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Tetracycline, sold under the brand name Sumycin among others, is an antibiotic used to treat a number of infections.
Common side effects include vomiting, diarrhea, rash, and loss of appetite.
Tetracycline was patented in 1953 and came into commercial use in 1978.
1 Medical uses
1.1 Spectrum of bacterial susceptibility
1.2 Mechanisms of resistance
2.1 Other uses
3 Mechanism of action
4.1 Evidence in antiquity
5 Society and culture
It is first-line therapy for Rocky Mountain spotted fever ( Rickettsia ), Lyme disease ( B. burgdorferi ), Q fever ( Coxiella ), psittacosis, and Mycoplasma pneumoniae and to eradicate nasal carriage of meningococci. Tetracycline tablets were used in the plague outbreak in India in 1994.
Spectrum of bacterial susceptibility
Tetracyclines have a broad spectrum of antibiotic action. Originally, they possessed some level of bacteriostatic activity against almost all medically relevant aerobic and anaerobic bacterial genera, both Gram-positive and Gram-negative, with a few exceptions, such as Pseudomonas aeruginosa and Proteus spp., which display intrinsic resistance. However, acquired (as opposed to inherent) resistance has proliferated in many pathogenic organisms and greatly eroded the formerly vast versatility of this group of antibiotics. Resistance amongst Staphylococcus spp., Streptococcus spp., Neisseria gonorrhoeae, anaerobes, members of the Enterobacteriaceae, and several other previously sensitive organisms is now quite common. Tetracyclines remain especially useful in the management of infections by certain obligately intracellular bacterial pathogens such as Chlamydia, Mycoplasma, and Rickettsia. They are also of value in spirochaetal infections, such as syphilis, leptospirosis, and Lyme disease. Certain rare or exotic infections, including anthrax, plague and brucellosis, are also susceptible to tetracyclines. These agents also have activity against certain eukaryotic parasites, including those responsible for diseases such as malaria and balantidiasis. The following represents MIC susceptibility data for a few medically significant microorganisms:
Escherichia coli : 1 μg/mL – >128 μg/mL
Shigella spp.: 1 μg/mL – 128 μg/mL
Mechanisms of resistance
Bacteria usually acquire resistance to tetracycline from horizontal transfer of a gene that either encodes an efflux pump or a ribosomal protection protein. Efflux pumps actively eject tetracycline from the cell, preventing the buildup of an inhibitory concentration of tetracycline in the cytoplasm.
See also: Tooth bleaching
Use of the tetracycline antibiotics group is problematic; they can:
Discolor permanent teeth (yellow-gray-brown), from prenatal period through childhood and adulthood
Be inactivated by Ca 2+ ions, so are not to be taken with milk, yogurt, and other dairy products
Be inactivated by aluminium, iron, and zinc, not to be taken at the same time as indigestion remedies (common antacids and over-the-counter heartburn medicines)
Cause skin photosensitivity, so exposure to the sun or intense light is not recommended
Cause drug-induced lupus, and hepatitis
Cause microvesicular fatty liver
Interfere with methotrexate by displacing it from the various protein-binding sites
Cause breathing complications, as well as anaphylactic shock, in some individuals
Affect bone growth of the fetus, so should be avoided during pregnancy
Fanconi syndrome may result from ingesting expired tetracyclines.
Caution should be exercised in long-term use when breastfeeding. Short-term use is safe; bioavailability in milk is low to nil.
Tetracycline hydrochloride is available as yellow crystalline powder.
Since tetracycline is absorbed into bone, it is used as a marker of bone growth for biopsies in humans. Tetracycline labeling is used to determine the amount of bone growth within a certain period of time, usually a period around 21 days. Tetracycline is incorporated into mineralizing bone and can be detected by its fluorescence.
Tetracycline is also used as a biomarker in wildlife to detect consumption of medicine- or vaccine -containing baits.
In genetic engineering, tetracycline is used in transcriptional activation.
It is also one of a group of antibiotics which together may be used to treat peptic ulcers caused by bacterial infections. The mechanism of action for the antibacterial effect of tetracyclines relies on disrupting protein translation in bacteria, thereby damaging the ability of microbes to grow and repair; however, protein translation is also disrupted in eukaryotic mitochondria leading to effects that may confound experimental results.
Tetracycline has been used as an engineered “control switch” in chronic myelogenous leukemia models in mice. Engineers were able to develop a retrovirus that induced a particular type of leukemia in mice, and could then “switch” the cancer on and off through tetracycline administration. This could be used to grow the cancer in mice and then halt it at a particular stage to allow for further experimentation or study.
A technique being developed for the control of the mosquito species Aedes aegypti uses a strain that is genetically modified to require tetracycline to develop beyond the larval stage. Modified males raised in a laboratory develop normally as they are supplied with this chemical and can be released into the wild. Their subsequent offspring inherit this trait, but find no tetracycline in their environments, so never develop into adults.
Mechanism of action
Tetracycline inhibits protein synthesis by blocking the attachment of charged aminoacyl-tRNA to the A site on the ribosome. Tetracycline binds to the 30S subunit of microbial ribosomes. Thus, it prevents introduction of new amino acids to the nascent peptide chain.
The tetracyclines, a large family of antibiotics, were discovered as natural products by Benjamin Minge Duggar in 1945 and first prescribed in 1948.
In 1950, Harvard University professor R.B. Woodward determined the chemical structure of the related substance, oxytetracycline (Terramycin);
Pfizer was of the view that it deserved the right to a patent on tetracycline and filed its Conover application in October 1952. Cyanamid filed its Boothe-Morton application for similar rights in March 1953, while Heyden Chemicals filed its Minieri application in September 1953, named after scientist P. Paul Minieri, to obtain a patent on tetracycline and its fermentation process.
Evidence in antiquity
Nubian mummies studied in the 1990s were found to contain significant levels of tetracycline; the beer brewed at the time was conjectured to have been the source.
Society and culture
According to data from EvaluatePharma and published in the Boston Globe, the price of tetracycline rose from $0.06 per 250- mg pill in 2013 to $4.06 a pill in 2015.
It is marketed under the brand names Sumycin, Tetracyn, and Panmycin, among others. Actisite is a thread-like fiber formulation used in dental applications.
It is also used to produce several semisynthetic derivatives, which together are known as the tetracycline antibiotics. The term “tetracycline” is also used to denote the four-ring system of this compound; “tetracyclines” are related substances that contain the same four-ring system.
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