Tetracyclines - Antimicrobics That Act on Cell Wall Synthesis

Tetracyclines

Tetracyclines are composed of four fused benzene rings. Substitutions on these rings pro-vide differences in pharmacologic features of the major members of the group, tetracy-cline, minocycline, and doxycycline. The tetracyclines inhibit protein synthesis by bindingto the 30S ribosomal subunit at a point that blocks attachment of aminoacyl-tRNA to the acceptor site on the mRNA ribosome complex. Unlike the aminoglycosides, their effect is reversible; they are bacteriostatic rather than bactericidal.

The tetracyclines are broad-spectrum agents with a range of activity that encompasses most common pathogenic species, including Gram-positive and Gram-negative rods and cocci and both aerobes and anaerobes. They are active against cell wall – deficient organ-isms, such as Mycoplasma and spheroplasts, and against some obligate intracellular bacteria, including members of the genera Rickettsia and Chlamydia. Differences in spec-trum of activity between members of the group are relatively minor. Acquired resistance to one generally confers resistance to all.

The tetracyclines are absorbed orally. In practice, they are divided into those agents that generate blood levels for only a few hours and those that are longer-acting (minocy-cline and doxycycline), which can be administered less often. The tetracyclines are chelated by divalent cations, and their absorption and activity are reduced. Thus, they should not be taken with dairy products or many antacid preparations. Tetracyclines are excreted in the bile and urine in active form.

The tetracyclines have a strong affinity for developing bone and teeth, to which they give a yellowish color, and they are avoided in children up to 8 years of age. Common complications of tetracycline therapy are gastrointestinal disturbance due to alteration of the normal flora, predisposing to superinfection with tetracycline-resistant organisms and vaginal or oral candidiasis (thrush) due to the opportunistic yeast Candidaalbicans.