Pharmacology; Mechanism of Action for Anti-Epileptic Drugs

In my last post, I wrote about seizures, explaining the triggers of seizures, the types of seizures, the pathophysiology, the diagnosis, and treatments. In this post, I will be looking into epilepsy, explaining its pathophysiology, causes of Epilepsy, mechanism of epilepsy, how to treat epilepsy, and the drugs to use in treating epilepsy. It is important to know that not all seizures are epilepsy. Being able to identify a seizure from an epileptic attack is very important.

As I said in my previous post, Seizures are abnormal electrical activity in the central nervous system causing convulsions, spasms, and loss of consciousness in a singular event. Epilepsy is the reoccurrence of multiple seizures, often two or more chronic seizures. Remember in my previous post, I discussed Focal and Generalized seizures where I talked about an area in the brain being agitated (an area in the cortex), sending a high electrical signal. It is important to know that when a patient starts to get abnormal electrical activities in the right side of the cortex, they start to exhibit left-sided types of seizures. I remember also stating in the post that with focal seizures, there can be a complete loss of consciousness (impairment), or there can be no loss of consciousness (without impairment). I explained further that the seizures can be motor, or sensory.,. There are the generalized seizures, where the entire area of the cortex are agitated, sending the entire electrical activity all around the cortex (brain) causing the patient to seize. These seizures usually cause impairment, as patients do not remember what happens towards the period of the seizure. The types of generalized seizures which includes Tonic Seizures, Clonic Seizures, Tonic-Clonic Generalized seizures, Absence seizures, and Myoclonic Seizures.,.

Talking about the triggers of epilepsy and seizures, I discussed them in my previous post, looking at the Vitamin D and E Mnemonic which I explained to be Vascular Causes, Infectious Causes, Traumatic Causes, Autoimmune Causes, Metabolic Causes, Idiopathic Causes, Neoplasia Causes, Drug causes, and Eclampsia Causes. I also explained the mechanism of seizures and epilepsy where there is sodium influx into the neuron cells through the voltage-gated sodium channel allowing positive charge, depolarizing the axonopening the voltage-gated calcium channel allowing calcium to flow in, releasing glutamate. The glutamate binds with receptors allowing sodium and calcium to rush in increasing the action potential pathways causing seizure.,,. The Gamma Aminobutyric Acid GABA pathway is released when there is an action potential released down the axon. GABA binds with GABA-A Receptor allowing for cloride ion to get into the cells, making the cells excessively negative, inhibiting the action potential to hyperpolarize the cell.,.

With this, It is known that increase action potentials are responsible for seizures. One of the causes is as a result of an increase in the glutamate activity but in other to treat epilepsy and seizure, it is important to work on a mechanism of drugs that would inhibit glutamate activities. The main goal is to decrease the the action potential in the neuron thereby decreasing the electric discharge in the brain which will decrease seizures. To do this, sodium influx should be blocked which would lead to depolarization. This is done by inhibiting the voltage-gated sodium channels which will in turn not stimulate the Calcium channels, which will not allow calcium to bind with the vesicles, as well as fuse with the synaptic membranes which will release glutamate. With this, Glutamate has been inhibited. Glutamate inhibition would prevent sodium influx, and calcium influx which would lead the depolarization, reducing action potential and decreasing seizures.,. Drugs that perform this mechanisms include Carbamazepine (it is taken via the mouth in form of tablets, its intake is depending on the severity of the seizure), Oxcarbazepine (it is a tablet used to treat epilepsy and other neurological conditions, such as trigeminal neuralgia), Phenytoin, Fosphenytoin, other drugs are Lamotrigine, Lacosamide, topiramate, and Valproate.

Calcium channel blocker drugs are another set of drugs that inhibits calcium influx which wouldhave stimulated the fusion of these vesicle with the membrane which would prevent the release of glumatate, preventing the stimulation of calcium and sodium influx into the neuron, preventing action potentials decreasing seizures. Drugs used to block the calcium channels are Ethosuximide.. Synaptic vesicle glycoprotein 2A in the neuron can be blocked from fusing with the cell membrane, thereby inhibiting the production of glutamate, which therefore doesn't allow for sodium calcium influx, therefore reducing action potential and not causing seizure. A drug that does this blockage is levetiracetam. . Another thing that can be blocked is the Glutamate from binding to the AMPA receptor. This is called the AMPA receptor blocker which inhibits Glutamate from binding to the AMPA receptor. An example of drug that allows this inhibition to happen is felbamate.. The NMDA receptor isn't behind, and the drug that inhibits the binding with the receptor is Ketamine..

When patients have little GABA activity, lead to less hyperpolarization which leads to an increase in action potentials leading to seizures. AEDs can help increase GABA activities. GABA is released from the GABAgic neurons, GABA is attached to the GABA receptor which causes cloride ion to influx into the cell making it negative, making it to hyperpolize, decreasing the action potentials and decreasing seizures.. GABA Receptor Agonists, are used to increase the activity of the receptors and allowing more current, more hyperpolarization and less action potential. These drugs includes Benzodiazepines, Barbiturates, probofol, and topiramate.,.

Conclusion

Treating seizures and epilepsy has to do with reducing action potentials either by increasing GABA or by reducing the inflow of calcium, sodium and Glutamate in the neural pathway. The Drugs explained in the post are very important for treating seizures.

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