Download presentation
Published byDamian Osborne Modified over 9 years ago
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
Similar presentations
© 2025 SlidePlayer.com. Inc.
All rights reserved.