Typhus

Doxycycline

Doxycycline
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
AHFS/Drugs.com monograph
MedlinePlus a682063
Licence data US FDA:link
Pregnancy cat. D (US)
Legal status POM (UK) ℞-only (US)
Routes oral, buccal, iv, im
Pharmacokinetic data
Bioavailability 100%
Metabolism hepatic,minimally
Half-life 18-22 hours
Excretion urine, feces
Identifiers
CAS number 564-25-0 YesY
ATC code J01AA02 A01AB22
PubChem CID 11256
DrugBank DB00254
ChemSpider 10482106 YesY
UNII 334895S862 YesY
KEGG D02129 N
ChEBI CHEBI:60648 YesY
ChEMBL CHEMBL1433 N
Chemical data
Formula C22H24N2O8 
Mol. mass 462.46 g/mol
SMILES eMolecules & PubChem

  • InChI=1S/C22H24N2O8.H2O/c1-7-8-5-4-6-9(25)11(8)16(26)12-10(7)17(27)14-15(24(2)3)18(28)13(21(23)31)20(30)22(14,32)19(12)29;/h4-7,10,14-15,17,25,27-29,32H,1-3H3,(H2,23,31);1H2/t7-,10+,14+,15-,17-,22-;/m0./s1 YesY
    Key:XQTWDDCIUJNLTR-CVHRZJFOSA-N YesY
 N (what is this?)  (verify)
Generic 100 mg doxycycline capsules

Doxycycline 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 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).

Contents

Indicated uses

Main article: Tetracycline antibiotics
Further information: Oxytetracycline

In addition to 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.

Spectrum of Bacterial Susceptibility and Resistance

Branhamella catarrhalis, Brucella melitensis, Chlamydia pneumoniae and Mycoplasma pneumoniae species are generally susceptible to Doxycycline, while some Haemophilus spp., Mycoplasma hominis and Pseudomonas aeruginosa have developed resistance to Doxycycline to varying degrees.

Antibacterial

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

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, it 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.

Doxycycline package

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

Anthelmintic

Elephantiasis is the end-stage condition of lymphatic filariasis 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 eight-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 sensitivity and thin skin, which may lead to sun damage.

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 that 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.

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 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. In the case of doxycycline, the absence of a hydroxyl group in C-6 prevents 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

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. Doxycycline has been demonstrated to reduce the in vitro growth of human breast and prostate cancer cells, possibly through G1 phase cell cycle arrest. 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. Doxycycline has been used successfully in the treatment of one patient with lymphangioleiomyomatosis, an otherwise progressive and fatal disease. It has also been shown to attenuate cardiac hypertrophy (in mice), a deadly consequence of prolonged hypertension. In chronic obstructive pulmonary disease, doxycycline has been 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 treating:


References

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