SN1 SHORT NOTE 5M ★ High-yield

Describe the fluoroquinolones with their classification, uses and adverse effects.

Pharmacology · 2nd Professional — Para-Clinical

Mechanism and Classification

Fluoroquinolones inhibit bacterial DNA gyrase (topoisomerase II) in gram-negative organisms and topoisomerase IV in gram-positive organisms, preventing DNA supercoiling and replication. They are bactericidal and concentration-dependent.

Generation	Drugs	Spectrum
First	Nalidixic acid	Gram-negative urinary organisms only; obsolete
Second	Ciprofloxacin, ofloxacin, norfloxacin	Broad gram-negative including pseudomonas; limited gram-positive; ciprofloxacin is the most active against Pseudomonas
Third	Levofloxacin	Added gram-positive and atypical cover — "respiratory quinolone"
Fourth	Moxifloxacin, gatifloxacin	Best gram-positive, atypical and anaerobic cover; moxifloxacin is not excreted renally, so it is unsuitable for urinary infection

Uses

Urinary tract infection, including complicated and pyelonephritis — though resistance is now high in India
Typhoid — formerly first-line, but resistance is now widespread in South Asia and azithromycin or ceftriaxone is generally preferred
Bacterial gastroenteritis — Shigella, Campylobacter, travellers diarrhoea
Respiratory — levofloxacin and moxifloxacin for community-acquired pneumonia and exacerbations of chronic bronchitis
Pseudomonas infections, including malignant otitis externa; ciprofloxacin is one of few oral options
Bone and joint infection, prostatitis (good penetration), gonorrhoea (where sensitive)
Meningococcal prophylaxis (single-dose ciprofloxacin); anthrax
Second-line antitubercular — levofloxacin and moxifloxacin are central to multidrug-resistant tuberculosis regimens

CLINICAL PEARL

Using a fluoroquinolone for a trivial infection can compromise tuberculosis treatment. These drugs are backbone agents in multidrug-resistant tuberculosis, and casual use selects resistance in an undiagnosed patient. Worse, giving one for an undiagnosed fever partially treats tuberculosis, producing temporary improvement that delays diagnosis. In India, where the burden is high, this is a specific and serious argument for restraint.

Adverse Effects

Tendinitis and tendon rupture, classically the Achilles tendon; risk increased by age over 60, corticosteroids and renal impairment; may occur weeks after the course
Arthropathy in immature animals, which led to their traditional avoidance in children and pregnancy; the human evidence is weaker, and they are used where the benefit is clear
CNS — headache, dizziness, insomnia, confusion; lower the seizure threshold, particularly with NSAIDs; psychosis in the elderly
QT prolongation and torsades, greatest with moxifloxacin
Peripheral neuropathy, sometimes irreversible
Aortic aneurysm and dissection — a recognised association, so they are avoided in those at risk
Gastrointestinal upset; Clostridioides difficile colitis; photosensitivity; dysglycaemia (gatifloxacin was withdrawn for this)

Interactions and Practical Points

Chelation — antacids, calcium, iron, zinc, magnesium, sucralfate and dairy products prevent absorption almost completely; doses must be separated by at least 2 hours. This is a very common and entirely avoidable cause of treatment failure
Ciprofloxacin inhibits CYP1A2 and raises theophylline and caffeine levels, risking seizures and arrhythmia
Increases warfarin effect; monitor the INR
With NSAIDs, the seizure risk rises
Excellent oral bioavailability, close to intravenous — so oral treatment is appropriate even in fairly sick patients, which saves cost and lines

Applied Aspects

Regulatory agencies now advise against fluoroquinolones for uncomplicated infections — simple cystitis, sinusitis, bronchitis — where safer alternatives exist, because of the disabling and sometimes permanent musculoskeletal and neurological effects
Resistance in India is very high for E. Coli, Salmonella typhi and Shigella, largely from unrestricted use; local antibiograms should guide empirical choice rather than textbook spectra
Warn patients to stop the drug and seek advice for tendon pain, and avoid strenuous exercise during and shortly after treatment
Avoid in epilepsy, myasthenia gravis and known QT prolongation
Never give with milk, antacids or iron, and say so explicitly — patients naturally take tablets with milk

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