Anticonvalsant Drug for the treatment of convulsion

Drugs used in the treatment of major and minor seizure

1. Anticonvulsant /Antiepileptic drugs Dr. Afsana Ferdous Associate Professor Department of Pharmacology Rangpur Medical College

2. Chemical classification Barbiturates & related drug: Phenobarbitone , Mephobarbitone Primidone Hydantoins : Phenytoin , Mephenytoin Fosphenytoin , Ethotoin Succinimides : Ethosuximide , Methosuximide Phensuximide

3. c onti … Oxazolidinediones - Trimethadione Paramethadione Benzodiazepines- Clonazepam Lorazepam Diazepam Oxazepam Miscellaneous Carbamazepine Valproic acid ACTH General Anesthetics d- cubocurarine Succinyl choline Newer drugs- Lamotrizine Gabapentine Oxcarbazepine Vigabatrin Topiramate Felbamate .  

4. According to mechanism of action Enhancement of GABA- ergic transmission/Facilitation of GABA mediated Cl- channel opening. e.g. Phenobarbitone Benzodiazepine Vigabatrin Na-valproate Gabapentine . Blockage of voltage sensitive Na+ channel/prolongation of Na+ channel inactivation e.g. Phenytoin Carbamazepine Lamotrigine Topiramate Valproic acid Na-valproate         

5. Cont. Blockage of T-type Ca++ channel e.g. Ethosuximide Phensuximde Methsuximide Trimethadione Valproate      

6. Guideline for anti- convulsant therapy Start with one first line drug. Start with low dose & increase gradually to control seizer & side effect. Check complains of pts. If 1 st line drug fails start with 2 nd line & gradually withdraw 1 st Be aware of drug interaction Don’t use more than two drugs in combination    If above measures fail, try to locate structural & metabolic lesion if present.      

7. Status Epilepticus 1 . Immediate care- * First aid by relative & witness * Move person away from danger (fire, water, machinery, ) * Ensure airway is clear. * Don’t insert anything in the mouth to prevent tongue bite. * If convulsion continue for than 5 minute urgent medical attention is needed. * If person regain consciousness he/she will remain drowsy or confused for 30-60 min.& should not be left alone until full recovery .

8. conti … 2 . Open I/V channel. 3. Draw blood for glucose, electrolyte & save for future analysis. 4.Give diazepam I/V or per rectally & repeats once after 15min. Or Lorazepam 4mg I/V. 5.Transfer to intensive care unit for monitoring neurological condition , BP , respiration & blood gasses.    

9. conti … Start anticonvulsant drug in the following way- Na+ valproate 10mg/Kg body weight I/V over 3-5 min. & then 800-2000 mg/day. Or, Phenytoin giving loading dose of 15mg/kg body weight & infuse less than 50mg/min. & daily dose 300mg /day. Or, Carbamazepin 400mg by a nasogastric tube & then 400-1200mg/day. Investigate immediately the cause.  

10. Phenytoin M/A- Blocks voltage sensitive Na+ channels---------  ----- Inhibits generation of rapidly repetitive action potentials ----- antiepileptic effects. Indications – Partial seizures GTCS Anti dysrrthymic Adverse effects of phenytoin- Nystagmus Diplopia Ataxia Gingival hyperplasia Hirtutism in female Sedation Hypersensivity Teratogenecity . Incase of long term use- Osteomalacia Megaloblastic anemia Mild peripheral neuropathy

11. Carbamazepine M/A- Same as Phenytoin Indications – Partial seizure GTCS Trigeminal neuralgia Mania Adverse effects— Diplopia Ataxia Mild GIT upset Drowsiness Hyponatremia & water retention. In long term use- Aplastic anemia Agranulocytosis Mild & persistent leucopenia

12. Questions Common adverse effects of phenytoin/carbamazepine Safe drug in pg.- Lamotrizine Carbamazepine Common fetal abnormality--> Cleft lips Cleft palate Spina bifida Congenital heart disease Slow growth & mental deficiency Drug interaction with OCP. Pharmacokinetic profile of phenytoin

13. Sleep Normal sleep pattern is two types characterized by movement of eye- NREM & REM . NREM sleep occurs first then REM sleep, occurs cyclically throughout the total period of sleep at the interval of 90min. REM sleep covers the 20-25% of total sleep . By decreasing the latency of sleep onset. By decreasing the duration of NREM sleep. By increasing the duration REM sleep. By decreasing the duration of slow wave sleep .

14. Anti-parkinsonism drugs 1.Drugs that increase central dopaminergic activity. a. Dopamine precursor- Levodopa b. Dopamine agonist- Bromocriptine Pargolide Pramipexole Ropinirole c. Increase synthesis, release & reuptake of dopamine- Amantidine d. Decrease dopamine metabolism- *MAO inhibitors- Selegiline , Rasagiline *COMT inhibitors- Tolcapone , Entacapone . 2)Drugs that decrease cholinergic activity- Procyclidine , Benztropine , Biperidine . *   Justify the combination use of Levoda & Carbidopa.

15. Anti-parkinsonism drugs Drugs causing parkinsonism: a. All antipsychotic drugs: Chlorpromazine Haloperidol b. Dopaminergic neuron blocker- Reserpine Tetrapenazine c. Metoclopramide d. A-methyl dopa e. Valproic acid *   Justify the combination use of Levodopa & Carbidopa . * Role of procyclidine in parkinsonism.