Paper II
Question
Mention two aminoglycosides. Explain four common properties of aminoglycosides. What is post-antibiotic effect. (1+4+1)
Answer
Two aminoglycosides: Gentamicin, Amikacin.
Four common properties
- Poor oral bioavailability — highly polar, charged molecules that cannot cross lipid membranes well; given parenterally for systemic infection.
- Concentration-dependent bactericidal killing — bind the bacterial 30S ribosomal subunit, causing misreading of mRNA and inhibiting protein synthesis; higher peak concentrations produce proportionally greater kill.
- Shared toxicity profile — nephrotoxicity (reversible, from proximal tubular accumulation) and ototoxicity (often irreversible, vestibular and/or cochlear).
- Synergy with beta-lactams — a beta-lactam’s cell-wall-weakening action improves aminoglycoside penetration to its intracellular ribosomal target, exploited in treating severe Gram-negative and enterococcal infections.
Post-antibiotic effect The persistent suppression of bacterial growth that continues even after the drug concentration falls below the minimum inhibitory concentration — aminoglycosides show a genuine, clinically significant post-antibiotic effect, which is the specific pharmacodynamic basis for once-daily, high-dose (extended-interval) dosing regimens, now standard practice; this strategy also reduces nephrotoxicity risk by allowing a trough period for renal tubular cells to partially clear accumulated drug between doses.