Tetracycline, sold under the brand name Sumycin among others, is an oral antibiotic in the tetracyclines family of medications, used to treat a number of infections, including acne, cholera, brucellosis, plague, malaria, and syphilis.
Common side effects include vomiting, diarrhea, rash, and loss of appetite.
Other side effects include poor tooth development if used by children less than eight years of age, kidney problems, and sunburning easily.
Use during pregnancy may harm the baby.
It works by inhibiting protein synthesis in bacteria.
Tetracycline was patented in 1953 and came into commercial use in 1978.
It is on the World Health Organization's List of Essential Medicines.
Tetracycline is available as a generic medication.
Tetracycline was originally made from bacteria of the Streptomyces type.
Medical uses
Spectrum of activity
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.
Tetracycline tablets were used in the plague outbreak in India in 1994.Lippincott's Illustrated Reviews: Pharmacology, 4th ed. Harvery RA, Champe, PC.
Lippincott, Williams & Wilkins, 2009  Tetracycline is first-line therapy for Rocky Mountain spotted fever (Rickettsia), Lyme disease (B. burgdorferi), Q fever (Coxiella), psittacosis, Mycoplasma pneumoniae, and nasal carriage of meningococci.
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 distrupting 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.
The following list presents MIC susceptibility data for some medically significant microorganisms:
Escherichia coli: 1 / to >128 μg/mL
Shigella : 1 μg/mL to 128 μg/mLhttp://www.toku-e.com/Assets/MIC/Tetracycline%20hydrochloride.pdf
Anti-eukaryote use
The tetracyclines also have activity against certain eukaryotic parasites, including those responsible for diseases such as dysentery caused by an amoeba, malaria (a plasmodium), and balantidiasis (a ciliate).
Use as a biomarker
thumb|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.Mayton CA.
Tetracycline labeling of bone  In "double tetracycline labeling", a second dose is given 11–14 days after the first dose, and the amount of bone formed during that interval can be calculated by measuring the distance between the two fluorescent labels.The Johns Hopkins Medical Institutions.
> Tetracycline Labeling  Last updated January 8, 2001.
Tetracycline is also used as a biomarker in wildlife to detect consumption of medicine- or vaccine-containing baits.
Side effects
Use of tetracycline antibiotics can:
Discolor permanent teeth (yellow-gray-brown), from prenatal period through childhood and adulthood.
Children receiving long- or short-term therapy with a tetracycline or glycylcycline may develop permanent brown discoloration of the teeth.
Be inactivated by calcium ions, so are not to be taken with milk, yogurt, and other dairy products
Be inactivated by aluminium, iron, and zinc ions, not to be taken at the same time as indigestion remedies (some 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
Cause tinnitus
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.Riordan, Jan."Breastfeeding & Human Lactation", Jones & Bartlett,2010 p.179 According to the U.S. Food and Drug Administration (FDA),  cases of Stevens–Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme associated with doxycycline use have been reported, but a causative role has not been established.FDA Adverse Events Reporting System  Retrieved on January 14, 2011 Pharmacology
Mechanism of action
Tetracycline inhibits protein synthesis by blocking the attachment of charged aminoacyl-tRNA at the P site peptide chain.
Tetracycline blocks the P-site so that a hydrogen bond is not formed between the amino acids.
Tetracycline binds to the 30S and 50S subunit of microbial ribosomes.
Thus, it prevents the formation of a peptide chain.
The action is usually not inhibitory and irreversible even with the withdrawal of the drug.
Mammalian cells are less vulnerable to the effect of tetracyclines, despite the fact that tetracycline binds to the small ribosomal subunit of both prokaryotes and eukaryotes (30S and 40S, respectively).
This is because bacteria actively pump tetracycline in, even against a concentration gradient, whereas mammalian cells are simply not affected by the mechanisms of tetracycline within the cytoplasm.
This accounts for the relatively small off-site effect of tetracycline on human cells.Kenneth Todar, Antimicrobial Agents in the Treatment of Infectious Disease.
Online Textbook of Bacteriology.
2012.
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.
Ribosomal protection proteins interact with the ribosome and dislodge tetracycline from the ribosome, allowing for translation to continue.
History
The tetracyclines, a large family of antibiotics, were discovered by Benjamin Minge Duggar in 1948 as natural products,  and first prescribed in 1948.Klajn, Rafal, Chemistry and chemical biology of tetracyclines , retrieved 20 June 2007.
Benjamin Duggar, working under Yellapragada Subbarow at Lederle Laboratories, discovered the first tetracycline antibiotic, chlortetracycline (Aureomycin),  in 1945.
In 1950, Harvard University professor R.B. Woodward, in collaboration with a group at Pfizer led by Francis A. Hochstein, determined the chemical structure of the related substance, oxytetracycline (Terramycin); the patent protection for its fermentation and production was also first issued in that year.
Pfizer was of the view that it deserved the right to a patent on tetracycline and filed its application in October 1952.
Cyanamid filed its own patent application for similar rights in March 1953, while Heyden Chemicals filed an application in September 1953, 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
Price
According to data from EvaluatePharma and published in the Boston Globe, in the USA the price of tetracycline rose from $0.06 per 250-mg pill in 2013 to $4.06 a pill in 2015.
The Globe described the "big price hikes of some generic drugs" as a "relatively new phenomenon" which has left most pharmacists "grappling" with large upswings" in the "costs of generics, with 'overnight' price changes sometimes exceeding 1,000%."
Names
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.
Media
Due to the drug's association with fighting infections, it serves as the main "commodity" in the science fiction series Aftermath, with the search for tetracycline becoming a major preoccupation in later episodes.
Research
Genetic engineering
In genetic engineering, tetracycline is used in transcriptional activation.
It 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 (the infection vector for yellow fever, dengue fever, Zika fever, and several other diseases) 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.
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