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3) DRUG EFFECTIVE IN SEIZURE DISORDERS.ppt
1. DRUGS EFFECTIVE IN SEIZURE DISORDERS:
Seizure is also referred as epilepsy.
It is a common neurological abnormality that effects
about 0.5 – 1 % of the population.
It is a chronic disorder characterised by recurrent seizures
often accompanied by episodes of unconsciousness and/
or amnesia.
It is a disorder of brain function.
It is an alteration of brain function because of abnormal
firing of some brain neurons.
May be caused due to trauma during birth process, head
injury, childhood fevers, brain tumors, meningitis or drug
induced.
4. Phenytoin:
It is the most effective drug against generalized tonic
clonic seizures and partial seizures.
MOA: causes blockade of the sodium channels and
stabilizes the neuronal membrane. It inhibits the
generation of repetitive action potentials.
Adverse effects: nausea, vomiting, epigastric pain,
anorexia. Peripheral neuropathy, gingival hyperplasia
(more common in children on prolong use). Acne,
coarsening of facial features. Hyperglycemia, decrease in
ADH, osteomalacia, hypocalcemia. Hypersensitivity to
rashes, hepatic necrosis, lymphadenopathy. Megaloblastic
anemia, teratogenicity. Toxic doses may cause drowsiness,
delirium, confusion, hallucinations, altered behaviour
followed by coma.
5. Uses: generalised tonic clonic seizures and partial
seizures. Status epilepticus, trigeminal neuralgia, cardiac
arrhythmias.
Drug interactions:
Given with phenytoin barbitone, both increase each others
metabolism. Also, phenytoin competitively inhibits
phenytoin metabolism.
Carmazepine and phenytoin enhance each others
metabolism.
Valproate displaces protein bound phenytoin.
Cimetedine and chloramphenicol inhibits the metabolism
of phenytoin resulting in toxicity.
Antacids decrease absorption of phenytoin.
6. Phenobarbitone:
It was the first effective anti-epileptic drug to be
introduced.
It has specific anti-epileptic activity and raises the seizure
threshold.
Primidone which is widely used now is metabolized into
phenobarbitone.
MOA: it enhances the inhibitory activity of GABA in the
Central Nervous System.
Uses: generalized tonic-clonic seizures, partial seizures,
neonaltal jaundice.
7. Carbamzepine:
It is closely related to imipramine.
MOA: acts by blocking sodium chanells.
Uses: used to treat trigrminal neuralgia, glossopharyngeal
neuralgia, mood disorders, tonic clonic seizures, simple
and complex partial seizures.
Adverse effects: drowsiness, vertigo, ataxia, diplopia,
blurring of vision, nausea, vomiting and dizziness.
Hypersensitivity reactions like skin rashes.
Haematological toxicity viz., leukopenia,
thrombocytopenia and rarely agranulocytosis and aplastic
anaemia.
8. Ethosuximide:
It is a primary agent for absence seizures.
It raises seizure threshold.
MOA: it reduces calcium currents (T-currents) in the
thalamic neurons.
Adverse effects:
Gastro intestinal symptoms like: nausea, vomiting, epigastric
pain, gastric irritation and anorexia. These can be avoided by
giving low dose and gradually increasing it.
CNS effects like drowsiness, fatigue, lethargy, euphoria,
dizziness, headache.
Hypersensitivity reactions like rashes, urticaria, leukopenia,
thrombocytopenia.
Uses: it is a drug of choice for absence seizures
9. Valproic acid:
It is a very effective anti-epileptic drug used to treat many
types of epilepsies including absence seizures, partial and
generalized tonic-clonic seizures.
MOA: it acts by multiple mechanisms:
It enhances the level of GABA by:
increasing the synthesis of GABA (by increasing GABA synthetase
enzyme)
Decreasing the metabolism of GABA (by inhibiting GABA
transaminase enzyme)
Like phenytoin, it blocks the sodium channels.
Adverse effects: gastro intestinal symptoms like nausea,
vomiting, epigastric distress. Tremors, sedation, ataxia,
rashes.
10. Uses:
partial and generalised seizures.
Particularly used in absence seizures.
In patients with both absence and tonic-clonic attacks,
valproate is drug of choice
Benzodiazepines:
Diazepam is a drug of choice for status epilepticus.
Clonazepam is a potent antiepileptic useful in absence
and myoclonic seizures. But tolerance develops.