antiepileptic and anticonvulsant
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Transcript of antiepileptic and anticonvulsant
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Part 9
Antiepileptic and
Anticonvulsant Drugs
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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.
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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.
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Classification of epilepsy
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Normal EEG
Absence EEG
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The pathways for
seizure propagation in
partial seizures and
primary generalized
seizures
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Stereotypical complex partial seizures
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Mechanisms of antiepileptic drugs
Electrophysiological
Inhibiting excessive discharges
Inhibiting spread of discharges
Molecular
Potentiating GABA neuronal functions
Modulating Na+, Ca2+, K+channel fuctions
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A. Antiepileptic drugs
Special drugs
Phenytoin Sodium
CO
N
N
HC6H5
C6H5
NaO
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1. Pharmacological effects and the mechanism
Inhibiting influx of Na+ and Ca2+
Inhibiting spread of abnormal discharges
A. Antiepileptic drugs
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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
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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
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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
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(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
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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
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Inhibiting both formation and spread of discharges
Effective for grand mal, partial simple seizures, status epilepticus
Phenobarbital
A. Antiepileptic drugs
C2H5
CO
NH
NH
CO
CO
C
C6H5
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Effective for psychomotor seizures, and grand mal
Effective for mania, depression, and neuralgia
Carbamazepine
N
CONH 2
A. Antiepileptic drugs
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Broad spectrum of antiepilepsy
Hepatic toxicity
Valproate sodium
A. Antiepileptic drugs
CH3CH2CH2
CHCOOH
CH3CH2CH2
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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
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Box Common toxicity of
antiepileptic drugs:
CNS reactions
Hemological reactions
Hepatic toxicity
A. Antiepileptic drugs
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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
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2. Dosage
small larger doses;
dose individualization;
plasma concentration monitoring if necessary
3. Usage drug combination
4. Withdrawalgradually and slowly
A. Antiepileptic drugs
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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
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Other anticovulsant drugs
Sedative-hypnotic drugs
A. Anticonvulsant drugs