Tetracyclin antibiotics

Dmg distribution into tissue reservoirs depends on the physicochemical properties of the dmg. Tissue reservoirs include fat, bone, and the principal body organs. Access of dmgs to these reservoirs depends on partition coefficient, charge or degree of ionization at physiological pH, and extent of protein binding. Thus, lipophilic molecules accumulate in fat reservoirs and this accumulation can alter considerably both the duration and the concentration—response curves of dmg action. Some dmgs may accumulate selectively in defined tissues, for example, the tetracycline antibiotics in bone (see Antibiotics,tetracyclines). 

Antibiotics were used in folk medicine at least as early as 2500 years ago when the Chinese reported the medicinally beneficial effects of moldy bean curd. Evidence for some type of tetracycline antibiotic usage by the Sudanese-Nubian civilization (350 AD) was reported in 1980 (6). Fluorescent areas in human bones from this eta were observed that were identical in location and characteristics to modern bone from patients treated with tetracyclines. Identification of tetracycline in the ancient bones was further substantiated by fluorescence spectmm measurements and microbiological inhibition studies (7). 

In 1939 the isolation of a mixture of microbial products named tyrotbricin from a soil bacillus was described. Further investigation showed this material to be a mixture of gramicidin and tyrocidine. In rapid succession the isolation of actinomycin (1940), streptothricin (1942), streptomycin (1943), and neomycin (1949), produced by Streptomjces were reported and in 1942 the word antibiotic was introduced. Chloramphenicol, the first of the so-called broad spectmm antibiotics having a wide range of antimicrobial activity, was discovered in 1947. Aureomycin, the first member of the commercially important tetracycline antibiotics, was discovered in 1948. 

Tetracycline antibiotics have found wide application in animal industries for treatment, preventive maintenance and stimulation of growth of large horned livestock owing to what their residue amounts can be present at milk and meat of animals. Residue amounts of antibiotics are not toxic, however, capable to cause allergic reactions and to promote development of tolerance of the some people pathogenic bacterias. According with the legislative requirements of a number of the European countries it is forbidden to deliver to the population production polluted residual contents of tetracyclines. 

Compound (3) is, appropriately enough, a useful intermediate for the synthesis of tetracycline antibiotics. Disconnection (a) gives considerable simplification. 

Fig. 5.7 Tetracycline antibiotics 1, oxytetracycline 2, chlortetracycline 3, tetracycline 4, demethylchlortetracycline 5, doxycycline 6, methacycline 7, clomocycline 8, minocycline 9, thiacycline (a thiatetracycline with a sulphur atom at 6).

Yang W, IF Moore, KP Koteva, DC Bareich, DW Hughe, GD Wright (2004) TetX is a flavin-dependent monooxygenase conferring resiatence to tetracycline antibiotics. J Biol Chem 279 52346-52352. 

There are problems as well in the absorption of certain drugs in the presence of specific food components. L-Dopa absorption may be inhibited in the presence of certain amino acids formed from the digestion of proteins [43], The absorption of tetracycline is reduced by calcium salts present in dairy foods and by several other cations, including magnesium and aluminum [115-117], which are often present in antacid preparations. In addition, iron and zinc have been shown to reduce tetracycline absorption [118], Figure 17 illustrates several of these interactions. These cations react with tetracycline to form a water-in-soluble and nonabsorbable complex. Obviously, these offending materials should not be co-administered with tetracycline antibiotics. 

Chemical drug interactions result when two administered substances combine with each other chemically Tetracyclines complex with Ca (in milk), with aluminum (Al) and magnesium (Mg) (often components of antacids), and with Fe (in some multiple vitamins) to reduce the absorption of the tetracycline antibiotic. 

On the other hand, the analgesic phenylbutazone, the antidepressant paroxetine, tetracycline antibiotics doxycycline and chlorotetracycline, the antibiotics tilmico-sin, danofloxacin, enoxacin, nifuroxazide, the (3-blockers betaxolol, carazolol, pindolol, the (3-agonist clenbuterol, barbiturates, the antihypertensive lisinopril, and the drug to treat cancer tamoxifen were never detected. 

Some of the early reports on the chromatography of the tetracycline antibiotics prior to 1957 are of limited value. Fischbach and Levine (43) described a continuous ascending technique and Berti and Cima (44) reported an ascending method using aqueous sodium arsenite as the mobile solvent. Other authors(45,46) reported descending techniques and bioautographic means for locating the zones of activity. 

The usual method of detecting chromatographed tetracycline antibiotics involves fuming the paper with ammonia vapor and observing the yellow fluorescence under UV light. As little as 0.2-0.5 pg can be visualized by this technique. 

Immunochemical methods have been developed and placed on the market to analyze tetracycline residues (see Table 4). Thus, a qualitative EIA has been developed and used to analyze tetracyclines in honey samples with a detection level of 20 pg/kg-1 [96]. A microplate-based indirect ELISA has been developed to analyze tetracyclines using polyclonal antibodies. The assay could measure tetracycline in the range between 0.1 and 6 ng mL L Other tetracycline antibiotics such as chlortetracycline, rolitetracycline, or minocycline are also highly recognized in this assay [98]. Several immunoassay kits are commercially available for the analysis of tetracyclines although, to our knowledge, none of them... 

The use of the Charm II RIA test to analyze tetracycline antibiotics in water (both surface and groundwater) has been reported [84, 97]. This RIA, which was initially developed to analyze tetracycline in serum, urine, and milk, was subsequently adapted to analyze water samples at concentration levels around 1 pg L-1. Thus, samples from hog lagoons, surface water samples, and ground-water samples were tested using the RIA method and the results confirmed by LC-MS. 

Treatment — A number of antibiotics are available for treatment including quinolone antibiotics (ciprofloxacin, levofloxacin, ofloxacin) and tetracycline antibiotics (doxycycline). Penicillin antibiotics (amoxicillin, penicillin V, and penicillin G) are effective only for penicillin-susceptible strains. 

Treatment — Doxycycline and tetracycline antibiotics should be considered for treating this disease.3... 

Quinolene antibiotics ciprofloxacin, levofloxacin, ofloxacin Tetracycline antibiotics doxycycline Penicillin antibiotics amoxicillin, penicillin V, Penicillin G Vaccines are available six doses at 0, 2, and 4 weeks, then 6, 12, and 18 months, followed by annual boosters See Tierno 2002 or other medical references for details on administration of medications and/or vaccines... 

Ranibizumab is produced in E. coli expression system in a nutrient medium containing the tetracycline antibiotic. It has a molecular weight of 48 kDa. 

Zhou, J. K., Gerhardt, G. C., Baranski, A., and Cassidy, R. (1999). Capillary electrophoresis of some tetracycline antibiotics coupled with reductive fast cyclic yoltammetric detection. J. Chromatogr. A 839, 193-201. 

Wang P, He Y-L, Huang C-H (2011) Reactions of tetracycline antibiotics with chlorine dioxide and free chlorine. Water Res 45 1838-1846... 

Pena A, Paulo M, Silva LJG, Seifrtova M, Lino CM, Solich P (2010) Tetracycline antibiotics in hospital and municipal wastewaters a pilot study in Portugal. Anal Bioanal Chem 396 2929-2936... 

Doxycyline is a tetracycline antibiotic. All tetracylines are bacteriostatic, have a broad spectrum and are the treatment of choice for infections caused by Chlamydia and Rickettsia and in brucellosis. Doxycyline and minocyline are the only two tetracyclines that may be administered in renal impairment. 

Moats, W. A. 198. Determination of Tetracycline Antibiotics in Tissues and Blood Serum of Cattle and Swine by High Performance Liquid Chromatography. J. Chromatog. (In Press)... 

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