Part 9

Antiepileptic and
Anticonvulsant Drugs

Epilepsy is not a single entity;

it is a family of different
recurrent seizure disorders
that have in common the
sudden, excessive and
disorderly discharge of
central neurons.
This results in abnormal
movement or perceptions
that are of short duration but
that tend to recur.

Grand mal (tonic-clonic)

Petit mal (absence)

Psychomotor seizures

Classification of epilepsy (older)

Generalized seizures (
Grand mal

tonic-clonic seizures
Petit mal

absence seizures

Partial seizures ()
Pshychomotor

temporal lobe seizures

Partial

motor, sensory, ANS, etc.

Classification of epilepsy

Normal EEG

Absence EEG

The pathways for

seizure propagation in
partial seizures and
primary generalized
seizures

Stereotypical complex partial seizures

Mechanisms of antiepileptic drugs

Electrophysiological
Inhibiting excessive discharges
Inhibiting spread of discharges
Molecular
Potentiating GABA neuronal functions
Modulating Na+, Ca2+, K+channel fuctions

A. Antiepileptic drugs
Special drugs
Phenytoin Sodium

C 6H 5
HN
NaO

CO

C 6H 5

A. Antiepileptic drugs
1. Pharmacological effects and the mechanism

Inhibiting influx of Na+ and Ca2+

Inhibiting spread of abnormal discharges

A. Antiepileptic drugs
2. Clinical uses
(1) Antiepilepsy
Grand mal, status epilepticus;
Partial seizures (simple and complex);
Ineffective for petit mal (absence seizures)

(2) Trigeminal and related neuralgia

(3) Antiarrhythmia

A. Antiepileptic drugs
3. ADME
Larger doses: non-linear kineticsplasma
concentration > 10 g/ml
Necessary to monitor plasma concentrations
Induction of hepatic drug-metabolizing
enzymes

A. Antiepileptic drugs
3. Adverse effects
(1) Local reactions
GI reactions; gingival hyperplasia

(2) CNS reactions

Particularly in the cerebellum and vestibular systems:
nystagmus (), ataxia (), etc.
Behavioral changes: confusion, hallucination

A. Antiepileptic drugs
(3) Hemological reactions
Megaloblastic anemia

(4) Allergic reactions

Skin reactions; blood cell abnormality (including
thrombocytopenia, agranulocytosis);
hepatic toxicity; ect.

(5) Skeletal reactions

Osteomalacia by abnormal vitamin D metabolism and
calcium absorption

A. Antiepileptic drugs
4. Drug interactions
(1) Increases plasma concentrations of drugs by
displacement of plasma protein binding
(salicylates) and inhibition of inactivation
(isoniazid, chloramphenicol)
(2) Decreases plasma concentrations of drugs
(phenobarbital, carbamazepine) by enhancing
metabolism
(3) Phenytoin enhances the metabolism of
corticosteroids and vitamin D

A. Antiepileptic drugs
Phenobarbital
NH
O

CO

C 2H 5
C

NH

CO

C 6H 5

Inhibiting both formation and spread of

discharges
Effective for grand mal, partial simple seizures,
status epilepticus

A. Antiepileptic drugs
Carbamazepine

N
CONH 2

Effective for psychomotor seizures, and grand mal

Effective for mania, depression, and neuralgia

A. Antiepileptic drugs
Valproate sodium

CH3CH2CH2

CHCOOH
CH3CH2CH2

Broad spectrum of antiepilepsy

Hepatic toxicity

A. Antiepileptic drugs
Other antiepileptic drugs
Primidone analogues of phenobarbital, used
for phenobarbital- and phenytoin-ineffective patients
Mephenytoin , Ethotoin analogues of
phenytoin
Ethosuximide peptit mal
Diazepam: status epilepticus (i.v.)
Nitrozepam , Clonazepam peptit mal
Lamotrigine

A. Antiepileptic drugs
Box Common toxicity of
antiepileptic drugs:
CNS reactions

Hemological reactions
Hepatic toxicity

A. Antiepileptic drugs
Principals of antiepileptic drug uses
1. Choice of drugs
(1) Grand mal / Partial

Phenytoin, Carbamazepine, Phenobarbital

Primidone, Valproate sodium

(2) Peptit mal: Ethosuximide

Clonazepam, Valproate sodium

(3) PsychomotorCarbamazepine, Phenytoin
(4) Status epilepticusDiazepan (i.v.)

Phenytoin (i.v.), Phenobrbital (i.m.)

A. Antiepileptic drugs
2. Dosage

small larger doses;

dose individualization;
plasma concentration monitoring if necessary

3. Usage drug combination

4. Withdrawalgradually and slowly

A. Anticonvulsant drugs
Magnesium Sulfate

1. Effectscentral depression;

vasodilatation, BP ;
relaxing skeletal muscles

2. Usesconvulsionhypertension crisis
3. Adverse effects
depression of respiratory and vasomotor centers,
antagonized by calcium preparations (i.v.)

A. Anticonvulsant drugs
Other anticovulsant drugs
Sedative-hypnotic drugs