, headache, ataxia, blood disorders, arthralgia
27. PhenytoinBlocks sodium-dependent action potentials; reduces neuronal calcium uptake and suppress the abnormal brain activity seen in seizure
28. Nerological SE include at therapeutic doses; nystagmus, which is harmless At toxic doses, SE include sedation, ataxiaOther SE include rash and severe allergic reactions.Hematologic SE: Reduction in folic acid levels, predisposing to megaloblastic anemia
29. Phenytoin has been associated with drug induced gingival enlargement (hyperplasia. Phenytoin is a known teratogenOther SE
30. ValproateReduces high-frequency neuronal firing and sodium-dependent action potentials; enhances GABA effects Indicated in all forms of epilepsySE include GI disturbances, ataxia, tremor, increased appetite and weight gain, transient hair loss, thrombocytopenia, inhibition of platelet aggregation, impaired hepatic function,
31. BenzodiazepinesClonazepamClobazam Occasionally use
32. EthosuximideIndicated in absence seizuresSE include GI disturbances,, ataxia, headache, depression, photophobia, hematological disorders
33. If not responding to treatmentPoor complianceInadequate doseWrong drugWrong diagnosisUnderlying progressive diseaseTriggers - alcohol
34. Withdrawal of medicationIf free of seizures for 3 –5 yearsRisk of seizure recurrence to be discussed with patientWithdraw slowly over a period of months to minimize relapse
35. Surgical treatmentFor drug resistant epilepsyFocal epilepsy- temporal lobe type – mesial temporal sclerosis - do a temporal lobectomy
36. What is unsafeDrivingRecreation – swimmingCooking - open fireEmployment – armed forces, machinery
37. Social stigmaSchool attendance is poor and drop out rate highFamily stops schooling and prevents participation in sports and other recreational activities Difficulty in obtaining a partner for marriageFear about pregnancy and child bearingFinding and keeping a job is the biggest challenge
38. Questions?
39. THANK YOU