Pharmacology of Fluoroquinolones

Fluoroquinolones are a class of synthetic antibiotics that are effective against a wide range of bacterial infections. They are commonly used to treat respiratory, urinary tract, gastrointestinal, and skin infections. Below is a comprehensive overview of the pharmacology of fluoroquinolones:

Classification

Fluoroquinolones can be classified based on their generation and spectrum of activity. Some of the commonly used fluoroquinolones include:

• Ciprofloxacin (Second Generation)
• Levofloxacin (Third Generation)
• Moxifloxacin (Fourth Generation)
• Ofloxacin (Second Generation)

Mechanism of Action

DNA Gyrase and Topoisomerase IV Inhibition: Fluoroquinolones inhibit bacterial DNA gyrase and topoisomerase IV, crucial enzymes for DNA replication and transcription, thereby preventing bacterial growth and multiplication​¹​. This action is more pronounced against aerobic or facultative Gram-negative bacilli, although newer fluoroquinolones like levofloxacin and moxifloxacin also show increased activity against Gram-positive organisms compared to earlier ones such as ciprofloxacin​^2, ​​¹​.

Resistance

Resistance to fluoroquinolones arises through mechanisms like efflux pump overexpression, plasmid-mediated resistance, and mutations in DNA gyrase or topoisomerase IV genes​¹​.

Pharmacokinetics

• Absorption: Fluoroquinolones are well absorbed orally, but their absorption can be reduced by divalent and trivalent cations such as calcium, magnesium, and iron.
• Distribution: They are widely distributed throughout the body, including in tissues, cells, and body fluids.
• Metabolism: Fluoroquinolones undergo limited metabolism in the liver.
• Excretion: They are primarily excreted unchanged in the urine, with some also excreted in feces.

Clinical Uses

• Upper and Lower Respiratory Tract Infections: Such as tuberculosis, mycobacterial infections, sinusitis, bronchitis, and pneumonia​³​.
• Urinary Tract Infections (UTIs): They are commonly used to treat UTIs, with examples including ciprofloxacin, levofloxacin, and norfloxacin​⁴​.
• Gastrointestinal Infections: Such as those caused by Shigella and Campylobacter​⁴​.
• Pseudomonas aeruginosa Infections: Ciprofloxacin and levofloxacin are effective against this pathogen​⁴​.
• Skin and Soft Tissue Infections
• Bone and Joint Infections
• Sexually Transmitted Infections: Including gonorrhea.

Adverse Effects

• Gastrointestinal Disturbances: Nausea, vomiting, diarrhea.
• Central Nervous System Effects: Headache, dizziness, and, in rare cases, seizures.
• Tendonitis and Tendon Rupture: Particularly in older adults, those taking corticosteroids, and kidney, heart, and lung transplant recipients.
• Phototoxicity: Increased sensitivity to sunlight.
• Cardiac Effects: moxifloxacin is most associated with QT prolongation​¹, leading to an increased risk of cardiac arrhythmias.

Drug Interactions

• Antacids, Iron, and Zinc: Can reduce the absorption of fluoroquinolones.
• Warfarin: Fluoroquinolones can increase the anticoagulant effects of warfarin.
• Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): Can increase the risk of central nervous system stimulation and seizures when taken with fluoroquinolones.

Contraindications

• Allergy to Fluoroquinolones: Patients with a history of allergy to any fluoroquinolone should not receive these antibiotics.
• Pregnancy and Breastfeeding: Fluoroquinolones can affect cartilage development in the fetus and newborn.
• Children and Adolescents: Due to the risk of cartilage damage and tendonitis.

Clinical Pharmacology

Concerns with fluoroquinolones include interactions with drugs that can prolong the QT interval and with multivalent ions present in antacids or other medicines like magnesium, aluminum, calcium, iron, or zinc-containing products. They should be used with caution in patients with epilepsy, cardiovascular disease, or those at increased risk of seizures. Moreover, their combination with NSAIDs increases the risk of seizures, and with prednisolone, it increases the risk of tendonitis or tendon rupture​¹​.