Evaluation of anti epileptic drugs practical

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anti epileptic drug practical

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  • 1. 9/15/2014 1

2. Introduction A Seizure (from the Latin is a paroxysmal event due to abnormal, excessive,hyper synchronous discharges from an aggregate ofcentral nervous system (CNS) neurons. Epilepsy describes a condition in which a person hasseizures due to a chronic, underlying process. Incidence ~0.30.5% Prevalence 510 persons per 1000.9/15/2014 2 3. Historical Aspects Over the centuries the epilepsy is known as thefalling sickness, the sacred disease, St. Johnsdisease. Among the famous who suffered from epilepsywere Julius Caeser, Alexander the great &Napolean Bonapart.9/15/2014 3 4. Hippocrates was the first person to dispel themyth of epilepsy, as not being caused by devilsand spirits.9/15/2014 4 5. John Jackson:.9/15/2014 5 6. Classification Of SeizuresA) Partial Simple Complex Secondary generalizedB) Primary Generalized Absence Tonic-clonic Tonic MyoclonicC) Unclassified Neonatal Infantile Spasms9/15/2014 6 7. Experimental methods for evaluatingantiepileptic drugs1)Electroconvulsion method.2)Chemically induced convulsion method9/15/2014 7 8. In vitro models Hippocampal slices model Electric recording from isolated brain cells GABA receptor binding assays Exitatory aminoacid receptor binding assays9/15/2014 8 9. Disadvantages of in vitro study Serve as initial screening for drug discovery Not give proper idea about pharmacokineticsand pharmacodynamics or PK-PD interactionof compound in living animals. Not possible to study compensatory changesthat occur in body when drug is given.9/15/2014 9 10. Electroconvulsion method: 1)Maximum ElectroshockSeizures(M.E.S.) Model of grand mal epilepsy End point : Tonic Hind Limb Extension The agents screened through this model consideredan antiepileptic drugs if it corrects or suppressesTonic Hind Limb Extension9/15/2014 10 11. Maximum current of such voltage is applied as to induceconvulsions in all the tested animals (rats, mice). A well characterized course of convulsion, (a short latent period, followed by a tonic extensor tonusand then by a phase of clonic convulsion) The drugs effective in the test alter the seizure pattern bysuppressing the tonic phase of convulsions. Such drugs arepotentially useful in Grand mal epilepsy(Generalized TonicClonic Seizures)9/15/2014 11 12. Materials and methods: Animal :Rat /Mouse: 150-250 gm Drugs :Phenytoin (20-30mg/kg,i.p./po) ,: Phenobarbitone sodium, 15 mg/kg i.p.:Diazepam (3-4mg/kg i.p.) Instrument: Electro convulsiometer: Rat:150 mA ,50 Hz for 0.2 sec Mouse:12 mA ,50 Hz for 0.2 sec9/15/2014 12 13. convulsiometer9/15/2014 13 14. 9/15/2014 14 15. Tonic Hind Limb Extension9/15/2014 15 16. Methods: Step 1: Weight the animals and mark properly Divide animals into 3 group They are given stimulus with ear electrode. Phases of convulsions are recorded in each mouse The drugs are injected Step 2: Group 1: Isotonic saline Group 2: Phenytoin sodium, 30 mg/kg i.p. Group 3: Phenobarbitone sodium, 15 mg/kg i.p.9/15/2014 16 17. After 1 hour animals are given electroconvulsions Observations are noted Record whether THLE Present /Absent Step 3: Observe the animal after MES Calculate percentage protection Percentage protection =No. of animals with THLEabsent /total no. animal 1009/15/2014 17 18. M.E.S.(Maximum Electroshock Seizure)Group no Latent period (sec) Extensor tonus(sec) Clonicconvulsions(sec)Before After Before After Before AfterA 1 2 3 8 8 10 10A 2 2 3 8 10 10 12B 1 2 2 8 ------- 10 11B 2 3 3 12 -------- 10 12C 1 3 3 8 -------- 10 10C 2 3 3 12 -------- 14 129/15/2014 18 19. Minimal Electroshock seizure Threshold: (MET) Measurement of minimal strength of currentrequired to elicit electroconvulsion.2) Hyponatremic Electroshock seizure Threshold(HET) animals injected with isomolar glucose solution(10 ml/100 gm body wt.). This induces hyponatremia and lowers the M.E.T. Drugs elevate the threshold used in grandmalepilepsy .9/15/2014 19 20. 3) Psychomotor Seizures Mice are subjected to unidirectional currentpulses animal becomes stunned and showsautomatism lasting for 15-20 sec. Drugs inhibiting the effect of current in thistest are potentially useful in Psychomotorseizures.9/15/2014 20 21. 4) Kindling model of epilepsy:A model for human focal epilepsy is that producedin animals by kindling.This consists of delivery of brief localized trains ofelectrical stimuli to an area of the brain,repeatedly, at about 24 hour intervals.After a time, generalized motor seizures areregularly elicited during such electricalstimulation.Useful in partial simple/complex seizure9/15/2014 21 22. Chemically induced convulsion: A threshold dose of a suitable convulsant (e.g.Leptazole, Strychnine) is injected in mice orrats. This induces clonic type of convulsions. Some of the anticonvulsants (ethosuccimide,sodium valproate) prevent these convulsions.Such drugs may be potentially useful inPetitmal epilepsy (Absence Seizures).9/15/2014 22 23. (B) Chemical method:- Two mice (D1, D2) are selected. One is injected with antiepileptic drug(sodium valproate) and other is kept as control. Then both mice are injected with leptazoleand observations are noted.9/15/2014 23 24. Chemical method:Convulsant Antiepileptic No. of animalshowingconvulsionsNo. of animalsshowing protectionfrom convulsionsDrug and dose Drug and doseLeptazole(70 mg/kg i.p)Normal Saline 1 nilLeptazole(70 mg/kg i.p)Sodium Valporate40 mg/kg i.p.nil 19/15/2014 24 25. Assignmenta) Define epilepsy.b) Classify epilepsy.c) Enumerate experimental methods forevaluation of anticonvulsant.d) Enlist one drug of choice each for commontype of epilepsy.9/15/2014 25 26. Selection Of Anti-epileptic Drug Primary GTC: Phenytoin Partial: Carbamazepine Absence: Ethosuxamide Myoclonic seizure: Valporic acid Drug resistant seizures: Lamotrigine Febrile convulsions: Diazepam9/15/2014 26 27. Classification Of SeizuresA) Partial Simple Complex Secondary generalizedB) Primary Generalized Absence Tonic-clonic Tonic MyoclonicC) Unclassified Neonatal Infantile Spasms9/15/2014 27