Chemistry:Glycylcycline
Glycylcyclines are a class of antibiotics derived from tetracycline. These tetracycline analogues are specifically designed to overcome two common mechanisms of tetracycline resistance, namely resistance mediated by acquired efflux pumps and/or ribosomal protection. Presently, tigecycline is the only glycylcycline approved for antibiotic use.
History
The development of these agents was spurred by the increasing prevalence of bacteria resistant to tetracyclines. These agents were first synthesized in the early 1990s by making modifications to the tetracyclines. By adding a bulky N,N-dimethylglycylamido side chain to position 9 of minocycline, the compound became less susceptible to tetracycline resistance mediated by acquired efflux pumps and/or ribosomal protection. Further development of this initial work led to the creation of tigecycline, the first glycylcycline available for clinical use.[citation needed]
Approvals
- Tigecycline (FDA approved May 27, 2005)[1]
Mechanism of action
Glycylcycline antibiotics have a similar mechanism of action as tetracycline antibiotics. They block protein synthesis hence preventing bacterial reproduction. Both classes of antibiotics bind to the 30S ribosomal subunit to prevent the amino-acyl tRNA from binding to the A site of the ribosome. However, the glycylcyclines appear to bind more effectively than the tetracyclines.[2]
Mechanisms of resistance
While glycylcyclines have greater efficacy against organisms with tetracycline resistance mediated by acquired efflux pumps and/or ribosomal protection, glycylcyclines are not effective against organisms with chromosomal efflux pumps, such as Pseudomonas and Proteae.[3]
Side effects and contraindications
Since glycylcyclines are similar to tetracyclines, they share many of the same side effects and contraindications as tetracyclines. These side effects may include nausea/vomiting, headache, photosensitivity, discoloration of growing teeth, and fetal damage.[4]
These antibiotics should not be given to pregnant women due to risk of fetal harm. Additionally, these drugs should not be administered during periods of tooth development because of the risk of tooth discoloration. Due to glycylcyclines' similarities with tetracyclines, hypersensitivity reactions to tetracycline antibiotics may predispose one to hypersensitivity reactions with glycylcycline antibiotics; hence, glycylcyclines should be used with caution in these patients.[citation needed]
References
- ↑ "Drugs@FDA: FDA Approved Drug Products – Tigecycline". United States Food and Drug Administration. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=091620.
- ↑ "Glycylcyclines bind to the high-affinity tetracycline ribosomal binding site and evade Tet(M)- and Tet(O)-mediated ribosomal protection". Antimicrob. Agents Chemother. 40 (9): 2226–8. September 1996. doi:10.1128/AAC.40.9.2226. PMID 8878615.
- ↑ Livermore DM (October 2005). "Tigecycline: what is it, and where should it be used?". J. Antimicrob. Chemother. 56 (4): 611–4. doi:10.1093/jac/dki291. PMID 16120626.
- ↑ "List of adverse events for Tigecycline". RxList.com. http://www.rxlist.com/tygacil-side-effects-drug-center.htm.
- "Tigecycline: A novel glycylcycline antiobiotic". Formulary. August 1, 2005. http://www.formularyjournal.com/formulary/article/articleDetail.jsp?id=177008. Retrieved November 26, 2005.
External links
- Tygacil (tigecycline IV) manufacturer website.
- "The glycylcyclines: a comparative review with the tetracyclines". Drugs 64 (1): 63–88. 2004. doi:10.2165/00003495-200464010-00005. PMID 14723559.
- RxList.com list of adverse reactions to Tigecycline
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