Tetracyclines are broad-spectrum antibiotics with a tetracyclic structure (made up of four rings with 6 terms each), which also gives the name of the whole class. When we talk about tetracycline we mean chlorotetracycline, which was the first tetracycline discovered in 1945 by Benjamin Duggar. Duggar discovered chlorotetracycline at Lederle Laboratories while working under the supervision of Indian scientist Yellapragada Subbarao.
In 1950, Professor Robert Woodward of Harvard University, collaborating with a team of researchers from the Pfizer pharmaceutical company (KJ Brunings, Peter P. Regna, Francis A. Hochstein, Abraham Bavley, CR Stephens, LH Conover and Richard Pasternack), isolated the molecule from the Streptomyces rimosus strain and determined the chemical structure of oxiteracyclin (commercial name Terramycin ®), for which it also obtained the patent on the production process. The research process that led to this discovery lasted more than two years.
Tetracyclines are antibiotics with a broad spectrum of action indicated for the treatment of many bacterial infections. Nowadays tetracyclines are used in the treatment of acne, in the triple therapy for the eradication of Helicobacter pylori, and in the treatment of rosacea; historically speaking, we can say that tetracyclines have been a very useful tool for the reduction of cholera deaths. Tetracyclines have been widely used both for the treatment of infectious diseases and as an additive to animal feed, with the aim of promoting their growth (the addition of antibiotics in the feed in order to exterminate the endogenous bacterial flora of the animals and increase them weight, can have serious consequences on consumers and is a strictly prohibited practice). This wide use has led to the appearance of bacterial strains resistant to tetracyclines, thus leading to a drastic reduction in their use in therapy.
Tetracyclines are considered the antibiotic of choice in rickettsial, mycoplasmas and chlamydial infections. In fact, tetracyclines are particularly effective in rickettsial infections including Rocky Mountain fever, recurrent epidemic typhus (Brill's disease) and vesicular rickettiosis. Tetracyclines are also widely used for the treatment of sexually transmitted diseases (STDs), because it appears that different forms of Chlamydia are sensitive to this class of drugs. Tetracyclines have also been shown to be effective in treating acute and chronic infections with Brucella melitensis, B. suis and B. abortus. The association of a tetracycline, for example doxycycline, with another antibiotic, for example an aminoglycoside antibiotic such as streptomycin, has given very convincing results in cases of acute brucellosis.
Tetracyclines inhibit bacterial protein synthesis by binding to their 30 S ribosomal subunit, thus preventing access of tRNA and mRNA to the ribosome; consequently, one does not have the correct reading of the DNA chain that encodes proteins, and all this leads to a halt of the bacterium's protein synthesis, followed later by its death.
The discovery of tetracyclines was a very important event because, in addition to allowing the treatment of many diseases, it opened new horizons for the discovery and synthesis of other antibiotics.
Posology and method of use
The recommended dose of tetracycline for acne treatment in adults is 1000 mg / day, divided into two daily administrations for a period of two weeks, which can vary depending on the severity and nature of the infection.
In the triple therapy for the eradication of Helicobacter pylori, the recommended dose of tetracycline is 2000 mg / day, divided into 4 daily administrations, one every six hours. The expected duration of the treatment is 14 days.
The recommended dose of tetracycline in the treatment of bronchitis is 2000 mg / day, divided into 4 daily administrations, one every six hours. The duration of treatment varies from 7 to 10 days and depends on the severity of the infection. In certain cases, especially in patients predisposed to bronchitis, it is used to administer tetracycline for 4 or 5 days in the winter months, to prevent the onset of chronic bronchitis.
In the treatment of brucellosis it is recommended to use the following therapeutic scheme: 2000 mg / day of tetracycline, to be divided into 4 daily administrations, one every six hours, for a period of three weeks, and 2000 mg / day of streptomycin intramuscularly, divided into two daily administrations throughout the first week of treatment, and then 1000 mg / day, in a single daily administration, intramuscularly, during the second week of treatment.
For the treatment of uncomplicated urethral infections, endocervical and rectal infections, the use of 2000 mg / day of tetracycline is recommended, divided into 4 daily administrations, one every six hours. The expected duration of treatment is at least a week. In the case of chlamydial infections it is advisable to also check and possibly treat the patient's sexual partner.
The recommended dose of tetracycline in the treatment of arthritis and carditis, caused by Lyme disease, is 2000 mg / day, to be divided into 4 daily administrations, one every six hours. The expected duration of treatment can vary from 2 weeks to 1 month, depending on the severity and nature of the infection. For the treatment of chronic migrant erythema, however, also caused by Lyme disease, it is recommended to use the same dose described above for a slightly different period, ranging from 10 to 30 days.
In the treatment of pneumonia the recommended dose of tetracycline is 2000 mg / day, to be divided into 4 daily administrations, one every 6 hours. The expected duration of treatment varies from 10 to 21 days, depending on the severity of the infection.
For the treatment of rickettsial infections the recommended dose of tetracycline is the one indicated above, and the recommended treatment duration is one week.
The recommended dose of tetracycline in the treatment of recent syphilis is 2000 mg / day, to be divided into 4 daily administrations, one every six hours for a period of two weeks; the same dose of tetracycline is recommended for the treatment of tertiary syphilis and late syphilis, except that the expected treatment time rises to 4 weeks; or, alternatively, a therapeutic plan can be devised that includes the intake of 30-40 grams of tetracycline for a period that can vary from 10 to 15 days, obviously calculating in advance doses and number of daily administrations. However, the use of tetracyclines is recommended only if the patient cannot use penicillins.
For the treatment of cystitis, however, the recommended dose of tetracycline remains the same as described above, ie 2000 mg / day, to be divided into 4 daily administrations, one every six hours; the expected duration of treatment varies from 3 to 7 days, depending on the severity of the infection. However, treatment of cystitis with tetracycline should only be done if there are no other therapeutic alternatives.
Contraindications and warnings for use
All tetracyclines have the tetracyclic structure in common and all are of an amphoteric character. Tetracyclines are compounds designed to give crystalline salts with both acids and strong bases (this is due precisely to their amphoteric character); tetracyclines have a complicated chromophore system that gives rise to absorption spectra characteristic of this class of antibiotics, which extend to the visible giving it the characteristic yellow color. All tetracyclines are able to chelate metal ions giving rise to chelates, which are insoluble in water and seem to have an appreciable role in the mechanism of action of these antibiotics. Due to their amphoteric character, tetracyclines are poorly soluble in water, while their hydrochlorates show a remarkable solubility in water.
Another important characteristic of tetracyclines is that of turning brown in the light and of deteriorating in the presence of humidity and in an acid environment to form anhydroders, which are lacking in antibiotic power and more toxic than the starting antibiotics, this is probably due to the ability to interact in a non-specific with cell membranes.
Tetracyclines: contraindications and side effects »
