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17 Cards in this Set

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  • Back
What are the major classes of antibiotics which inhibit nucleic acid synthesis?
Sulfonamides & Benzylpyrimidines
Which major classes of antiobiotics inhibit DNA duplication and transcription?
What is the basis of sulfonamide selectivity?
Bacteria synthesize folic acid; mammalian cells lack enzymes required to synthesize folate
How do the Sulfonamides work?
They are structural analogs and competetive antagonists of PABA at dihydropteroate synthase (used to make dihydrofolic acid, precursor to THF.)
Cross the BBB and the placenta
What is the pathway for PURINE synthesis?
Where do sulfonamides and Benzylpyrimidines muck this up?
Sulfonamides inhibit Dihydropteroate synthase
(PABA ---->Dihydrofolic Acid)

Benzylpyrimidines inhibit Dihydrofolate Reductase
(Dihydrofolic Acid---->Tertrahydrofolic Acid (THF))

What are the sulfonamides?
What are the Benzylpyrimidines?
How do they work?

These drugs inhibit dihydrofolate reductase

They do not BIND the enzyme, they only compete; therefore the action is BACTERIOSTATIC.
What else is there to know about the benzylpyrimidines?
They cross the BBB and the placenta.
They are weak bases so they get trapped in the prostate and the vagina.
May cause megaloblastic anemia, leukopenia and granulocytopenia (preventable by administration of folinic acid)
Why do we combine sulfamethoxazole and trimethoprim?
The Sulfonamide/Benzylpyrimidine combination (SEPTRA) becomes BACTERICIDAL even if the organism is resistant to one of the two. This is because of the sequential blockade.
What are the adverse effects of combining sulfamethoxazole and Trimethoprim?
CNS disturbances and high incidence of adverse effects in AIDS pts.
What is the basis of the selectivity of Flouroquinolones?
Bacteria have DNA gyrase; mammalian cells lack DNA gyrase.
Eukaryotic cells DO have a type II DNA topoisomerase that can be inhibited by quinolones, but only at much higher concentrations.
How do the flouroquinolones work?
G- spectrum, inhibit DNA gyrase (topoisomerase II.) Prevents relaxation of supercoiled DNA, which mucks up transcription and replication.
G+ spectrum, inhibits topoisomerase IV. DNA can't separate in mitosis. BACTERICIDAL.
What are the adverse effects of flouroquinolones?
Potential cartilage damage in pregnant/nursing mothers or children.
DNV (pseudomembranous colitis)
Will INCREASE levels of theophylline- which can lead to seizures, cardiac arrest & respiratory failure.
What are the flouroquinolones?
What is the Nitroinidazole that we are studying?
What is its spectrum?
For ANAEROBES, can be used for VANCO-resistant C. difficile
What is the mechanism and specificity of the Nitroinidazoles?
Inhibition of DNA replication; the drug is reduced by an e- transport protein. The reduced drug causes strand breaks in DNA.
Mammalian cells are unharmed bc they lack enzymes to reduce the nitro group of these agents.
What are the adverse effects of Nitroimidazoles?
Can cause leukopenia
Can interact with Barbituates, and interfere with the metabolism of alcohol.