Antibacterial Agents IV - DNA Function Inhibitors

Question 1

Fluoroquinolenes: mechanism of action

Answer 1

Target: Bacterial DNA gyrase and topoisomerase IV

-bactericidal

Question 2

Fluoroquinolenes: pharmacokinetics

Answer 2

• Absorption: Well absorbed orally - levofloxacin and ciprofloxacin are also available parenterally
• Distribution: Good penetration into most tissues including - high urinary levels
• Metabolism/excretion: Primarily excreted by kidney - Half-life increased in renal failure for ciprofloxacin, levofloxacin –> renal dosing

Question 3

Fluoroquinolenes: spectrum/ clinical uses

Answer 3

g+c, g-c, g+r, g-r, anaerobes, atypical

Levo and Moxi:

• S. pneumoniae
• S. aureus (MSSA)

cipro and levo:

• pseudamonas,
• E. coli

Moxi:

• anaerobes
• atypical - chlamydia and M. pneumoniae

Question 4

Fluoroquinolenes: adverse reactions and DDIs

Answer 4

Overall well tolerate

• GI (c. diff related)
• CNS (dizz, HA, insomnia)
• Black box warning
• –inc risk of tendon rupture
• –arthropathy potential (limits use in pregnancy and younger children)

Question 5

Nitrofuratoin: mechanism of action

Answer 5

• Reduced by bacterial enzymes to intermediates that damage bacterial DNA
• selective toxicity
• bactericidal = [dependent] effect

Question 6

Nitrofuratoin: pharmacokinetics

Answer 6

• rapid and complete oral absorption

- renal excretion –> renal impairment can decrease drug efficacy and increase systemic toxicity

Question 7

Nitrofuratoin: spectrum of activity and clinical uses

Answer 7

most commonly UTI antiseptic

-gram neg rods (E. coli!!)

Question 8

Nitrofuratoin: adverse reactions and DDIs

Answer 8

• GI probs (anorexia NVD)
• occasional hypersensitivity and neuropathies with chronic use
• possible preg probs

Question 9

Metronidazole: mechanism of action

Answer 9

• Prodrug transformed to highly reactive nitro radical anion in susceptible organisms –> protozoa and anaerobic bacteria with negative redox potential
• Anion kills these organisms by radical-mediated mechanisms - DNA strand breaks + inhibition of replication
• Bactericidal

Question 10

Metronidazole: pharmacokinetics

Answer 10

• good bioavailibility and distrubition
• hepatic metab (adjust dosage if liver impairment)
• excreted in breast milk –> breast feeding should cease until 24-48 hours after therapy

Question 11

Metronidazole: spectrum of use and clinical uses

Answer 11

anaerobes

• bacteriodes
• c. diff
• c. perfringens

Question 12

Metronidazole: adverse reactions and DDIs

Answer 12

-common: N, HA, dry mouth metallic taste

• **inhibits aldehyde deydrogenase
• Antabuse®-like effect (GI upset, vomiting, headache) if alcohol consumed within 3 days of metronidazole
• pregnancy risk
• possible DDIs with CYP450