Quinolones, also known as fluoroquinolones, are a class of drugs used in the treatment of bacterial infections. The first quinolone – nalidixic acid – was introduced in 1962 for the treatment of urinary tract infections. Since that time, quinolones have diversified to become broad-spectrum agents; drugs which work by inhibiting replication of bacterial DNA – meaning they are bactericidal in effect. Examples of quinolones include ciprofloxacin, moxifloxacin, and norfloxacin. Common adverse effects with quinolones include CNS effects, tendonitis, rash, nausea, vomiting, and QT prolongation (particularly with moxifloxacin). First, though, let’s take a closer look at the pharmacology of quinolones – how and why they work.

Nalidixic Acid Ciprofloxacin Moxifloxacin Gemifloxacin
Levofloxacin Ofloxacin Norfloxacin Enoxacin

Pharmacology of Quinolones

Quinolones are a class of drugs used in the treatment of bacterial infections. In terms of pharmacology, they work by inhibiting replication of bacterial DNA. They achieve this by using two enzymes: DNA gyrase and DNA topoisomerase. These enzymes are implicated in the development of DNA supercoils – vital elements in the replication process. Most quinolones are fluorinated at the C6 position – something which distinguishes modern-day quinolones from their earlier counterparts. However, studies show that fluorination is a sufficient, but not necessary condition for antibacterial effect.

Quinolones are bactericidal in effect and target a broad range of bacteria: both gram-positive and gram-negative:

  • Ciprofloxacin is broad-spectrum in effect, particularly against pathogens resistant to penicillins, cephalosporins, and aminoglycosides.
  • Moxifloxacin is inactive against Pseudomonas aeruginosa, but has greater activity against pneumococci when compared to ciprofloxacin.
  • Norfloxacin is primarily used in the treatment of urinary tract infections.
  • Gemifloxacin is mostly used in the treatment of chronic bronchitis and mild-to-moderate pneumonia.
  • Levofloxacin is used to treat a wide variety of infections – from respiratory tract to urinary tract, prostatitis, pelvic inflammatory disease, and endocarditis.
  • Ofloxacin is particularly useful in lower abdominal infections such as urethritis, cervicitis, pelvic inflammatory disease, cystitis, urinary tract infections, and prostatitis. It may also be used for bronchitis and pneumonia, however.
  • Enoxacin use is mostly limited to urinary tract infections and gonorrhoea.

Quinolones

Pharmacokinetics

Quinolones are available in a wide variety of preparations. Ciprofloxacin is, for example, formulated in oral, intravenous and topical forms. It has variable, but sufficient, oral absorption and is widely distributed among body tissues and fluids. CSF penetration is, however, rather poor. Most of the drug is eliminated unchanged in the urine, partly by tubular secretion – but 20 percent is excreted in the bile, and approximately the same amount is metabolised in the liver. It has a short half-life of 3-4h. Moxifloxacin has a longer half-life of 12h, whereas norfloxacin has a half-life of approximately 3h. Norfloxacin is moderately absorbed from the gut.

Adverse Effects

Quinolones are associated with a diverse array of adverse effects including nausea, vomiting, abdominal pain, and diarrhoea. CNS effects are also quite common such as drowsiness, headache, tremor and seizures. Moxifloxacin has been shown to prolong the QT interval on the ECG – a risk exacerbated in patients taking pro-arrhythmic drugs. Absorption of quinolones is diminished in patients taking oral iron salts.

Quinolones are contraindicated, or used with caution, in the following cases:

  • Patients with epilepsy or QT prolongation
  • Patients with pre-existing CNS lesions, CNS inflammation
  • Patients who have suffered a stroke
  • Ciprofloxacin is contraindicated in patients taking tizanidine

Quinolones may also be avoided in athletes, not least because of the former’s propensity to cause tendon pain and inflammation.

The pharmacology of quinolones is, as we have learned, remarkably simple. These drugs have since gone on to become some of the most widely prescribed antibacterial drugs in modern times. The rise of antimicrobial resistance is, though, posing an ever greater challenge to their long-term efficacy. If you’d like to test your knowledge of the pharmacology of quinolones, see here for more.

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