antiepileptic and anticonvulsant

Part 9

Antiepileptic and

Anticonvulsant Drugs

Psychomotor seizures

Petit mal (absence)

Grand mal (tonic-clonic)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.

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

CO

N

N

HC6H5

C6H5

NaO

1. Pharmacological effects and the mechanism

Inhibiting influx of Na+ and Ca2+

Inhibiting spread of abnormal discharges


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


3. ADME

Larger doses: non-linear kineticsplasma concentration > 10 g/ml

Necessary to monitor plasma concentrations

Induction of hepatic drug-metabolizing enzymes


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


(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


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


Inhibiting both formation and spread of discharges

Effective for grand mal, partial simple seizures, status epilepticus

Phenobarbital


C2H5

CO

NH

NH

CO

CO

C

C6H5

Effective for psychomotor seizures, and grand mal

Effective for mania, depression, and neuralgia

Carbamazepine

N

CONH 2


Broad spectrum of antiepilepsy

Hepatic toxicity

Valproate sodium


CH3CH2CH2

CHCOOH

CH3CH2CH2

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


Box Common toxicity of

antiepileptic drugs:

CNS reactions

Hemological reactions

Hepatic toxicity


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.)


2. Dosage

small larger doses;

dose individualization;

plasma concentration monitoring if necessary

3. Usage drug combination

4. Withdrawalgradually and slowly


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.)

Magnesium Sulfate

A. Anticonvulsant drugs

Other anticovulsant drugs

Sedative-hypnotic drugs

A. Anticonvulsant drugs

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antiepileptic and anticonvulsant