Tetracycline
Actisite ®, Sumycin ®, Topicycline® | Brodspec | Emtet | Panmycin | Tetra 250 | Tetracon
Classification:
Antiinfective Agents
Ophthalmic Agents
- Ophthalmic Antiinfectives
Oropharyngeal Agents
- Dental and Peridontal Agents
Description: Tetracycline is semisynthetically produced from chlortetracycline, which is derived from Streptomyces aureofaciens. It is classified as a short-acting tetracycline, although this classification scheme is somewhat artificial since tetracycline can be dosed at longer intervals than usually occurs in clinical practice. It has a wide spectrum of activity against many gram-negative and gram-positive organisms, but is inactive against viruses and fungi. The most common uses of tetracycline are to treat Chlamydia, Mycoplasma pneumoniae, and rickettsial infections. Tetracycline is also effective in combination with bismuth subsalicylate, metronidazole, and appropriate acid-suppressive therapy to treat H. pylori-associated peptic ulcer disease. Tetracycline is available in oral and topical preparations, including an ophthalmic ointment. The drug first received FDA approval in 1953. Tetracycline periodontal fibers were approved March 1994 for adjunct treatment of periodontitis. Helidac® (which contains BSS, metronidazole, and tetracycline) was approved by the FDA in August 1996 for use in conjunction with acid suppression therapy to eradicate H. pylori infection associated with duodenal ulcer disease.
Mechanism of Action: Tetracycline is generally bacteriostatic against most organisms, but high concentrations of tetracyclines can be bactericidal. Bacteriostatic action appears to be a result of reversible binding to ribosomal units of susceptible organisms and inhibition of protein synthesis. Tetracyclines gain access to the ribosome after passive diffusion through porin channels in the bacterial membrane. An active transport process also exists in bacterial cells. Tetracyclines bind to the 30 S ribosomal subunit, which prevents binding of tRNA to the mRNA-ribosome complex, thus interfering with protein synthesis. Only multiplying organisms are affected. In general, gram-positive bacteria are more susceptible than are gram-negative bacteria.
Tetracyclines are effective against many gram-positive and gram-negative organisms, although they should not be routinely used for gram-positive bacteria because many of these organisms exhibit resistance. Streptococcus pyogenes, S. pneumoniae, and alpha-hemolytic streptococci are usually sensitive, but the enterococcus group (Streptococcus faecalis and S. faecium) is universally resistant. Gram-negative coverage includes Haemophilus influenzae, H. ducreyi, Vibrio cholera, Bartonella bacilliformis, Yersinia pestis, and Brucella species. Other infectious organisms that are susceptible to tetracyclines are Rickettsiae, Chlamydia species, Mycoplasma pneumoniae, Bacillus anthracis, Propionbacterium acnes, Borrelia recurrentis, Treponema pallidum (syphilis), and Actinomyces species. Tetracycline has demonstrated in vitro activity against most susceptible strains of Helicobacter pylori; and development of resistance to tetracycline has not been documented for H. pylori.
Despite their relatively broad spectrum, tetracyclines have limited use. Clinical applications for tetracycline include treatment of infections due to rickettsia, Mycoplasma pneumonia, and chlamydia. Tetracycline is also used to treat Lyme disease, brucellosis, and syphilis in patients who cannot take penicillin. It also is effective for treating nongonococcal urethritis, although doxycycline is more commonly used, and for treating exacerbations of chronic bronchitis, although amoxicillin, co-trimoxazole, and oral cephalosporins are more commonly used.
Tetracycline is used in combination with multiple drug therapy for the treatment of patients with H. pylori gastrointestinal infection and associated peptic ulcer disease. Tetracycline demonstrates in vitro activity against most susceptible strains of Helicobacter pylori; development of resistance is rare.
The action of tetracycline in the treatment of acne vulgaris has not been fully established but is believed to be due in part to its antibacterial actions. Skin bacteria produce lipase that breaks down triglycerides present in sebum into free fatty acids, which are comedogenic and may be the cause of the inflammatory lesions of acne. Reduction in the number of lipase-producing bacteria or inhibition of lipase production are two possible mechanisms of tetracyclines. Several other mechanisms have been proposed but not studied.
Injectable tetracycline, until its availability was recently discontinued, was also used for pleurodesis. Injectable doxycycline has also been used for this procedure, although data are limited.
Pharmacokinetics: Tetracycline is administered orally. It is no longer available for parenteral administration. Tetracycline oral absorption is about 75-77% in the fasting state. Absorption takes place mainly in the stomach and upper intestine. As the dosage is increased, the percentage absorbed decreases. Divalent and trivalent cations that are present in antacids and dairy products reduce absorption through chelation.
Tetracycline is widely distributed into body fluids, including CSF. All tetracyclines tend to concentrate in bone, liver, tumors, spleen, and teeth. They cross the placenta and are distributed into breast milk. Tetracycline is about 65% bound to plasma protein and does not appear to undergo hepatic metabolism. It does undergo enterohepatic circulation and is excreted in the feces by way of the bile. Some fecal excretion is due to incomplete gastrointestinal absorption and occurs even from parenteral administration because of enterohepatic circulation. The primary excretion route is renal (about 60%). The serum half-life of tetracycline hydrochloride is between 6 and 12 hours in adults with normal renal function but is greatly increased in patients with severely impaired renal function.
Tetracycline periodontal fibers are inserted into periodontal pockets. The fiber releases tetracycline in vitro at a rate of approximately 2 mcg/cm/hour. Tetracycline is released this continuous rate for 10 days at concentrations far exceeding inhibitory concentrations for most periodontal organisms. Serum concentrations remain below the lower limit of assay detection (< 0.1 mcg/ml) during treatment of 11 teeth (average tetracycline dose of 105 mg).
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