Antiepliepsy drugs:-
Nature of epilepsy:-
1. Epilepsy affects about 0.5% of the population.
2. The characteristic event is the seizure which is often associated with convulsions but may occur in many other forms.
3. The seizure is caused by an asynchronous high-frequency discharge of a group of neurons, starting locally and spreading to a varying extent to affect other parts of the brain. In absence seizures, the discharge is regular and oscillatory.
4. Partial seizures affect localized brain regions, and the attack may involve mainly motor, sensory or behavioral phenomena. Unconsciousness occurs when the reticular formation is involved. Generalized seizures affect the whole brain.
5. Two common forms of epilepsy are the tonic-clonic fit (grand mal) and the absence seizure (petite mal), status epileptics is a life-threatening condition in which seizure activity is uninterrupted.
6. The neurochemical basis of the abnormal discharge isn't well understood. It may be associated with enhanced excitatory amino acid transmission, impaired inhibitory transmission, or abnormal electrical properties of the affected cells. The glutamate ******* in areas surrounding an epilepsy focus may be increased.
7. repeated epileptic discharge can cause neuronal death (excitotoxicity )
8. current drug therapy is effective in 70%-80% of patients
Mechanism of action of Antiepliepsy drugs:-
• current anti-epilepsy drugs are thought to act mainly by three main mechanisms :-
1. Reducing electrical excitability of cell membranes, mainly through use-dependent block of sodium channels.
2. enhancing GABA-mediated synaptic inhibition: this may be achieved by an enhanced postsynaptic action of GABA, by inhibiting GABA transaminase or by drugs with direct GABA- agonist properties
3. Inhibiting T-type calcium channels (important in controlling absence seizures).
• Newer drugs act by other mechanisms, yet to be elucidated.
• Drugs that block glutamate receptors are effective in animal models but aren't yet developred for clinical use.
Clinical uses of anti-epilepsy drugs:-
1. Tonic-clonic (grand mal) seizure:-
• Carbamazepine (preferred because of low incidence of side-effects), phenytion, valproate.
• Use of a single drug is preferred when possible to avoid pharmacokinetic interactions.
• Newer agents (not yet fully assessed) include vigabatrin. Lamotrigine, felbamate, gabapentin.
2. Partial (focal) seizure: - carbamazipine, valproate, clonazepam or phenytoin is alternatives.
3. absence seizure (petit mal) :- ethosuximide or valproate
• Valproate is used when absence seizures coexist with tonic-clonic seizure, since most other drugs used for tonic-clonic seizure can worsen absence seizures.
4. Myoclonic seizure: - diazepam intravenously or (in absence of accessible veins) rectally.
5. neuropathic pain :- carbamazipine, gabapentin
6. To stabilize mood (as an alternative to lithium), carbamazepine, valproate
Treatment of anti-epilepsy drugs:-
Drug name
Trade name
Carbamazepine
Carbatol ®
Phenytoin
Epanutin ®
Vigabatrin
Sabril ®
Lamotrigine
Lamictal ®
Clonazepam
Rivotril ®
Ethosuximide
Zarontin ®
Gabapentin
Neurontin ®300mg & Neurontin ® 400mg