This document provides an overview of epilepsies and antiepileptic drugs (AEDs). It defines epilepsy as a brain disorder characterized by recurrent seizures. Seizures are caused by abnormal electrical discharges in the brain. The document classifies seizures as partial or generalized, discusses the neurobiology and diagnosis of epilepsy, and outlines various AEDs used to treat different types of seizures. It also addresses the economic and social implications of epilepsy, and provides an introduction to the author's research on the essential oil of Curcuma longa and its neuropharmacological effects in mice.

1. EPILEPSIES AND ANTIEPILEPTIC
DRUGS(AEDs)
By: KPALAP, AUGUSTINE BARIDOMA
PHA/2006/081

2. Contents
1. Introduction
2. Definition of Epilepsy and seizures
3. Epidemiology
4. Aetiology
5. Classification
6. Neurobiology of seizures
7. Diagnosis
8. Management/Treatment
9. Economic importance and social
implications.
10. Overview of my project work

3. INTRODUCTION
Etymology: From Greek word epilepsia=“seize” or
“possess”
Believed to a demonic possession
Countered by Hippocrates, 400BC; and Galen, 2nd
Century AD
Associated with the indigent?
Communicable?

4. Definition of epilepsy and seizures
Epilepsy is a disorder of the brain
characterized by an enduring predisposition to
generate epileptic seizures (ILAE and IBE)
Seizures are episodes of abnormal high
frequency electrical discharges of a group of
neurons in the brain.

5. Some causes of seizures
 Seizures may be caused by:
 Hypoxia
 Hypoglycemia
 Stroke
 Brain tumours
 Head trauma
 Withdrawal from alcohol

6. Epidemiology
2nd most common neurological disorder(next
to stroke)
0.5-1%(Rang et al, 2007) of world population.
USA=1-2%

7. Aetiology
 idiopathic
 Environmental perturbation e.g. intrauterine or
neonatal complications.
 Traumatic/Symptomatic: due to lesions in the foci.
 Cryptogenic
 Precipitating factors;
 Primary reading epilepsy
 Catamenial epilepsy
 Photosensitive epilepsy
 Emotional stress, hyperventilation etc.

8. Classification
1. Partial(focal) seizures: one
hemisphere only. No loss of
consciousness
2. Generalized seizures: both
hemispheres. Loss of memory. Involves
the whole brain including reticular
system.

9. Partial seizures
a. Simple partial seizures-memory fully is retain
b. Complex partial seizures-altered
consciousness, repetitive behaviour
(automatism)
c. Jacksonian epilepsy-progress along anatomic
lines as discharge spread across the cortex
Partial seizures may evolve into generalized
seizure termed secondarily generalized
seizures.

10. Generalized seizures
1. Primarily generalized tonic-clonic seizures
or grand mal (Yoruba=warapa;
Ogoni(Gokana)=goi)
 Brief tonic phase followed by clonic
phase
 Last 3-5mins
 Confusion, drowsiness after recovery.

11. Generalized seizures
2.Absence seizure or petit mal
 Common in children
 No falling, short loss of consciousness
Lasts 10-15secs
 child concentration is affected

12. Generalized seizures
3.Status epilepticus
 A medical emergency
 More than 30minutes of continuous
seizure
 Recurrent episodes of tonic-clonic
seizures
 No full recovery of consciousness
between sequential episodes

13. Classification of Epileptic Seizures
2 major classes (ILAE 1981):
• Partial-onset seizures
– begin in a focal area of the cerebral
cortex
• Generalized-onset seizures
– have an onset recorded
simultaneously in both cerebral
hemispheres.

14. Neurobiology of epilepsy
Neuronal mechanism is poorly understood
Evidence suggest excessive excitatory
neurotransmission mediated by glutamate in
the brain.
• Glutamate=major excitatory neurotransmitter
• Binds to NMDA receptors===> Ca influx; NO
release===>excitation

15. Neurobiology of epilepsy
Suppression of inhibitory GABA action.
Increase in neuronal Na and Ca influx.

16. Diagnosis
Seizure must be recurrent with at least 24hrs
interval
Differential diagnosis is made by the use of
electroencephalogram (EEG)

17. Management/treatment
First aid:
 Keep patient away from source of injury
 Support respiration if suffocating
 Allow foams to drip out freely
 Take to a doctor
Accurate diagnosis of the type of seizure and
then a rational use of drugs.

18. Management and treatment
• Pharmacological
• Non-pharmacological
Pharmacological: Drugs based on 3 principles
1. Inhibition of excitatory glutamate
neurotransmission
2. Inhibition of Na and Ca
influx==>suppression of repetitive
depolarization
3. Augmentation of GABA inhibitory
neurotransmission

19. Classification of AEDs
• Sodium channel blockers
• Calcium current inhibitors
• Gamma-amino butyric acid (GABA) enhancers
• Glutamate blockers
• Drugs with unknown mechanism of action

20. Sodium Channel Blockers
Sodium Channel Blockers
They prevent the return
of Na channels to the
active state by stabilizing
them in the inactive state.
:. prevent repetitive firing
of the axons

21. Calcium
Channel
Blockers
• The influx of calcium ions produces a partial
depolarization of the membrane which causes an
action potential to be generated in the cell.
• CCBs inhibit T-calcium channels

22. GABA Enhancers
The GABA system
can be enhanced by
• Binding directly to
GABA-A receptors
• Blocking
presynaptic GABA
uptake
• Inhibiting GABA
metabolism by
GABA transaminase
• Increasing GABA
synthesis.

23. Glutamate
Blockers

24. The role of astrocytes
Non neuronal cells in the brain
Maintain homeostasis
Found to be morphologically and functionally
altered in different epileptiforms
Target of new drugs

25. Drugs of choice for epilepsy types
 Partial and secondarily generalized seizures
1. Carbamazepine………..100-200mg 1-2x(up to 0.8-
1.2g)daily
2. Sodium valproate……..200mg b.i.d (up to 1-2g)
 Phenytoin………………….3-4mg/kg b.i.d( up to 200-
400mg)
 Lamotrigine………………..200-400mg daily in divided
doses
 Gabapentine………………0.9-1.2g daily in divided
doses
 Topiramate…………………200-400mg daily in divided
doses

26. Drugs of choice for epilepsy types
Generalized tonic-clonic seizure
1. Sodium valproate…..200mg b.i.d(up to 1-2g)
2. Lamotrigine……………200-400mg in divided doses
 Clonazepam…………….2-6mg daily in divided doses
 Topiramate……………..200-400mg in divided doses
 Carbamazepine……….100-200mg 1-2x (up to0.8-
1.2mg) daily
 Phenytoin……………….3-4mg/kg b.i.d(max.200-
400mg)

27. Drugs of choice for epilepsy types
 Absence seizure
1. Ethosuximide ………..1-1.5g in divided doses of
500mg
2. Sodium valproate….200mg b.i.d(up to 1-2g)
 Clonazepam…………….2-6mg daily in divided
doses
 Lamotrigine…………….200-400mg daily in divided
doses

28. Drugs of choice for epilepsy types
Atypical seizures, tonic, myclonic, atonic etc.
1. Sodium valproate…1-2g
2. Clonazepam………..2-6mg daily in divided doses
3. Lamotrigine………..200-400mg
4. Phenytoin…………..200-400mg
5. Ethosuximide……..1-1.5g daily in divided doses
6. Phenobarbital…….60-90mg nocte

29. Drugs of choice for epilepsy types
Status epilepticus
1. Lorazepam……..1mg i.v. repeat over 10mins
2. Clonazepam……1mg i.v. over 30mins
3. Diazepam……….10-20mg i.v. over 2-4mins
 Phenytoin……….15-18mg/kg i.v. @ 50mg/min
 Phenobarbital….10-20mg/kg i.v. @100mg/min

30. General guide to AED therapy
Start with monotherapy .
Give the most minimal dose possible.
Drug withdrawal should be gradual.
Treatment should span over 2years.
For pregnant women, lowest dose of
monotherapy should be given.
Epileptic fits are self limiting-do not panic.
Epileptics should not operate machines.

31. Non-pharmacological management
Use of ketogenic diet.
Vagus nerve stimulation.
Surgery.
Lifestyle modification/Relaxation.
Alternative therapy: Yoga, Ayurveda,
Acupuncture, etc.

32. Botanicals
• Valerian (European traditional botanical),
• Passiflora incarnata (native North and South
American botanical),
• Kava kava (Pacific native botanical),
• Piper nigrum (traditional Chinese medicine),
and
• Withania somnifera (Ayurvedic medicine)

33. Economic and social implication
Loss of jobs==>poverty.
Career termination==>withdrawal,depression.
Loss of lives==>loss of human resources.
Stigmatization==>feelings of dejection.

34. Overview of my research work
TITLE: The neuropharmacological effects of the
essential oil of Curcuma longa in mice.
The Plant Curcuma longa (Syn Tumeric)
Family; Zingiberaceae
vernacular: ata le funfun---Yoruba
sila kavanda----Gokana(Bodo)
 other spp C. domestica, C. xanthorrhiza, C.
zedoaria, C. wenyujin, etc.

35. The plant
C. domestica
C. longa

36. The plant
C. domestica
C. longa

37. Ethnomedicinal uses of C.spp.
 liver ailments, skin diseases and wound
healing, jaundice, gastric ulcer, joint
inflammation, diabetics, cold and flu
symptoms, biliary disorders, anorexia, cough,
hepatic disorders, rheumatism, and sinusitis
(Jain et al, 1991).
Gonorrhea, peptic ulcers, appetite stimulant,
carminative, astringent and anti-diarrheal
agent, aromatic stomachic and diuretic

38. Ethnosocial uses
• Spice in ‘pepper soup’
• Major component of curry (spice)
• Spice in local drinks called ‘Kunnu’
• Tumeric tea
• Larvicidal
• Insect repellant

39. The scope of my work
 Plant collection and identification
 Hydrodistillation of the rhizomes to obtain EO
 Density determination and formulation of the EO
 Acute toxicity studies(LD50 ), (Lorke, 1983) i.p., p.o.
 Parameters studied/models
• Novelty induced Behaviours (NIB)-
Rearing/Locomotor
• Anxiolytic test (EPM)
• Anticonvulsant assessment (PTZ/Strychnine)
• Antidepressant activities (Forced Swimming Test)

40. PRELIMINARY RESULTS
1. Density of the essential oil
2. Acute Toxicity/LD50
3. NIB
• Rearing
• Locomotion
4. Anxiolytic
5. Anticonvulsant:-Pro-convulsant
6. Antidepressant

41. RESULTS
• Density: 0.98g/ml
• Acute Toxicity/LD50
 P.O.: 693mg/kg
 I.P.: 490mg/kg
• Anticonvulsant: Pro-convulsant (≥400 mg/kg)
• Other results are being analysed

42. Discussion/conclusion
• The essentail oil (EO) demonstrated significant
CNS activities-CNS stimulant
• The EO is moderately toxic
• Preliminary results indicate that the EO
possesses anxiolytic, antidepressant and pro-
convulsant effects in mice
• The plant may be further evaluated for other
neuropharmacological activities
• These results may serve as lead-finding for
novel drug discovery

43. References
• Bennet, P. N. and Brown, M.J. Clinical pharmacology 9th edition, Churchhill
Livingstone 2003. Pp. 414-421.
• Bruton, L.L., Lazo, S.J., Parker, L.K. Goodman and Gilman’s the Pharmacological
basis of therapeutics, 11th edition. McGraw-Hill Companies 2007.
• EMDEX, The complete drug formulary for Nigeria’s health professionals,
2008/09 edition. Pp 34-42.
• Katzung, B.G. Basic and clinical pharmacology 10th edition.
• Losi, G., Cammarota, M. and Carmignoto, G. The role of astrologia in
epileptic brain, Frontiers in Pharmacology, 2012.
• Rang, H.P., Dale, M.M., Ritter J.M., Flower, R.J. Rang and Dale’s
pharmacology, 6th edition, Elsevier Inc 2007. Pp 575-587.
• Roth, J.L. Status epilepticus, Medscape 2011.
• Saxena VS, Nadkarni VV. Nonpharmacological treatment of epilepsy. Ann
Indian Acad Neurol 2011; 14:148-152.

44. Thank you.