Antibacterial drug macrolides

Antibacterial drugs that affect bacterial protein synthesis include the aminoglycosides, tetracyclines, macrolides, and the single drug chloramphenicol. 

Periti P, Mazzei T, Mini E, Novelli A. Adverse effects of macrolide antibacterials. Drug Saf 1993 9(5) 346-64. 

Su, W. G. (1999). Novel macrolide C-4" carbamate derivative Chemistry and structure activity relationship. Presented at 3rd International Antibacterial Drug Discovery Development (March 8-9, Princeton). 

Von Rosenstiel, N. A., and Adam, D. (1995). Macrolide antibacterials Drug interactions of clinical significance. Drug Safety 13, 105-122. 

This section deals with interactions where the effects of the antibacterial are altered. In many cases the antibacterial drugs interact by affecting other drugs, and these interactions are dealt with elsewhere in this publication. Some of the macrolides and the quinolones are potent enzyme inhibitors the macrolides exert their effects on the cytochrome P450 isoenzyme CYP3A4, whereas many quinolones inhibit CYP1A2. Ri-fampicin (rifampin) is a potent non-specific enzyme inducer and therefore lowers the levels of many drugs. 

Several studies support the notion that the basic mechanism by which many drugs prolong the QT interval is related to blockade of potassium currents. For instance, several antihistamines, antibacterial macrolides, fluoroquinolones and antipsychotics were shown to inhibit the rapid component of the delayed rectifier K+ current (fKr) in electrophysiological studies and to block potassium channels encoded by hERG [37-42]. 

Tegretol consists of carbamazepine, which is an anti-epileptic drug. There is a clinically significant drug interaction between carbamazepine and clarithromycin (macrolide antibacterial agent) resulting in higher plasma concentrations of carbamazepine. 

The quinolone antibiotics feature as the one main gronp of antibacterial agents that is totally synthetic, and not derived from or based upon natural products, as are penicillins, cephalosporins, macrolides, tetracyclines, and aminoglycosides. The first of these compounds to be employed clinically was nalidixic acid more recent drugs in current use include ciprofloxacin, norfloxacin, and ofloxacin... 

The macrolide antibacterials (including erythromycin, clarithromycin and telithromycin) are often implicated in interactions, most frequently as a result of inhibition of the CYP3A4 enzyme system in the liver and enterocytes. Erythromycin inhibits the metabolism of carbamazepine, ciclosporin and theophylline significant increases in serum levels and features of toxicity have been documented. Careful clinical and pharmacokinetic monitoring are required in a patient taking any of these drugs who requires concomitant erythromycin. 

The arsenal of antibacterials available for the treatment of infectious diseases has expanded exponentially since then. Currently, as illustrated in Fig. 1, the repertoire includes the (J-lactams (e.g. 3) sulfa drugs (e.g. 4) macrolides (e.g. 5, erythromycin A), nitrofuran drugs (e.g. 6, furazolidone), and many aminoglycosides. 

Erythromycin and the other macrolides exhibit a very broad spectrum of antibacterial activities and are active against many gram-positive bacteria, as well as some gram-negative bacteria. These agents are often used as the primary or alternative drug in a variety of clinical conditions (see Table 33-5). Macrolides may be especially useful in patients who are allergic to penicillin. 

Reboxetine Reboxetine should not be given, even after termination of MAOI therapy. Care must be exercised when treating with antihypertensive drugs, antiar-rhythmics, cyclosporin, antipsychotics, tricyclics, fluvoxamine, antidepressants, azole antifungals, and macrolide antibacterials. 

An interesting exception to the absolute validity of the tifth postulate is the considerable activity of chloramphenicol derivatives in cell-free model systems of protein synthesis when these derivatives are substituted with amino acyl residues instead of with dichloroacetyl as is the antibiotic itself (rev. in 2°)). This has been traced to the necessity of the dichloroacetyl grouping in aiding in the permeation of the antibiotic through the bacterial envelope 21 The amino acyl derivatives have very low antibacterial activity 20. Permeation failures of actinomycin D, macrolides and distamycin A with respect to certain families of bacteria occlude the action of these antibiotics on their intracellular drug receptors and target reactions but can be overcome experimentally by measures which render test organisms permeable. 

Macrolide antibiotics are a homogeneous group of antimicrobial drugs that have been used to treat clinical infections for several decades. The most clinically useful classification of the macrolides is based on the size of the lactone ring that forms the chemical nucleus of each macrolide molecule [1, 2]. The 14- and 15-membered macrolides include erythromycin, clarithromycin, dirithromycin, roxithromycin, and azithromycin. Erythromycin is the oldest and still the most important of the macrolide antibiotics because it is a useful alternative to penicillin G. It is one of the safest antibiotics available. Clarithromycin and azithromycin have shown some advantages over erythromycin in their antibacterial activity,... 

The antibacterial spectrum of these macrolides is broader. For example, the clinical modification at C6 [e.g., O-methylation (clarithromycin)] or at C9 [e.g., some 9-ether oxime derivatives (roxithromycin and dirithromycin)] stabilizes 14-membered lactone rings in acidic media, even when the modified drugs have been orally administered. Drugs with an expanded erythromycin A-lactone ring (e.g., azithromycin) are also more stable in acidic media and display better antigram-negative activity than does erythromycin A. 

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