Understanding Epilepsy: Seizure Types, Medications, and Side Effects

1. Brief blackout followed by period of confusion (the person cannot remember a period of time) • Frothing at the mouth • Eye movements • Loss of bladder or bowel control • Mood changes such as sudden anger, unexplainable fear, panic, joy, or laughter • Shaking of the entire body • Sudden falling • Tasting a bitter or metallic flavor • Teeth clenching • Temporary halt in breathing • Uncontrollable muscle spasms with twitching and jerking limbs

3. Epilepsy ??? group of disorders of the CNS with brief episodes (seizures) of loss of disturbance of consciousness with or without characteristic body movements

4. Classification of epilepsy GENERALISED SEIZURES • Generalised tonic-clonic seizures (GTC, grand mal): aura- unconsciousness-tonic spasm-clonic jerking –prolonged sleep-depression of all CNS functions. Commonest, lasts 1-2min 2.Absence seizures (petit mal) : momentary loss of consciousness, freezes and stares in one direction, no muscular compartment or jerking. prevalent in children 3. Atonic seizures(akinetic epilepsy): unconsciousness with relaxation of all muscles due to excessive inhibitory discharges. 4. Myoclonic seizures: shock-like momentary contraction of muscles of a limb or the whole body 5. Infantile spasm(hypsahythmia): intermittent muscle spasm and progressive mental deterioration

5. Partial seizures • Simple partial seizures(SPS, cortical focal): convulsions confined to a group of muscles or localised sensory disturbance, without loss of consciousness • Complex partial seizure : attacks of bizarre & confused behaviour and purposeless movements emotional changes lasting 2 min with impairment of consciousness. • Simple partial or complex partial seizures: the partial seizures occur first and evolve into generalised tonic clonic seizures with loss of consciousness

7. Classification • Barbiturate: Phenobarbitone • Deoxybarbiturate : Primidone • Hydantoin : Phenytoin, Fosphenytoin • Iminostilbene : Carbamazepine • Succimide : Ethosuximide

8. Classification 6. Aliphatic carboxylic acid: Valproic acid 7. Benzodiazepines: Clonazepam, Diazepam,Lorazepam, Clobazam 8. Phenyltriazine : Lamotrigine 9. Cyclic GABA analogue : Gabapentin 10. Newer drugs: Vigabatrin, Topiramate, Zonisamide, Levetiracetam

9. Phenobarbitone • Cheapest and least toxic • GABA receptor mediated synaptic inhibition • Generalised tonic clonic seizures (GTC), simple partial (SP), complex partial seizures • 60mg, 1-3 times a day in adults, status epilepticus • Adverse effects: sedation, behavioral abnormalities, impairment of learning & memory, hyperactivity in children, mental confusion

10. Phenytoin • Prolongs inactivated state of voltage sensitive neuronal Na+ channel

11. Phenytoin • Absorption by oral route is slow • widely distributed in the body and is 80-90% bound to plasma proteins. • Metabolized by hydroxylation & glucuronide conjugation, follows zero order kinetics

12. Adverse effects of Phenytoin At therapeutic levels: • Gum hypertrophy • Hirsutism • Coarsening of facial features • Hypersensitivity reactions • Megaloblastic anaemia • Osteomalacia • Hypergycemia • Fetal hydantoin syndrome

13. Adverse effects of Phenytoin At high plasma levels: • cerebellar and vestibular manifestations • drowsiness, • mental confusion & hallucination • epigastric pain, • fall in BP • cardiac arrhythmia

14. Phenytoin Interactions • Phenobarbitone inhibits phenytoin metabolism • Carbamazepine & phenytoin increase each others metabolism • Valproate displaces protein bound phenytoin • Chloramphenicol, isoniazid, cimetidine inhibits phenytoin metabolism • Phenytoin induces microsomal enzymes & increases degradation of steroids, OCPs

15. Phenytoin Uses • Generalized tonic-clonic, simple & complex partial seizures • Status epilepticus • Trigeminal neuralgia • Cardiac arrhythmia

16. Carbamazepine • MOA similar to phenytoin P.K- • oral absorption slow, 75% protein bound , metabolised by liver. • Half life20-40 hrs but decreases due to autoinduction A/E- • sedation, dizziness, vertigo • diplopia, ataxia • vomiting, diarrhoea • coma, cardiovascular collapse • hypersensitivity reactions • water retention Enzyme inducer

17. Carbamazepine Uses • Most effective for CPS • First choice- GTC, SPS • Trigeminal neuralgia- drug of choice • Manic depressive illness

18. Valproic acid MOA • Phenytoin like frequency dependant prolongation of Na + channel activation • Attenuation of Ca 2+ mediated T current • Augmentation of release of GABA by inhibiting its degradation as well as increasing its synthesis P.K • oral absorption good, 90% protein bound, completely metabolised A/E • anorexia, vomiting, drowsiness, • tremor, alopecia, rashes, • hepatitis, pancreatitis, • spina bifida

19. Valproic acid Uses • drug of choice in absence seizures • GTCS, SPS, CPS • myoclonic & atonic seizures • mania & bipolar illness Interactions -plasma levels of phenobarbitone by inhibiting metabolism -displaces phenytoin from protein binding -valproate & carbamazepine induce each others metabolism

20. ETHOSUXIMIDE • Reduces low threshold of Ca2+ ‘T’ type current in thalamus PK • completely absorbed from GIT • not protein bound, evenly distributed in body • metabolized in liver. • Plasma half life - 48 hrs. A/E • tiredness, mood changes, agitation, headache, drowsiness, hypersensitivity reaction. USES - Absence seizures.

21. DIAZEPAM • Drug of Choice for Emergency control of Convulsions, Tetanus, Febrile convulsions in children – Rectally. • Sedative action, • Rapid Development of Tolerance.

22. CLONAZEPAM • Primarily used in absence seizures. • Adjuvant in Myoclonic, Akinetic Epilepsy CLOBAZAM • Partial, secondarily generalized tonic-clonic, absence, myoclonic, atonic seizures including Respiratory cases.

23. Choice of Antiseizure Drugs