- D Byron May, PharmD, BCPS
D Byron May, PharmD, BCPS
- Professor and Chairman, Department of Pharmacy Practice
- Campbell University College of Pharmacy & Health Sciences
Chlortetracycline was the first tetracycline discovered, in 1948. Since then five additional tetracyclines have been isolated or derived (oxytetracycline, tetracycline, demeclocycline, doxycycline and minocycline), but only the last four are available for systemic use in the United States. Of these four agents, doxycycline and minocycline are the most frequently prescribed. Research to find tetracycline analogues lead to the development of the glycylcyclines. Tigecycline is the first of this new class of agents and exhibits broad-spectrum antibacterial activity similar to the tetracyclines .
Doxycycline is one of the most active tetracyclines and is the most often used clinically since it possesses many advantages over traditional tetracycline and minocycline. Doxycycline can be administered twice daily, has both intravenous (IV) and oral (PO) formulations, achieves reasonable concentrations even if administered with food, and is less likely to cause photosensitivity . Doxycycline may be an alternative for use in children since it binds calcium to a lesser extent than tetracycline, which can cause tooth discoloration and bony growth retardation. The increase in frequency of multidrug-resistant organisms has led to the resurgence of IV minocycline for the treatment of infections caused by these organisms .
MECHANISM OF ACTION
The tetracyclines enter the bacterial cell wall in two ways: passive diffusion and an energy-dependent active transport system, which is probably mediated in a pH-dependent fashion. Once inside the cell, tetracyclines bind reversibly to the 30S ribosomal subunit at a position that blocks the binding of the aminoacyl-tRNA to the acceptor site on the mRNA-ribosome complex. Protein synthesis is ultimately inhibited, leading to a bacteriostatic effect .
In contrast to many other antibiotics, tetracyclines are infrequently inactivated biologically or altered chemically by resistant bacteria. Resistance to these agents develops primarily by preventing accumulation of the drug inside the cell either by decreasing influx or increasing efflux. Once resistance develops to one of the drugs in this class, it is typically conferred to all tetracyclines.
However, there are differences in resistance among species of bacteria. Resistance genes to tetracyclines often occur on plasmids or other transferable elements such as transposons . Bacteria carrying a ribosome protection type of resistance gene produce a cytoplasmic protein that interacts with the ribosomes and allows the ribosomes to proceed with protein synthesis even in the presence of high intracellular levels of the drug [5,6].
Subscribers log in hereLiterature review current through: May 2017. | This topic last updated: Mar 02, 2016.References
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- MECHANISM OF ACTION
- SPECTRUM OF ACTIVITY
- Combination of tetracyclines and penicillins
- Absorption of the tetracyclines
- Serum concentrations
- Routes of elimination
- SPECIAL POPULATIONS
- Pregnant or breastfeeding women
- Renal failure
- ADVERSE REACTIONS
- Allergic and skin reactions
- Teeth and bone
- Liver and renal
- DRUG INTERACTIONS
- SUMMARY AND RECOMMENDATIONS