Brandy Hollums fdn383@uthsc.edu Med Chem II Tutoring Brandy Hollums fdn383@uthsc.edu

Antiepileptic agents Classical AEDs 1. Recognize drugs by name, structure, and chemical class 2. SAR of classical AEDs 3. Acidity and water solubility 4. Prodrugs (Primidone and Fosphenytoin) 5. Hydantoin and its bioisotere 6. Uses and side effects (metabolites and idiosyncratic toxicity; teratogenicity e.g. cleft palate)

Classical aeds -Minimum structure requirement is Imide -If R and R’ are lower alkyls (CH3 and CH2CH3) will treat absence seizures (petit mal) -If aryl group (aromatic) will treat generalized tonic clonic and partial seizures **This means we can look at the structure to know what kind of seizure they treat without knowing anything else about the drug!**

What kind of seizure would the following drug not treat? A. absence seizures B. status epilepticus C. grand mal seizures D. partial seizures A. Phenobarbital-has aryl group…will not treat absence seizures

Which of the following are prodrugs? phenobarbital-no Mephobarbital-yes Primidone-yes Phenytoin-no

Mephobarbital undergoes n-demethylation and is converted to _________. A. Primidone B. Diazepam C. Phenobarbital D. Phenytoin C.

The major metabolite of primidone is: A. Phenobarbital B. PEMA C. Deoxybarbituate D. Mephobarbital B.

Primidone

The following structure would be used for all seizures except: A. absence seizures B. tonic clonic seizures C. partial seizures D. grand mal seizures A. Structure is phenytoin

Which of the following is not true of hydantoins? A. Retain antiepileptic activity but not as sedative as barbiturates B. Hydantoins are more acidic that barbiturates C. Structurally similar to barbiturates D. Have shorter stability than barbiturates once mixed with water. B. Less acidic

Which of the following are side effects of phenytoin that make it undesirable for preschool children? A. Sedative effects B. gingival hyperplasia C. neurotoxicity D. hirsutism B and D

The formation of _______ may lead to the idiosyncratic and teratogenic effects of Aeds/ A. Catechols B. Glutathione C. Haptens D. Diols C.

What are side effects of all AEDs that contain aromatic rings? A. SJS B. TEN C. Neurotoxicity D. Nephrotoxicity

Which of the following class of AEDS is the bioisoteric replace of hydantoins? A. Barbiturates B. Succinimides C. Phenacemides D. Benzodiazepines B.

What is the DOC for absence seizures? A. methsuximide B. phenytoin C. ethosuximide D. carbamazepine

1,4-Benzodiazepines 1. Recognize the drugs by name and structure 2. MOA *only 3 BZDs used to treat epilepsy-clonazepam, clorazepate, diazepam.

Miscellaneous AEDs 1. Recognize the drugs by name and structure. 2. Note those that cause the following side effects: idiosyncratic toxicity; teratogenicity; hepatotoxicity; kidney stones; visual disturbances. 3. Note their effect on CYPs (i.e., induction of CYPs; inhibition of CYPs; or no effect on CYPs) 4. Functional groups (amide, amine, carboxylic acid; sulfamate; ether, ester, lactam lactone, alcohol; sulfonamide; ketone; carbamate). 5. MOA of the AEDs. 6. Effect of pKa and pH on the absorption and excretion of drugs.

Which has the highest risk of cleft palate? A. Lamotrigine B. Valproic Acid C. Carbamazepine D. Gabapentin B.

Which Aed has the structure of gaba? A. acetazolamide B. carbamazepine C. valproic acid D. gabapentin D.

Which aed has CYP interactions? A. Levetiracetam B. Zonisamide C. Gabapentin D. Tigabine B. Reduction by CYP3A4

Which AED acts on voltage gated Calcium channels? A. Carbamazepine B. Ethosuximide C. tigabine D. lamotrigine B

Which aed has irreversible visual disturbances? A. gabapentin B. felbamate C. topiramate D. vigabatrin D.