ANTISEIZURE DRUGS Zenaida N. Maglaya,MD,FPSECP Department of Pharmacology
SEIZURE <ul><li>Finite episodes of brain dysfunction resulting from abnormal discharge of cerebral neurons. </li></ul><ul>...
CLASSIFICATION OF EPILEPTIC SEIZURES <ul><li>I. PARTIAL SEIZURES </li></ul><ul><li>Simple partial seizures </li></ul><ul><...
II. GENERALIZED SEIZURES <ul><li>Generalized tonic-clonic (grand mal seizures) </li></ul><ul><li>Absence (petit mal) seizu...
PRIMARY DRUGS <ul><li>CARBAMAZEPINE </li></ul><ul><li>PHENYTOIN </li></ul><ul><li>VALPROIC ACID </li></ul><ul><li>PHENOBAR...
ADJUNCTIVE DRUGS <ul><li>FELBAMATE  GABAPENTIN  </li></ul><ul><li>LAMOTRIGINE   TIAGABINE </li></ul><ul><li>TOPIRAMATE  VI...
ANTISEIZURES CLASSIFICATION <ul><li>I.  TONIC-CLONIC SEIZURES </li></ul><ul><li>Carbamazepine. valproic acid, Phenytoin, P...
II.ABSENCE SEIZURES Ethosuximide, valproic acid,  clonazepam Recent: Lamotrigine III  MYOCLONIC SEIZURES Valproic acid, cl...
PARTIAL SEIZURES <ul><li>SIMPLE/PARTIAL:  </li></ul><ul><li>CARBAMAZEPINE, VALPROATE </li></ul><ul><li>PHENYTOIN, </li></u...
PARTIAL W/ 2 0  GENERALIZED TONIC-CLONIC SEIZURES CARBAMAZEPINE, VALPROATE   PHENOBARBITAL PHENYTOIN  Recent : gabapentin,...
MECHANISM OF ACTION <ul><ul><li>Inhibition of sodium channels function :  </li></ul></ul><ul><ul><li>phenytoin  VALPROATE ...
 
Mechanism of Action <ul><ul><li>Inhibition of calcium channel function: </li></ul></ul><ul><ul><li>ethosuximde </li></ul><...
 
MECHANISM OF ACTION <ul><ul><li>Enhancement of GABA action :  </li></ul></ul><ul><ul><li>benzodiazepines,phenobarbital gab...
 
PHENYTOIN <ul><li>BLOCK SODIUM CHANNELS </li></ul><ul><li>Modify pattern of maximal electroshock seizures but not inhibit ...
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>...
Phenytoin Adverse Effects <ul><li>nystagmus, diplopia, ataxia, sedation, gingival hyperplasia & hirsutism, coarsening of f...
PHENYTOIN DRUG INTERACTIONS <ul><li>Sulfonamides, valproate  & phenylbutazone:  displace  phenytoin from binding sites </l...
PHENYTOIN DRUG INTERACTIONS <ul><li>3.Barbiturates & carbamazepine, pyridoxine, theophylline:  enhance  phenytoin metaboli...
CARBAMAZEPINE (IMINOSTILBENES) <ul><li>BLOCK SODIUM CHANNELS </li></ul><ul><li>DOC for partial seizures </li></ul><ul><li>...
CARBAMAZEPINE Adverse EFfects <ul><li>diplopia & ataxia </li></ul><ul><li>idiosyncratic blood dyscrasias, </li></ul><ul><l...
CARBAMAZEPINE DRUG INTERACTIONS <ul><li>1.  I ncreas e  carbamazepine levels via metabolism: cimetidine, erythromycin, iso...
CARBAMAZEPINE  Drug Interactions 4. Carbamazepine  increases   drug levels : cimetidine, isoniazid 5. Lithium  induces  ca...
PHENOBARBITAL <ul><li>Inhibits tonic hind limb extension in the maximal electroshock model, clonic seizures evoked by pent...
PHENOBARBITAL DRUG INTERACTIONS <ul><li>Increase  phenobarbital levels via metabolism; acute ethanol ingestion, chloramphe...
PRIMIDONE <ul><li>Metabolized to: </li></ul><ul><li>PHENOBARBITAL </li></ul><ul><li>PHENYLETHYLMALONAMIDE(PEMA) </li></ul>...
VIGABATRIN <ul><li>Inhibits GABA transaminase </li></ul><ul><li>Partial seizures & ‘WEST syndrome </li></ul><ul><li>In pat...
LAMOTRIGINE <ul><li>Inhibits sodium channels </li></ul><ul><li>Partial seizures </li></ul><ul><li>Absense seizures </li></...
FELBAMATE <ul><li>MOA : blocks glumate NMDA receptors </li></ul><ul><li>For partial seizures </li></ul><ul><li>Broad thera...
GABAPENTIN <ul><li>MOA: alters GABA metabolism, its nonsynaptic release or its reuptake by GABA transporters </li></ul><ul...
TOPIRAMATE <ul><li>Complex action: GABA effect, blocks voltage dependent sodium channels </li></ul><ul><li>Blocks glutamat...
TIAGABINE <ul><li>Nicotinic acid derivative </li></ul><ul><li>GABA uptake inhibitor in both neurons & glia </li></ul><ul><...
LEVETIRACETAM  <ul><li>A pyrolidine </li></ul><ul><li>Inhibits partial & secondarily generalized tonic- clonic seizures </...
ZONISAMIDE <ul><li>Inhibits the  t-type Ca 2+  currents </li></ul><ul><li>Na +  channels block </li></ul><ul><li>For parti...
ETHOSUXIMIDE <ul><li>DOC for absense seizures </li></ul><ul><li>↓   calcium channels  (T type) currents </li></ul><ul><li>...
ETHOSUXIMIDE (Succinimides) <ul><li>ADVERSE EFFECTS </li></ul><ul><li>gastric distress </li></ul><ul><li>lethargy  </li></...
VALPROIC ACID <ul><li>On partial seizures sodium channel effects </li></ul><ul><li>Increased levels of GABA inhibits GABA ...
VALPROIC ACID <ul><li>CLINICAL USES: </li></ul><ul><li>1. ABSENCE SEIZURES </li></ul><ul><li>2. MYOCLONIC SEIZURES </li></...
VALPROIC ACID <ul><li>Well absorbed; ppc within 2 hrs </li></ul><ul><li>Bioavailability > 80% </li></ul><ul><li>T ½ is 9 -...
VALPROIC DRUG INTERACTIONS <ul><li>Decrease  valproic acid levels from increase metabolism with carbamazepine </li></ul><u...
BENZODIAZEPINES <ul><li>Diazepam,  lorazepam, clonazepam, clorazepate, Nitrazepam,  clobazam </li></ul><ul><li>Well absorb...
STATUS EPILPETICUS <ul><li>DIAZEPAM </li></ul><ul><li>LORAZEPAM </li></ul><ul><li>PHENYTOIN </li></ul><ul><li>PHENOBARBITA...
EFFECTIVE PLASMA LEVELS > 100 50 - 100 Valproic Acid > 100 50 -100 Ethosuximide > 40 10 - 40 Phenobarbital >20 10 - 20 Phe...
THERAPEUTIC PRINCIPLES <ul><li>1 .  When to initiate </li></ul><ul><li>2. Choice of a drug </li></ul><ul><li>Monotherapy <...
THERAPEUTIC PRINCIPLES <ul><li>4.  Duration of Therapy </li></ul><ul><li>at least 2 years </li></ul><ul><li>taper over sev...
<ul><li>And we know that all things work together  for good to those who love God, to those who who are called according t...
Upcoming SlideShare
Loading in...5
×

Antiseizure drugs

6,148

Published on

0 Comments
7 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total Views
6,148
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
535
Comments
0
Likes
7
Embeds 0
No embeds

No notes for slide

Antiseizure drugs

  1. 1. ANTISEIZURE DRUGS Zenaida N. Maglaya,MD,FPSECP Department of Pharmacology
  2. 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. 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. 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. 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. 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. 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. 8. II.ABSENCE SEIZURES Ethosuximide, valproic acid, clonazepam Recent: Lamotrigine III MYOCLONIC SEIZURES Valproic acid, clonazepam Recent: Lamotrigine /topiramate
  9. 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. 10. PARTIAL W/ 2 0 GENERALIZED TONIC-CLONIC SEIZURES CARBAMAZEPINE, VALPROATE PHENOBARBITAL PHENYTOIN Recent : gabapentin, tiagabine lamotrigine,levetiracetam, topiramate, zonisamide
  11. 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>
  13. 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>
  14. 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>
  15. 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>
  16. 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>
  17. 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>
  18. 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>
  19. 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>
  20. 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>
  21. 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>
  22. 25. CARBAMAZEPINE Drug Interactions 4. Carbamazepine increases drug levels : cimetidine, isoniazid 5. Lithium induces carbamazepine toxicity.
  23. 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>
  24. 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>
  25. 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>
  26. 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>
  27. 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>
  28. 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>
  29. 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>
  30. 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>
  31. 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>
  32. 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>
  33. 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>
  34. 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>
  35. 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>
  36. 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>
  37. 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>
  38. 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>
  39. 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>
  40. 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>
  41. 44. STATUS EPILPETICUS <ul><li>DIAZEPAM </li></ul><ul><li>LORAZEPAM </li></ul><ul><li>PHENYTOIN </li></ul><ul><li>PHENOBARBITAL </li></ul>
  42. 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
  43. 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>
  44. 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>
  45. 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!!!
  1. A particular slide catching your eye?

    Clipping is a handy way to collect important slides you want to go back to later.

×