Into which drug class do rifampin and rifapentine belong, and what is their general mechanism?

• A. Rifamycins; inhibit bacterial DNA-dependent RNA polymerase
• B. Fluoroquinolones; inhibit DNA gyrase
• C. Aminoglycosides; inhibit protein synthesis
• D. Macrolides; inhibit 50S ribosomal subunit

Answer: (A)

Rifampin and rifapentine are rifamycins. Their main action is to bind the bacterial DNA-dependent RNA polymerase, specifically the beta subunit, and block initiation of RNA synthesis. This effectively halts transcription, making them bactericidal against many bacteria, including Mycobacterium tuberculosis. Because human RNA polymerase isn’t affected in the same way, these drugs achieve selective toxicity. In TB therapy, rifamycins are valued for their ability to act on intracellular mycobacteria and for their tissue penetration, though they also induce hepatic enzymes, leading to many drug interactions.

Fluoroquinolones inhibit DNA gyrase, not RNA polymerase. Aminoglycosides inhibit protein synthesis by binding the 30S ribosomal subunit. Macrolides inhibit translation at the 50S ribosomal subunit.