1. “Anti Epileptic Drugs II”
PHARMACOLOGY
Neuropsychiatry Block
2017/ 2018
Mrs. Sandra Hababeh

2. Learning objectives Describe types of epilepsy
List the antiepileptic drugs
Describe briefly the mechanism of action and rational of use of anti epileptic drugs
Enumerate the clinical uses of each drug
Describe treatment of status epilepticus
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6/23/2019

3. Newer Drugs
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4. 1. Gabapentin (Neurontin)
Used as Adjunctive therapy in partial and generalized tonic- clonic seizures.
Mechanism of action
Decreased release of glutamate from presynaptic terminals (most likely due to blockade of presynaptic voltage-gated Ca++ channels)
Increased brain GABA concentration
Note: An Analog of GABA that does not act on GABA receptors, it may alter its metabolism, release and transport.
Adverse effects:
Somnolence, dizziness, ataxia, headache, tremor
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6/23/2019

5. 2. Lamotrigine Used as Adjunctive therapy with valproate.
Use: against generalized seizures.
M.O.A:
blocks sodium channels, as well as high voltage- dependent calcium channels.
Adverse effects: Dizziness, Headache, Diplopia, Nausea, Somnolence, Life threatening rash “Stevens- Johnson”
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6/23/2019

6. 3. Felbamate M.O.A: modulation of NMDA receptor (glutamate receptor)
Because of its severe side effects, it has been relegated to a third-line drug used only for refractory cases.
Adverse effects: aplastic anemia and severe hepatitis restricts its use.
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6/23/2019

7. 4. Tiagabine Adjunctive therapy for partial seizures
Interferes with GABA reuptake
Adverse effects: CNS sedative
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8. 5. Zonisamide Mechanism of action: Likely multiple, including
Blockade of Na+ channels
Blockade of T type CA++ channels.
Enhancement of GABAergic transmission
Inhibition of glutamatergic transmission
Adverse effects
Drowsiness, dizziness, headache, irritability.
Allergic reactions (it is a sulfonamide)
Therapeutic uses: adjunctive therapy in :
Partial and tonic clonic seizures.
Myoclonic seizures
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9. 6. Topimerate
M.O.A: blockade of Na+ channels, increases frequency of GABAA channel openings, may interfere with glutamate binding to AMPA/KA receptor
Use: Effective as monotherapy for partial or generalized seizures.
Adverse effects: CNS sedative
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6/23/2019

10. 7. Levetiracetam
It is approved for adjunct therapy of focal onset, myoclonic, and primary generalized tonic–clonic seizures in adults and children.
The exact mechanism of anticonvulsant action is unknown.
The drug is well absorbed orally and excreted in urine mostly unchanged, resulting in few to no drug interactions.
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11. Inhibitory and stimulation mechanisms of AEDS
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12. اسم ورقم المقرر – Course Name and No.
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13. Status Epilepticus
In status epilepticus, two or more seizures occur without recovery of full consciousness in between episodes, it is called “status epilepticus”.
Status epilepticus is life threatening and requires urgent hospital treatment.
If untreated immediately by IV medications, it can lead to death due aspiration, hypotension, cardiac arrhythmia, renal or hepatic failure.
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14. Management of Status Epilepticus
Initial:
Ensure airway is patent, give oxygen to prevent cerebral hypoxia
Check pulse, Bp, glucose and respiratory rate.
Secure intravenous access
Send blood for: glucose, urea and electrolytes, calcium and magnesium, liver function, anti epileptic levels.
If seizures last >5mins, diazepam 10mg IV (or rectally) or lorazepam 4mg IV, repeat once only after 15 min.
Correct any metabolic trigger, e.g. hypoglycemia
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6/23/2019

15. Management of Status Epilepticus cnt’d
Ongoing:
If seizures continue > 30mins:
IV infusion of ; Phenytoin , fosphenytoin (more expensive), or phenobarbital, with cardiac monitoring
If seizures still continue after 30mins-60mins (refractory status):
Transfer to ICU
Intubation, Ventilation and general anesthesia with propofol or thiopental.
EEG monitor
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6/23/2019

16. Management of Status Epilepticus cnt’d
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17. Antiepeliptics and Pregnancy:
Monotherapy usually better than drugs combination.
All women considering pregnancy should be on high doses (1 to 5 mg) of folic acid prior to conception.
If possible, women already taking valproate should be placed on other therapies prior to pregnancy (Lamotrigine)
Phenytoin, sodium valproate are absolutely contraindicated in pregnancy
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18. FDA Pregnancy Risk for Antiseizure Drugs

19. Treatment of Epilepsy:
Drugs
Vagal nerve stimulation
Surgery
Ketogenic diet

20. Vagal Nerve Stimulation
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21. Summary
Epilepsy is classified into partial or generalized according to the site of lesion.
The exact mechanism of action of antiepileptics is not known.
Phenytoin is mainly used for treatment of generalized tonic-clonic seizure
Carbamazepine is mainly used for treatment of partial seizures

22. Summary ( con.)
Sodium valproate is a broad spectrum antiepileptic drug.
Lamotrigine & levetiracetam are used as monotherapy or adjunctive therapy in refractory cases.
Lorazepam , diazepam , phenytoin are used intravenously for treatment of status epilepticus.

23. Recommended Reference:
“Lippincott's Illustrated Reviews” “Davidson’s Principles & Practise of Medicine ”

24. Good luck 
Mrs.Sandra Hababeh