Doxycycline

Doxycycline (INN) (pronounced /ˌdɒksɪˈsaɪkliːn/) is a member of the tetracycline antibiotics group and is commonly used to treat a variety of infections. Doxycycline is a semi-synthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc. and marketed under the brand name Vibramycin. Vibramycin received FDA approval in 1967, becoming Pfizer's first once-a-day broad-spectrum antibiotic. Other brand names include Monodox, Periostat, Vibra-Tabs, Doryx, Vibrox, Adoxa®, Doxyhexal and Atridox (topical doxycycline hyclate for Periodontitis).

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Indicated uses

Main article: tetracycline antibiotics

Further information: oxytetracycline

As well as the general indications for all members of the tetracycline antibiotics group, Doxycycline is frequently used to treat chronic prostatitis, sinusitis, syphilis, chlamydia, pelvic inflammatory disease^[1][2], acne and rosacea^[3][4]. In addition it is used in the treatment and prophylaxis of Bacillus anthracis (anthrax) and in prophylaxis against malaria. It should not be used alone for initial treatment of malaria, even when the parasite is doxycyline-sensitive, because the antimalarial effect of doxycyline is delayed. This delay is related to its mechanism of action. Its mechanism of action against malaria is to specifically impair in the progeny the apicoplast genes resulting in their abnormal cell division.^[5]

It is also effective against Yersinia pestis (the infectious agent of bubonic plague) and is prescribed for the treatment of Lyme disease^[6][7][8], ehrlichiosis^[9][10] and Rocky Mountain spotted fever. Doxycycline, like other antibiotics, will not work for colds, flu, or other viral infections.

Elephantiasis is a disease caused by a nematode (worm) Wuchereria bancrofti. It causes swollen limbs and genitals (Filariasis) and affects over 120 million people in the world. Previous anti-nematode treatments have been limited by poor levels of effectiveness, drug side effects and high costs. Doxycycline was shown in 2003 to kill the symbiotic Wolbachia bacteria upon which the nematodes are dependent.^[11] Field trials in 2005 showed that Doxycycline almost completely eliminates blood-borne filaria when given for an 8 week course.^[12][13]

When bacteriologic testing indicates appropriate susceptibility to the drug, doxycycline may be used to treat:

• Escherichia coli
• Enterobacter aerogenes (formerly Aerobacter aerogenes)
• Lyme Disease
• Acne
• Shigella species
• Acinetobacter species (formerly Mima species and Herellea species)
• Respiratory tract infections caused by Haemophilus influenzae
• Respiratory tract and urinary tract infections caused by Klebsiella species
• Upper respiratory infections caused by Streptococcus pneumoniae (formerly Diplococcus pneumoniae)
• [[Methicillin-resistant Staphylococcus aureus (MRSA)]] infections

Cautions and side effects

Cautions and side effects are similar to other members of the tetracycline antibiotic group. However the 10% risk of photosensitivity skin reactions is of particular importance for those intending long-term use for malaria prophylaxis. Reports of GERD have been cited with the use of Doxycycline.

Unlike some other members of the tetracycline group, it may be used in those with renal impairment.

Doxycycline impairs the effectiveness of many types of hormonal contraception due to CYP450 induction, and physicians recommend the use of barrier contraception for people taking the drug to prevent unwanted pregnancy. It may also reduce the effectiveness of oral contraceptives by decreasing the normal flora in the intestines. Normally, estrogens inside oral contraceptives are glucuronidated in the liver and re-circulated to the gut. Flora presence in the gut help to remove glucuronide groups off of estrogen as it re-enters the GI tract via enterohepatic circulation and thus the estrogen takes effect. However, the decrease of number of flora inside the gut reduce the flora's glucuronide groups removal ability. Therefore, Doxycycline's decrease the efficacy of oral contraceptives up to two-fold.

It should be taken with a full glass of water to prevent irritation of the esophagus and stomach. Also, there is a slim risk of liver damage during prolonged use of the drug.^[14]

Experimental applications

At subantimicrobial doses, doxycycline is an inhibitor of matrix metalloproteinases, and has been used in various experimental systems for this purpose. Doxycycline has been used successfully in the treatment of one patient with lymphangioleiomyomatosis, an otherwise progressive and fatal disease.^[15]

Doxycycline is also used in "Tet-on" and "Tet-off" tetracycline controlled transcriptional activation to regulate transgene expression in organisms and cell cultures.

Other experimental applications include:

• Vancomycin-Resistant Enterococcus (VRE)^[16]
• Infected animal bite wounds (Pasteurella multocida, Pasteurella pneumotropica)^[17]
• Rheumatoid arthritis^[18][19] and reactive arthritis.
• Chronic inflammatory lung diseases (panbronchiolitis, asthma, cystic fibrosis, bronchitis)^[20][21]
• Sarcoidosis^[22][23]
• Prevention of aortic aneurysm in people with Marfan Syndrome.
• Multiple sclerosis ^[24]

References