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| Trade names | Terramycin |
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| Routes of administration | By mouth,topical (eye drop) |
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| Pharmacokinetic data | |
| Eliminationhalf-life | 6–8 hours |
| Excretion | Kidney |
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| PDB ligand | |
| E number | E703(antibiotics) |
| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.001.103 |
| Chemical and physical data | |
| Formula | C22H24N2O9 |
| Molar mass | 460.439 g·mol−1 |
| 3D model (JSmol) | |
| Melting point | 181 to 182 °C (358 to 360 °F) |
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Oxytetracycline is abroad-spectrumtetracycline antibiotic, the second of the group to be discovered.
Oxytetracycline works by interfering with the ability of bacteria to produce essential proteins. Without these proteins, the bacteria cannot grow, multiply and increase in numbers. Oxytetracycline therefore stops the spread of the infection, and the remaining bacteria are killed by the immune system or eventually die.
Oxytetracycline is active against a wide variety of bacteria. However, some strains of bacteria have developed resistance to this antibiotic, which has reduced its effectiveness for treating some types of infections.
Oxytetracycline is used to treat infections caused byChlamydia, such aspsittacosis,trachoma, andurethritis, and infections caused byMycoplasma organisms, such aspneumonia.
Oxytetracycline is used to treatacne, due to its activity against the bacteria on the skin that influence the development of acne (Cutibacterium acnes). It is used to treat flare-ups ofchronic bronchitis, due to its activity againstHaemophilus influenzae. Oxytetracycline may be used to treat other rarer infections, such as those caused by a group of microorganisms calledrickettsiae (e.g.,Rocky Mountain spotted fever). To make sure the bacteria causing an infection are susceptible to it, a tissue sample is usually taken; for example, a swab from the infected area or a urine or blood sample.[citation needed]
Oxytetracycline was patented in 1949 and came into commercial use in 1950.[1] It is on theWorld Health Organization's List of Essential Medicines as an alternative totetracycline.[2]
Oxytetracycline, like othertetracyclines, is used to treat many infections, both common and rare. Its better absorption profile makes it preferable to tetracycline for moderately severeacne at a dosage of 250–500 mg four times a day for usually six to eight weeks at a time, but alternatives should be sought if no improvement occurs by three months.[3]
It is sometimes used to treatspirochaetal infections,clostridial wound infection, andanthrax in patients sensitive topenicillin. Oxytetracycline is used to treat infections of the respiratory and urinary tracts, skin, ear, eye andgonorrhoea, although its use for such purposes has declined in recent years due to large increases inbacterial resistance to this class of drugs. The drug is particularly useful when penicillins and/ormacrolides cannot be used due to allergy. It may be used to treatLegionnaire's disease as a substitute for a macrolide orquinolone.
Oxytetracycline is especially valuable in treating nonspecific urethritis,Lyme disease,brucellosis,cholera,typhus,tularaemia, and infections caused byChlamydia, Mycoplasma, andRickettsia. Doxycycline is now preferred to oxytetracycline for many of these indications because it has improved pharmacologic features.[clarification needed]
The standard dose is 250 to 500 mg every six hours by mouth. In particularly severe infections, this dose may be increased accordingly. Occasionally, oxytetracycline is given byintramuscular injection ortopically in the form of creams, ophthalmicointments, or eye drops.
Side effects are mainly gastrointestinal andphotosensitive allergic reactions common to thetetracycline antibiotics group. It can damage calcium-rich organs, such as teeth and bones, although this is very rare. It sometimes causes nasal cavities to erode; because of this, tetracyclines should not be used to treat pregnant or lactating women and children under age twelve except in certain conditions where it has been approved by a specialist because there are no obvious substitutes.[citation needed]Candidiasis (thrush) is not uncommon following treatment with broad-spectrum antibiotics.
It was first found nearPfizer laboratories in a soil sample yielding the, then new,actinomyceteStreptomyces rimosus by Finlayet al.[4] In 1950, a group at Pfizer led by Francis A. Hochstein, working in a loose collaboration with the Harvardorganic chemistRobert B. Woodward, worked out the chemical structure of oxytetracycline, enabling Pfizer tomass-produce the drug under the trade name Terramycin.[5][6] This discovery was a major advancement in tetracycline research and paved the way for the discovery of an oxytetracycline derivative,doxycycline, which is one of the most popularly used antibiotics today.[6]
Oxytetracycline belongs to a structurally diverse class of aromaticpolyketide antibiotics, also known as bacterial aromatic polyketides, produced byStreptomyces via type IIpolyketide synthases (PKSs).[7] Other compounds produced via type II PKSs are important bioactive compounds ranging from anticancer agents likedoxorubicin to antibiotics such astetracycline. The biosynthesis of oxytetracycline can be broken down into three general portions:[6] first is the formation of an amidated polyketide backbone with minimalpolyketide synthases (PKSs), second is the cyclization of the polyketide backbone, and finally, the formation of anhydrotetracycline—a shared intermediate with tetracycline—to produce oxytetracycline.
The biosynthesis of oxytetracycline begins with the utilization of PKS enzymesketosynthase (KS), the chain length factor (CLF), theacyl carrier protein (ACP), and anacyltransferase (encoded asOxyA,OxyB,OxyC andOxyP in the oxytetracyclinegene cluster)[8] tocatalyze the extension of the malonamyl-CoA starting unit with eightmalonyl-CoA extender units. The process of elongating the polypeptide skeleton occurs through a series ofClaisen-likedecarboxylation reactions until the linear tetracyclic skeleton is formed.[9] Thus, minimal PKSs form a completedamidated polyketide backbone without any additional post-synthase tailoring enzymes (Figure 1).
Following the formation of the linear tetracyclic skeleton, four successivecyclization reactions must occur in aregioselective manner to produce thearomatic natural product known as pretetramid, a common precursor to both oxytetracycline and other tetracycline antibiotics.[10] In the oxytetracycline gene cluster, these enzymes are encoded asOxyK (aromatase),OxyN (cyclase), andOxyI (cyclase).[11] Formation of pretetramid allows for one of the most important intermediates en route to the biosynthesis of oxytetracycline; this is the generation of anhydrotetracycline.[12][full citation needed] Anhydrotetracycline contains the first functionalizedA ring in this biosynthetic pathway.
After the formation of anhydrotetracycline, ATCmonooxygenase (OxyS)oxidizes the C-6 position in anenantioselective manner in the presence of thecofactorNADPH andatmospheric oxygen to produce 5a,11a-dehydrotetracycline.[13] Next, ahydroxylation occurs at the C-5 position of 5a,11a-dehydrotetracycline via theoxygenase encoded asOxyE in the oxytetracycline gene cluster. This produces the intermediate 5a,11a-dehydro-oxytetracycline. However, the exact mechanism of this step remains unclear. The final step of this biosynthesis occurs through thereduction of adouble bond in theα, β—unsaturated ketone of 5a,11a-dehydro-oxytetracycline. In this final step, the cofactor NADPH is employed byTchA (reductase) as thereducing agent. Upon reduction, theenol form is favored due toconjugation, thus producing the aromatic polyketide oxytetracycline. Figure 2 shows the biosynthesis as described above, as well as an arrow-pushing mechanism of NADPH being used as the final cofactor in the biosynthesis of oxytetracycline.
Oxytetracycline is used to control the outbreak ofAmerican foulbrood and European foulbrood inhoneybees.
Oxytetracycline can be used to correct breathing disorders inlivestock. It is administered in a powder or through an intramuscular injection. American livestock producers apply oxytetracycline to livestock feed to prevent diseases and infections in cattle and poultry. The antibiotic is partially absorbed in thegastrointestinal tract of the animal and the remaining is deposited in manure. Researchers at theAgricultural Research Service studied the breakdown of oxytetracycline in manure depending on various environmental conditions. They found the breakdown slowed with increased saturation of the manure and concluded this was a result of decreased oxygen levels.[14] This research helps producers understand the effects of oxytetracycline in animal feed on the environment, bacteria, and antimicrobial resistance.
Oxytetracycline is used to mark fish which are released and later recaptured. The oxytetracycline interferes with bone deposition, leaving a visible mark on growing bones.
Oxytetracycline has been formulated as a broad-spectrumanti-infective for fish under the name Terramycin 200 (TM200).[15] It is used to control certain diseases that adversely affectsalmonids,catfish, andlobsters.
