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Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
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Antiseizure drugs
Antiseizure drugs
Antiseizure drugs
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Antiseizure drugs

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  • 1. ANTISEIZURE DRUGS Zenaida N. Maglaya,MD,FPSECP Department of Pharmacology
  • 2. SEIZURE <ul><li>Finite episodes of brain dysfunction resulting from abnormal discharge of cerebral neurons. </li></ul><ul><li>EPILEPSY: disorder </li></ul><ul><li>PRIMARY SEIZURES: idiopathic </li></ul><ul><li>SECONDARY SEIZURES: primary problem </li></ul>
  • 3. CLASSIFICATION OF EPILEPTIC SEIZURES <ul><li>I. PARTIAL SEIZURES </li></ul><ul><li>Simple partial seizures </li></ul><ul><li>Complex partial seizures </li></ul><ul><li>Partial w/ secondarily generalized tonic clonic </li></ul><ul><li>seizures </li></ul>
  • 4. II. GENERALIZED SEIZURES <ul><li>Generalized tonic-clonic (grand mal seizures) </li></ul><ul><li>Absence (petit mal) seizures </li></ul><ul><li>Myoclonic seizures </li></ul><ul><li>Febrile Seizures </li></ul><ul><li>Status Epilepticus </li></ul>
  • 5. PRIMARY DRUGS <ul><li>CARBAMAZEPINE </li></ul><ul><li>PHENYTOIN </li></ul><ul><li>VALPROIC ACID </li></ul><ul><li>PHENOBARBITAL </li></ul><ul><li>PRIMIDONE </li></ul><ul><li>DIAZEPAM /LORAZEPAM CLONAZEPAM </li></ul><ul><li>ETHOSUXIMIDE </li></ul>
  • 6. ADJUNCTIVE DRUGS <ul><li>FELBAMATE GABAPENTIN </li></ul><ul><li>LAMOTRIGINE TIAGABINE </li></ul><ul><li>TOPIRAMATE VIGABATRIN </li></ul><ul><li>LEVETIRACETAM ZONISAMIDE </li></ul>
  • 7. ANTISEIZURES CLASSIFICATION <ul><li>I. TONIC-CLONIC SEIZURES </li></ul><ul><li>Carbamazepine. valproic acid, Phenytoin, Primidone, Phenobarbital </li></ul><ul><li>Recent: Lamotrigine, Topiramate </li></ul>
  • 8. II.ABSENCE SEIZURES Ethosuximide, valproic acid, clonazepam Recent: Lamotrigine III MYOCLONIC SEIZURES Valproic acid, clonazepam Recent: Lamotrigine /topiramate
  • 9. PARTIAL SEIZURES <ul><li>SIMPLE/PARTIAL: </li></ul><ul><li>CARBAMAZEPINE, VALPROATE </li></ul><ul><li>PHENYTOIN, </li></ul><ul><li>Recent : gabapentin, tiagabine lamotrigine,levetiracetam topiramate, zonisamide </li></ul>
  • 10. PARTIAL W/ 2 0 GENERALIZED TONIC-CLONIC SEIZURES CARBAMAZEPINE, VALPROATE PHENOBARBITAL PHENYTOIN Recent : gabapentin, tiagabine lamotrigine,levetiracetam, topiramate, zonisamide
  • 11. MECHANISM OF ACTION <ul><ul><li>Inhibition of sodium channels function : </li></ul></ul><ul><ul><li>phenytoin VALPROATE </li></ul></ul><ul><ul><li>Carbamazepine </li></ul></ul><ul><ul><li>lamotrigine </li></ul></ul><ul><ul><li>Topiramate </li></ul></ul><ul><ul><li>zonisamide </li></ul></ul>
  • 12.  
  • 13. Mechanism of Action <ul><ul><li>Inhibition of calcium channel function: </li></ul></ul><ul><ul><li>ethosuximde </li></ul></ul><ul><ul><li>VALPROATE </li></ul></ul>
  • 14.  
  • 15. MECHANISM OF ACTION <ul><ul><li>Enhancement of GABA action : </li></ul></ul><ul><ul><li>benzodiazepines,phenobarbital gabapentin,vigabatrin, tiagabine </li></ul></ul><ul><ul><li>VALPROATE </li></ul></ul>
  • 16.  
  • 17. PHENYTOIN <ul><li>BLOCK SODIUM CHANNELS </li></ul><ul><li>Modify pattern of maximal electroshock seizures but not inhibit clonic seizures by pentylenetetrazole </li></ul><ul><li>USE: </li></ul><ul><li>partial seizures; </li></ul><ul><li>generalized tonic-clonic seizures </li></ul>
  • 18. PHENYTOIN <ul><li>Oral, IV </li></ul><ul><li>highly bound to plasma proteins </li></ul><ul><li>T ½ 12 -36 hrs </li></ul><ul><li>Metabolized, dose dependent elimination </li></ul><ul><li>Fosphophytoin </li></ul>
  • 19. Phenytoin Adverse Effects <ul><li>nystagmus, diplopia, ataxia, sedation, gingival hyperplasia & hirsutism, coarsening of facial features, mild peripheral neuropathy, megaloblastic anemia fever, skin rash </li></ul><ul><li>fetal hydantoin syndrome </li></ul>
  • 20. PHENYTOIN DRUG INTERACTIONS <ul><li>Sulfonamides, valproate & phenylbutazone: displace phenytoin from binding sites </li></ul><ul><li>2. Cimetidine, disulfiram, doxycycline, isoniazid, phenylbutazone, sulfas, warfarin, chloramphenicol: i nhibits phenytoin metabolism </li></ul>
  • 21. PHENYTOIN DRUG INTERACTIONS <ul><li>3.Barbiturates & carbamazepine, pyridoxine, theophylline: enhance phenytoin metabolism </li></ul><ul><li>4.PHENYTOIN decreases serum levels of: carbamazepine, chloramphenicol,corticosteroids, haloperidol, quinidine, theophylline, oral contraceptives </li></ul><ul><li>warfarin </li></ul>
  • 22. CARBAMAZEPINE (IMINOSTILBENES) <ul><li>BLOCK SODIUM CHANNELS </li></ul><ul><li>DOC for partial seizures </li></ul><ul><li>Generalized tonic-clonic seizures </li></ul><ul><li>Trigeminal neuralgia </li></ul><ul><li>Mania:bipolar disorders </li></ul><ul><li>Orally absorbed with slow distribution </li></ul><ul><li>Completely metabolized </li></ul>
  • 23. CARBAMAZEPINE Adverse EFfects <ul><li>diplopia & ataxia </li></ul><ul><li>idiosyncratic blood dyscrasias, </li></ul><ul><li>aplastic anemia </li></ul><ul><li>agranulocytosis </li></ul><ul><li>leukopenia </li></ul>
  • 24. CARBAMAZEPINE DRUG INTERACTIONS <ul><li>1. I ncreas e carbamazepine levels via metabolism: cimetidine, erythromycin, isoniazid </li></ul><ul><li>2. Decrease carbamazepine levels via increase metabolism: phenytoin, valproic acid </li></ul><ul><li>3. Carbamazepine decreases drug levels :warfarin, oral contraceptives, doxycycline, phenytoin, haloperidol </li></ul>
  • 25. CARBAMAZEPINE Drug Interactions 4. Carbamazepine increases drug levels : cimetidine, isoniazid 5. Lithium induces carbamazepine toxicity.
  • 26. PHENOBARBITAL <ul><li>Inhibits tonic hind limb extension in the maximal electroshock model, clonic seizures evoked by pentylenetrazol, and kindled seizures </li></ul><ul><li>Enhancement of inhibitory process </li></ul><ul><li>Dimimution of excitatory transmission </li></ul><ul><li>USE: </li></ul><ul><li>partial & generalized tonic-clonic seizures </li></ul>
  • 27. PHENOBARBITAL DRUG INTERACTIONS <ul><li>Increase phenobarbital levels via metabolism; acute ethanol ingestion, chloramphenicol, valproic acid </li></ul><ul><li>Decrease phenobarbital levels via increase metabolism, chronic alcohol ingestion, pyridoxine, rifampin </li></ul><ul><li>Barbiturates decrease serum levels: tricyclics, warfarin, beta blockers, oral contraceptives, digitoxin, doxycycline, metronidazole, theophyllline </li></ul>
  • 28. PRIMIDONE <ul><li>Metabolized to: </li></ul><ul><li>PHENOBARBITAL </li></ul><ul><li>PHENYLETHYLMALONAMIDE(PEMA) </li></ul><ul><li>Mechanism of action similar to phenytoin </li></ul><ul><li>May cause sedation, ataxia, vertigo, GIT upset, megaloblastic anemia </li></ul><ul><li>CI: porphyria, hypersensitivity </li></ul>
  • 29. VIGABATRIN <ul><li>Inhibits GABA transaminase </li></ul><ul><li>Partial seizures & ‘WEST syndrome </li></ul><ul><li>In patients unresponsive to conventional drugs </li></ul><ul><li>Rapid absorption </li></ul><ul><li>T ½ 6 -8 hrs </li></ul><ul><li>CAUSES: drowsiness, behavioral & mood changes, weight gain, visual field defect </li></ul>
  • 30. LAMOTRIGINE <ul><li>Inhibits sodium channels </li></ul><ul><li>Partial seizures </li></ul><ul><li>Absense seizures </li></ul><ul><li>Completely absorbed </li></ul><ul><li>T ½ of 24 hours </li></ul><ul><li>Broad therapeutic profile </li></ul><ul><li>CAUSES: hypersensitivity rxns, diplopia, ataxia, headache, dizziness, life threatening skin disorders, hematotoxicity </li></ul>
  • 31. FELBAMATE <ul><li>MOA : blocks glumate NMDA receptors </li></ul><ul><li>For partial seizures </li></ul><ul><li>Broad therapeutic profile </li></ul><ul><li>For intractable cases </li></ul><ul><li>T ½ is 20 hrs </li></ul><ul><li>CAUSES: severe hypersensitivity rxs aplastic anemia, hepatotoxicity ↑ </li></ul><ul><li>↑↑ plasma phenytoin & valproic acid </li></ul><ul><li>↓↓ carbamazepine levels </li></ul>
  • 32. GABAPENTIN <ul><li>MOA: alters GABA metabolism, its nonsynaptic release or its reuptake by GABA transporters </li></ul><ul><li>Also binds to the α 2 δ subunit of voltage sensitive calcium channels </li></ul><ul><li>FOR PARTIAL & GENERALIZED SEIZURE </li></ul><ul><li>CAUSE: somnolence, dizziness, ataxia, headache & tremor </li></ul>
  • 33. TOPIRAMATE <ul><li>Complex action: GABA effect, blocks voltage dependent sodium channels </li></ul><ul><li>Blocks glutamate receptors </li></ul><ul><li>Similar to phenytoin with lower side effects & simpler pharmacokinetics </li></ul><ul><li>Risk of teratogenesis </li></ul><ul><li>Sedation, mental dulling, renal stones, weight loss </li></ul>
  • 34. TIAGABINE <ul><li>Nicotinic acid derivative </li></ul><ul><li>GABA uptake inhibitor in both neurons & glia </li></ul><ul><li>Partial seizures </li></ul><ul><li>Dizziness, tremor, difficulty in concentration, psychosis </li></ul>
  • 35. LEVETIRACETAM <ul><li>A pyrolidine </li></ul><ul><li>Inhibits partial & secondarily generalized tonic- clonic seizures </li></ul><ul><li>MOA: unknown </li></ul><ul><li>Add on to drugs used for partial seizures </li></ul><ul><li>AE: somnolence, asthenia and dizziness </li></ul>
  • 36. ZONISAMIDE <ul><li>Inhibits the t-type Ca 2+ currents </li></ul><ul><li>Na + channels block </li></ul><ul><li>For partial & secondarily gen tonic clonic S </li></ul><ul><li>T1/2: 63 hrs </li></ul><ul><li>AE: somnolence, fatigue, nervousness, anorexia, ataxia </li></ul><ul><li>Phenytoin, pheno, carba ↓ its conc </li></ul><ul><li>Lamotrigine ↑ it </li></ul>
  • 37. ETHOSUXIMIDE <ul><li>DOC for absense seizures </li></ul><ul><li>↓ calcium channels (T type) currents </li></ul><ul><li>Inhibits NA/K/ ATPase, depresses the cerebral metabolic rate & inhibits GABA aminotransferase </li></ul><ul><li>Absorption is complete </li></ul><ul><li>Completely metabolized </li></ul>
  • 38. ETHOSUXIMIDE (Succinimides) <ul><li>ADVERSE EFFECTS </li></ul><ul><li>gastric distress </li></ul><ul><li>lethargy </li></ul><ul><li>headache </li></ul><ul><li>DI: valproic acid inhibits its metabolixm </li></ul>
  • 39. VALPROIC ACID <ul><li>On partial seizures sodium channel effects </li></ul><ul><li>Increased levels of GABA inhibits GABA transaminase & succinic semialdehyde dehydrogenase </li></ul><ul><li>Sodium channel blockade </li></ul>
  • 40. VALPROIC ACID <ul><li>CLINICAL USES: </li></ul><ul><li>1. ABSENCE SEIZURES </li></ul><ul><li>2. MYOCLONIC SEIZURES </li></ul><ul><li>3. GENERALIZED TONIC-CLONIC TYPE OF SEIZURES </li></ul><ul><li>4. ATONIC ATTACKS </li></ul><ul><li>5. PARTIAL SEIZURES </li></ul><ul><li>6. MIGRAINE PROPHYLAXIS </li></ul><ul><li>7. BIPOLAR DISORDER </li></ul>
  • 41. VALPROIC ACID <ul><li>Well absorbed; ppc within 2 hrs </li></ul><ul><li>Bioavailability > 80% </li></ul><ul><li>T ½ is 9 -18 hrs </li></ul><ul><li>CAUSES: nausea, vomiting, pain & heart burn, sedation uncommon, fine tremors, weight gain, increase in appetite & hair loss, hepatotoxicity, thrombocytopenia, </li></ul><ul><li>SPINA BIFIDA </li></ul>
  • 42. VALPROIC DRUG INTERACTIONS <ul><li>Decrease valproic acid levels from increase metabolism with carbamazepine </li></ul><ul><li>Increase valproic acid levels with antacid (increase absorption) </li></ul><ul><li>salicylates (displacements from binding sites) </li></ul><ul><li>When used with clonazepam may precipitate absence status </li></ul>
  • 43. BENZODIAZEPINES <ul><li>Diazepam, lorazepam, clonazepam, clorazepate, Nitrazepam, clobazam </li></ul><ul><li>Well absorbed, widely distributed </li></ul><ul><li>Extensively metabolized with many active metabolites </li></ul><ul><li>May cause sedation, tolerance </li></ul><ul><li>DIAZEPAM: DOC for status epilepticus </li></ul>
  • 44. STATUS EPILPETICUS <ul><li>DIAZEPAM </li></ul><ul><li>LORAZEPAM </li></ul><ul><li>PHENYTOIN </li></ul><ul><li>PHENOBARBITAL </li></ul>
  • 45. EFFECTIVE PLASMA LEVELS > 100 50 - 100 Valproic Acid > 100 50 -100 Ethosuximide > 40 10 - 40 Phenobarbital >20 10 - 20 Phenytoin > 8 4 - 12 Carbamzepine TOXIC LEVEL (ug/mL) Effective Level(ug/m DRUG
  • 46. THERAPEUTIC PRINCIPLES <ul><li>1 . When to initiate </li></ul><ul><li>2. Choice of a drug </li></ul><ul><li>Monotherapy </li></ul><ul><li>Combined therapy: adverse effects </li></ul><ul><li>drug interaction </li></ul><ul><li>3. Measurement of plasma drug concn </li></ul><ul><li>Compliance </li></ul><ul><li>toxicity </li></ul>
  • 47. THERAPEUTIC PRINCIPLES <ul><li>4. Duration of Therapy </li></ul><ul><li>at least 2 years </li></ul><ul><li>taper over several months </li></ul><ul><li>5. Infantile Spasms with hypsarrhythmia </li></ul><ul><li>Corticotropin/glucocorticoids </li></ul><ul><li>6. Lennox-Gastauf Syndrome: cognitive impairment, multiple types of seizures </li></ul><ul><li>+ lamotrigine </li></ul><ul><li>7. PREGNANCY </li></ul><ul><li>teratogenecity </li></ul>
  • 48. <ul><li>And we know that all things work together for good to those who love God, to those who who are called according to His purpose. </li></ul><ul><li>ROMANS 8: 28 </li></ul>Thank You!!!

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