A woman presenting with symptoms of urinary tract infection was prescribed a drug that causes tendon rupture and arthropathy. What is the mechanism of action of the drug?

Explanation

## Correct Answer: C. DNA gyrase inhibition The drug described is a **fluoroquinolone** (e.g., ciprofloxacin, levofloxacin, ofloxacin), commonly prescribed for UTIs in India. Fluoroquinolones inhibit **DNA gyrase** (topoisomerase II in bacteria), an enzyme essential for bacterial DNA replication and transcription. By blocking DNA gyrase, these drugs prevent the unwinding and supercoiling of bacterial DNA, leading to bacterial cell death. However, fluoroquinolones are notorious for causing **tendon rupture** (particularly Achilles tendon) and **arthropathy**, especially with prolonged use, in older patients, and when combined with corticosteroids—a critical adverse effect that distinguishes them from other antibiotic classes. The mechanism is direct inhibition of the bacterial topoisomerase II enzyme, making this the discriminating feature for fluoroquinolone identification in Indian medical exams. This adverse effect profile is well-documented in KD Tripathi and Harrison, and fluoroquinolones remain first-line for uncomplicated UTIs in India despite these risks. ## Why the other options are wrong **A. Ribosomal inhibition** — This is wrong because ribosomal inhibitors (aminoglycosides, tetracyclines, macrolides, chloramphenicol) do NOT cause tendon rupture or arthropathy. These drugs inhibit bacterial protein synthesis at the 30S or 50S ribosomal subunit. While aminoglycosides cause ototoxicity and nephrotoxicity, and tetracyclines cause photosensitivity and tooth discoloration, none are associated with the characteristic fluoroquinolone-induced tendon and joint complications. This is a classic NBE trap pairing antibiotics with wrong adverse effects. **B. Inhibition of folic acid synthesis** — This is wrong because sulfonamides and trimethoprim inhibit folic acid synthesis (dihydrofolate reductase inhibition), not fluoroquinolones. These drugs cause Stevens-Johnson syndrome, hemolytic anemia in G6PD deficiency, and crystalluria—NOT tendon rupture or arthropathy. Sulfonamides are rarely used for UTIs in modern Indian practice due to high resistance. This option tests whether students confuse different antibiotic classes and their distinct toxicity profiles. **D. Cell wall synthesis** — This is wrong because beta-lactams (penicillins, cephalosporins) and glycopeptides inhibit cell wall synthesis, not fluoroquinolones. Beta-lactams cause hypersensitivity reactions and C. difficile colitis, not tendon rupture or arthropathy. While beta-lactams are also used for UTIs in India, they lack the characteristic fluoroquinolone-induced musculoskeletal toxicity. This is a straightforward class confusion trap. ## High-Yield Facts - **Fluoroquinolone mechanism**: DNA gyrase (topoisomerase II) inhibition prevents bacterial DNA supercoiling and replication. - **Tendon rupture risk**: Fluoroquinolones increase risk 2–3 fold, especially Achilles tendon; risk increases with age >60, corticosteroid co-use, and renal impairment. - **Arthropathy**: Fluoroquinolones cause cartilage damage and are contraindicated in children and pregnancy (teratogenic in animal models). - **Common fluoroquinolones in India**: Ciprofloxacin, levofloxacin, ofloxacin, moxifloxacin; levofloxacin is preferred for respiratory infections. - **UTI first-line in India**: Fluoroquinolones remain empiric choice for uncomplicated UTIs despite musculoskeletal risks, per ICMR guidelines. ## Mnemonics **FQ-TOXIN** **F**luoroquinolones → **Q**uinolone toxicity: **T**endon rupture, **O**phthalmologic (QT prolongation), **X**anthine stones, **I**nterstitial nephritis, **N**eurotoxicity (seizures). Use this when recalling fluoroquinolone adverse effects in exams. **DNA Gyrase = Topoisomerase II** Fluoroquinolones inhibit **DNA Gyrase** (bacterial topoisomerase II), not ribosomal or cell wall targets. Remember: **G**yrase = **G**enetic material unwinding. Use when differentiating fluoroquinolone mechanism from other antibiotic classes. ## NBE Trap NBE pairs fluoroquinolones with tendon rupture to test whether students know the specific mechanism (DNA gyrase inhibition) versus confusing fluoroquinolones with ribosomal inhibitors or cell wall inhibitors, which have entirely different toxicity profiles. The trap is that students may recognize "tendon rupture = fluoroquinolone" but fail to link it to DNA gyrase inhibition if they haven't memorized the mechanism. ## Clinical Pearl In Indian clinical practice, fluoroquinolones remain the empiric choice for uncomplicated UTIs in women despite their musculoskeletal risks, because resistance to older agents (sulfonamides, nitrofurantoin) is high. However, in elderly patients (>60 years) or those on corticosteroids, alternative agents (cephalosporins, nitrofurantoin) should be considered to avoid tendon rupture—a critical bedside decision that can prevent significant morbidity. _Reference: KD Tripathi Ch. 47 (Fluoroquinolones); Harrison Ch. 139 (Antimicrobial Agents)_