Doxycycline

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Doxycycline
Doxycycline.svg
Doxycycline 3d structure.png
Systematic (IUPAC) name
(4S,4aR,5S,5aR,6R,12aS)-4-(dimethylamino)- 3,5,10,12,12a-pentahydroxy- 6-methyl- 1,11-dioxo- 1,4,4a,5,5a,6,11,12a-octahydrotetracene- 2-carboxamide
Clinical data
Trade names Vibramycin Monodox, Microdox, Periostat, Vibra-Tabs, Oracea, Doryx, Vibrox, Adoxa, Doxyhexal, Doxylin, Doxoral, Doxy-1', Atridox
AHFS/Drugs.com monograph
MedlinePlus a682063
Licence data US FDA:link
Pregnancy cat.
Legal status
Routes oral, buccal, intravenous therapy, intramuscular injection
Pharmacokinetic data
Bioavailability 100%
Protein binding 90%
Metabolism Hepatic
Half-life 15-25 hours
Excretion Urine (40%)
Identifiers
CAS number 564-25-0 YesY
ATC code J01AA02 A01AB22
PubChem CID 11256
DrugBank DB00254
ChemSpider 10482106 YesY
UNII 334895S862 YesY
KEGG C06973 N
ChEBI CHEBI:60648 YesY
ChEMBL CHEMBL1433 N
Chemical data
Formula C22H24N2O8 
Mol. mass 444.43 g/mol
 N (what is this?)  (verify)
Generic 100 mg doxycycline capsules

Doxycycline (IPA: /ˌdɒksiˈsklin/) is an antibiotic useful for the treatment of a number of infections. It is in the tetracycline antibiotic class.

Under the brand name Vibramycin, Pfizer's doxycycline product received US Food and Drug Administration approval in 1967.[1] Other brand names include Monodox, Microdox, Periostat, Vibra-Tabs, Oracea, Doryx,[2] Vibrox, Adoxa, Doxyhexal, Doxylin, Doxoral, Doxy-1 and Atridox (topical doxycycline hyclate for periodontitis) It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.[3]

Medical uses[edit]

Further information: Oxytetracycline

In addition to the general indications for all members of the tetracycline antibiotics group, doxycycline is frequently used to treat Lyme disease, chronic prostatitis, sinusitis, pelvic inflammatory disease,[4][5] acne, rosacea,[6][7] and rickettsial infections.[8]

Antiprotozoal[edit]

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.[9]

It can be used in a treatment plan in combination with other agents, such as quinine.[10]

Antibacterial[edit]

Moraxella catarrhalis, Brucella melitensis, Chlamydia pneumoniae, and Mycoplasma pneumoniae are generally susceptible to doxycycline, while some Haemophilus spp., Mycoplasma hominis, and Pseudomonas aeruginosa have developed resistance to varying degrees.[11]

It is used in the treatment and prophylaxis of anthrax (caused by Bacillus anthracis) and Leptospirosis.[12] It is also effective against Yersinia pestis (the infectious agent of bubonic plague), and is prescribed for the treatment of Lyme disease,[13][14][15][16] ehrlichiosis[17][18] 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, it is not indicated for use in children under the age of eight years.

Doxycycline is indicated for treatment of:[19][20]

  • Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever,[21] rickettsialpox, and tick fevers caused by Rickettsia
  • Respiratory tract infections caused by Mycoplasma pneumoniae[22]
  • Lymphogranuloma venereum, trachoma, inclusion conjunctivitis, and uncomplicated urethral, endocervical, or rectal infections in adults caused by Chlamydia trachomatis
  • Psittacosis (ornithosis) caused by Chlamydia psittaci
  • Nongonococcal urethritis caused by Ureaplasma urealyticum
  • Relapsing fever due to Borrelia recurrentis
  • Chancroid caused by Haemophilus ducreyi
  • Plague due to Yersinia pestis
  • Tularemia due to Francisella tularensis
  • Cholera caused by Vibrio cholerae
  • Campylobacter fetus infections
  • Brucellosis caused by Brucella species (in conjunction with streptomycin)
  • Bartonellosis caused by Bartonella bacilliformis
  • Granuloma inguinale caused by Calymmatobacterium granulomatis

When bacteriologic testing indicates appropriate susceptibility to the drug, doxycycline may be used to treat these infections caused by Gram-negative bacteria:[19][20]

Some Gram-positive bacteria have developed resistance to doxycycline. Up to 44% of Streptococcus pyogenes and up to 74% of S. faecalis specimens have developed resistance to the tetracycline group of antibiotics. When bacteriologic testing indicates appropriate susceptibility to the drug, doxycycline may be used to treat these infections caused by Gram-positive bacteria:[19][20]

Doxycycline package

When penicillin is contraindicated, doxycycline can be used to treat:[19][20]

  • Uncomplicated gonorrhea caused by Neisseria gonorrhoeae
  • Syphilis caused by Treponema pallidum
  • Yaws caused by Treponema pertenue
  • Listeriosis due to Listeria monocytogenes
  • Vincent’s infection caused by Fusobacterium fusiforme
  • Actinomycosis caused by Actinomyces israelii
  • Infections caused by Clostridium species.

Doxycycline may also be used as adjunctive therapy for severe acne.[19][20]

Doxycycline combination

The first-line for treatment brucellosis is combination of Doxycycline and streptomycin and the second-line is combination of Doxyxycline and rifampin (rifampicin).[23]

Antihelminthic[edit]

Doxycycline kills the symbiotic Wolbachia bacteria in the reproductive tracts of parasitic filarial nematodes, making the nematodes sterile, and thus reducing transmission of diseases such as onchocerciasis and elephantiasis.[24] Field trials in 2005 showed an eight-week course of doxycycline almost completely eliminates the release of microfilariae.[25][26]

Spectrum of susceptibility[edit]

Doxycycline has been used successfully to treat sexually transmitted, respiratory, and ophthalmic infections. Representative pathogenic genera include Chlamydia, Streptococcus, Ureaplasma, Mycoplasma, and others. The following represents MIC susceptibility data for a few medically significant microorganisms.

  • Chlamydia psittaci: 0.03 μg/ml
  • Mycoplasma pneumoniae: 0.016 μg/ml - 2 μg/ml
  • Streptococcus pneumoniae: 0.06 μg/ml - 32 μg/ml[27]

Adverse effects[edit]

Cautions and side effects are similar to those of other members of the tetracycline antibiotic group.

An erythematous rash in sun-exposed parts of the body has been reported to occur in 7.3–21.2% of persons taking doxycycline for malaria prophylaxis. One study examined the tolerability of various malaria prophylactic regimens and found doxycycline did not cause a significantly higher percentage of all skin events (photosensitivity not specified) when compared with other antimalarials. The rash resolves upon discontinuation of the drug.[28]

Unlike some other members of the tetracycline group, it may be used in those with renal impairment.[29] Doxycycline is contraindicated in the pediatric treatment of acute bacterial rhinosinusitis.

Interactions[edit]

The combination of doxycycline with dairy, antacids, calcium supplements, iron products, and laxatives containing magnesium is not inherently dangerous, but any of these foods and supplements may decrease doxycycline's effectiveness.[30][verification needed]

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.[31][32][33]

Pregnancy and lactation[edit]

Doxycycline is categorized by the FDA as a class D drug in pregnancy. As with all tetracycline antibiotics, it is contraindicated in pregnancy through infancy and childhood up to eight years of age, due to the potential for disrupting bone and tooth development.[34] Therefore, doxycycline should not be administered to children under the age of eight except in the treatment of anthrax, or where other medications are contraindicated or ineffective.[19]

Doxycycline crosses into breastmilk. The adverse effects on teeth and long bones of children directly administered tetracycline antibiotics is documented, but these effects have not been recorded in infants exposed through breastmilk. Although the dose an infant would receive through breastfeeding would likely be minimal, a theoretical risk exists.[35]

Pharmacokinetics[edit]

Doxycycline–metal ion complexes are unstable at acid pH, therefore more doxycycline enters the duodenum for absorption compared with the earlier tetracycline compounds. In addition, food has less effect on absorption than on absorption of earlier drugs with doxycycline serum concentrations being reduced by about 20% by test meals compared with 50% for tetracycline.[36]

Physical and chemical properties[edit]

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[37][38] causing Fanconi syndrome.[39] In the case of doxycycline, the absence of a hydroxyl group in C-6 prevents the formation of the nephrotoxic compound.[38] 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.[39]

Experimental applications[edit]

Tet-ON inducible shRNA system

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.[40] Doxycycline has been demonstrated to reduce the in vitro growth of human breast and prostate cancer cells, possibly through G1 phase cell cycle arrest.[41][42] Doxycycline and other tetracyclines are also highly osteotropic, and in animal models of breast cancer bone metastases, doxycycline treatments have reduced the growth of breast cancer tumours in the bone.[43] Doxycycline has been used successfully in the treatment of one patient with lymphangioleiomyomatosis, an otherwise progressive and fatal disease.[44] It has also been shown to attenuate cardiac hypertrophy (in mice), a deadly consequence of prolonged hypertension.[45] In chronic obstructive pulmonary disease, doxycycline has been shown to improve lung functions in patients with stable symptoms.[46] 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 treating:

History[edit]

Doxycycline is a semisynthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc.[citation needed] and marketed under the brand name Vibramycin.

References[edit]

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External links[edit]