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Discuss the mechanisms underlying generalised and partial seizures and suggest drugs that might be used to control these seizure states, describing how these drugs work.
The characteristic event of epilepsy is the seizure. This is associated with the episodic high-frequency discharge of impulses by a group of neurons in the brain.
All types of epileptic attack start with an abnormal paroxysmal discharge of neurones from the brain. The discharge may spread locally to neighbouring groups of neurones or may travel via the axons to more distant group of neurones where the effect may be excitatory or inhibitory. The site of origin of discharge is called the focus. Generalised seizures involve the whole brain, including the reticular system, thus producing abnormal activity through both hemispheres. Immediate loss of consciousness is characteristic of generalised seizures. Generalised seizures can be classified into tonic-clonic seizures (grand mal), absence seizures (petit mal), myoclonic jerking, atonic seizures and infantile spasms. Partial seizures are those in which the seizure begins locally and often remains localised. There are two types simple partial seizure and complex partial seizure.
The underlying neuronal abnormality in epilepsy is poorly understood. However, studying an EEG gives some insight. The record from an EEG electrode represents the activity from only a small part of the brain, but during an epileptic episode abnormal activity spreads out and the EEG pattern is usually changed. The manifestations of the epileptic attack depend on the neurones involved. When the discharge remains confined to a small part of the cortex and is of short duration, it may not lead to any obvious symptoms but yet may be detected in the EEG. When the motor system is involved, there is loss of voluntary power and there are usually tonic (increased tone) or clonic (repetitive contraction and relaxation) spasms or both. When a large part of the cortex or specific parts of the reticular activating system are involved, the patient loses consciousness. In partial epilepsy, the discharge is confined to one portion of the cortex.
Custom Essays on Epilepsy
Two main methods appear to be important in the action of anticonvulsant drugs
„P enhancement of GABA action
„P inhibition of sodium function.
phenytoin blocks the opening of Na-gated channels and therefore prevents the development and propagation of action potentials. The important feature of these compounds is that they act selectively on repetitively active ion channels, thus they permit the initial action potential but prevent high-frequency firing. Carbamazepine and phenytoin are effective only against grand mal seizure but valproate is also effective against petit mal seizure, possibly because of an action on a particular type of sodium channel.
Another drug useful in the treatment of petit mal epilepsy is ethosuximide, this agent is ineffective against tonic-clonic seizures. The mechanism of action may be dependent upon inhibition of a particular subtype of calcium channel.
Sodium valproate is effective against most forms of seizure. This drug acts by increasing the effects of GABA, possibly by preventing its metabolism, although it also has effects on sodium ion channels similar to those of phenytoin. More recent advances in the treatment of epilepsy have been the development of agents such as vigabatrin, which also increases GABA activity by inhibiting the enzyme responsible for the breakdown of GABA and tiagabine which prevents reuptake of GABA into the presynaptic terminal.
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