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Antibiotics: The Need for Innovation
Published in Nathan Keighley, Miraculous Medicines and the Chemistry of Drug Design, 2020
There is a wide diversity of antibiotics designed to target bacterial protein synthesis. Tetracycline antibiotics are a broad spectrum class of antibiotics that also bind to the 30S subunit, but have a different mode of action. They prevent aminoacyl tRNA from binding and stop growth of the protein. Other antibiotics target the 50S subunit of ribosomes, such as chloramphenicol, and work by inhibiting the movement of ribosomes along the mRNA strand. Chloramphenicol is the drug of choice for treating typhoid in some parts of the world, where more expensive drugs cannot be afforded.
Ultraviolet and Light Absorption Spectrometry
Published in Adorjan Aszalos, Modern Analysis of Antibiotics, 2020
Zoltan M. Dinya, Ferenc J. Sztaricskai
Several methods have been described for the determination of the contaminants (including the respective epimers and anhydroderivatives) of tetracycline antibiotics. For assay of the total anhydro content (ATC and EATC) of TC samples, spectrophotometric procedures have been described by Dijkhuis [198] and Walton [199].
ExperimentaL Oral Medicine
Published in Samuel Dreizen, Barnet M. Levy, Handbook of Experimental Stomatology, 2020
Samuel Dreizen, Barnet M. Levy
The tetracycline antibiotics have been shown to concentrate in growing bones and teeth. Children treated with such antibiotics during the period of tooth formation develop irreversible yellow to yellow-brown discoloration of the teeth. Owen85 studied the capacity of different tetracyclines to localize in the teeth of young dogs. A litter of crossbred retriever dogs, 7 weeks old, were dosed for 1 month with therapeutic amounts of various tetracyclines. Each dog received either tetracycline, chlortetracycline, oxytetracycline, or dimethylchlortetracycline. Another litter received very high doses of the same drugs.
Isotretinoin for acne vulgaris – an update on adverse effects and laboratory monitoring
Published in Journal of Dermatological Treatment, 2022
Haady Fallah, Marius Rademaker
Initial concerns regarding a possible association between isotretinoin and the development of inflammatory bowel disease arose from several case reports and a single case-control study indicating that exposure to isotretinoin was associated, in a dose-dependent fashion, with an increased risk of ulcerative colitis but not Crohn disease (30). Interestingly, a subsequent study using the same database found no increased risk for either ulcerative colitis or Crohn’s disease, in patients taking isotretinoin (31). The main difference between the two case-control studies was that the latter study was a nested study in patients taking the combined oral contraceptive pill, which reduces the effect of possible confounding from the oral contraceptive pill. The authors were able to adjust for the confounder of diagnosis (nodulocystic acne) and prior use of tetracycline antibiotics. This is important as tetracyclines, especially doxycycline, may be associated with the development of inflammatory bowel disease, particularly Crohn’s disease (32,33). While doxycycline has been shown to mediate detrimental long-term changes in murine gut microbiota, isotretinoin has no significant effect on fecal microbiota (34).
Binding site comparisons for target-centered drug discovery
Published in Expert Opinion on Drug Discovery, 2019
With the onset of resistance to ribosomal inhibitors, arguably the most successful antimicrobial agents, there is a renewed interest in the development of new protein synthesis inhibitors. Binding site comparison between the pathogenic and the non-pathogenic bacterial ribosomes revealed differences in the binding sites, which enabled the development of new erythromycin derivative antibiotics that specifically bind only to ribosomes of pathogenic species [86,87]. Similarly, challenging is the lack of selectivity of tetracyclines. While these drugs act by inhibiting the 30S ribosomal subunit [88], it was recently discovered that they also influence translation by binding to the human 80S subunit [89]. Here, the comparison between human and bacterial rRNA could enable development of more specific tetracycline antibiotics or repurpose them as anticancer or anti-inflammatory drugs [89]. A methodological challenge is presented by thiopeptide antibiotics whose binding sites are composed of the rRNA as well as of the protein [90]. Currently, there is no known method that would allow comparison of such composite binding sites.
Ocular Chlamydia trachomatis infection: elimination with mass drug administration
Published in Expert Review of Anti-infective Therapy, 2019
Meraf A. Wolle, Sheila K. West
Oral doxycycline is in the tetracycline class of antibiotics; more specifically it is a semi-synthetic derivative of tetracycline thus sharing many of its characteristics. It is given as a single dose once a day, 5 days a week, for a total of 6 weeks. The dose given is 2.5–4 mg/kg of body weight [64]. An oral form of tetracycline was initially felt to be a more practical and less expensive alternative to tetracycline ointment. It was never implemented for individual treatment or community-wide administration on a large scale, however, because it cannot be administered to pregnant or lactating women nor children less than 12; it can permanently damage calcium-rich organs (such as teeth and bone) and cause nasal cavities to erode [65]. Other adverse events have also been reported including gastrointestinal upset and photosensitivity as well as allergic reactions. While these are common to the tetracycline antibiotics given orally, they are not seen with topical administration because of the lack of significant systemic absorption.