nucleic acid syntehsis inhibitors dukhande

who discovered prontosil (Sulfamidochrysoidine) in 1930? And what was found to be effective against?

Gerhard Domagk; strepococci

What do sulfonimides do?

Inhibit folate synthesis through DHPS

What does Trimethoprim do?

Inhibits DHFR

What do Quinolones do?

Inhibit DNA gyrase and topoisomerase IV

What does Nitrofurantoin do?

Produces reactive metabolites that damage multiple bacterial components

What are all the general purpose sulfonamides?

All orally absorbable

What are the sulfonamides for special applications?

what are two Non-sulfonamide folate inhibitors?

Combination medication: TMP-SMX

Why would a drug that inhibits bacterial folate synthesis interfere with the bacteria's ability to produce DNA?

Bacteria need folate to produce nucleotide precursors, including purines, that are necessary for nucleic acid synthesis. Blocking folate synthesis reduces these building blocks and therefore interferes with DNA synthesis.

why sulfonamides inhibit DHPS

their structural similarity to PABA

what do sulfonamides inhibit?

DHPS

what do Trimethoprim inhibit?

DHFR

Why is TMP-SMX synergistic?

• SMX blocks DHPS, reducing folate production upstream.

• TMP blocks DHFR, preventing conversion of DHF into THF downstream

What kind of inhibitors are Sulfonamides and trimethoprim

Competitive inhibitors

Compare TMP, pyrimethamine, and methotrexate

What type of DHFR does TMP and pyrimethamine prefer?

Remember that TMP prefers bacterial DHFR, while pyrimethamine targets protozoal DHFR

sulfonamides

Bacteriostatic, broad spectrum, once used widely

sulfanilamide in pic

What organisms that are not covered well by sulfonamides?

SMX resistance vs TMP resistance

A bacterial isolate produces large amounts of PABA. Which antibiotic is most likely to lose effectiveness?

Sulfamethoxazole, because PABA competes with sulfonamides at DHPS