Essay on the Treatment of Epilepsy | Diseases | Medical Science

Here is an essay on the ‘Drugs Used for the Treatment of Epilepsy’ for class 11 and 12. Find paragraphs, long and short essays on the ‘Drugs Used for the Treatment of Epilepsy’ especially written for college and medical students.  

Essay # 1. Antiepileptic Drugs:

Antiepileptic drugs are used in the treatment of epilepsy which includes a group of disorders of CNS characterized by partial seizures with or without secondary generalization or generalized seizures. The object of the treatment is to prevent the occurrence of seizures by maintaining an effective plasma concentration of the drug.

There are several varieties of epilepsy and they vary in their response to drugs. Although, there are now a number of drugs which are useful in controlling epilepsy, it is usually best to start treatment with one drug only and use multiple drug regimens in resistant cases. Table 3.2 gives the type of epilepsy (seizures) and the choice of antiepileptic drugs.

Mechanism of action:

Glutamate is the excitatory neurotransmitter and γ-aminobutyric acid (GABA) is the inhibitory transmitter in the CNS. Most of the antiepileptic drugs act by inhibiting GABA transaminase, the enzyme that catabolizes GABA, thus increasing the activity of the inhibitory neurotransmitter GABA or by inhibition of the activity of glutamate. Some act by directly blocking sodium and/or calcium channels in the nerve cell membrane.

i. Phenytoin (Diphenylhydantoin):

Phenytoin is well absorbed orally and does not produce drowsiness or sleep. It probably acts by reducing the excitability of nerve cells by blocking sodium channels in nerve membranes and thus prevents the abnormal discharge from the epileptic foci in the brain.

Phenytoin is effective in all forms of epilepsy except petit mal. It has a narrow therapeutic index and serves as an alternative to carbamazepine or sodium valproate as an antiepileptic. Monitoring of plasma concentration is necessary for optimum efficacy and avoidance of acute toxic effects.

Adverse effects:

Side effects are fairly common and include drowsiness, memory impairment, ataxia, nystagmus, gum hyperplasia, hirsutism, greasy skin, macrocytic anaemia, rashes, liver damage and osteomalacia.

Drug interactions:

These are common and necessitate regular measurement of plasma levels of phenytoin. Plasma phenytoin concentration is increased by NSAIDs, antibacterials, oral anticoagulants, antifungal drugs, calcium channel blockers, cimetidine and uricosuric drugs. Phenytoin accelerates the metabolism of a number of drugs such as corticosteroids, oral contraceptives, theophylline, tricyclic antidepressants and thyroxine among others.

ii. Fosphenytoin:

Fosphenytoin is a pro-drug and is converted into phenytoin by the liver enzyme alkaline phosphatase. It is given by injection when phenytoin cannot be given by mouth, e.g. during status epilepticus or seizures associated with head injuries or surgery. It causes less irritation than phenytoin at the injection site.

iii. Phenobarbitone:

Phenobarbitone is not the drug of choice in epilepsy because of its potential neurotoxicity. It is a long acting barbiturate which is particularly effective in grand mal, but may also be used in other types of epilepsy except petit mal. Primidone is largely converted to phenobarbitone which is responsible for its antiepileptic action. Phenobarbitone is slowly absorbed; the major portion is metabolized in the liver and the rest excreted by the kidneys.

Adverse effects:

Side effects are not uncommon and include drowsiness, memory impairment, ataxia, skin rash resembling measles and behavior disorders. Phenobarbitone is a powerful inducer of enzymes in the liver and increases the metabolism of a large number of drugs thereby lowering their plasma concentration and consequent reduction in their pharmacological effects.

iv. Primidone:

Primidone is in many ways similar to phenobarbitone and is also effective in all forms of epilepsy except petit mal. Side effects are like phenobarbitone and include drowsiness, ataxia, nausea, visual disturbances and rashes.

v. Carbamazepine (Tegretol):

Carbamazepine is the drug of choice for psychomotor and grand mal epilepsy. It is also used to relieve the pain of trigeminal neuralgia and for prophylaxis of bipolar depression unresponsive to lithium. It is of no value in petit mal. The dose of carbamazepine depends more on the patient’s response than its plasma levels.

Adverse effects:

Common side effects include drowsiness, dizziness, ataxia, diplopia, rashes, leucopenia, heart block, hyponatremia, occasionally jaundice and excessive salivation. Carbamazepine is contraindicated in AV conduction abnor­malities, history of bone marrow depression and porphyria.

Carbamazepine, like phenytoin and phenobarbitone, causes induction of hepatic enzymes which may reduce the efficacy of oral contraceptives. Erythromycin increases the serum concen­trations of carbamazepine. Oxcarbazepine is a pro-drug that is converted into an active metabolite. Its actions are similar to carbamazepine and are used in patients allergic to carbamazepine.

vi. Sodium Valproate:

Valproate acts by inhibiting GABA metabolism in the brain. It has a much broader range of anticonvulsant action and is effective in all forms of epilepsy including petit mal.

Adverse effects:

An attractive feature of valproate is its relative freedom from sedative cognitive (mental activity), and behavioural effects as compared with phenytoin, phenobarbitone, and the benzo­diazepines. Drowsiness, thinning of the hair and weight gain is common. Platelet count and fibrinogen concentration may be reduced but serious hemorrhagic complications are rare. Rare idiosyncratic metabolic reactions that produce fatal hepatotoxicity are the most serious complications. Valproate is contraindicated in active liver disease, family history of severe hepatic dysfunction and porphyria.

Drug interactions:

Aspirin, erythromycin and cimetidine increase plasma valproate concentration. Antidepressants, antimalarials, antipsychotics antagonise the anticonvulsant effects of valproate.

vii. Vigabatrin:

Vigabatrin irreversibly inhibits GABA transaminase, resulting in an increase in synaptic GABA. Vigabatrin is particularly effective in psychomotor seizures—a condition where carbamazepine, valproate and phenytoin fail to offer complete control of the seizures in 40% of patients. Antiepileptic effects do not correlate with serum concentrations, and plasma monitoring is therefore not necessary.

Adverse effects:

These are reported to be mild, reversible and similar to those for other anti-epileptics such as sedation, confusion, amnesia and visual field defects. Vigabatrin is relatively free of adverse cognitive effects. The most important adverse effect is the production or exacerbation of psychosis. Vigabatrin is contraindicated in visual field defects.

viii. Lamotrigine:

Lamotrigine is a novel antiepileptic drug, which reduces the release of the excitatory neurotransmitter, glutamate. It is indicated in psychomotor and grand mal epilepsy and better tolerated than carbamazepine.

Adverse effects:

Ataxia, drowsiness, diplopia and nausea occur in a small proportion of patients. Rashes, which may be dangerous, occur particularly in children. It should not be used in patients with hepatic or renal impairment.

ix. Clonazepam:

Clonazepam is a benzodiazepine and is useful in all forms of epilepsy, but its sedative effects may be prominent. It is con­traindicated in respiratory disease, hepatic and renal impairment.

x. Clobazam:

Clobazam is also a benzodiazepine and is used as an adjunct in epilepsy. Its side effects are similar to that of diazepam.

xi. Felbamate:

Felbamate is effective over a wide range of epileptic conditions. Because of its dangerous adverse effects such as hepatitis and aplastic anemia, the use of felbamate is restricted to only one particular childhood epilepsy called the Lennox-Gastaut syndrome, which does not responds to other drugs.

xii. Ethosuximide:

Ethosuximide is the drug of choice for petit mal. It may aggravate grand mal and may, if necessary be, combined with a drug which controls grand mal epilepsy.

Adverse effects:

Gastrointestinal disturbances, weight loss, drowsiness, ataxia, photophobia, headache and depression are common. Rarely psychotic states, rashes, hepatic and renal changes and blood disorders may occur.

Essay # 2. Other Drugs:

Acetazolamide, a carbonic anhydrase inhibitor, is a second-line drug for psychomotor and grand mal. Piracetam, gabapentin, topiramate and tiagabine are used as adjunctive treatment for psychomotor epilepsy.

i. Status Epilepticus:

Diazepam is the most effective and is given intravenously in a dose of 10 mg. In young children rectal diazepam is quite effective and useful particularly if intravenous injection is difficult. There is high risk of venous thrombophlebitis with diazepam, which is minimized by giving diazepam emulsion (as Diazemuls). Other benzodiazepines, clonazepam and lorazepam are also used; lorazepam has the advantage of a long duration of action.

Although diazepam will usually stop the fits, relapse quite commonly occurs within the next hour. To prevent relapses phenytoin or more usually fosphenytoin is given intravenously with ECG monitoring, since it is a cardiac depressant.

Alternatively, phenobarbitone sodium can be given by intravenous injection. If the fits still persist chlomethiazole should be given intravenously. It should not be given in acute pulmonary insufficiency. Finally, if all therapies fail, thiopentone can be given by intravenous injection, using artificial ventilation, if necessary.

Paraldehyde is an oily liquid with pungent smell. It is a CNS depressant which controls status epilepticus. It is given rectally or by deep intramuscular injection. It is not the first line treatment for status epilepticus, but has the advantage of relatively freedom from severe respiratory depression seen with other drugs and does not require close monitoring and respiratory support.

ii. Anti-Epileptics and Pregnancy:

Antiepileptic drugs given during pregnancy are associated with an increased risk of fetal malformations. Carbamazepine, phenytoin and valproate carry the risk of neural tube and other defects. To counteract the risk of congenital defects, women should receive folic acid (5 mg) daily before and throughout pregnancy.

In view of the risk of neonatal bleeding associated with carbamazepine, phenobarbitone and phenytoin, prophylactic vitamin K is recommended before the delivery. Antiepileptic drugs induce liver enzymes and thus increase the rate of breakdown of oral contraceptives, which requires necessary changes in the patient’s method of contraception.