Nitrofurantoin Flashcards
What is the mechanism of action of nitrofurantoin?
Nitrofurantoin is reduced by bacterial flavoproteins to reactive intermediates that inactivate or damage bacterial ribosomal proteins, DNA, and other macromolecules. This multi-mechanism damage is bactericidal in the urine.
Describe the spectrum of activity of nitrofurantoin.
Nitrofurantoin’s activity is mostly against common urinary tract pathogens. It covers many Gram-negatives (E. coli, Klebsiella, Enterobacter) and Gram-positives (Staph saprophyticus, Enterococci) that cause UTIs. Many Proteus and Pseudomonas species are inherently resistant.
How rare is resistance to nitrofurantoin and how can it occur?
Resistance is relatively rare despite long use. When it occurs, it may be due to mutations in bacterial nitroreductase enzymes (e.g., nfsA/nfsB in E. coli) that reduce the activation of nitrofurantoin. Some bacteria also reduce drug uptake or increase efflux.
Outline key pharmacokinetic features of nitrofurantoin.
Nitrofurantoin is given orally and is well absorbed. It is rapidly excreted into urine by the kidneys; high levels accumulate in urine (site of action) while serum levels remain low. It works best for lower UTIs because it concentrates in bladder urine (not effective for pyelonephritis). Nitrofurantoin should be taken with food to improve absorption. It is contraindicated when creatinine clearance is low (e.g., <30-60 mL/min) because inadequate drug reaches the urine and toxicity risk increases.
What major drug interactions involve nitrofurantoin?
Antacids containing magnesium trisilicate can reduce nitrofurantoin absorption. Drugs that alkalinize the urine may reduce its efficacy (works better in acidic urine). Probenecid or sulfinpyrazone (which decrease renal excretion) can increase nitrofurantoin blood levels and toxicity while decreasing urinary levels. Nitrofurantoin is not a significant CYP inhibitor or inducer.
What are the clinical indications for nitrofurantoin?
Nitrofurantoin is primarily used for uncomplicated lower urinary tract infections (cystitis), especially in women. It’s often a first-line agent for cystitis, including in pregnancy (except near term). It’s also used for UTI prophylaxis in patients with recurrent UTIs. It should not be used for pyelonephritis or perinephric abscess (insufficient tissue penetration).
When is nitrofurantoin contraindicated or to be avoided?
Nitrofurantoin is contraindicated in patients with significantly reduced kidney function (e.g., creatinine clearance <30 mL/min) because it won’t reach effective concentrations in urine and risk of systemic accumulation rises. Avoid in the late third trimester of pregnancy and in neonates <1 month old due to risk of hemolytic anemia (immature RBC enzyme systems/G6PD). Also avoid in individuals with G6PD deficiency due to risk of hemolytic anemia.
List major adverse effects of nitrofurantoin.
Nitrofurantoin can cause GI upset (take with food to reduce nausea). It may turn urine a harmless brown color. A notable adverse effect is hemolytic anemia in patients with G6PD deficiency or in neonates. Long-term use can lead to pulmonary reactions: an acute hypersensitivity pneumonitis (fever, cough) or, with chronic use, nitrofurantoin can cause interstitial lung fibrosis. Peripheral neuropathy is a rare side effect, usually in the context of renal impairment or long-term therapy.
Is there a mnemonic to remember nitrofurantoin’s key point?
Think ‘NitroFURantoin – put the FURry nitro bomb in the urine.’ It highlights its action site (urine for UTIs) and reminds that it can ‘explode’ (cause hemolysis) in G6PD deficiency.
