Medical Pharmacology Topics   

Quinolone Antibiotics

 Most established members of the quinolone antibiotics have a quinoline ring. The naphthyridine group (?) includes old agents for urinary tract infections like nalidixic acid, and newer agents that contain fluorine for increased potency: alatrofloxacin, enoxacin, trovafloxacin, ciprofloxacin, gatifloxacin, grepafloxacin, levofloxacin, lomefloxacin, moxifloxacin, norfloxacin, ofloxacin and sparfloxacin.

The quinolone antibiotics have rapid bactericidal effects by inhibiting Type II and Type IV topoisomerases and inhibiting the A subunit of DNA gyrase. Inhibition of Type II topoisomerase occurs after the DNA strand is cut, preventing reanealing. By inhibiting DNA gyrase, DNA supercoiling is altered, promoting double-stranded DNA breakage. Topoisomerase IV inhibition blocks decatenation of daughter bacterial chromosomes.

Ciprofloxacin is used against urinary track infections, pneumonia and bronchitis caused by gram-negative aerobes, bacterial gastroenteritis, gonorrhea and Pseudomonas infections.

Levofloxacin is used against urinary track infections, pneumonia and bronchitis caused by gram-negative aerobes and community-acquired pneumonia (not always successful).

Ofloxacin is used against Chlamydia cervicitis or urethritis and gonorrhea. Life threatening pneumonia, pelvic, abdominal or soft tissue infections are treated with alatrofloxacin or trovafloxacin, which are drugs of restricted use (?).

The quinolone antibiotics are administered orally, with 40-95% bioavailability. Food delays but does not greatly diminishes total absorption. They are widely distributed to most tissues, including the CNS (concentrate in leukocytes and are transported to the site of infection). Tissue levels of ciprofloxacin and ofloxacin may exceed serum levels. A small percentage of the total dose undergoes hepatic metabolism to less active compounds. Alatrofloxacin is a prodrug, rapidly hydrolyzed to trovafloxacin. Renal excretion eliminates 40-90% of the dose unchanged, while bile also excretes a significant amount of unchanged drug into feces. Renal impairments requires dosage adjustment.

These agents are contraindicated during pregnancy and in patients with allergic reactions to nalidixic acid or any fluoroquinolone. Common CNS side effects include headache, dizziness, insomnia, nervousness. Seizures rarely occur, but are possible in patients with previous seizure activity, alcohol abuse, or on theophylline. Common GI side effects include pain, nausea and vomiting. The QT interval may be prolonged, and other cardiovascular symptoms include slow or irregular heart rate and fainting. This reaction is more common with grepafloxacin and may be fatal. Unpredictable liver failure may be fatal while using trovafloxacin or alatrofloxacin. Other side effects include phlebitis if using IV ciprofloxacin or ofloxacin, photosensitivity (lomefloxacin, sparfloxacin), and tendonitis or tendon rupture.

The quinolone antibiotics interact with many other drugs, mainly metals, theophylline, warfarin, antiarrhythmics and antidepressants. Drugs containing metals will chelate quinolones, blocking their absorption. The antibiotic should be taken 2-6 hours after this medications. Ciprofloxacin, enoxacin and grepafloxacin compete with theophylline for P450, allowing theophylline to accumulate. This increases risk of nausea, vomiting and CNS effects (tremors, agitation, seizures). Warfarin may have greater anticoagulant effect, especially with ciprofloxacin and norfloxacin. Fluoroquinolones, especially grepafloxacin and sparfloxacin are contraindicated with antiarrhythmics, antidepressants and other drugs that prolong the QT interval because of documented risk of Torsade de Pointes.

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