1. Zenaida N. Maglaya,MD,FPSECP Department of Pharmacology
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 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 decreases serum 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 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
DRUG
Effective Level(ug/m
TOXIC LEVEL
(ug/mL)
Carbamzepine
4 - 12
> 8
Phenytoin
>20
Phenobarbital
> 40
Ethosuximide
> 100
Valproic Acid

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