Doxycycline

Doxycycline INN is a member of the tetracycline antibiotics group, and is commonly used to treat a variety of infections. Doxycycline is a semisynthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc. and marketed under the brand name Vibramycin. Vibramycin received U.S. Food and Drug Administration (FDA) approval in 1967, becoming Pfizer's first once-a-day, broad-spectrum antibiotic. Other brand names include Monodox, Microdox, Periostat, Vibra-Tabs, Oracea, Doryx, Vibrox, Adoxa, Doxyhexal, Doxylin, Doxoral,Doxy-1 and Atridox (topical doxycycline hyclate for periodontitis).

Indicated uses
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, acne, rosacea,  and rickettsial infections.

Antiprotozoal
It is used in prophylaxis against malaria. It should not be used alone for initial treatment of malaria, even when the parasite is doxycycline-sensitive, because the antimalarial effect of doxycycline is delayed. This delay is related to its mechanism of action, which is to specifically impair the progeny of the apicoplast genes, resulting in their abnormal cell division.

It can be used in a treatment plan in combination with other agents, such as quinine.

Antibacterial
It is used in the treatment and prophylaxis of Bacillus anthracis (anthrax).

It is also effective against Yersinia pestis (the infectious agent of bubonic plague), and is prescribed for the treatment of Lyme disease,  ehrlichiosis  and Rocky Mountain spotted fever. In fact, because doxycycline is one of the few medications shown to be effective in treating Rocky Mountain spotted fever (with the next-best alternative being chloramphenicol), doxycycline is indicated even for use in children for this illness. Otherwise, doxycycline is not indicated for use in children under the age of eight years. Doxycycline, like other antibiotics, will not work for colds, influenza, or other viral infections. When bacteriologic testing indicates appropriate susceptibility to the drug, doxycycline may be used to treat and prevent:
 * Escherichia coli
 * Chlamydia trachomatis
 * Enterobacter aerogenes (formerly Aerobacter aerogenes)
 * Lyme disease, aka Lyme borreliosis complex (B. burgdorferi)
 * Rocky mountain spotted fever
 * Folliculitis
 * Acne and other inflammatory skin diseases, such as hidradenitis suppurativa
 * Shigella species
 * Acinetobacter species (formerly Mima species and Herellea species)
 * Respiratory tract infections caused by Haemophilus influenzae
 * Respiratory tract and urinary tract infections
 * Upper respiratory infections caused by Streptococcus pneumoniae (formerly Diplococcus pneumoniae)
 * Methicillin-resistant Staphylococcus aureus (MRSA) infections

Anthelmintic
Elephantiasis is the end-stage condition of lymphatic filariases caused by one of two genera of filarial nematodes (roundworms): Wuchereria or Brugia (primarily Wuchereria bancrofti). Elephantiasis is characterized by permanently swollen limbs or genitals and permanent damage to the lymph system (often accompanied by severe secondary fungal and bacterial infections). This results from blockage of lymph flow caused by immune response against dead or dying adult worms in the lymphatics. This condition affects over 120 million people worldwide, with 1 billion at risk. Previous antinematode 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 in the filarial worms' reproductive tracts, rendering them sterile, thus reducing transmission of the disease. Field trials in 2005 showed doxycycline almost completely eliminates the release of microfilariae when given for an 8 week course. However, doxycycline only reduces transmission and the relatively light pathology associated with microfilaraemia; there is currently no cure for lymphatic filariasis.

Cautions and side effects
Cautions and side effects are similar to those of other members of the tetracycline antibiotic group. However, the risk of photosensitivity skin reactions is of particular importance for those intending long-term use for malaria prophylaxis, because it can cause permanent sensitive and thin skin.

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

Previously, doxycycline was believed to impair the effectiveness of many types of hormonal contraception due to CYP450 induction. Recent research has shown no significant loss of effectiveness in oral contraceptives while using most tetracycline antibiotics (including doxycycline), although many physicians still recommend the use of barrier contraception for people taking the drug to prevent unwanted pregnancy.

Food, including dairy products, does not interfere with the absorption of doxycycline, unlike most other tertacycline antibiotics.

Doxycycline, like all tetracyclines, is not approved for general use in children, but specific exceptions are made for potentially fatal illnesses where the benefits outweigh the risks and there are few or no other alternatives, such as with Rocky Mountain spotted fever and anthrax.

Expired tetracyclines or tetracyclines allowed to stand at a pH less than 2 are reported to be nephrotoxic due to the formation of a degradation product, anhydro-4-epitetracycline causing Fanconi's syndrome. In the case of doxycycline, the absence of an hydroxyl group in C-6 prevent the formation of the nephrotoxic compound. Nevertheless, tetracyclines and doxycycline itself have to be taken with precaution in patients with kidney injury, as they can worsen azotemia due to catabolic effects.

Experimental applications
At subantimicrobial doses, doxycycline is an inhibitor of matrix metalloproteases, and has been used in various experimental systems for this purpose, such as for recalcitrant recurrent corneal erosions. Doxycycline has been used successfully in the treatment of one patient with lymphangioleiomyomatosis, an otherwise progressive and fatal disease. Doxycycline has also been shown to attenuate cardiac hypertrophy (in mice), a deadly consequence of prolonged hypertension. In chronic obstructive pulmonary disease, doxycycline has shown to improve lung functions in patients with stable symptoms. 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)
 * Infected animal bite wounds (Pasteurella multocida, Pasteurella pneumotropica)
 * Rheumatoid arthritis and reactive arthritis
 * Chronic inflammatory lung diseases (panbronchiolitis, asthma, cystic fibrosis, bronchitis)
 * Sarcoidosis
 * Prevention of aortic aneurysm in people with Marfan syndrome and Vascular Ehlers-Danlos syndrome
 * Multiple sclerosis
 * Meibomian gland dysfunction
 * Treatment of filariasis and onchocerciasis due to filariae and onchocercae, in general, harbouring endosymbiotic Wolbachia bacteria, doxycycline kills the bacteria, and (by removal of the endosymbiotes) the nematodes.
 * New daily persistent headache
 * Idiopathic pulmonary fibrosis (IPF)