Tetracycline

This article deals with the specific antibiotic called tetracycline. For the group of antibiotics known as the tetracyclines, see tetracycline antibiotics.

Tetracycline

File:Tetracycline structure.svg
Systematic (IUPAC) name
2-(amino-hydroxy-methylidene)-4-dimethylamino- 6,10,11,12a-tetrahydroxy-6-methyl-4,4a,5, 5a-tetrahydrotetracene-1,3,12-trione OR 4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro- 3,6,10,12,12a-pentahydroxy- 1,11-dioxo-naphthacene-2-carboxamide OR (4S,6S,12aS)-4-(dimethylamino)- 3,6,10,12,12a-pentahydroxy- 6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a- octahydrotetracene-2-carboxamide
Clinical data
Pregnancy category	AU: D US: D (Evidence of risk)
Routes of administration	oral, topical (skin & eye), im, iv
Legal status
Legal status	℞ (Prescription only)
Pharmacokinetic data
Bioavailability	60-80% Oral, while fasting <40% Intramuscular
Metabolism	Not metabolised
Biological half-life	6-11 hours
Excretion	Fecal and Renal
Identifiers
CAS Number	60-54-8 64-75-5 (hydrochloride)
ATC code	A01AB13 (WHO) D06AA04 J01AA07 S01AA09 S02AA08 S03AA02 QG01AA90 QG51AA02 QJ51AA07
PubChem	CID 643969
DrugBank	DB00759
ChemSpider	10257122
Chemical data
Formula	C22H24N2O8
Molar mass	444.435 g/mol[[]]
(verify)

Tetracycline (INN) (pronounced /ˌtɛtrəˈsaɪkliːn/) is a broad-spectrum polyketide antibiotic produced by the Streptomyces genus of Actinobacteria, indicated for use against many bacterial infections. It is a protein synthesis inhibitor. It is commonly used to treat acne today, and, more recently, rosacea, and played a historical role in reducing the incidence of mortality because of cholera. It is sold under the brand names Sumycin, Terramycin, Tetracyn, and Panmycin, among others. Actisite is a thread-like fiber form, used in dental applications. It is also used to produce several semi-synthetic derivatives, which together are known as the tetracycline antibiotics.

Mechanism of action

File:TetSystem.png

Tetracycline antiporter system

Tetracyclines work by binding the 30S ribosomal subunit, and, through an interaction with 16S rRNA, they prevent the docking of amino-acylated tRNA.

Resistance to tetracyclines can arise through drug efflux, ribosomal protection proteins, 16S rRNA mutation, and drug inactivation through the action of a monooxygenase.

History

The tetracyclines are a large family of antibiotics that were discovered as natural products by Benjamin Minge Duggar and first described in 1948. Under Yellapragada Subbarao, Benjamin Duggar made his discovery of the world's first tetracycline antibiotic, Aureomycin, in 1945.

In 1950, Harvard Professor Robert Woodward determined the chemical structure of Terramycin, the brand name for a member of the tetracycline family; the patent [1] protection for its fermentation and production was also first issued in 1950. A research team of seven scientists (Drs. K.J. Brunings, Francis A. Hochstein, C.R. Stephens, L.H. Conover, Abraham Bavley, Richard Pasternack, and Peter P. Regna) at Pfizer [2] [3], in collaboration with Woodward, participated in the two-year research leading to the discovery [4].

Nubian mummies have been studied in the 1990s and were found to contain significant levels of tetracycline; there is evidence that the beer brewed at the time could have been the source. Tetracycline sparked the development of many chemically altered antibiotics and in doing so has proved to be one of the most important discoveries made in the field of antibiotics. It is used to treat many gram-positive and gram-negative bacteria and some protozoa. It, like some other antibiotics, is also used in the treatment of acne.

Cautions, contraindications, side-effects

Are as those of the tetracycline antibiotics group:

• Can stain developing teeth (even when taken by the mother during pregnancy)
• Can cause permanent teeth discoloration (yellow-gray-brown); infancy and childhood to eight (8) years old
• Inactivated by Ca²⁺ ion, not to be taken with milk, yogurt, and other dairy products
• Inactivated by aluminium, iron and zinc, not to be taken at the same time as indigestion remedies
• Inactivated by common antacids and over-the-counter heartburn medicines.
• Skin photosensitivity; exposure to the Sun or intense light is not recommended
• Drug-induced lupus, and hepatitis
• Can induce microvesicular fatty liver.
• Tinnitus
• May interfere with methotrexate by displacing it from the various protein binding sites
• Can cause breathing complications as well as anaphylactic shock in some individuals
• Should be avoided during pregnancy as it may affect bone growth of fetus.
• Passes into breast milk and is harmful to breast-fed infants, and should therefore be avoided during breastfeeding if possible.

Indication

It is first-line therapy for Rocky Mountain spotted fever (Rickettsia), Q fever (Coxiella), Psittacosis and Lymphogranuloma venereum (Chlamydia), and to eradicate nasal carriage of meningococci. Tetracycline tablets were used in the plague outbreak in India in 1992.

Doxycycline is also one (of many) recommended drugs for chemoprophylatic treatment of malaria in travels to areas of the world where malaria is endemic.

Other uses

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 of approximately 21 days. Tetracycline is incorporated into mineralizing bone and can be detected by its fluorescence. 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.

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. Tetracycline is also one of the antibiotics used to treat ulcers caused by bacterial infections. In cancer research at Harvard Medical School, tetracycline has been used to reliably cause regression of advanced stages of leukemia in mice, by placing it in their drinking water.

Cell culture

Tetracycline is used in cell biology as selective agent in cell culture systems. It is toxic to prokaryotic and eukaryotic cells and selects for cells harboring the bacterial tet^r gene, which encodes a 399-amino acid membrane-associated protein. This protein actively exports tetracycline out of the cell, rendering cells harboring this gene more resistant to the drug. The yellow crystalline powder can be dissolved in water (20 mg/ml) or ethanol (5 mg/ml) and is routinely used at 10 mg/l in cell culture. In cell culture at 37 °C, it is stable for 4 days.

Notes

af:Tetrasiklien tr:Tetrasiklin