Inhibitors of Nucleic Acid Synthesis

Question 1

Rifamycin

- Rifampin

Answer 1

Mechanism: Binds bacterial RNA polymerase at the active center (Beta-subunit) blocking the elongation of mRNA

Spectrum: +/-

Bacteriocidal? yes

Resistance:
Intrinsic: the drug is unable to bind to the beta-subunit of polymerase
Acquired: the strain acquires mutations in rpoB gene, which prevents drug binding

Side Effects:

• GI side effects, Hypersensitivity – Fever
• Hepatotoxic: use caution when administering to patients w/ chronic liver disease

Notes:

• Turns body fluids orange/red
• Induction of cytochrome p450 enzymes can induce metabolism of other medicines leading to organ rejection/loss of seizure control

Question 2

Fidaxomicin

Answer 2

Mechanism: Binds bacterial RNA polymerase at the active center (Beta-subunit) blocking the elongation of mRNA

Spectrum: -Narrow

• Spares many of the gut flora
• Gram + anaerobes
  e. g. C. diff

Bacteriocidal? yes

Resistance: Point mutation in RNA polymerase has been observed in vitro

Side Effects:-Low absorption
-Nausea, vomiting

Question 3

Fluoroquinolones

• Ciprofloxacin
• Levofloxacin
• Moxifloxacin

Answer 3

Mechanism: Inhibit DNA replication by binding bacterial DNA topoisomerase

• Gram neg. = topoisomerase II, prevents relaxation of supercoiled DNA
• Gram pos. = topoisomerase IV, interferes with sepearation of replicated chromosomal DNA

Spectrum: -Broad spectrum
-Gram +/- and atypical organisms like Mycoplasma

Bacteriocidal? yes

Resistance: -Overprescribed

• Active efflux of the drug
• Mutations in topoisomerases

Side Effects: -GI side effects, confusion and photosensitivity

• Tendon rupture
• Contraindicated in pregnant women
• Prolongation of QT interval

Notes: -Chelate cations (don’t take w/ Ca, Fe, Al, and Zn)

• Avoid dairy products or calcium-fortified juice
• Adjust for renal dysfunction for all agents except moxifloxacin (not secreted into the urin)
• Good for UTI’s