Epilepsy

Epilepsy
Epilepsy is a group is neurological disorder. An epileptic seizure is a paroxysm(sudden) of uncontrolled discharges of neurons causing an event that is discernible(visible) by the person experiencing the seizures or by the observer. The tendency to have recurrent attacks is known as epilepsy.
phenytoin,phenobarbital,sodium valporate ,carbamazepine,clonazepam and diazepam, lamotrigine,pregabalin,felbamate,zonisamide, ETHOSUXIMIDE, LEVETIRACETAM, OXACARBAZEPINE, PRIMIDONE

1. Epilepsy Dr. Asra Hameed Pharm.D (JUW) [email protected]

2. Introduction Epilepsy is a group is neurological disorder. An epileptic seizure is a paroxysm(sudden) of uncontrolled discharges of neurons causing an event that is discernible(visible) by the person experiencing the seizures or by the observer. The tendency to have recurrent attacks is known as epilepsy.

3. Epidemiology Diagnosis is essentially clinically, relying heavily on eyewitness descriptions of the attacks. A global campaign has been established to aware about epilepsy, provide information and improve care. Around 50 million people worldwide have epilepsy. Nearly 90% of the people with epilepsy are found in developing regions. Epilepsy ressponds to treatment 70% of the time. Upto 5% of people will suffer at least one seizure in their lifetime.

4. Aetiology Epileptic seizures are produced by abnormal discharges of neurons that may be caused by any pathological process which affects the cortical layer of the brain

5. SYMPTOMATIC EPILEPSY: Epilepsy is called symptomatic when it has a known cause. IDIOPATHIC EPILEPSY: where no apparent cause for epilepsy can be found, but there may be a family history, suggesting that the condition is inherited CRYPTOGENIC EPILEPSY: This is when the cause for a person's epilepsy has not yet been found, despite investigations

6. Pathophysiology IN NORMAL CASE :

7. IN CASE OF EPILEPSY :

8. Generalized seizures Generalized seizures result in impairment of consciousness from the on set TYPES OF GENERALIZED SEIZURES: There are various types of generalized seizures Tonic clonic convulsions Absence attack Myoclonic seizures Atonic seizures

9. MYOCLONIC SEIZURES : In myoclonic seizures very brief involuntary shock like jerks which may involve in the whole body or arms or head usually Happen in morning they may cause person fall. ATONIC SEIZURES: These comprise a sudden loss of muscles tone causing person to collapse to the ground recovery after ward is quick much commonin pateint with severe epilepsy starting in infancy

10. TONIC CLONIC SEIZURES: Often called “grand mal” attacks with out warning the patient suddenly goes stiff,fall,tongue bitting with laboured breathing and salivation it over come after few minutes ABSENCE ATTACKS: Aften called “petit mal” these are much rarer form it happen in child hood , child goes bland and stares fluttering of eyelids and flopping of head may occur it last only few seconds and un recognized even by child experencing them

11. PARTIAL OR FOCAL SEIZURES SIMPLE PARTIAL SEIZURES: Discharge remains localized & consciousness is fully preserved. EXAMPLES : Localized jerking of a limb or face, stiffness or twitching of one part of the body, numbness or abnormal sensations.

12. COMPLEX PARTIAL SEIZURES : Seizure progresses with impairment of consciousness. Originate in the frontal or temporal lobes of the brain and can progress to secondarily generalized seizures. EXAMPLES: Lip smacking , undressing, performing aimless activities, acting in a confused manner.

13. SECONDARILY GENERALISED SEIZURES : These are partial seizures, either simple or complex. Discharge spreads to the entire brain. ECG can demonstrate the partial nature of the seizure. Involvement of the entire brain leads to a convulsive attack with same characteristics as a generalized tonic clonic convulsion.

14. DIAGNOSIS Diagnosis of epilepsy is clinical & depends on a reliable account of what happened during the attacks. Epilepsy must only be diagnosed when seizures occur spontaneously and are recurrent. EEG (electroencephalogram) is the only examination required, particularly in generalized epilepsies & aims to record abnormal neuronal discharges.

15. Magnetic resonance imaging (MRI) is the most valuable investigation when structural abnormalities such as stroke, tumor, congenital abnormalities are suspected. MRI to be used in people who develop epilepsy as adults or in whom seizures persist or when a structural lesion on the brain may be responsible for seizures.

16. Treatment National Institute for Health and Clinical Excellence issued guidance on the treatment of the epilepsies in adults and children in primary and secondary care. Treatment individualised according to seizure type, epilepsy syndrome, co-medication and co-morbidity, the individual's lifestyle and personal preference.

17. Treatment during seizures Made the patient as comfortable as possible ( lying down, cushioning the head, loosening any tight clothing or neckwear) Should not be moved unless they are in a dangerous place (road, fire, top of stairs, edge of water) No attempt should be made to open a person’s mouth or don’t force any thing between the teeth When seizure stops, turned over to recovery phase and check air ways for any blockage No drinks or extra anti-epileptic drugs required. If seizure persist for more than 10min, IV or Rectal diazepam(10-20mg) in adults can be given. Lower doses of diazepam advisable for children.

18. Status epilepticus Initially: Positioning the person to avoid injury Supporting respiration Maintaining Blood Pressure Correcting hypoglycemia Drugs: DOC= Lorazepam or diazepam IV Alternative= midazolam

19. Febrile convulsions Convulsions associated with fever May occur in young Aim to reduce the temperature Use of paracetamol is usual If Prolonged febrile convulsions, DOC is Diazepam. (IV or PR)

20. Long term treatment Long term and regular drug therapy of epilepsy usually for atleast 3 years or for life time Objective: Suppress epileptic discharges Prevent the development of epileptic seizures Treatment is initiated by specialist only with consideration of all relevant factors. AED treatment may fails unless the patient fully understands the importance of regular therapy and the objectives of treatment. Poor adherence is still a major factor lead to hospitalization and poor seizure control and lead to clinical use of multiple AED.

21. General principle of treatment Therapy aims to control seizures using one drug with the lowest possible dose that cause the fewest side effects possible. The choice of drugs depends largely on the seizure type, and so correct diagnosis and classification are essential .

22. Initiation of therapy in newly diagnosed patients The first line AED most suitable for the person’s seizure type should be introduced slowly, starting with a small dose. This is because too rapid an introduction may include side-effects that will lose the patient’s confidence.

23. Maintenance dosage There is no single optimum dose of AED Dose varies from person to person and drug to drug. Drug should be introduce slowly and then increased incrementally to an initial maintenance dosage. Seizure control then be assessed and the dose of rug changed if necessary. Most specialists prefer people to remain on the same brand of medication, and this is also preferred by the majority of people with epilepsy.

24. Altering drug regimens

25. Withdrawal of drugs

26. Newer AEDs

27. Follow-up and monitoring of treatment It is essential to follow up patients in whom AED treatment has been started Monitornig the efficacy and side effects of treatment upon which drug drug dosage will depend This follow up is particularly important in early stages of treatment

28. Stopping treatment With drawl therapy is an individual one and the person shouldbe made aware of the risk and benefits of withdrawl Drug withdrawl should be carried out only very slowly in staged decrements and only one drug at a time should be withdrawn Withdrawn therapy should be considered in people who have been free seizure free for a considerable period of time

29. Monitoring antiepileptic therapy TDM involves the measurement of serum drug s and their pharmacokinetics interpretation .TDM may be useful to establish adherence with the treatment At the onset of action If seizure control is poor or sudden changes in seizure control occur If toxicity is suspected When changes AED therapy or making changes to other aspects of a persons drug regimen that may interact with the AED

30. Drug development and action Established AEDs such as phenytoin,phenobarbital,sodium valporate , carbamazepine,clonazepam and diazepam New drugs include lamotrigine,pregabalin,felbamate,zonisamide Unlike most older agents vigabatrin,zonisamide.lacosamide

31. 1 . CARBAMAZAPINE Carbamazepine is a dibenzapine derivative with antiepileptic and anticonvulsant properties. Pharmacodynamics : Na-Channel Antagonist Indications: Aggression Diabetes insipidus Epilepsy Mood disorder Trigeminal neuralgia Prophylaxis of bipolar disorder.

32. Contra-indications: Bone marrow depression Porphyrias Av conduction abnormalities. Adverse Drug Reaction: Proteinuria Skin rashes Stevens johnson syndrome Hyponatremia Agranulocytosis Hematuria Drug Interaction : Amitriptyline Chloroquine Bromazepam Fluoxetine Diltiazem

33. 2 . CLONAZEPAM Clonazepam is a benzodiazipine . Benzdiazipines are the most widely used anxiolytic drugs. Pharmacodynamics : Chloride Channel Potentiater (GABA operated) Indications: Atypical absence Bipolar affective disorder Drug induced dyskinesias

34. Contra-indications: Respiratory depression Acute pulmonary insufficiency Hypersensitivity Adverse Drug Reaction: Thrombocytopenia Blood dyscrasias Apnea Hypotension, Dizziness, Drowsiness, Fatigue, Anorexia, Drug Interactions: Alcohol Carbamazepine Iproniazid Phosphate Phenobarbitone Valproic Acid

35. 3 . ETHOSUXIMIDE Ethosuximide is antiepileptic agent. its popularity continues, based on its safety and efficacy. Pharmacodynamics : Pyrrolidinedione Indications: Generalised epilepsy with absence seizures.

36. Contra-indications: Hypersensitivity to any component of product. Adverse Drug Reaction: Tonic- clonic seizures Nausea Vomiting Anorexia GI symptoms, Drug Interactions: Alcohol, Carbamazepine Isoniazid Phenobarbitone Phenytoin (Na), Sodium Valproate

37. 4 . LAMOTRIGINE Lamotrigine is a triazine derivarive . Lamotrigine is oral antiepileptic and anticonvulsant agent. Pharmacodynamics : Triazine Derivatives Indications: Bipolar disorders Epilepsy Partial seizures Tonic-clonic seizures Generalised epilepsy with absence seizures

38. Contra-indications: Renal failure Hepatic failure Hypersensitivity. Adverse Drug Reaction: Ataxia Thrombocytopenia Stevens johnson syndrome Angioedema Nystagmus , Extrapyramidal symptoms Tremors Drug Interactions: Carbamazepine Fosphenytoin Phenobarbitone Phenytoin (Na)

39. 5 . Phenobarbitone Phenobarbitone is oral and parenteral barbiturate with anticonvulsant and sedative-hypnotic properties. Phenobarbitone is also the longest-acting agent in the barbiturate group. Pharmacodynamics : Chloride Channel opener ( Gaba operated) I ndications: Benign febrile convulsions of infancy Seizures Short-term treatment of severe congestive heart failure Status epilepticus .

40. Contra-indications: Porphyrias Hepatic disease. Adverse Drug Reaction: Ataxia Confusion Irritability Mental disturbances Aplastic Anemia Hepatitis Drug Interactions: Alcohol Chlorpropamide Clonazepam Diltiazem ( HCl ) Ritonavir Verapamil ( HCl ) Vitamin K, Warfarin (Na

41. 6: LEVETIRACETAM Levetiracetam is an anti epileptic pyrrolidone derivative. Pharmacodynamic: The exact mechanism by which levetiracetam acts to treat epilepsy is unknown. However, the drug binds to a synaptic vesicle glycoprotein, SV2A. Indications: Levetiracetam is an anti-epileptic drug which is used for the adjunctive treatment of partial seizures, with or without secondary generalisation. alternative drug of choice in Iron deficiency anaemia . Contra-indications: Breast feeding Adverse Drug Reaction: Dizziness , Vertigo, Headache, Drowsiness, Ataxia, Anorexia, Nervousness, Rashes, Depression, Tremor, Asthenia, Aggression. Drug interactions: phenytoin , phenobarbital , primidone , carbamazepine , valproic acid, lamotrigine , gabapentin , digoxin , oral contraceptives ethinylestradiol , and warfarin

42. 7 . OXACARBAZEPINE Oxacarbazepine is an antiepileptic and anti convulsant drug. Pharmacodynamic: blockade of voltagesensitive sodium channels could contribute to the antiepileptic efficacy of OCBZ. Indications: adjunctive treatment of partial seizures with or without secondary generalised tonic- clonic seizures. Contra-indications: Oxcarbazepine is contraindicated in conditions like Hypersensitivity to any component of product Adverse Drug Reaction: Dizziness , Vertigo, Headache, Drowsiness, Ataxia, Alopecia, Diarrhea , Constipation, Abdominal pain, Rashes, Confusion, Urticaria , Depression, Tremor, Diplopia,nausea,vomiting . Drug Interactions: Amiodarone , Amlodipine, Felodipine , Nifedipine , Nimodipine , Verapamil ( Calan , Covera , Isoptin , Verelan ) Cyclosporine Lansoprazole ( Prevacid ) Omeprazole (Prilosec)

43. 8 . PHENYTOIN Phenytoin exerts its anticonvulsant effect mainly by limiting the spread of seizure activity and reducing seizure propagation. Pharmacodynamics : Na-Channel Antagonist Indications: Convulsions , Epilepsy, Migraine prophylaxis, Myotonia , Prophylaxis of epilepsy, Status epilepticus, Status epilepticus; seizures in neurosurgery, TIC douloureaux , Ventricular arrhythmias . Contra-indications: conditions like Porphyrias . Adverse Drug Reaction: Ataxia , Nausea, Vomiting, Hypotension, Drowsiness, Nystagmus , Coma, Hyperglycemia , Stupor, Blurred vision. Drug Interactions: Alprazolam , Amiodarone ( HCl ), Amitriptyline ( HCl ),Amlodipine, Ciprofloxacin, Clarithromycin,carbamazepine .

44. 9 . Sodium Valproate Sodium Valproate is anticonvulsant drug Pharmacodynamics : Na-Channel Antagonist. Indications: Sodium Valproate is primarily indicated in conditions like All forms of epilepsy, Generalised epilepsy with absence seizures, Prophylaxis of febrile convulsion, Prophylaxis of post traumatic epilepsy, Status epilepticus Contra-indications: pregnancy. Adverse Drug Reaction: Thrombocytopenia, Pancreatitis, Liver damage, Extrapyrimidal symptoms, Hyperammonemia , Death, Deepening coma, Weight gain, Tremor, Hair loss, GI disorders, Hematological disorder, Leucopenia . Drug Interactions: Aspirin, Carbamazepine, Erythromycin, Ethosuximide , Fosphenytoin , Lamotrigine , Mefloquine ( HCl ), Meropenem , Methotrexate, Phenobarbitone , Phenytoin.

45. 10 . PRIMIDONE It resembles phenobarbital in its anticonvulsant activity. Primidone is a derivative of barbituric acid. Pharmacodynamics : work via interactions with voltage-gated sodium channels which inhibit high-frequency repetitive firing of action potentials Indications: Primidone is primarily indicated in conditions like Epilepsy, Essential tumor . Contra-indications: Primidone is contraindicated in conditions like Porphyrias . Adverse Drug Reaction: Vertigo, Ataxia, Nausea, Vomiting, Drowsiness, Sleepiness, Irritability, Ataxia, Tremors, Impotence, Loss of libido, Loss of memory,depression . Drug Interactions: Acetazolamide (Na), Alcohol, Carbamazepine, Chloramphenicol, Cortisone (Acetate), Desogestrel , Desonide , Estradiol ( Valerate ), Ethynodiol ,Na valporate .

46. Conclusion