Tetracyclines indications

Fig. 2. Tetracycline (1) indicating the titratable hydrogens and showing (a) the BCD-chromophore and (b) the A-chromophore (15).

Tetracyclines are used as alternative dnigs in a variety of circumstances when the patient is unable to take the dnig of choice, eg, in patients allergic to penicillin (88,89). Tetracyclines are widely known to cause staining of teeth (and are therefore contra-indicated in children developing permanent teeth), photosensitivity, and, in the case of minocycline, vestibular toxicity. Details of these adverse effects and others associated with administration of tetracyclines have been comprehensively reviewed (96—101). 

Ribosomal Protein Synthesis Inhibitors. Figure 3 The chemical structure of tetracycline and possible interactions with 16S rRNA in the primary binding site. Arrows with numbers indicate distances (in A) between functional groups. There are no interactions obseived between the upper portion of the molecule and 16S rRNA consistent with data that these positions can be modified without affecting inhibitory action (from Brodersen et al. [4] with copynght permission). 

Systemic antibiotics are indicated for moderate-severe inflammatory acne not responding to topical treatments. Systemic antibiotics act on 1) suppression of P. acnes growth 2) inhibition of bacterial lipases 3) reduction of free fatty acids and 4) reduction of inflammation. Oxytetracycline and its derivatives are the most commonly used oral antibiotics. Second-generation tetracyclines such as minocycline, doxy-cycline and lymecycline present longer half-lives, enhanced bacterial activity and lower... 

Aligned sequences of 16 members of the sugar transporter family. Residues which are identical in 5=50% of the 16 sugar-transporter sequences (excluding the quinate transporter (qa-y), the citrate transporter (CIT), the tetracycline transporter (pBR322) and lac permease (LacY)) are highlighted, and recorded below the sequences as CONSERVED . The locations of predicted membrane-spanning helices are indicated by horizontal bars. The sequences were taken from the references cited in the text. 

Table 37.3 shows the complete table of eight indicator variables for 10 triply substituted tetracyclines [31 ] that have been tested for bacteriostatic activity (1/Z), which is defined here as the ratio of the number of colonies grown with a substituted and with the unsubstituted tetracycline. In this application we have three substitution positions, labelled U, V and W. The number of substituents at the three sites equals 2,3 and 3, respectively. Arbitrarily, we chose the compound with substituents H, NOj and NO2 at the sites U, V and W as the reference compound. This leads to a reduction of the number of indicator variables from eight to five, as shown in Table 37.4. The solution of the Free-Wilson model can be obtained directly by means of multiple regression ...

In the above expression the indicator variable I(X) takes the value 0 or 1, depending upon the absence or presence of the substituent X in a particular compound. The overall result of the regression is not significant at the 0.05 level of probability. This may be due to the unfavorable proportion of the number of compounds to the number of parameters in the regression equation (10 to 6). Only the indicator variable for substituent NHj at position W in the tetracycline molecule reaches significance (p = 0.02). This can be confirmed by looking at Table 37.4... 

Complete indicator table and bacteriostatic activities of 10 triply substituted tetracyclines. The three substitution positions are labeled U, V and W [31]. 

As indicated, the ionized form of a drug will be more soluble than the nonionized form in the aqueous fluids of the GIT. The classic studies on the beneficial effects of changing nonionized drugs into salt forms were reported by Nelson for tetracycline [25], and Nelson et al. for tolbutamide [26]. Table 2 combines portions of the data from each study. Urinary excretion of the drug or its metabolite was taken as the in vivo measure of the relative absorption rate for the salt and the nonionized... 

ELISA) followed by Western blotting are used. As for treatment, doxicycline and rifampin for a minimum of six weeks. Ofloxacin plus rifampin is also effective. Therapy with rifampin, a tetracycline, and an aminoglycoside is indicated for infections with complications such as endocarditis or meningoencephalitis. 

A number of laboratories have studied the effect of methylation on nucleosome placement and/or positioning. Methylation of several sequences did not seem to affect this parameter sequences from the tetracycline resistance gene [165], Alu repeats from human DNA [166], 5S rDNA from X. borealis [164]. On the other hand, nucleosomes were excluded from a specific region in the /6-globin gene, when methylated [167], indicating the importance of the DNA sequence. Earlier data by Keshet et al. [118] showed disappearance of nucleosome-free regions (i.e., formation of nucleosomes) in methylated promoters in vivo. This effect, however, may be only indirectly connected to the methylation status of the promoters. 

Minocycline differs from the other tetracyclines in that it is active against Neisseria meningitidis. Topical and systemic preparations of tetracyclines are indicated in acne. 

NRDC concluded that there will be no significant negative effect on animal health from banning subtherapeutlc uses of penicillin and the tetracyclines In animal feeds. They Indicated that the use of these drugs for purposes of Improving feed efficiency and weight gain Is for economic reasons only and no... 

The committee recommended a comparison of subtherapeutic with therapeutic use of antibiotics on the prevalence of resistant transfer factors in meat animals. Also recommended was a study comparing the enteric flora of vegetarians and meat-eaters. A third study would involve workers in abattoirs and their contacts. These studies are in progress under the direction of Dr. Edward Kass at Harvard University and investigators at the Loma Linda Medical School. The committee also recommended further research on the mechanisms of the antibiotic growth effect. The report (7) said there is little indication that sale of antibiotics, including penicillin and tetracyclines, for feed and veterinary use, "has decreased as a result of the Swann Report."... 

In terms of antibacterial spectrum, this drug is similar to chlorotetracycline. It is used for the same indications. It belongs to the group of short-lasting tetracyclines. Synonyms of this drug are tetramycin, oxymycin, and others. 

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