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ANTISEIZURE DRUGS

ANTISEIZURE DRUGS. Zenaida N. Maglaya,MD,FPSECP Department of Pharmacology. SEIZURE. Is a finite episodes of brain dysfunction resulting from abnormal discharge of cerebral neurons. PRIMARY SEIZURES SECONDARY SEIZURES. CLASSIFICATION OF SEIZURE TYPES. PARTIAL SEIZURES

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ANTISEIZURE DRUGS

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  1. ANTISEIZURE DRUGS Zenaida N. Maglaya,MD,FPSECP Department of Pharmacology

  2. SEIZURE • Is a finite episodes of brain dysfunction resulting from abnormal discharge of cerebral neurons. • PRIMARY SEIZURES • SECONDARY SEIZURES

  3. CLASSIFICATION OF SEIZURE TYPES PARTIAL SEIZURES • Simple partial seizures • Complex partial seizures • Partial seizures secondarily generalized

  4. CLASSIFICATION OF SEIZURE TYPES GENERALIZED SEIZURES • Generalized tonic-clonic (grand mal) Sz • Absence (petit mal) seizures • Tonic/ Atonic Seizures • Clonic & myoclonic seizures • Infantile Spasms • Febrile Seizures • Status Epilepticus

  5. PRIMARY DRUGS • CARBAMAZEPINE • PHENYTOIN • VALPROIC ACID • PHENOBARBITAL • PRIMIDONE • DIAZEPAM /LORAZEPAM • CLONAZEPAM • ETHOSUXIMIDE

  6. ADJUNCTIVE DRUGS FELBAMATE GABAPENTIN LAMOTRIGINE TIAGABINE TOPIRAMATE VIGABATRIN LEVETIRACETAM ZONISAMIDE

  7. ANTISEIZURES CLASSIFICATION I. TONIC-CLONIC & PARTIAL SEIZURES • Carbamazepine. Phenytoin, valproic acid II.ABSENCE SEIZURES • Ethosuximide, valproic acid, clonazepam III MYOCLONIC SEIZURES • Valproic acid, clonazepam IV. ADJUNCT/NEWER ANTICONVULSANTS

  8. MECHANISM OF ACTION • Inhibition of sodium channels function: phenytoin, carbamazepine, lamotrigine • Inhibition of calcium channel function:ethosuximde • Enhancement of GABA action: benzodiazepines,phenobarbital gabapentin,vigabatrin, tiagabine • Multiple & Complex Mechanism: Valproic Acid

  9. PHENYTOIN • BLOCK SODIUM CHANNELS • USE: partial seizures; generalized tonic-clonic seizures, Antiarrhymic drug0 • Oral, IV • highly bound to plasma proteins • T ½ 12 -36 hrs • Metabolized, dose dependent elimination • Fosphophytoin, mephenytoin, ethotoin. • phenacemide

  10. Phenytoin Adverse Effects • nystagmus, diplopia, ataxia, sedation, gingival hyperplasia & hirsutism, coarsening of facial features, mild peripheral neuropathy, megaloblastic anemia fever, skin rash, fetal hydantoin syndrome

  11. PHENYTOIN DRUG INTERACTIONS • Sulfonamides, valproate & phenylbutazone: displace phenytoin from binding sites • Cimetidine, disulfiram, doxycycline, isoniazid, phenylbutazone, sulfas, warfarin, chloramphenicol: inhibits phenytoin metabolism

  12. PHENYTOIN DRUG INTERACTIONS 3.Barbiturates & carbamazepine, pyridoxine, theophylline: enhance phenytoin metabolism 4.PHENYTOIN decreasesserum levels of: carbamazepine, chloramphenicol, corticosteroids, haloperidol, quinidine, theophylline, oral contraceptives, warfarin

  13. CARBAMAZEPINE • BLOCK SODIUM CHANNELS • DOC for partial seizures • Generalized tonic-clonic seizures • Trigeminal neuralgia • Mania:bipolar disorders • Orally absorbed with slow distribution • Completely metabolized • CAUSE: diplopia & ataxia, idiosyncratic blood dyscrasias, aplastic anemia & agranulocytosis, leukopenia

  14. CARBAMAZEPINE DRUG INTERACTIONS 1. Increase carbamazepine levels via metabolism: cimetidine, erythromycin, isoniazid 2. Decrease carbamazepine levels via increase metabolism: phenytoin, valproic acid 3. Carbamazepine decreases drug levels :warfarin, oral contraceptives, doxycycline, phenytoin, haloperidol 4. Carbamazepine increases drug levels : cimetidine, isoniazid 5. Lithium induces carbamazepine toxicity.

  15. PHENOBARBITAL • Enhancement of inhibitory process • Dimimution of excitatory transmission • USE: partial seizures, generalized tonic-clonic seizures • May cause: CNS depression • Tolerance & dependence CI in porphyria disorders

  16. PHENOBARBITAL DRUG INTERACTIONS • Increase phenobarbital levels via metabolism; acute ethanol ingestion, chloramphenicol, valproic acid • Decrease phenobarbital levels via increase metabolism, chronic alcohol ingestion, pyridoxine, rifampin • Barbiturates decrease serum levels: tricyclics, warfarin, beta blockers, oral contraceptives, digitoxin, doxycycline, metronidazole, theophyllline

  17. PRIMIDONE • Metabolized to: • PHENOBARBITAL • PHENYLETHYLMALONAMIDE(PEMA) • Mechanism of action similar to phenytoin • May cause sedation, ataxia, vertigo, GIT upset, megaloblastic anemia • CI: porphyria, hypersensitivity

  18. VIGABATRIN • Inhibits GABA transaminase • Partial seizures & ‘WEST syndrome • In patients unresponsive to conventional drugs • Rapid absorption • T ½ 6 -8 hrs • CAUSES: drowsiness, behavioral & mood changes, weight gain, visual field defect

  19. LAMOTRIGINE • Inhibits sodium channels • Partial seizures • Absense seizures • Completely absorbed • T ½ of 24 hours • Broad therapeutic profile • CAUSES: hypersensitivity rxns, diplopia, ataxia, headache, dizziness, life threatening skin disorders, hematotoxicity

  20. FELBAMATE • MOA is unknown • For partial seizures • Broad therapeutic profile • For intractable cases • T ½ is 20 hrs • CAUSES: severe hypersensitivity rxs aplastic anemia, hepatotoxicity • Increase plasma phenytoin & valproic acid • Decrease carbamazepine levels

  21. GABAPENTIN • MOA: alters GABA metabolism, its nonsynaptic release or its reuptake by GABA transporters • Also binds to the α2δ subunit of voltage sensitive calcium channels • FOR PARTIAL & GENERALIZED SEIZURES • SATURABLE ABSORPTION CAUSE: somnolence, dizziness, ataxia, headache & tremor

  22. TOPIRAMATE • Complex action: GABA effect, blocks voltage dependent sodium channels • Similar to phenytoin with lower side effects & simpler pharmacokinetics • Risk of teratogenesis • Sedation, mental dulling, renal stones, weight loss

  23. TIAGABINE • Nicotinic acid derivative • GABA uptake inhibitor in both neurons & glia • Partial seizures • Dizziness, tremor, difficulty in concentration, psychosis

  24. ETHOSUXIMIDE • DOC for absense seizures • Effect on calcium channels( reduce low threshold (T type) currents • Inhibits NA/K/ ATPase, depresses the cerebral metabolic rate & inhibits GABA aminotransferase • Absorption is complete • Completely metabolized • CAUSES; gastric distress, lethargy & headache • DI: valproic acid inhibits its metabolixm

  25. VALPROIC ACID • On partial seizures sodium channel effects • Increased levels of GABA inhibits GABA transaminase & succinic semialdehyde dehydrogenase • Sodium channel blockade

  26. VALPROIC ACID • CLINICAL USES: 1. ABSENCE SEIZURES 2. MYOCLONIC SEIZURES 3. GENERALIZED TONIC-CLONIC TYPE OF SEIZURES 4. ATONIC ATTACKS 5. PARTIAL SEIZURES 6. MIGRAINE PROPHYLAXIS 7. BIPOLAR DISORDER

  27. VALPROIC ACID • Well absorbed; ppc within 2 hrs • Bioavailability > 80% • T ½ is 9 -18 hrs • CAUSES: nausea, vomiting, pain & heart burn, sedation uncommon, fine tremors, weight gain, increase in appetite & hair loss, hepatotoxicity, thrombocytopenia, • SPINA BIFIDA

  28. VALPROIC DRUG INTERACTIONS • Decrease valproic acid levels from increase metabolism with carbamazepine • Increase valproic acid levels with antacid (increase absorption) • salicylates (displacements from binding sites) • When used with clonazepam may precipitate absence status

  29. BENZODIAZEPINES • Diazepam, lorazepam, clonazepam, clorazepate, Nitrazepam, clobazam • Well absorbed, widely distributed • Extensively metabolized with many active metabolites • May cause sedation, tolerance • DIAZEPAM: DOC for status epilepticus

  30. STATUS EPILPETICUS • DIAZEPAM • LORAZEPAM • PHENYTOIN • PHENOBARBITAL

  31. EFFECTIVE PLASMA LEVELS

  32. Thank You!!! 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. ROMANS 8: 28

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