Epilepsy.ppt
- 1. Epilepsy and Antiepileptic drugs
- 2. Epilepsy Seizure associated with the episodic high- frequency discharge of impulses by a group of neurons in the brain Starts as a local abnormal discharge may then spread to other areas of the brain Site of the primary discharge and extent of its spread determine symptoms that are produced
- 3. The particular symptoms produced depend on the function of the region of the brain that is affected Involvement of motor cortex- convulsions hypothalamus-peripheral autonomic discharge reticular formation in the upper brain stem - loss of consciousnes
- 4. Types of epilepsy A. Generalized seizures Generalized tonic-clonic (grand mal) seizures Absence (petit mal) seizures Atonic seizures Clonic and myoclonic seizures Infantile spasm (hypsarrhythmia)
- 5. B. Partial seizures Simple partial seizures Complex partial seizures Partial seizures secondarily generalized Types of epilepsy
- 6. A.Generalized seizures(GS) Involves the whole brain Abnormal electrical activity throughout both hemispheres Immediate loss of consciousness
- 7. 1.Generalized tonic-clonic seizures(grand mal, major epilepsy) - GTCS Tonic phase (< 1 min) Sudden loss of consciousness Patient become rigid and falls to ground , respiration arrested Clonic phase (2mins) -Jerking of the body musculature Clonic phase followed by prolonged sleep and depression of all CNS functions defecation, micturition and salivation often occur Generalized seizures
- 8. Immediately after the seizure the patient may recover consciousness drift in to sleep have further convulsion (status epilepticus or serial seizure) Convulsion with out recovery of consciousness (status epilepticus)- May lead to brain damage and death Further convulsion, after recovering consciousness (serial seizure) grand mal
- 9. 2. Absence (petit mal) seizures minor epilepsy Prevalent in child and cease at the age of 20 Momentary loss of consciousness, patient freezes and stares in one direction Onset and termination of attacks are abrupt Patient abruptly ceases whatever he/she was doing Impairment of external awareness is so brief that patient is unaware of it Many seizures each day may occur as compared to GTCS Generalized seizures
- 10. 3. Atonic seizures (akinetic epilepsy) Unconsciousness with relaxation of all muscles due to excessive inhibitory discharges 4.Clonic and myoclonic seizures Shock like momentary movement, contraction of muscles of a limb or whole body 5.Infantile spasm ( hypsarrythmia) Intermittent muscle spasm and progressive mental deterioration Epileptic syndrome rather than a specific seizure type Generalized seizures
- 11. B. Partial seizure The discharge begins locally and often remains localized Symptoms depend on the brain region/regions involved involuntary muscle contractions abnormal sensory experiences autonomic discharge effects on mood and behaviour (psychomotor epilepsy) The EEG discharge in this type of epilepsy is normally confined to one hemisphere
- 12. 1.Simple partial seizures (cortical focal epilepsy) Lasts 0.5 1 min Convolutions are confined to a group of muscles or localized sensory disturbance depends on the area of cortex involved E.g. If motor cortex supplying to left thumb is affected then jerking of left thumb occurs With out loss of consciousness Partial seizure
- 13. 2. Complex partial seizures (temporal lobe epilepsy, psychomotor) Confused behaviors, purposeless movements, emotional changes Seizure focus is located in temporal lobe 3. Simple or complex partial seizures secondarily generalized Partial seizures occurs followed by GTCS with loss of consciousness Partial seizure
- 14. Possible causes of seizures primary (idiopathic) most of the cases secondary to trauma/ surgery on head, intracranial tumor, tuberculoma,cerebral ischemia, etc
- 15. Mechanism of action of antiepileptic drugs 1. Enhancement of GABA action Barbiturates & BZDs Vigabartrin and valproat (GABA transaminase inhibitor)-increase synaptic GABA conc. Gabapentin (increase GABA release from presynaptic neuron) Tiagabine (inhibit GABA reuptake to presynapticneuron) All these facilitate GABA mediated Cl- channel opening and end up with inhibitory effect
- 16. 2. Inhibition of Na+ channel function Drugs: Phenytoin, Carbamazepine, Valproic acid, Lamotrigine, Topiramate, Zonisamid prolong Na+channel inactivation state 3. Inhibition of Ca 2+ channel function Drugs: Ethosuximide, Trimethadione, Valproate Inhibit T-type Ca2+ current Mechanism of action of antiepileptic drugs
- 17. Phenytoin (diphenylhydantoin) Oldest nonsedative antiseizure drug Used against partial seizures and generalized tonic-clonic seizures Mechanism of action Prolonging inactive state of voltage sensitive Na+ channel------ use-dependent effect Inhibition of high frequency discharge with little effect on low frequency discharges At high/ toxic conc: reduce ca 2+ influx, inhibition of glutamate and facilitate GABA responses Individual drugs
- 18. Adverse effects At therapeutic concentration Gum hypertrophy/ gingival hyperplasia (20%) Hirsutism, coarsening of facial feature, acne Megaloblastic anemia(decrease absorption and increased excretion of folate) Abnoramal Vit D, Vit K and Ca+ metabolism (Osteomalecia, Hemorrhage) Hyperglycemia / inhibit insulin release Fetal hydantoin syndrome (hypoplastic phalanges, cleft palate, microcephally ) Phenytoin
- 19. At high plasma level Dose related toxicity -Ataxia, vertigo,diplopia, nystagmus -drowsiness, behavioral alterations ,mental confusion , hallucination -Epigastria pain, nausea and vomiting Phenytoin adverse effects
- 20. Drug interaction Drug interactions related to plasma protein binding or drug metabolism 90% plasma proteins binding Hypoalbuminemia and drugs which displace phenytoin from plasma proteins alter total plasma conc. of the drug Phenytoin induce microsomal enzymes Enhance metabolism of drugs which get metabolized by microsomal enzyme Phenytoin
- 21. Fosphenytion Water soluble prodrug of phenytoin Introduced to over come difficulties in i.v. administration of phenytoin in status epilepticus
- 22. Phenobarbitone Effective against GTC,SP and CP seizures Can be used for status epilepticus but with slow onset of action Ineffective in absence seizure less commonly used than phenytoin, carbamazepam,or valproate Similar clinical use as phenytoin Phenytoin is preferred because of the absence of sedation
- 23. Mechanism of action Exact mechanism of action is unknown Probably through enhancement of inhibitory processes and diminution of excitatory transmission Binds to allosteric regulatory site of GABAA receptor ( inhibitory effect) Enhances the GABA receptor-mediated current by prolonging the openings of the Cl- channels Inhibiting excitatory responses by glutamate Phenobarbitone
- 24. Adverse effects Sedation Tolerance and dependence with prolonged use Hypersensitivity Nystagmus and ataxia occur at excessive dosage Agitation and confusion in the elderly Irritability and hyperactivity in children Phenobarbitone
- 25. Drug interaction Additive effect with CNS depressants Induce metabolism of many drugs (warferin,oral contraceptives,chloramphinicol,theophyline,griseof ulvin) Phenobarbitone competitively inhibits as well as induces phenytoin and impramine metabolism It decrease GIT absorption of griseofulvin Plasma conc increased by sodium valproat Phenobarbitone
- 26. Carbamazepine Is tricyclic compound and closely related to TCA Pharmacological actions resemble phenytoin Exert lithium like therapeutic effect in mania and bipolar mood disorder Effective in most forms of epilepsy (except absence seizures) Particularly effective in psychomotor epilepsy (CPS)
- 27. Adverse effects Sedation, dizzines, vertigo, diplopia,and ataxia Vomiting, diarrhoea Worsening of seizure with higher dose Water retention and hyponatremia Foetal malformation reported Teratogenesity doubled if combined with valproate Carbamazepine
- 28. Drug interaction Enzyme inducer Its metabolism induced by phenobarbitone, phenytoin, valproate and vice vesa Erythromycine, fluoxetine and isoniazid inhibit carmamazepine metabolism Carbamazepine
- 29. Valproic acid (sodium valproate) Effective against GTCS, partial seizures as well as absence seizures Ethosuximide is the drug of choice when absence seizures alone occur Valproate is better in mixed absence seizures and GTCS Mixed absence seizures and GTCS is more common than pure absence seizures
- 30. Mechanism of action Phenytoin like frequency dependent prolongation of Na+ channel inactivation Effect on GABA metabolism (degradation & uptake inhibition, increase synthesis from glutamic acid) Adverse effects (low toxicity) Anorexia, vomiting, hear burn, drowsiness, ataxia, tremor Spinal bifid and other neural tube defects in the offspring( during pregnancy) valproate
- 31. Drug interaction Inhibit phenobarbitone metabolism Displaces phenytoin plasma protein binding and decrease metabolism (phenytoin toxicity) Valproate and carbamazepine induce each others metabolism Foetal abnormality if valproate and carbamazepine given together valproate
- 32. Ethosuximide Introduced as a "pure petit mal" drug Drug used to treat absence seizures and may exacerbate other forms Both ethosuximide and valproate are equally effective for absence seizure However, valpraote is more commonly used Mechanism of actions : blocking T-type calcium channels Relatively few unwanted effects mainly nausea and anorexia
- 33. Other drugs Topiramate & lamotrigine Felbamate, zonisamide & levatiracetum Vigabatrine,Gabapentine & Tiagabine Oxazolidinediones ( trimethadione, dimethadione & paramethadione) BZDs (diazepam & clonazepam)
- 34. Drug of choice for. 1.GTCS/ SP with or with out generalization 1st choice: carbamazepine, phenytoin 2nd choice : valproate, phenobarbitone 2. Complex partial with or with out generalization 1st choice : carbamazepine,valproate, phenytoin 2nd choice: gabapentin,lamotrigine 3. Absence seizure 1st choice: valproate , 2nd choice: ethosuximide,lamotrigine
- 35. 4. Status epilepticus 1st choice: diazepam(i.v.), lorazepam(i.v.) 2nd choice: fosphenytoin, phenobarbitone Alternative/add on drugs : general anesthetics