Rifampin Flashcards
What is the mechanism of action of rifampin (rifampicin)?
Rifampin binds to the beta subunit of bacterial DNA-dependent RNA polymerase, inhibiting RNA synthesis. It prevents transcription by blocking elongation, which is bactericidal to Mycobacterium tuberculosis and many other bacteria.
Describe rifampin’s spectrum of activity.
- Rifampin has broad activity against Mycobacteria (M. tuberculosis, M. leprae, MAI complex).
- Some Gram-positive cocci (it can be used against MRSA in combination therapy).
- Prophylaxis for some Gram-negatives, such as Neisseria meningitidis and H. influenzae.
- It is rarely used alone for typical bacteria due to rapid resistance development.
How do bacteria develop resistance to rifampin?
Resistance arises quickly if rifampin is used as monotherapy. The most common mechanism is a mutation in the rpoB gene encoding the beta subunit of RNA polymerase, which reduces drug binding.
Outline key pharmacokinetic features of rifampin.
Rifampin is well absorbed orally, but food can decrease absorption. It widely distributes to tissues and body fluids (and even CSF), imparting an orange-red color to secretions (tears, urine, sweat). It undergoes hepatic metabolism and is a strong inducer of hepatic microsomal enzymes. It’s primarily excreted through bile into feces, with about 30% in urine.
What are major drug interactions with rifampin?
Rifampin is a potent inducer of cytochrome P450 enzymes and P-glycoprotein. It can significantly decrease levels of many drugs, requiring dose adjustments.
What are the clinical indications for rifampin?
Rifampin is a first-line drug for active tuberculosis and is used in latent TB as an alternative to isoniazid. It’s also used for leprosy, prophylaxis in close contacts of patients with Neisseria meningitidis or Haemophilus influenzae type b infection, and in combination with other antibiotics to treat serious Staph aureus infections.
When is rifampin contraindicated or used with caution?
Rifampin should be used with caution in patients with liver disease and those on multiple medications due to drug interactions. It’s contraindicated if the patient is on certain critical medications that cannot be dose-adjusted.
List major adverse effects of rifampin.
Notable effects include hepatotoxicity, orange discoloration of body fluids, flu-like syndrome if given intermittently, and rarely, thrombocytopenia, hemolytic anemia, or interstitial nephritis.
What are the “4 R’s” mnemonic for rifampin?
Rifampin’s ‘4 R’s’: RNA polymerase inhibitor, Ramps up microsomal P450 (strong inducer), Red/orange body fluids, Rapid resistance if used alone.
