Antimicrobials - Nucleic Acid Synthesis Inhibitors

Question 1

What is the mechanism of action of fluoroquinolones (1st gen ciprofloxacin, 2nd gen levofloxacin)?

Answer 1

• inhibits action of DNA gyrase (cipro) + topoisomerase IV (levo)
• this interferes with DNA synthesis
• works exclusively in G- bacteria
• levofloxacin also works for drug resistant S. pnuemoniae

Question 2

What are the main mechanisms of resistance to fluoroquinolones?

Answer 2

• alteration of binding site on DNA gyrase

- alteration of binding site on topoisomerase IV

Question 3

Why do fluoroquinolones interfere with DNA synthesis in prokaryotes but not eukaryotes?

Answer 3

• Since prokaryotes are super small, they need their DNA to be supercoiled when not replicating and correctly uncoiled/oriented when needed
• DNA gyrase is responsible for this and is only found in prokaryotes

Question 4

What are the adverse effects of fluoroquinolones?

Answer 4

• allergy
• tendonitis and tendon rupture
• levofloxacin may cause torsades de point

Question 5

What is the mechanism of action and use of rifampin?

Answer 5

• inhibits DNA-dependent RNA polymerase and stops the replication of RNA from the daughter DNA strand
• used for M. tuberculosis and S. aureus

Question 6

What are the side effects of rifampin?

Answer 6

• drug allergy
• hepatitis
• red-orange metabolites
• induces P450

Question 7

What is the mechanism of action of metronidazole?

Answer 7

• activated in an anaerobic environment to a toxin for nucleic acids

Question 8

What are the adverse effects of metronidazole?

Answer 8

• drug allergy
• metallic taste
• inhibits aldehyde dehydrogenase - profound vasodilation and tachyarrhythmias

Question 9

What is the antimicrobial spectrum for metronidazole?

Answer 9

• anaerobic bacteria (H. pylori, C. difficile)

- protozoa (Giardia, Entamoeba, Trichomonas)