Introduction to Nitrofurantoin Pharmacology

Nitrofurantoin – marketed under names such as Macrodantin and Macrobid – is used in the treatment of bladder infections. It is not effective at treating kidney infections. Here, we learn more about the essential facts behind nitrofurantoin pharmacology.

Interest in nitrofurantoin has increased in recent years.

Previously, fluoroquinolones and trimethoprim-sulfamethoxazole were used, and still are used, in the treatment of urinary tract infections (UTIs). Resistance to these drugs has, however, increased. As a result, more eyes are now focussed on nitrofurantoin as a clinically effective means to treat this common ailment.

Nitrofurantoin is effective at treating uncomplicated urinary tract infections. It remains a first-line agent. Other first-line drugs include trimethoprim and amoxicillin.

There are two great advantages of nitrofurantoin in the treatment of UTIs:

  • First, that it reaches therapeutic concentrations in urine after it has passed though renal excretion.
  • Second, nitrofurantoin is most bactericidal in acidic environments; the urine being a prominent example of this.

With these facts in mind, let’s take a closer look at the pharmacology of nitrofurantoin, how the drug works to exert its therapeutic effect.

Mechanism of action

Nitrofurantoin is known, at least among antibacterial drugs, for its unique mechanism of action.

Nitrofurantoin works by damaging bacterial DNA. In bacterial cells, nitrofurantoin is reduced by nitrofuran reductase; the resulting metabolite is highly reactive and attack ribosomal proteins, DNA and pyruvate metabolism. It is not yet known which specific action is responsible for its bactericidal activity.

Nitrofurantoin is active against both Gram-positive and Gram-negative causes of urinary tract infections – including E. coli and S. saprophticus, some of the most common causes of UTIs.

Side effects

Side effects associated with nitrofurantoin include:

  • Gastrointestinal upset – nausea, diarrhea etc.
  • Immediate and delayed hypersensitivity reactions
  • Brown discoloration of urine (harmless)

Prolonged use of nitrofurantoin is likely to cause more serious effects:

  • Pulmonary toxicity – pneumonitis or fibrosis
  • Hepatotoxicity – detected in patients whose use exceeds 6 weeks
  • Neuropathy – a rare side effect

Other potential side effects include dizziness, drowsiness, pruritis and malaise.

Clinical considerations

When we talk about the clinical pharmacology of nitrofurantoin, we need to think about the following factors:

  • That nitrofurantoin should be avoided in renal impairment. Renal impairment increases the risk of toxicity. It also distorts the therapeutic concentration needed to effectively eliminate the urinary tract infection.
  • That caution is warranted in the long-term use of nitrofurantoin. It may be used to prevent UTIs, for example. However, long-term use increases the risk of adverse effects – including serious pulmonary and hepatic effects. The risk of these effects increases in elderly patients.
  • To reduce the risk of gastrointestinal side effects, nitrofurantoin should be taken with food.
  • Nitrofurantoin should not be used for complicated urinary tract infections. Instead, other medicines – such as gentamicin – should be used.
  • Nitrofurantoin is pregnancy category B (US) – meaning it can be used safely to treat UTIs in pregnancy. However, it should be avoided in late pregnancy due to the risk of hemolytic anemia.
  • Due to weak tissue penetration, nitrofurantoin should not be used to treat pyelonephritis or prostatitis.

That concludes our review of the pharmacology of nitrofurantoin. For even more facts and pharmacology quiz questions, register with PharmaFactz today. Check back to our pharmacy blog soon for even more great facts on this essential antibacterial drug!