Doxycycline

Doxycycline

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Doxycycline INN
International Nonproprietary Name
An International Nonproprietary Name is the official nonproprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization...

 (icon ) is a member of the tetracycline antibiotics
Tetracycline antibiotics
Tetracyclines are a group of broad-spectrum antibiotics whose general usefulness has been reduced with the onset of bacterial resistance. Despite this, they remain the treatment of choice for some specific indications....

 group, and is commonly used to treat a variety of infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

s. Doxycycline is a semisynthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc.
Pfizer
Pfizer, Inc. is an American multinational pharmaceutical corporation. The company is based in New York City, New York with its research headquarters in Groton, Connecticut, United States...

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
Tetracycline antibiotics
Tetracyclines are a group of broad-spectrum antibiotics whose general usefulness has been reduced with the onset of bacterial resistance. Despite this, they remain the treatment of choice for some specific indications....

 group, doxycycline is frequently used to treat chronic prostatitis
Prostatitis
Prostatitis is an inflammation of the prostate gland, in men. A prostatitis diagnosis is assigned at 8% of all urologist and 1% of all primary care physician visits in the United States.-Classification:...

, sinusitis
Sinusitis
Sinusitis is inflammation of the paranasal sinuses, which may be due to infection, allergy, or autoimmune issues. Most cases are due to a viral infection and resolve over the course of 10 days...

, syphilis
Syphilis
Syphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum subspecies pallidum. The primary route of transmission is through sexual contact; however, it may also be transmitted from mother to fetus during pregnancy or at birth, resulting in congenital syphilis...

, chlamydia, pelvic inflammatory disease
Pelvic inflammatory disease
Pelvic inflammatory disease is a generic term for inflammation of the uterus, fallopian tubes, and/or ovaries as it progresses to scar formation with adhesions to nearby tissues and organs. This may lead to infections. PID is a vague term and can refer to viral, fungal, parasitic, though most...

, acne
Acne vulgaris
Acne vulgaris is a common human skin disease, characterized by areas of skin with seborrhea , comedones , papules , pustules , Nodules and possibly scarring...

, rosacea
Rosacea
Rosacea is a chronic condition characterized by facial erythema . Pimples are sometimes included as part of the definition. Unless it affects the eyes, it is typically a harmless cosmetic condition...

, and rickettsial infections.

Antiprotozoal


It is used in prophylaxis against malaria
Malaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...

. 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
Apicoplast
An apicoplast is a derived non-photosynthetic plastid found in most Apicomplexa, including malaria parasites such as Plasmodium falciparum, but not in others such as Cryptosporidium. It originated from an algae through secondary endosymbiosis...

 genes, resulting in their abnormal cell division.

It can be used in a treatment plan in combination with other agents, such as quinine
Quinine
Quinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine which, unlike quinine, is an anti-arrhythmic...

.

Antibacterial


It is used in the treatment and prophylaxis of Bacillus anthracis
Bacillus anthracis
Bacillus anthracis is the pathogen of the Anthrax acute disease. It is a Gram-positive, spore-forming, rod-shaped bacterium, with a width of 1-1.2µm and a length of 3-5µm. It can be grown in an ordinary nutrient medium under aerobic or anaerobic conditions.It is one of few bacteria known to...

(anthrax
Anthrax
Anthrax is an acute disease caused by the bacterium Bacillus anthracis. Most forms of the disease are lethal, and it affects both humans and other animals...

).

It is also effective against Yersinia pestis
Yersinia pestis
Yersinia pestis is a Gram-negative rod-shaped bacterium. It is a facultative anaerobe that can infect humans and other animals....

(the infectious agent of bubonic plague), and is prescribed for the treatment of Lyme disease
Lyme disease
Lyme disease, or Lyme borreliosis, is an emerging infectious disease caused by at least three species of bacteria belonging to the genus Borrelia. Borrelia burgdorferi sensu stricto is the main cause of Lyme disease in the United States, whereas Borrelia afzelii and Borrelia garinii cause most...

, ehrlichiosis
Ehrlichiosis
Ehrlichiosis is a tick-borne disease of dogs usually caused by the organism Ehrlichia canis. Ehrlichia canis is the pathogen of animals. Humans can become infected by E. canis and other species after tick exposure. German Shepherd dogs are thought to be particularly affected by the disease, other...

 and Rocky Mountain spotted fever
Rocky Mountain spotted fever
Rocky Mountain spotted fever is the most lethal and most frequently reported rickettsial illness in the United States. It has been diagnosed throughout the Americas. Some synonyms for Rocky Mountain spotted fever in other countries include “tick typhus,” “Tobia fever” , “São Paulo fever” or “febre...

. 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
Chloramphenicol
Chloramphenicol is a bacteriostatic antimicrobial that became available in 1949. It is considered a prototypical broad-spectrum antibiotic, alongside the tetracyclines, and as it is both cheap and easy to manufacture it is frequently found as a drug of choice in the third world.Chloramphenicol is...

), 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
    Escherichia coli
    Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...

  • Chlamydia trachomatis
    Chlamydia trachomatis
    Chlamydia trachomatis, an obligate intracellular human pathogen, is one of three bacterial species in the genus Chlamydia. C. trachomatis is a Gram-negative bacteria, therefore its cell wall components retain the counter-stain safranin and appear pink under a light microscope.The inclusion bodies...

  • Enterobacter aerogenes
    Enterobacter aerogenes
    Enterobacter aerogenes is a Gram-negative, oxidase negative, catalase positive, citrate positive, indole negative, rod-shaped bacterium....

    (formerly Aerobacter aerogenes)
  • Lyme disease
    Lyme disease
    Lyme disease, or Lyme borreliosis, is an emerging infectious disease caused by at least three species of bacteria belonging to the genus Borrelia. Borrelia burgdorferi sensu stricto is the main cause of Lyme disease in the United States, whereas Borrelia afzelii and Borrelia garinii cause most...

    , aka Lyme borreliosis complex (B. burgdorferi)
  • Rocky mountain spotted fever
    Rocky Mountain spotted fever
    Rocky Mountain spotted fever is the most lethal and most frequently reported rickettsial illness in the United States. It has been diagnosed throughout the Americas. Some synonyms for Rocky Mountain spotted fever in other countries include “tick typhus,” “Tobia fever” , “São Paulo fever” or “febre...

  • Folliculitis
    Folliculitis
    Folliculitis is the inflammation of one or more hair follicles. The condition may occur anywhere on the skin with the exception of the palms of the hands and soles of the feet.- Causes :...

  • Acne
    Acne
    Acne is a general term used for acneiform eruptions. It is usually used as a synonym for acne vulgaris, but may also refer to:*Acne aestivalis*Acne conglobata*Acne cosmetica*Acne fulminans*Acne keloidalis nuchae*Acne mechanica...

     and other inflammatory skin diseases, such as hidradenitis suppurativa
    Hidradenitis suppurativa
    Hidradenitis suppurativa is a skin disease that most commonly affects areas bearing apocrine sweat glands or sebaceous glands, such as the underarms, breasts, inner thighs, groin and buttocks.-Overview:...

  • Shigella
    Shigella
    Shigella is a genus of Gram-negative, nonspore forming, non-motile, rod-shaped bacteria closely related to Escherichia coli and Salmonella. The causative agent of human shigellosis, Shigella causes disease in primates, but not in other mammals. It is only naturally found in humans and apes. During...

    species
  • Acinetobacter
    Acinetobacter
    Acinetobacter [asz−in−ée−toe–back−ter] is a genus of Gram-negative bacteria belonging to the Gammaproteobacteria. Acinetobacter species are non-motile and oxidase-negative, and occur in pairs under magnification....

    species (formerly Mima species and Herellea species)
  • Respiratory tract infections caused by Haemophilus influenzae
    Haemophilus influenzae
    Haemophilus influenzae, formerly called Pfeiffer's bacillus or Bacillus influenzae, Gram-negative, rod-shaped bacterium first described in 1892 by Richard Pfeiffer during an influenza pandemic. A member of the Pasteurellaceae family, it is generally aerobic, but can grow as a facultative anaerobe. H...

  • Respiratory tract and urinary tract infection
    Urinary tract infection
    A urinary tract infection is a bacterial infection that affects any part of the urinary tract. Symptoms include frequent feeling and/or need to urinate, pain during urination, and cloudy urine. The main causal agent is Escherichia coli...

    s
  • Upper respiratory infections caused by Streptococcus pneumoniae
    Streptococcus pneumoniae
    Streptococcus pneumoniae, or pneumococcus, is Gram-positive, alpha-hemolytic, aerotolerant anaerobic member of the genus Streptococcus. A significant human pathogenic bacterium, S...

    (formerly Diplococcus pneumoniae)
  • Methicillin-resistant Staphylococcus aureus (MRSA) infections

Anthelmintic


Elephantiasis
Elephantiasis
Elephantiasis is a disease that is characterized by the thickening of the skin and underlying tissues, especially in the legs and male genitals. In some cases the disease can cause certain body parts, such as the scrotum, to swell to the size of a softball or basketball. It is caused by...

 is the end-stage condition of lymphatic filariases caused by one of two genera of filarial nematode
Nematode
The nematodes or roundworms are the most diverse phylum of pseudocoelomates, and one of the most diverse of all animals. Nematode species are very difficult to distinguish; over 28,000 have been described, of which over 16,000 are parasitic. It has been estimated that the total number of nematode...

s (roundworms): Wuchereria or Brugia (primarily Wuchereria bancrofti
Wuchereria bancrofti
Filaria, is a parasitic filarial nematode spread by a mosquito vector. It is one of the three parasites that cause lymphatic filariasis, an infection of the lymphatic system by filarial worms. It affects over 120 million people, primarily in Africa, South America, and other tropical and...

). 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
Wolbachia
Wolbachia is a genus of bacteria which infects arthropod species, including a high proportion of insects , as well as some nematodes. It is one of the world's most common parasitic microbes and is possibly the most common reproductive parasite in the biosphere...

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
Filariasis
Filariasis is a parasitic disease and is considered an infectious tropical disease, that is caused by thread-like nematodes belonging to the superfamily Filarioidea, also known as "filariae"....

.

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
Photodermatitis
Photodermatitis, sometimes referred to as "sun poisoning" or photoallergy is a form of allergic contact dermatitis in which the allergen must be activated by light to sensitize the allergic response, and to cause a rash or other systemic effects on subsequent exposure...

 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
Hormonal contraception
Hormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The original hormonal method—the combined oral contraceptive...

 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 tetracycline 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 syndrome
Fanconi syndrome
Falconi syndrome is a disease of the proximal renal tubules of the kidney in which glucose, amino acids, uric acid, phosphate and bicarbonate are passed into the urine, instead of being reabsorbed. Fanconi syndrome affects the proximal tubule, which is the first part of the tubule to process fluid...

. 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 erosion
Recurrent corneal erosion
Recurrent corneal erosion is a disorder of the eyes characterized by the failure of the cornea's outermost layer of epithelial cells to attach to the underlying basement membrane...

s. Doxycycline has been used successfully in the treatment of one patient with lymphangioleiomyomatosis
Lymphangioleiomyomatosis
Lymphangioleiomyomatosis is a rare lung disease that results in a proliferation of disorderly smooth muscle growth throughout the lungs, in the bronchioles, alveolar septa, perivascular spaces, and lymphatics, resulting in the obstruction of small airways and lymphatics...

, 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
Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease , also known as chronic obstructive lung disease , chronic obstructive airway disease , chronic airflow limitation and chronic obstructive respiratory disease , is the co-occurrence of chronic bronchitis and emphysema, a pair of commonly co-existing diseases...

, 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
Transgene
A transgene is a gene or genetic material that has been transferred naturally or by any of a number of genetic engineering techniques from one organism to another....

 expression in organisms and cell culture
Cell culture
Cell culture is the complex process by which cells are grown under controlled conditions. In practice, the term "cell culture" has come to refer to the culturing of cells derived from singlecellular eukaryotes, especially animal cells. However, there are also cultures of plants, fungi and microbes,...

s.

Other experimental applications include:
  • Vancomycin-resistant enterococcus
    Vancomycin-Resistant Enterococcus
    Vancomycin-resistant Enterococcus, or vancomycin-resistant enterococci , are bacterial strains of the genus Enterococcus that are resistant to the antibiotic vancomycin. To become VRE, vancomycin-sensitive enterococci typically obtain new DNA in the form of plasmids or transposons which encode...

     (VRE)
  • Infected animal bite wounds (Pasteurella multocida
    Pasteurella multocida
    Pasteurella multocida is a Gram-negative, non-motile coccobacillus that is penicillin-sensitive and belongs to the Pasteurellaceae family . It can cause avian cholera in birds and a zoonotic infection in humans, which typically is a result of bites or scratches from domestic pets...

    , Pasteurella pneumotropica)
  • Rheumatoid arthritis
    Rheumatoid arthritis
    Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...

     and reactive arthritis
    Reactive arthritis
    Reactive arthritis , is classified as an autoimmune condition that develops in response to an infection in another part of the body. Coming into contact with bacteria and developing an infection can trigger the disease. Reiter's syndrome has symptoms similar to various other conditions collectively...

  • Chronic inflammatory lung diseases (panbronchiolitis, asthma
    Asthma
    Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...

    , cystic fibrosis
    Cystic fibrosis
    Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...

    , bronchitis
    Bronchitis
    Acute bronchitis is an inflammation of the large bronchi in the lungs that is usually caused by viruses or bacteria and may last several days or weeks. Characteristic symptoms include cough, sputum production, and shortness of breath and wheezing related to the obstruction of the inflamed airways...

    )
  • Sarcoidosis
    Sarcoidosis
    Sarcoidosis , also called sarcoid, Besnier-Boeck disease or Besnier-Boeck-Schaumann disease, is a disease in which abnormal collections of chronic inflammatory cells form as nodules in multiple organs. The cause of sarcoidosis is unknown...

  • Prevention of aortic aneurysm in people with Marfan syndrome
    Marfan syndrome
    Marfan syndrome is a genetic disorder of the connective tissue. People with Marfan's tend to be unusually tall, with long limbs and long, thin fingers....

     and Vascular Ehlers-Danlos syndrome
    Ehlers-Danlos syndrome
    Ehlers–Danlos syndrome is a group of inherited connective tissue disorders, caused by a defect in the synthesis of collagen . The collagen in connective tissue helps tissues to resist deformation...

  • Multiple sclerosis
    Multiple sclerosis
    Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...

  • Meibomian gland dysfunction
  • Treatment of filariasis
    Filariasis
    Filariasis is a parasitic disease and is considered an infectious tropical disease, that is caused by thread-like nematodes belonging to the superfamily Filarioidea, also known as "filariae"....

     and onchocerciasis
    Onchocerciasis
    Onchocerciasis , also known as river blindness and Robles' disease, is a parasitic disease caused by infection by Onchocerca volvulus, a nematode . Onchocerciasis is the world's second-leading infectious cause of blindness. It is not the nematode, but its endosymbiont, Wolbachia pipientis, that...

     due to filariae and onchocerca
    Onchocerca
    Onchocerca is a genus of roundworm. It contains one human parasite - Onchocerca volvulus - which is responsible for the neglected disease Onchocerciasis, also known as "River Blindness" because the infected humans tend to live near rivers where host black flies live...

    e, in general, harbouring endosymbiotic Wolbachia
    Wolbachia
    Wolbachia is a genus of bacteria which infects arthropod species, including a high proportion of insects , as well as some nematodes. It is one of the world's most common parasitic microbes and is possibly the most common reproductive parasite in the biosphere...

    bacteria, doxycycline kills the bacteria, and (by removal of the endosymbiotes) the nematodes.
  • New daily persistent headache
  • Idiopathic pulmonary fibrosis (IPF)

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