Metronidazole
315139
222616490
2008-06-30T07:57:56Z
Antonello41
7199824
added "antibiotic" in the right hand side of the page for a quick glance because i noticed that if someone is looking to find out what a drug is, it is not easily visible
{{drugbox |
|image=Metronidazole.png
| width=200
| IUPAC_name = 2-(2-methyl-5-nitro-1''H''-imidazol-1-yl)ethanol
| CAS_number = 443-48-1
| ATC_prefix=A01
| ATC_suffix=AB17
| ATC_supplemental={{ATC|D06|BX01}}, {{ATC|G01|AF01}}, {{ATC|J01|XD01}}, {{ATC|P01|AB01}}
| PubChem=4173
| DrugBank=APRD00631
| C=6|H=9|N=3|O=3
| molecular_weight = 171.15 g/mol
| bioavailability = 100% (oral)<br />59–94% (rectal)
| metabolism = [[Hepatic]]
| elimination_half-life = 6–7 hours
| excretion = [[Renal]] (60-80%), [[biliary]] (6–15%)
| type of medicine = antibiotic
| pregnancy_category = B2 <small>([[Australia|Au]])</small>
| legal_AU = S4
| legal_UK = POM
| routes_of_administration = Oral, [[topical]], [[suppository|rectal]], [[intravenous|IV]], [[vaginal]]
}}
'''Metronidazole''' ([[International Nonproprietary Name|INN]]) ({{pronEng|mɛtrəˈnaɪdəzoʊl}}) is a [[nitroimidazole]] [[antibiotic|anti-infective]] medication used mainly in the treatment of infections caused by susceptible organisms, particularly [[anaerobe|anaerobic]] [[bacterium|bacteria]] and [[protozoa]]. It is marketed by [[Pfizer]] under the trade name '''Flagyl''' in the US, while [[Sanofi-Aventis]] markets metronidazole globally under the same tradename, '''Flagyl''', and also by various generic manufacturers, who sell it at a lower price.
Metronidazole is also used as a gel preparation in the treatment of the [[dermatology|dermatological]] conditions such as [[rosacea]] ('''Rozex''' and '''MetroGel''' by [[Galderma]]) and [[neoplasia|fungating]] [[tumour]]s ('''Anabact''', Cambridge Healthcare Supplies).
Metronidazole is a [[prodrug]]. It is converted in [[anaerobic organism]]s by the [[redox]] [[enzyme]] [[pyruvate]]-[[ferredoxin]] [[oxidoreductase]]. The nitro group of metronidazole is chemically reduced by ferredoxin (or a ferredoxin-linked metabolic process) and the products are responsible for disrupting the [[DNA]] helical structure, thus inhibiting [[nucleic acid]] synthesis.
Metronidazole is selectively taken up by [[anaerobic bacteria]] and sensitive [[protozoa]]l organisms because of the ability of these organisms to reduce metronidazole to its active form intracellularly.
==Indications==
Systemic metronidazole is indicated for the treatment of:
*[[Vaginitis]] due to ''[[Trichomonas vaginalis]]'' (protozoal) infection in both symptomatic patients as well as their asymptomatic sexual contacts
* [[Bacterial vaginosis]], commonly associated with overgrowth of ''[[Gardnerella]]'' species, in symptomatic patients
*[[Pelvic inflammatory disease]] in conjunction with other antibiotics such as [[ofloxacin]], [[levofloxacin]], or [[ceftriaxone]]
*[[Protozoa]]l infections due to ''[[Entamoeba histolytica]]'' ([[dysentery|Amoebic dysentery]] or [[abscess|Hepatic abscess]]es), and ''[[Giardia lamblia]]'' ([[Giardiasis]]) should be treated alone or in conjunction with [[iodoquinol]] or [[diloxanide furoate]]
*Anaerobic bacterial infections such as ''[[Bacteroides|Bacteroides fragilis, spp]]'', ''[[Fusobacterium|Fusobacterium spp]]'', ''[[Clostridium|Clostridium spp]]'', ''[[Peptostreptococcus|Peptostreptococcus spp]]'', ''[[Prevotella|Prevotella spp]]'', or any other anaerobes in [[intraabdominal abscess]], [[peritonitis]], [[empyema]], [[pneumonia]], [[aspiration pneumonia]], [[lung abscess]], diabetic foot ulcer, meningitis and [[brain abscess]], bone and joint infections, septicemia, [[endometritis]], [[tubo-ovarian abscess]], or [[endocarditis]]
*[[Pseudomembranous colitis]] due to ''[[Clostridium difficile]]''
*''[[Helicobacter pylori]]'' eradication therapy, as part of a multi-drug regimen in [[peptic ulcer disease]]
*Prophylaxis for those undergoing potentially contaminated colorectal surgery and may be combined with [[neomycin]]
*Acute [[gingivitis]] and other dental infections ([[Therapeutic Goods Administration|TGA]] approved, non-[[Food and Drug Administration]] (FDA) approved)
*[[Crohn's disease]] with colonic or perianal involvement (non-FDA approved)- believed to be more effective in combination with [[ciprofloxacin]]
*With [[amphotericin B]] and certain other drugs, it is used as an adjunct in the attempted treatment of [[primary amoebic meningoencephalitis]] caused by [[Naegleria fowleri]] infection
Topical metronidazole is indicated for the treatment of [[rosacea]], and in the treatment of malodorous [[neoplasia|fungating]] wounds.<ref name="AMH2006">{{cite book | editor=Rossi S | title=[[Australian Medicines Handbook]] 2006 | publisher=Australian Medicines Handbook Pty Ltd, Adelaide | year=2006 | isbn=0-9757919-2-3}}</ref>
===Prevention of preterm births===
Metronidazole has also been used in women to prevent preterm birth associated with [[bacterial vaginosis]], amongst other risk factors including the presence of cervicovaginal fetal fibronectin (fFN). A [[randomised controlled trial]] demonstrated that metronidazole was ineffective in preventing preterm delivery in high-risk pregnant women and, conversely, the incidence of preterm delivery was actually higher in women treated with metronidazole.<ref name="Shennan2006">{{cite journal | author=Shennan A, Crawshaw S, Briley A, Hawken J, Seed P, Jones G, et al. | title=A randomised controlled trial of metronidazole for the prevention of preterm birth in women positive for cervicovaginal fetal fibronectin: the PREMET Study | journal=BJOG | volume=113 | issue=1 | pages=65–74 | year=2006 | pmid=16398774 | doi=10.1111/j.1471-0528.2005.00788.x}}</ref>
Lamont has argued that Metronidazole is not the right antibiotic to administer in these circumstances and was often administered too late to be of use. [[Clindamycin]] administered early in the second trimester to women who test positive for [[bacterial vaginosis]] seems to be more effective.<ref name="Lamont2005">{{cite journal | author=Lamont RF | title=Can antibiotics prevent preterm birth—the pro and con debate | journal=BJOG | volume=112(suppl) | pages=67–73 | year=2005 | pmid=15715599 | doi=10.1111/j.1471-0528.2005.00589.x}}</ref>
==Adverse effects==
Common [[adverse drug reaction]]s (≥1% of patients) associated with [[systemic]] metronidazole therapy include: [[nausea]], [[diarrhea]], and/or metallic taste in the mouth. [[Intravenous]] administration is commonly associated with [[thrombophlebitis]]. Infrequent adverse effects include: [[hypersensitivity]] reactions (rash, itch, flushing, fever), headache, dizziness, [[vomiting]], [[glossitis]], [[stomatitis]], dark urine, and/or [[paraesthesia]].<ref name="AMH2006" />
High doses and/or long-term systemic treatment with metronidazole is associated with the development of [[black hairy tongue]], [[leukopenia]], [[neutropenia]], increased risk of [[peripheral neuropathy]] and/or [[central nervous system|CNS]] toxicity.<ref name="AMH2006" />
Metronidazole is listed by the [[International Agency for Research on Cancer]] (IARC) as a potential human [[carcinogen]]. Although some of the testing methods have been questioned, it has been shown to cause cancer in experimental animals.<ref>National Toxicology Program. Metronidazole. In: Report on carcinogens. 11th ed. Research Triangle Park (NC): U.S. Department of Health and Human Services. [updated 2005 Aug 26; cited 2006 Jun 20]. Available from: [http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s112metr.pdf http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s112metr.pdf]</ref> Nevertheless, it appears to have a fairly low potential for cancer risk and under most circumstances the benefits of treatment outweigh the risk.
Common adverse drug reactions associated with topical metronidazole therapy include local redness, dryness, and/or skin irritation; and eye watering (if applied near eyes).<ref name="AMH2006" />
===Interaction with alcohol===
Consuming [[ethanol]] (alcohol) while using metronidazole causes a [[disulfiram]]-like reaction with effects that can include [[nausea]], [[vomiting]], [[flushing (physiology)|flushing]] of the skin, [[tachycardia]] (accelerated heart rate), [[shortness of breath]], and even death.<ref name="cina">{{cite journal | author=Stephen J Cina, Roger A Russell, Sandra E Conradi | title=Sudden death due to metronidazole/ethanol interaction | journal=American Journal of Forensic Medical Pathology | year=1996 | volume=17 | issue=4 | pages=343–346 | doi=10.1097/00000433-199612000-00013}}</ref> Consumption of alcohol should be avoided by patients during systemic metronidazole therapy and for at least 24 hours after completion of treatment.<ref name="AMH2006" /> However, the mechanism of this reaction in the clinical setting has recently been questioned by some authors,<ref name="Williams2000">{{cite journal | author=Williams CS, Woodcock KR | title=Do ethanol and metronidazole interact to produce a disulfiram-like reaction? | journal=Ann Pharmacother | volume=34 | issue=2 | pages=255–7 | year=2000 | pmid=10676835 | doi=10.1345/aph.19118}}</ref><ref name="Visapaa2002">{{cite journal | author=Visapaa JP, Tillonen JS, Kaihovaara PS, Salaspuro MP | title=Lack of disulfiram-like reaction with metronidazole and ethanol | journal=Ann Pharmacother | volume=36 | issue=6 | pages=971–4 | year=2002 | pmid=12022894 | doi=10.1345/aph.1A066}}</ref> and a possible central toxic serotonin reaction for the alcohol intolerance suggested.<ref name="pmid17963129">{{cite journal |author=Karamanakos PN, Pappas P, Boumba VA, ''et al'' |title=Pharmaceutical agents known to produce disulfiram-like reaction: effects on hepatic ethanol metabolism and brain monoamines |journal=Int. J. Toxicol. |volume=26 |issue=5 |pages=423–32 |year=2007 |pmid=17963129 |doi=10.1080/10915810701583010}}</ref>
==References==
{{reflist}}
==External links==
* [http://www.wedgewoodpharmacy.com/monographs/metronidazole.asp Metronidazole monograph]
* [http://www.merck.com/mmpe/lexicomp/metronidazole.html Merck manuals]
* [http://www.patient.co.uk/showdoc/30003224/]
{{Stomatological preparations}}
{{Antibiotics and chemotherapeutics for dermatological use}}
{{Gynecological anti-infectives and antiseptics}}
{{Other antibacterials}}
{{Agents against amoebiasis and other protozoal diseases}}
[[Category:Nitroimidazole antibiotics]]
[[Category:Antiprotozoal agents]]
[[Category:Dermatological preparations]]
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