nitrofurazone
{{short description|Chemical compound}}
{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 462261893
| IUPAC_name = (2E)-2-[(5-Nitro-2-furyl)methylene]hydrazine
carboxamide
| image = Nitrofural.svg
| alt = Skeletal formula of nitrofural
| width = 250
| image2 = Nitrofural 3D spacefill.png
| alt2 = Space-filling model of the nitrofural molecule
| width2 = 215
| tradename =Aldomycin, Amifur, Chemfuran, Coxistat, Furacin, Furan-2, Furacinetten, Furaplast, Furazol W, Furesol Furracoccid, Mammex, Nefco, Nifuzon, Nitrofural, Vabrocid
| Drugs.com = {{drugs.com|CONS|nitrofurazone}}
| pregnancy_AU =
| pregnancy_US = C
| pregnancy_category =
| legal_AU =
| legal_CA =
| legal_UK =
| legal_US =
| legal_status =US: Discontinued
| routes_of_administration =
| bioavailability =
| protein_bound =
| metabolism =
| elimination_half-life =5 hours
| excretion =
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 59-87-0
| CAS_supplemental =
| ATC_prefix = B05
| ATC_suffix = CA03
| ATC_supplemental = {{ATC|D08|AF01}} {{ATC|D09|AA03}} (dressing) {{ATC|P01|CC02}} {{ATC|S01|AX04}} {{ATC|S02|AA02}} {{ATCvet|G01|AX90}} {{ATCvet|P51|AC02}}
| PubChem = 5447130
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00336
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4566720
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = X8XI70B5Z6
| KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = C08042
| ChEBI = 44368
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 869
| chemical_formula =
| C=6 | H=6 | N=4 | O=4
| smiles = O=[N+]([O-])c1oc(/C=N/NC(=O)N)cc1
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C6H6N4O4/c7-6(11)9-8-3-4-1-2-5(14-4)10(12)13/h1-3H,(H3,7,9,11)/b8-3+
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = IAIWVQXQOWNYOU-FPYGCLRLSA-N
|drug_name=|caption=|type=|MedlinePlus=|licence_EU=|licence_US=}}
Nitrofurazone (INN, trade name Furacin) is an antimicrobial organic compound belonging to the nitrofuran class.{{Cite web|url=https://www.drugbank.ca/drugs/DB00336|title=Nitrofural|website=www.drugbank.ca|access-date=2018-03-14}} It is most commonly used as a topical antibiotic ointment. It is effective against gram-positive bacteria, gram-negative bacteria, and can be used in the treatment of trypanosomiasis.{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/nitrofurazone#section=Top|title=Nitrofurazone| work = Pubchem | publisher = U.S. National Library of Medicine |access-date=2018-03-14}}{{Cite web |url= https://www.glowm.com/resources/glowm/cd/pages/drugs/n026.html |title=nitrofurazone|website=www.glowm.com|access-date=2018-03-14}} Its use in medicine has become less frequent, as safer and more effective products have become available.{{Cite web |url=http://adpen.com/2010/05/nitrofurans/ |title= Nitrofuran Analyses |last=Perez |first=Steven | name-list-style = vanc |date=26 May 2010|website=Adpen Laboratories|access-date=14 March 2018}} Nitrofurazone is listed under California Prop 65, and has demonstrated clear evidence to be mutagenic and carcinogenic during animal studies, and has been discontinued for human use in the USA.{{cite web | work = Drugs.com | url = https://www.drugs.com/cons/nitrofurazone-topical.html | title = Nitrofurazone (Topical route) }}{{Cite news | url= https://oehha.ca.gov/chemicals/nitrofurazone |title=Nitrofurazone |date=2015-03-22|work=Office of Environmental Health Hazard Assessment |access-date=2018-03-14}}{{Cite journal|last=National Toxicology Program|date=June 1988|others=NIH Publication No. 88-2593|title=NTP Toxicology and Carcinogenesis Studies of Nitrofurazone in F344/N Rats and B6C3F1 Mice (Feed Studies)|url=https://ntp.niehs.nih.gov/ntp/htdocs/lt_rpts/tr337.pdf|journal=National Toxicology Program Technical Report Series|series=337|publisher=National Institute of Health|pages=1–186 }} The substance is pale yellow and crystalline. It was once widely used as an antibiotic for livestock.{{cite journal|title=Nitrofuran antibiotics: a review on the application, prohibition and residual analysis| vauthors = Vass M, Hruska K, Franek M |journal=Veterinarni Medicina|year=2008|volume=53| issue = 9 |pages=469–500|doi=10.17221/1979-VETMED|doi-access=free}}{{Cite news |url= https://www.drugs.com/vet/nitrofurazone-ointment.html |title= Nitrofurazone Ointment for Animal Use - Drugs.com|work=Drugs.com|access-date=2018-03-14|language=en-US}}
Medical uses
= Human use =
Nitrofurazone was previously available as a prescription in the U.S., and was indicated as a topical solution, topical cream, or topical ointment for the treatment of bacterial skin infections, wounds, burns, and ulcers. It was also used as a prophylactic measure to prevent infection that could potentially result in skin graft rejection.{{Cite web |url= http://www.minclinic.ru/drugs/drugs_eng/A/Aldomycin.html |title=Aldomycin | work = Minimally Invasive Neurosurgery Clinic |access-date=2018-03-14}} Nitrofurazone is still very popular as a topical solution for the treatment of tonsillitis in Russia.{{cn|date=December 2022}}
= Animal use =
Nitrofurazone is indicated for topical use in dogs, cats, and horses, for the treatment or prophylactic treatment of superficial bacterial infections, burns, and cutaneous ulcers. Preparations for treating infections, such as fin rot, in ornamental fish are also still commercially available.{{cite web |url= http://edis.ifas.ufl.edu/fa084|title=Use of Antibiotics in Ornamental Fish Aquaculture|last=Yanong|first=Roy P. E. | name-list-style = vanc |date=2017-01-05|website=edis.ifas.ufl.edu |access-date=2018-03-14}}{{Cite book |url=https://books.google.com/books?id=GykB84HU6LoC&pg=PA71|title=Discus Fish |last=Giovanetti |first=Thomas A. | name-list-style = vanc |date=1991|publisher=Barron's Educational Series |isbn=9780812046694 }} The use of nitrofurazone, or related compounds, in animals raised for human consumption has been strictly banned.{{Cite web|url=https://www.fda.gov/downloads/Food/GuidanceRegulation/UCM251970.pdf|title=Fish and Fishery Products Hazards and Controls Guidance|last=Center for Food Safety and Applied Nutrition|first=U.S. Department of Health and Human Services|date=April 2011|website=www.fda.gov|publisher=Food and Drug Administration|pages=183–208|language=en|access-date=2018-03-14|edition=Fourth}}
Pharmacokinetics
The metabolism of topically applied nitrofurazone is thought to be by 5-nitro reduction and cleavage of the -CH=N- linkage to generate a reactive species which can covalently bond to cellular macromolecules, none of the end products are thought to be antimicrobial.{{cite book |url= https://books.google.com/books?id=2IepBlgVqZcC&pg=PA107 |title=Residues of Some Veterinary Drugs in Animals and Foods: Monographs Prepared by the Fortieth Meeting of the Joint FAO/WHO Expert Committee on Food Additives, Geneva, 9-18 June 1992| work = Joint FAO/WHO Expert Committee on Food Additives Meeting |date=1993 |publisher= Food and Agriculture Organization of the United Nations |isbn=9789251032886 }}
Mechanism of action
The mechanism of action is not fully understood, but nitrofurazone's antimicrobial properties are suspected to be due to the interference of DNA synthesis in the microorganism by inhibiting certain enzymes that are involved with glycolysis. Other enzymes this may affect include, pyruvate dehydrogenase, citrate synthetase, malate dehydrogenase, glutathione reductase, and pyruvate decarboxylase.
Adverse effects
Adverse effects for topical use are generally mild and include, erythema, pruritus, dermatitis, rash, edema or inflammation.
Contraindications
People with chronic kidney disease and large total body surface area (TBSA) burns should not use nitrofurazone, as topical preparations commonly contain polyethylene glycol, which is readily absorbed through the skin. Rapid absorption of the medication induces increased serum osmolalities and anion gap, leading to death.{{Cite journal|date=2017-12-29|title=Thermal Burns: Overview, Pathophysiology, Quantifying Burn Severity|url=https://emedicine.medscape.com/article/1278244-overview#a7}} Symptoms are similar to ethylene glycol poisoning, in that increased serum calcium levels occur concurrently with decreased ionized calcium.
Nitrofurans have been found in honey, meat and seafood. In people who have glucose-6-phosphate dehydrogenase deficiency (G-6-PD deficiency), ingestion of fish, poultry, or other foodstuff that has been treated with nitrofurans, will likely suffer from hemolysis of red blood cells as a result of eating the contaminated food.
Toxicities
Nitrofurazone is suspected to be a human carcinogen and is included in California's list of toxic chemicals as defined by Proposition 65.{{cite journal | vauthors = Ryan A, Kaplan E, Laurieri N, Lowe E, Sim E | title = Activation of nitrofurazone by azoreductases: multiple activities in one enzyme | language = En | journal = Scientific Reports | volume = 1 | issue = 1 | pages = 63 | date = 2011-08-12 | pmid = 22355582 | pmc = 3216550 | doi = 10.1038/srep00063 | bibcode = 2011NatSR...1...63R }} Studies demonstrate that nitrofurazone induces mammary tumors (fibroadenoma and adenocarcinoma) in rats and ovarian tumors in mice. In addition, animal studies demonstrated an increased incidence in convulsive seizures, ovarian atrophy, testicular degeneration, and degeneration of articular cartilage.{{Cite web|url=https://ntp.niehs.nih.gov/results/pubs/longterm/reports/longterm/tr300399/abstracts/tr337/index.html|title=Abstract for TR-337|website=ntp.niehs.nih.gov|language=en|access-date=2018-03-14}} Proper personal protective equipment should be utilized when handling nitrofurazone.
References
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{{Agents against leishmaniasis and trypanosomiasis}}
{{Otologicals}}