1. Lecture 2 Dr.Narmin Hussen14
Lecture 2 Dr.Narmin Hussen

2. Q/ Explain, which position of benzodiazepine structure is important for metabolism? How ?

3. What Is Epilepsy?

4. Normally, nerve cells in the brain transmit electrical and chemical signals to other nerve cells, glands, and muscles.
Seizures happen when too many of these nerve cells, or neurons, fire electrical signals at the same time at a much faster rate than they normally would. Usually, a seizure lasts a few seconds to several minutes..

5. Causes of seizures In children In middle age High fever
Congenital abnormality
Infections
Birth trauma
In middle age
Head injuries
Brain tumors

6. In the elderly
Brain tumors
Strokes

7. Classification of Epileptic Seizures
Primary Generalized Seizures:
Two major types of generalized seizures are the primarily generalized tonic–clonic seizures (grand mal) and the absence (petit mal) seizures.
Partial Seizures:
The two kinds of partial seizures are simple partial seizures and complex partial.

8. Diagnosis: Electroencephalogram EEG , CT and MRI
Each of the epilepsy types is characterized by an abnormal pattern in the EEG. The EEG indicates sudden, excessive electrical activity in the brain.
Images from the CT or MRI scans are useful because they help the physician identify certain causes of seizures such as tumors or blood clots or they may suggest other causes responsible for the seizures.

9. Mechanisms of Action of Anticonvulsants
Modulation of voltage-gated ion channels (Na+, Ca2+, and K+).
Enhancement of γ-aminobutyric acid (GABA)-mediated inhibitory neurotransmission.
Aattenuation of excitatory (particularly glutamate-mediated) neurotransmission in the brain

10. GABAA Receptors as Targets for Anticonvulsants

11. Treatment
Valproic Acid (Depakene):
hepatotoxicity and teratogenicity

12. Valrocemide (valproyl glycinamide, VLR) and DPVPA:
Unlike VPA, both of these drugs are said to have low drug-interaction potentials.

13. Phenytoin (Dilantin) and Fosphenytoin (Cerebyx):
against all seizure types except absence

15. Carbamazepine (Tegretol) and Oxcarbazepine (Trileptal):
generalized tonic–clonic and partial seizures.

16. Gabapentin (Neurontin) and Pregabalin (Lyrica):

17. Lamotrigine (Lamictal): Topiramate (Topamax):
Only about 20% of the drug is eliminated by hepatic metabolism
weak carbonic anhydrase inhibitory activity

18. partial seizures
1,2-benzisoxazole ring to 2-sulfamoyl-acetyl-phenol
carbonic anhydrase inhibitors

19. Felbamate (Felbatol) carbamate ester 3- propandiol monocarbamate
3-carbamoyl-2- phenylpropionic acid (CPPA)

20. absence seizures.

21. Questions
1- Explain the causes of hypersensitivity reaction of phenytoin? How these reactive metabolites are detoxified in the body? 2-Provide a biochemical reason why pregabalin has better bioavailability than gabapentin?