Tetracyclines action

Resistance to tetracyclines is often caused by the acquisition of genes (e.g. tetO and tetM) coding for so-called ribosome protection proteins. These proteins bind to the ribosome and protect them from tetracycline action. 

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). 

Under acidic conditions, dehydration to an anhydrotetracycline [20154-34-1] (8), C22H22N20y, occurs under basic ones, ring C opens to an isotetracycline [3811-31-2] (9), C22H24N20g. The anhydrotetracyclines, such as (8), appear to exhibit a mode of antibacterial action, but it is unlike that of tetracycline (24). Epimerization (23,25,26) at C-4 occurs in a variety of solvents within the pH range 2—6, particularly in acetic acid (25). A number of anions (27) facihtate this reaction. The reverse process, from 4-epitetracycline [79-85-6] C22H24N20g, to tetracycline, is promoted by chelation with ions such as calcium and magnesium (28). 

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). 

Brodersen DE, Clemons WM, Carter AP et al (2000) The structural basis for the action of the antibiotics tetracycline, pactamycin and hygromycin B on the 30S ribosomal subunit. Cell 103 1143-1154... 

Discuss the uses, general drug action, adverse reactions, contraindications, precautions, and interactions of the tetracyclines, macrolides, and... 

The tetracyclines exert their effect by inhibiting bacterial protein syndiesis, which is a process necessary for reproduction of die microorganism. The ultimate effect of diis action is tiiat the bacteria are either destroyed or dieir multiplication rate is slowed. The tetracyclines are bacteriostatic (capable of slowing or retarding die multiplication of bacteria), whereas die macrolides and lincosamides may be bacteriostatic or bactericidal (capable of destroying bacteria). 

Bacterial ribosome function Aminoglycosides Tetracyclines Chloramphenicol Macrolides, azalides Fusidic acid Mupirocin Distort SOS ribosomal subunit Block SOS ribosomal subunit Inhibits peptidyl transferase Block translocation Inhibits elongation factor Inhibits isoleucyl-tRNA synthesis No action on 40S subunit Excluded by mammalian cells No action on mammalian equivalent No action on mammalian equivalent Excluded by mammalian cells No action on mammalian equivalent... 

Plasmid- or transposon-encoded tetracycline efflux proteins have been described in a number of bacteria. These efflux profeins are fhoughf to span fhe cytoplasmic membrane and are dependenf on the proton-motive force for their action, ft is thought that the efflux proteins bind tetracyclines and initiate proton transfer, although no functional domains have been identified. Eight distinct tetracycline efflux profeins have been idenfified thus far. 

The broad antibacterial activity of rifaximin as well as its topical action make this antibiotic suitable for intrapocket administration in periodontal disease. As a matter of fact, local application of rifaximin compares well with tetracyclines and metronidazole in other extra-GI diseases, i.e. skin infections and BY, respectively (see above). On the other hand, rifampicin (rifampin), another rifamy-cin derivative, has been successfully used in the treatment... 

In 1971, Great Britain implemented a ban on subtherapeutic use of tetracyclines in animal production. This action was taken after considerable debate and was greatly influenced by antibiotic resistant Sa Imone 1 la infections (S. typhimurium phage type 29) in humans in the mid-1960 s, which appeared to be related to similar infections in calves (Anderson, 23 Antibiotics were not approved as feed additives for calves at that time nor previously. Thus, earlier implementation of the Swann Committee (Ifi) recommendations would have had no apparent impact on that particular epidemic, nor did it prevent a similar epidemic later (Rowe et al., 12J. 

Also, there are effective alternatives to antibiotics, such as vaccines, to prevent diseases. NRDC also advocated changing certain farm management practices, such as reducing the crowding of animals In feedlots, which should reduce stress and transmission of diseases. Both of those actions It was said should reduce the need for disease prevention. NRDC pointed out that It Is not advocating a ban of penclllln and the tetracyclines used at therapeutic levels to treat diseases. 

The conventional bioassays based on methodology developed by FDA and expanded by FSIS use four extractant buffers, five test organisms, five growth media, two incubation temperatures, and penicillinase to detect, identify, and/or quantify antibiotics such as the penicillins, streptomycins, tetracyclines, neomycins, erythromycin, tylosin, etc. Bioassay laboratory results are used by FSIS to take regulatory action and by FDA to prosecute farmers with histories of improperly withdrawing antibiotics before marketing their herds or flocks. 

Drug/Lab test interactions The antianabolic action of tetracyclines may cause an increase in blood urea nitrogen. During doxycycline or minocycline therapy, false elevations of urinary catecholamine levels may occur... 

Tetracyciine ciass antibiotics Glycylcycline class antibiotics are structurally similar to tetracycline class antibiotics and may have similar adverse effects. Such effects may include photosensitivity, pseudotumor cerebri, pancreatitis, and antianabolic action (which has led to increased serum urea nitrogen [BUN], azotemia, acidosis, and hypophosphatemia). 

Alginic Acid + Aluminum Hydroxide Magnesium Tnsilicate (Gaviscon) [Antacid] [OTC] Uses Heartburn hiatal hernia pain Action Protective layer blocks gastric acid Dose 2—4- tabs or 15-30 mL PO qid followed by H2O Caution [B, -] Avoid in renal impair or Na -restricted diet Disp Tabs, susp SE D, constipation Interactions T Absorption OF tetracyclines EMS None OD May cause constipation, loss of appetite, muscle weakness, and peripheral edema symptomatic and supportive... 

Atovaquone (Mepron) [Antiprotozoal] Uses Rx prevention PCP Action 4- nucleic acid ATP synth Dose Rx 750 mg PO bid for 21 d Prevention 1500 mg PO once/d (w/ meals) Caution [C, ] Disp Susp SE FevCT, HA, anxiety, insomnia, rash, N/V Interactions X Effects W/ metoclopramide, rifabutin, rifampin, tetracycline EMS None OD Sxs unknown but may cause a rash symptomatic and supportive... 

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