The Details of Epilepsy with Regard to Its Pathophysiology - Term Paper Example

Epilepsy Pathophysiology And Drug Therapy Contents Introduction 3 Pathophysiology of Epilepsy 4 Causes of Epilepsy 4 Types of Seizures 5 Drug Therapies 6 Bibliography 9 Introduction Epilepsy is the continuing tendency to epileptic seizures and epileptic seizure is a clinical phenomenon which occurs due to the synchronous and sustained discharge of the neurons of the cerebral hemisphere of the brain. This further can cause a disturbance in behavior, emotions, motor functions and sensations. A single seizure is not considered to be epilepsy; there will be repeated episodes of seizures in epilepsy. The group of neurons in which epileptic seizures occur shows an odd electrical behavior known as paroxysmal depolarizing shift, in which the membrane potential decreases rapidly by about 30 millivolts and this depolarized state is maintained for a few seconds. Neurons normally generate electrical impulses and send them to every parts of the body which further control the bodily functions. Hyper excitability of the neurons cause seizures so the very first question which arises when one asks about Epilepsy is as to what are the causes of the hyper excitability of the neurons? The neuronal cell may be hyper excited by the imbalance of the neurotransmitter released by the pre-synaptic terminal or by the abnormalities in the voltage gated channels in the membrane of the post-synaptic neuron. This assignment would further discuss the details of epilepsy with regard to its pathophysiology and the drug therapies which are being used to cure it (Hopkins et al 1995 & ENGELBORGHS S, DHOOGE & DE DEYN 2000). Pathophysiology of Epilepsy Sometimes if a part of brain gets excited it will excite the next part and this second part in turn will excite the next and so on until the same signal re-excites the first part and then a continuous cycle of re-excitation of all the parts of brain will set off. The neurotransmitters are excitatory and inhibitory. Glutamate and Aspartate are the examples of the excitatory neurotransmitters and GABA is an example of an inhibitory neurotransmitter. Some people have high level of excitatory neurotransmitters and some people have low levels of inhibitory neurotransmitters. In both the situations neuronal activity is increased which causes seizures. Increased permeability of the neuronal cell membrane also increases excitability, if the permeability for Sodium ions increases, then more and more sodium ions will tend to move to the interior of the neuronal cell which will increase the potential of the neuronal cells causing seizures. Repetitive and uncontrolled signals from the neurons causes Epileptic seizures and these are the common causes which cause seizures. That is if the sodium ions enter the neurons excessively depolarizing the neurons again and again and the inhibitory mechanism of compensating with this hyperexcitability is not working properly then the seizures will take place (Purves 2008). Causes of Epilepsy Traumatic brain injury, head injury, meningitis, encephalitis can also cause epilepsy. Some neurological diseases can also be the cause of epilepsy like Alzheimer’s disease. Lack of sleep, hypertension, stress, diabetes, alcoholism and smoking can also cause seizure. Nicotine in cigarette acts on the receptors for excitatory neurotransmitter acetylcholine on the post-synaptic neuron which increases the discharge rate of the neuron and will cause seizure (LOPES DA SILVA & WADMAN 1999) Types of Seizures Seizures are divided into two major groups, focal seizures and generalized seizures. Focal seizures also known as partial seizures occur in one part of the brain like focal frontal lobe seizure. Focal seizures are of two types, simple focal seizures and complex focal seizures. In simple focal seizures, the patient will be conscious but will have strange sensations. He will experience the feeling of anger, happiness and sadness without any cause. In complex focal seizures the patient will lose his consciousness or he will feel like he is dreaming. People having complex focal seizures experience automatism, which is repetitive movement like blinking, twitches or movement in a circle. Focal seizures may become generalized secondarily (Hopkins et al 1995 & MOLITOR 2008). Generalized seizures are the results of abnormal functioning of the neurons on the different parts of the brain. Generalized seizures may cause unconsciousness and falls. Generalized seizures are of many types like the Absence seizures also known as Petit mal seizures which is an old name, Tonic seizures, Clonic seizures, Myoclonic seizures, Atonic seizures. In absence seizures, the patient may stare to the space and may have jerking and twitching muscles. In tonic seizures the muscles of the patient go into tonic contractions. In clonic seizures the muscle on both sides of the body will jerk repetitively. In myoclonic seizures only the muscles of upper body and arms will show jerky movements. In atonic seizures the patient will experience loss of normal muscle tone in the whole body. Another type of generalized seizures which will cause both, the contraction or stiffening of the muscles and jerky movements of the muscles is named as tonic-clonic seizure. The older name for tonic-clonic seizures was grand mal seizures (Hopkins et al 2005 & Mollitor 2008). The epilepsy syndromes are of different types. They are named by their symptoms or by the point of origin in the brain for example frontal lobe epilepsy (FLE), temporal lobe epilepsy (TLE), neocortical epilepsy, absence epilepsy etc (Purves 2008 & Mollitor 2008). Temporal lobe epilepsy is one of the most common types of epilepsy which implies progressive development of seizures in the temporal lobe. Repetitive temporal lobe epileptic seizures cause the shrinkage of a hippocampus and mossy fibre sprouting. Hippocampus is a brain component which has a significant role in long term memory. In neocortical epilepsy the seizures arise from the cortex. Neocortical seizures at the onset are badly restricted to one point and explosive. The seizures are of generalized type sometimes of focal type. Absence epilepsy causes lapses of consciousness for a short time. The absence epilepsy runs in family which means that it is related to genes and mutation in genes can cause absence epilepsy. The absence seizures mostly start at childhood and usually stop at puberty but sometimes they may start at puberty (Hopkins et al 1995 & Mollitor 2008). Drug Therapies Antiepileptic drugs are used for the controlling the epileptic seizures. Usually epileptic patients take the drugs for long interval of time continuously and it becomes necessary for them. It can be derived from the pathophysiology of epilepsy that the drugs used for it would have two important counters for the disease which are (a) enhancement of GABA action which is done by the excessive activation of GABAA- receptors or by inhibiting the enzyme GABA- transaminase whose functions is to inactivate GABA. GABA is an inhibitor which will open channels for negatively charged ions mainly for chloride and entrance of chloride to neuron will increase the negativity of neuron resulting in decreased chances of epileptic seizures. (b) Inhibition of sodium channel function. Voltage gated sodium channels are responsible for depolarization, when a lot of sodium channels open it will allow the movement of sodium ions to the interior of the neuron. Sodium is a positively charged ion which will increase the potential of neuron and will cause hyper excitation of neuron which results in seizures. So the inhibition of sodium channels function means reduced opening of voltage gated sodium channel which will decrease the entrance of sodium to the neuronal cell. The antiepileptic drugs inhibit the function of sodium channels by binding preferentially to the sodium channels thus decreasing the number of functional channels for generating action potential. Some antiepileptic drugs also inhibit the calcium channel and glutamate receptor which both decrease the chances of seizures (MacDonald & Kelly 1995 Meldrum 1996 & Perucca 1996). The main antiepileptic drugs are phenytoin, carbamazepine, valproate, ethosuximide, phenobarbitone, vigabatrin, gabapentin etc. Phenytoin is the most useful antiepileptic drug which blocks the sodium channels so inhibits the spread of seizure and is used in all types of seizures except absence seizure. It may have adverse effects which are ataxia, vertigo, gum hypertrophy and megaloblastic anemia. Carbamazepine is the most widely used antiepileptic drug. It also blocks the sodium channel and inhibits the seizure spreading. It is used in all types of seizures especially in temporal lobe epilepsy but it is not again used in absence seizure. Its adverse effects are sedation, blurred vision, water retention, hypersensitivity reaction and leucopenia. Valproate has weak effect on GABA-transaminase and on sodium channels and it is used in most types of seizures bur it is especially used in absence seizure. Its side effects are nausea, hear loss, weight gain and fetal malformations. Ethosuximide inhibits T-types of calcium channels and is used in absence seizure. Its adverse effects are anorexia, nausea, mood changes and headache. Phenobarbitone enhances the GABA action and inhibits the glutamate mediated exciatation. It inhibits the initiation of discharge and is used all types except absence seizures. Vigabatrin inhibits GABA-transaminase and increase brain GABA content. It is used in all types of epilepsies. It adverse effects are sedation, behavioral and mood changes and occasionally psychosis (Meldrum 1996 & Perucca 1996). Conclusion A brief introduction about the mechanism of action of these drugs clearly illustrates the importance of the pathophysiology of epilepsy. It tells how the mechanisms are derived after studying the exact cause of the seizures. These drugs are manufactured specially keeping in mind the pathophysiology of the seizure. Bibliography Top of Form MOLITOR, S. C. (2008). Neuroscience. JAMA : the Journal of the American Medical Association. 299, 2689. Bottom of Form Top of Form HOPKINS, A., SHORVON, S. D., & CASCINO, G. (1995).Epilepsy. London, Chapman & Hall Medical. Top of Form MACDONALD, R. L., & KELLY, K. M. (1995). Antiepileptic Drug Mechanisms of Action. Epilepsia : the Journal of the International League against Epilepsy. 36, S2. ENGELBORGHS S, DHOOGE R, & DE DEYN PP. (2000). Pathophysiology of epilepsy. Acta Neurologica Belgica. 100, 201-13. LOPES DA SILVA, F. H., & WADMAN, W. J. (1999). Pathophysiology of epilepsy. HANDBOOK OF CLINICAL NEUROLOGY. 72, 39-82. Top of Form PURVES, D. (2008). Neuroscience. Sunderland, Mass, Sinauer. Bottom of Form Top of Form MELDRUM, B. S. (1996). Update on the Mechanism of Action of Antiepileptic Drugs. Epilepsia : the Journal of the International League against Epilepsy. 37, S4. Top of Form PERUCCA, E. (1996). The new generation of antiepileptic drugs: advantages and disadvantages. British Journal of Clinical Pharmacology. 42, 531. Bottom of Form Bottom of Form Bottom of Form Bottom of Form Read More