Title: ANTISEIZURE DRUGS
1ANTISEIZURE DRUGS
- Zenaida N. Maglaya,MD,FPSECP
- Department of Pharmacology
2SEIZURE
- Is a finite episodes of brain dysfunction
resulting from abnormal discharge of cerebral
neurons. - PRIMARY SEIZURES
- SECONDARY SEIZURES
3CLASSIFICATION OF SEIZURE TYPES
- PARTIAL SEIZURES
- Simple partial seizures
- Complex partial seizures
- Partial seizures secondarily generalized
4CLASSIFICATION 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
5PRIMARY DRUGS
- CARBAMAZEPINE
- PHENYTOIN
- VALPROIC ACID
- PHENOBARBITAL
- PRIMIDONE
- DIAZEPAM /LORAZEPAM
- CLONAZEPAM
- ETHOSUXIMIDE
6ADJUNCTIVE DRUGS
- FELBAMATE GABAPENTIN
- LAMOTRIGINE TIAGABINE
- TOPIRAMATE VIGABATRIN
- LEVETIRACETAM ZONISAMIDE
7ANTISEIZURES 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
8MECHANISM OF ACTION
- Inhibition of sodium channels function
phenytoin, carbamazepine, lamotrigine - Inhibition of calcium channel function
ethosuximde - Enhancement of GABA action benzodiazepines,phenob
arbital gabapentin,vigabatrin, tiagabine - Multiple Complex Mechanism Valproic Acid
9PHENYTOIN
- 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
10Phenytoin Adverse Effects
- nystagmus, diplopia, ataxia, sedation, gingival
hyperplasia hirsutism, coarsening of facial
features, mild peripheral neuropathy,
megaloblastic anemia fever, skin rash, fetal
hydantoin syndrome
11PHENYTOIN DRUG INTERACTIONS
- Sulfonamides, valproate phenylbutazone
displace phenytoin from binding sites - Cimetidine, disulfiram, doxycycline, isoniazid,
phenylbutazone, sulfas, warfarin,
chloramphenicol inhibits phenytoin metabolism
12PHENYTOIN 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
13CARBAMAZEPINE
- BLOCK SODIUM CHANNELS
- DOC for partial seizures
- Generalized tonic-clonic seizures
- Trigeminal neuralgia
- Maniabipolar disorders
- Orally absorbed with slow distribution
- Completely metabolized
- CAUSE diplopia ataxia, idiosyncratic blood
dyscrasias, aplastic anemia agranulocytosis,
leukopenia
14CARBAMAZEPINE 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.
15PHENOBARBITAL
- 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
16PHENOBARBITAL 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
17PRIMIDONE
- Metabolized to
- PHENOBARBITAL
- PHENYLETHYLMALONAMIDE(PEMA)
- Mechanism of action similar to phenytoin
- May cause sedation, ataxia, vertigo, GIT upset,
megaloblastic anemia - CI porphyria, hypersensitivity
18VIGABATRIN
- 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
19LAMOTRIGINE
- 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
20FELBAMATE
- 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
21GABAPENTIN
- MOA alters GABA metabolism, its nonsynaptic
release or its reuptake by GABA transporters - Also binds to the a2d subunit of voltage
sensitive calcium channels - FOR PARTIAL GENERALIZED SEIZURES
- SATURABLE ABSORPTION
- CAUSE somnolence, dizziness, ataxia, headache
tremor
22TOPIRAMATE
- 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
23TIAGABINE
- Nicotinic acid derivative
- GABA uptake inhibitor in both neurons glia
- Partial seizures
- Dizziness, tremor, difficulty in concentration,
psychosis
24ETHOSUXIMIDE
- 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
25VALPROIC ACID
- On partial seizures sodium channel effects
- Increased levels of GABA inhibits GABA
transaminase succinic semialdehyde
dehydrogenase - Sodium channel blockade
26VALPROIC 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
27VALPROIC ACID
- Well absorbed ppc within 2 hrs
- Bioavailability gt 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
28VALPROIC 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
29BENZODIAZEPINES
- 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
30STATUS EPILPETICUS
- DIAZEPAM
- LORAZEPAM
- PHENYTOIN
- PHENOBARBITAL
31EFFECTIVE PLASMA LEVELS
DRUG Effective Level(ug/m TOXIC LEVEL (ug/mL)
Carbamzepine 4 - 12 gt 8
Phenytoin 10 - 20 gt20
Phenobarbital 10 - 40 gt 40
Ethosuximide 50 -100 gt 100
Valproic Acid 50 - 100 gt 100
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