Anticonvulsants Med Chem Flashcards
1
Q
Epilepsy
A
- Brief, sudden paroxsymal disorder of cerebral dysfunction
- Electrical charges in the gray matter, convulsions resulted when normal brain tissue invaded by the seizure activity initiated in abnormal focus
- Not curative therapy, suppresses seizures and requires compliance
2
Q
Fosphenytoin
A
- Prodrug of phenytoin
- Finally approved in 1996
- Made to circumvent some difficulties associated with phenytoin formulation
3
Q
Carbamazepine
A
- Dibenazaepine derivative related to TCAs
- Carbamyl substituent at position 5 is essential for antiepileptic activity
- Very similar 3D structure between itself and phenytoin
- Active metabolite, 10,11-epoxide is responsible for its many side effects
- SE: nausea, diplopia, night blindness, drowsiness
4
Q
Oxcarbazepine
A
- Analog of carbamazepine with a ketone added to its 10 position on the reduces azepine ring
- Advantages: improve side effect, tolerability due to elimination of epoxide
- Fewer drug interaction, weaker P450 inducer
5
Q
Benzodiazepines
A
- 1955, chlordiazepoxide was discovered
- Amidine and N-oxide moieties aren’t essential for pharmacological activity
- Hydrolysis of amidine => demoxepam (active)
- Reduction of demoxepam => nordiazepam (active), metabolic pathways converge here (long-acting anti-anxiety agent)
- Extremely complex metabolism/PD due to formation of several active metabolites
6
Q
Benzodiazepine Structures
A
- R1 - alkyl substituents are common, but not essential
- R2 - more essential, contain aryl or cyclohexenyl substituents here (Ortho-substitution with an electron withdrawing group increases potency)
- R3 - electron withdrawing groups enhance potency
7
Q
Nordiazepine
A
- Half Life > 2 days
- Produced metabolically from chlordiazepoxide, prazepam and diazepam, and chemically from clorazepate (gastric acid)
8
Q
Oxazepam/Lorazepam
A
-Don’t generate active product metabolically
9
Q
Benzo MoA
A
- Actions from drugs result from action on CNS
- Effects: sedation, hyponosis, muscle relaxation, anticonvulsant activity, anti-anxiety
- Stimulates GABA-A ligand receptors
10
Q
Benzos + Abuse
A
- Minimal euphoric actions
- Slowly absorbed after oral administration
- Uncommon as drugs of abuse
11
Q
Benzodiazepine Antagonists
A
- Pure antagonists have been identified
- Possible treatment in benzodiazepine overdose
12
Q
Benzos for Seizure
A
- Clonazepam
- Lorazepam
- Diazepam
13
Q
Felbamate
A
- Dicarbamate structure related to meprobamate (different pharmacologically)
- Limited use due to development of aplastic anemia and acute hepatic failure
14
Q
Lamotrigine
A
- Developed after seeing that many drugs cause reduction in folate levels
- Approved for partial seizures
- Metabolized by P450s, has ~24 hr half life on its own and it can be reduced or increased based on coadministration with other medications
15
Q
Gabapentin
A
- No drug interactions are known with its use
- Due to its renal clearance
- Originally developed as a GABA-mimetic that could cross the BBB more readily because of its higher lipophilicity
