1. خالد سليمان عبدالله السلومي معيد بكلية الصيدلة / قسم الصيدلة الإكلينيكية
الأوراق الثبوتية لبدل الحاسب الآلي # استخدام الحاسب لتقديم محاضرة في موضوع مختص عن طريق برامج التقديم والشرح مثل بوربوينت . ( power point )

2. Case presentation
Khalid S. Alsallumi Umm AL-Qura University Faculty of Pharmacy Clinical Pharmacy Department Therapeutic 3

3. Definition of Epilepsy
 Seizure: the clinical manifestation of an abnormal and excessive excitation and synchronization of a population of cortical neurons
 Epilepsy: two or more recurrent seizures unprovoked by systemic or acute neurologic insults

4. Epidemiology of Seizures and Epilepsy
Incidence: approximately 80/100,000 per year
Lifetime prevalence: 9% (1/3 benign febrile convulsions)
Epilepsy
Incidence: approximately 45/100,000 per year
Point prevalence: 0.5-1%

5. Classification of Seizures
Partial seizures
Simple partial seizures
Complex partial seizures
Impaired consciousness at outset
Simple partial evolving to lost consciousness
Partial seizures evolving to general tonic-clonic seizures (GTCS)

6. Secondarily Generalized Seizures
 Begins focally, with or without focal neurological symptoms  Variable symmetry, intensity, and duration of tonic (stiffening) and clonic (jerking) phases  Typical duration up to 1-2 minutes  Postictal confusion, somnolence, with or without transient focal deficit

7. Classification of Seizures (cont.)
Generalized seizures
Absence seizures
Tonic-clonic seizures
Myoclonic seizures
Tonic seizures
Clonic seizures
Atonic seizures

8. Seizure Precipitants  Metabolic and Electrolyte Imbalance
 Stimulant/other proconvulsant intoxication
 Sedative or ethanol withdrawal
 Sleep deprivation
 Antiepileptic medication reduction or inadequate AED treatment
 Hormonal variations
 Stress
 Fever or systemic infection
 Concussion and/or closed head injury

9. Etiology of Seizures and Epilepsy (cont.)
 Adolescence and young adult
Head trauma
Drug intoxication and withdrawal*
 Older adult
Stroke
Brain tumor
Acute metabolic disturbances*
Neurodegenerative
CNS infection
Trauma

10. Questions Raised by a First Seizure
 Seizure or not?
 Focal onset?
 Evidence of interictal CNS dysfunction?
 Metabolic precipitant?
 Seizure type? Syndrome type?
 Studies?
 Start AED?

11. Choosing Antiepileptic Drugs
 Seizure type  Epilepsy syndrome  Pharmacokinetic profile  Interactions/other medical conditions  Efficacy  Expected adverse effects  Cost

12. Medical Treatment of First Seizure
Whether to treat first seizure is
controversial
 % will recur within 5 years
 Relapse rate might be reduced by antiepileptic drug treatment
 Abnormal imaging, abnormal neurological exam, abnormal EEG or family history increase relapse risk
 Quality of life issues are important

13. Case 13-year-old girl with past history of febrile seizures and GTCS
Series of right upper limb jerking with altered speech (early afternoon)
Then 10 pm, first generalized seizure
Description suggests GTCS
EMS called: one seizure before arrival, a second in ambulance
Arrival at ER: postictal with right hemiparesis

14. Case (cont.) Data: bumped head about one week ago
Grades in past 6 months falling
Suggested evaluation

15. Investigation Clinical exam EEG CT MRI Metabolic studies (Lab)
Drug screen
Lumbar puncture
CT scan: normal
Choices

16. Case (cont.) She begins to seize – GTCS Treatment Which drug? Why?
How long?
What other data needed (timing of EEG)?
Plan for follow up?

17. Cont.

18. Cont.

19. Treatment of Epilepsy Reasons to treat Actively seizing
History of seizures
Stop seizures
Prevent brain injury

20. Outcome of Acute Seizures
Outcome influenced by
Age of the patient
Underlying illnesses
Duration of seizures
Etiology of seizures
Treatment given

21. Epilepsy Treatment Choices
Begin chronic AED
Choose a first line therapy
Carbamazepine
Phenytoin
Valproate
Oxycarbamazepine

22. Carbamazepine
Start with Carbamazepine 200mg po TID + 400mg at bedtime.
If the seizure still not control add 2nd line drug.
Monitor the patient for the side effect :
Rash (Stevens-Johnson syndrome)
leukopenia (check WBC if less than 2500/mm3 discontinue the drug), anemia.
Also check the drug interaction

23. Phenytoin It is enzyme inducer. Lupus-like reactions, rash.
Vit D deficiency.
Gingival hyperplasia.
Hepatotoxicity.
Teratogenic during pregnancy( hare lip, cleft palate)

24. Valproic acid It is enzyme inhibitor. Alopecia Obesity Hepatotoxicity.
Hematologic (thrombocytopenia)

25. Commonly Used IV Drugs for Acute Seizures
Benzodiazepines
Lorazepam
Diazepam
Phenytoin/Fosphenytoin
Valproic acid
Phenobarbital

26. Classic Versus Newer Anticonvulsants
Classic AEDs
Phenobarbital
Phenytoin (Dilantin®)
Primidone (Mysoline®)
Carbamazepine (Tegretol®)
Valproate (Depakote®/Depacon®)
Ethosuximide (Zarontin®)
Newer AEDs
Felbamate (Felbatol®)
Gabapentin (Neurontin®)
Lamotrigine (Lamictal®)
Levetiracetam (Keppra®)
Oxcarbazepine (Trileptal®)
Tiagabine (Gabitril®)
Topiramate (Topamax®)
Vigabitrin (Sabril®)
Zonisamide (Zonegran®)

27. Choice and Use of Drugs Partial Generalized Tonic- clonic Tonic
Myoclonic
Atonic
Infantile Spasms
Absence
PHT, CBZ, PB, GBP, TGB, LVT, OCBZ
ACTH
TPM? TGB? VGB?
ESX
VPA, LTG, TPM, ZNS
FBM
Simple
Complex
Secondary generalized
Generalized

28. Response to AED Therapy
Success 47%
Success 46%
Failure 54%
Toxicity 16%
Toxicity + 38% inadequate sz control
Inadequate 0% sz control
Failure 53%
Toxicity 20%
Toxicity + 30% inadequate sz control
Inadequate 3% sz control
Initial AED
(N = 421)
Alternate AED
(N = 89)
Mattson RH, et al. N Engl J Med. 1985;313:145.
Mattson RH, et al. Epilepsia. 1986;27:645.

29. Review of Safety and Efficacy of New AEDs
A review of randomized clinical trials of gabapentin, lamotrigine, tiagabine, topiramate, vigabatrin, and zonisamide for add-on therapy in refractory partial epilepsy found
No conclusive evidence of effectiveness or safety between the drugs
Tiagabine had the highest efficacy rating, gabapentin had the lowest
Zonisamide was most likely to cause withdrawal, while lamotrigine was least likely
Chadwick DW. Epilepsia. 1997;38:S59-S62.

30. Summary Complaint Scores
Efficacy of New Antiepileptic Drugs 35
200 30
150 25 20
Summary Complaint Scores
100
% Improved 15 10 50 5
GPT
LTG
TGB
TPM
VGB
Responder rate (%): Drug minus placebo
Sum of % complaints: Drug minus placebo
GPT = gabapentin, LTG = lamotrigine, TGB = tiagabine, TPM = topiramate, VGB = vigabatrin

31. Lennox-Gastaut Syndrome Treatment: Drop Attacks75
P = 0.002
P = 0.02
P = 0.04 50 44 34
% Seizure Reduction 25 15 7 9 -5
FBM Placebo
(N = 37) (N = 36)
LTG Placebo
(N = 75) (N = 89)
TPM Placebo
(N = 46) (N = 49)
-25
Felbamate Study Group. N Engl J Med. 1993;328:29-33.
Motte J. N Engl J Med. 1997;337:
Sachdeo RC, et al. Neurology. 1999;52:

32. Lennox-Gastaut Syndrome Treatment: GTC Seizures75
P = 0.017
P = 0.03
P  0.01 50 40 36 35
% Seizure Reduction 25 -4
-10
-12
-25
FBM Placebo
(N = 16) (N = 13)
LTG Placebo
(N = 60) (N = 64)
TPM Placebo
(N = 17) (N = 21)
-50
Felbamate Study Group. N Engl J Med. 1993;328:29-33.
Motte J. N Engl J Med. 1997;337:
Sachdeo RC, et al. Neurology. 1999;52:

33. AED Adverse Effects in Children
Neurotoxicity most common
Cognitive
Behavioral
Rare idiosyncratic
Dermatologic (Stevens-Johnson syndrome)
Generalized hypersensitivity
Hepatic failure
Pancreatitis
Hematologic (aplastic anemia)

34. Advantages of Extended Release
Cmax-Toxicity Risk
Drug Concentration
AUC
Cmin-inefficacy Risk 6 12 18
Time (hrs)
Cloyd, 1998.

35. Advantages of ER Formulations
Good medication compliance essential when treating chronic disorders
Compliance decreases as number of daily doses increases
ER formulations may
Improve patient compliance
Improve treatment
Decrease peak-related side effects
Improved efficacy with higher blood levels