Epilepsy

Types of seizures and drug used in it

1. EPILEPSY By M.ASIYABI .,M.PHARM (PHARMACOLOGY) ASSISTANT PROFESSOR DEPARTMENT OF PHARMACY

2. Definition Epilepsy : The occurrence of transient (short-term) paroxysms (sudden attack) of excessive or uncontrolled discharges of neurons in the cerebral cortex , which may be caused by a number of different etiologies, leading to epileptic seizures . The term seizure needs to be carefully distinguished from convulsions and epilepsy.

3. What is the differences between Seizure and Epilepsy Epilepsy is a disorder characterized by recurring seizures (also known as “seizure disorder ”) A seizure is a brief, temporary disturbance in the electrical activity of the brain “A seizure is a symptom of epilepsy”

4. Historical Background Epilepsy derived from a Greek term : Epilambane -to posses, to take hold of, to grab or to seize. Vedic period of 4500-1500BC : Ancient Indian Medicine refined and developed the basic concept of epilepsy Charaka Samhita - The Ayurvedic literature 400 BC : Describe epilepsy as ‘ Apasmara ’ means loss of consciousness.

5. Cont… Hippocrates 400 BC : ‘This is not a sacred disease rather disorder of brain’ . He described some physical treatment of epilepsy and stated it is an incurable chronic illness. Ibn Sina 370 AH : describe epilepsy as a brain disease

6. Timeline 1909 : Formation International league against epilepsy (ILAE). 1912 : Use Phenobarbitone as AED. 1938 : Use Phenytoin as AED. 1950-1970 : Developed many AED. 1981 : ILAE classified epilepsy. 1997 : ILAE, IBE and WHO jointly established Global campaign against epilepsy.

7. The Brain Is the Source of Epilepsy All brain functions -- including feeling, seeing, thinking, and moving muscles -- depend on electrical signals passed between nerve cells in the brain A seizure occurs when too many nerve cells in the brain “ fire ” too quickly causing an “ electrical storm ”

8. Epidemiology The most common ages of incidence are under the age of 18 and over the age of 65. About 1% of the population meets the diagnostic criteria for epilepsy at any given time. Prevalence: Developed countries- 0.5% (0.4% - 1%) Developing countries- five times higher Incidence: After infancy annual incidence- 20-70/100000 in developed countries. Developing countries- Incidence is double. (100/100000 )

9. Causes In 28% cases cause can be determined. Rests (72%) are Idiopathic. Determined causes : Inherited genetic Acquired : trauma, Neuro surgery, Inflammatory, Metabolic, Infections, Tumor, Toxic disorders, drugs, etc. Congenital : inborn error of metabolism. Withdrawal of drugs : Alcohol,Benzodiazepine , Barbiturates, Other Anti-Epileptics

10. Drugs That Induce Seizures Antibiotics : Penicillin, INH, Cycloserin , Ciprofloxacin, Metronidazole . Anti Diabetic : Insulin,Phenformin . Hormonal : Prednisolone, OCP, Oxytocin Cardiac : Lidocaine,Procaine , Disopiramide Anesthetics : Methohexital , Ketamin , Halothane,Propofol Antimalarial : Chroloquine , Mefloquine , Proguanil . Anti Spastic : Baclofen Stimulant : Aminophylline , Theophyline .

11. Cont… Radiographic contrast : Meglumine derivatives, Metrizamide . Antidepressant : TCA- ( Amitriptaline , Imipramine , Clomipramine ), Dosulepin , Buproprion , Venlafaxine , Duloxitine,Reboxetine Antipsychotics : Chlorpromazine, Zotepine , Loxapine,Depot Anti- psychotics,Clozapine Mood Stabilizer : Lithium Psycho stimulant : Amphetamine

12. Safe Psychiatric medication in Epilepsy Antidepressant : Moclobemide , SSRI (with cautious) Antipsychotics : Haloperidol, Trifluphenazine , Sulpiride

13. Groups at higher risk The risk is higher in people with certain medical conditions: Mental retardation Cerebral palsy (movement disorder) Alzheimer’s disease ( neuro -degeneration) Stroke (poor blood flow to brain Autism (troubles with social interaction)

14. Triggers • Missed medication (#1 reason) • Stress/anxiety • Hormonal changes • Dehydration • Lack of sleep • Extreme fatigue • Photosensitivity • Drug/alcohol use; drug interactions

15. Symptoms Confused memory Occasional “fainting spells” Episodes of blank staring (looking somewhere without any reason) in children Sudden falls for no apparent reason Episodes of blinking or chewing at inappropriate times A convulsion, with or without fever Swift jerking movements in babies

16. First Aids Stay calm and track time Do not restrain the person, but help them avoid hazards – Protect head, remove glasses, loosen tight neckwear – Move anything hard or sharp out of the way – Turn person on one side, position mouth to ground Check for epilepsy or seizure disorder ID Understand that verbal instructions may not be obeyed Stay until person is fully aware and help reorient them Call ambulance if seizure lasts more than 5 minutes or if it is unknown whether the person has had prior seizures

17. NOT TO DO Put anything in the person’s mouth Try to hold down or restrain the person Attempt to give oral anti-seizure medication Keep the person on their back face up throughout convulsion

18. P A T H O P H Y S I O L O G Y Decreased inhibitory system Increased excitation Epilepsy is generated ( Epileptogenesis ) Imbalance occurs

19. Classification Of Seizures I. Partial seizures A. Simple partial seizures B. Complex Partial Seizures C. Partial Seizures evolving to secondary generalized seizures II. Generalized seizures A. Absence seizures B. Myoclonic seizures C. Clonic seizures D. Tonic seizures E. Tonic- Clonic seizures F. Atonic seizures III. Unclassified epileptic seizures a. Febrile epilepsy b. Infantile spasm

20. Partial seizures A. Simple seizures (without impairment of consciousness) With motor symptoms With special sensory or somatosensory symptoms With psychic symptoms Signs &symptoms: Motor – convulsive jerking, chewing motions, lip smacking Sensory & somatosensory – paresthesias , auras Automatic – sweating, flushing, pupil dilation Behavioral – hallucinations, dysphasia, impaired consciousness (rare)

21. B.Complex seizures (with impairment of consciousness) 1.Simple partial onset followed by impairment of consciousness 2.Impaired consciousness at onset Impairment of consciousness Purposeless behaviour is common Affected person may wander about aimlessly Aggressive behaviour (violence) Automatism ( eg : picking at clothes) Visual, auditory, or olfactory hallucinations

22. Generalised Seizures Generalized Tonic- clonic (grand mal) Convulsive seizures No Aura but have prodormal phase- general malaise a.) Tonic phase : These are characterized by rigid violent muscular contraction with stiff and fixed extended b.) Clonic phase : These are characterized by repetitive muscle jerks. Duration : few minutes Post ictal period: drowsiness, confusion, headache, deep sleep

23. C.) Typical Absence Seizures (Petit mal): There is no aura associated with this disorder and attack appears without warning. There is usually no loss of consciousness. Absence seizures are characterized by subtle bilateral motor symptoms such as rapid blinking of eyelids, chewing movements. Attacks last only a few seconds (<10 sec) and often pass un- recognized. About 100-200 attacks may occur/day. Attacks precipitate by fatigue, drowsiness, relaxation , photic stimulation or hyperventilation

24. D.) Myoclonic seizures : Bilateral epileptic myoclonus - sudden and brief skeletal muscle contraction (entire or part of the body) - sudden jerking movements appearing during sleep. E.) Atonic seizures ( Akinetic seizures): - sudden loss of postural tone. - The head may sag to one side or the patient may fall all of a sudden. - The consciousness may be impaired

25. Unclassified Seizures Febrile seizures : wherein young children frequently develop seizures with illness accompanied by hyperpyrexia. Infantile spasm : with progressive mental retardation. These are generalized tonic- clonic convulsions of short duration . These have not yet been classified because of insufficient data or atypical pattern of the seizures

26. Classification Based On Epilepsy Syndrome Idiopathic in which no cause could be identified except for genetic linkage. Examples : Juvenile myoclonic epilepsy syndrome. Symptomatic in which the seizures are associated with some identifiable underlying disorders. Examples : Lennox- Gastaut epilepsy syndrome (impaired cognitive functions) Cryptogenic in which the epilepsy appears to be symptomatic but the exact cause is unknown. Examples : west’s syndrome (infantile spasm).

27. Diagnosis Thorough History taking : From patients From reliable valid informants From observer (who observed seizures) Physical Examination: Specially neurological system Higher Psychic function Laboratory Investigation: Serum Electrolytes, Serum Prolactin , Blood sugar, Complete blood count, Function tests (liver, thyroid, renal), CSF study Imaging: EEG, Video EEG telemetry, CT Scan of Brain, MRI of Brain. Polysomnography (a type of sleep study)

28. Anti-Epileptic Drug (AED)

29. S.NO DRUG DOSE (in mg) MECHANISM OF ACTION 1 Phenytoin 100 Blocks Na+ channels  inhibits the generation of repetitive action potential. Reduces the influx of Ca2+  decrease the glutamate synthesis. 2 Phenobarbitol 30, 60 Binds to the GABA Receptors and enhances the GABA mediated inhibitory effects by increasing the duration of Cl - channel opening. 3 Carbamazepine 100,200 It also blocks the use-dependent Na+ channels and inhibits high-frequency repetitive firing of neurons in brain

30. S.NO DRUG DOSE (in mg) MECHANISM OF ACTION 4 Ethosuximide 500 inhibits T-type Ca2+ channels  generates thalamic cortical pacemaker current. 5 Valproic acid 200 , 300 Blocks Na+ channels  increase the GABA activity by activating glutamic acid decarboxylase and inhibiting GABA transaminase . 6 Benzodiazepines 5 , 10, 20 Enhances the frequency of GABA-mediated Cl - channels opening.

31. Screening methods of Anti-epileptic drugs

32. In-vitro methods Hippocampal slices. Electrial recording from isolated brain cells. GABA uptake in rat cerebral cortex. TBPS binding assay

33. Withdrawal Of Anti-epileptic Drugs After complete control of seizures for 2-4 years, withdrawal of Anti Epileptic drugs may be considered. But in case of special professional group (car driver, machine man etc) withdraw the AED after keen follow-up. AED should be tapered during the stopping of medications. Slow reduction by increments over at least 6 months. If the patient is taking two AEDs one drug should be slowly withdrawn before the second is tapered

34. AED SIDE EFFECTS Nausea Rashes vomitting Altered sleep cycles Behavioural changes Blurred vision Diarrhoea Ataxia Stevens – johnson syndrome Aplastic anaemia Hepatic failure Weight gain Menstrual irregularity Hair loss Osteomalacia (long term use) Neuropathy (long term use) Dermatitis e.t.c ….. Even causesDeath .

35. Some famous persons had epilepsy ARISTOTLE SOCRATES

36. Julius Caesar Alfred Nobel Napoleon Bonaparte