This MedLibrary.org supplementary page on Nitrofurantoin is provided directly from the open source Wikipedia as a service to our readers. Please see the note below on authorship of this content, as well as the Wikipedia usage guidelines. To search for other content from our encyclopedia supplement, please use the form below:
Related Sponsors
 |
|
|
Nitrofurantoin
|
|
| Systematic (IUPAC) name | |
| 1-[(5-nitro-2-furyl)methylideneamino]imidazolidine-2,4-dione | |
| Identifiers | |
| CAS number | |
| ATC code | J01 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C8H6N4O5 |
| Mol. mass | 238.16 |
| Pharmacokinetic data | |
| Bioavailability | 40% |
| Metabolism | liver (75%) |
| Half life | 20 minutes |
| Excretion | urine and bile |
| Therapeutic considerations | |
| Pregnancy cat. |
B |
| Legal status |
Rx, PoM |
| Routes | oral |
Nitrofurantoin is an antibiotic. It is usually used in treating urinary tract infection. Like many other drugs, it is often used for killing E Coli.
Contents |
Pharmacology
Organisms are said to be susceptible to nitrofurantoin if their Minimum inhibitory concentration (MIC) is 32μg/ml or less. The peak blood concentration of nitrofurantoin following an oral dose of nitrofurantoin 100mg, is less than 1 μg/ml and may be undetectable; tissue penetration is negligible; the drug is well concentrated in the urine: 75% of the dose is rapidly metabolised by the liver, but 25% of the dose is excreted in the urine unchanged, reliably achieving levels of 200 μg/ml or more. For this reason, nitrofurantoin cannot be used to treat anything other than simple cystitis.
At the concentrations achieved in urine, nitrofurantoin is bacteriocidal. The mechanism of action of nitrofurantoin is unique and complex. The drug works by damaging bacterial DNA, since its reduced form is highly reactive. This is made possible by the rapid reduction of nitrofurantoin inside the bacterial cell by flavoproteins (nitrofuran reductase) to multiple reactive intermediates that attack ribosomal proteins, DNA,[1] respiration, pyruvate metabolism and other macromolecules within the cell. It is not known which of the actions of nitrofurantoin is primarily responsible for its bacteriocidal acitivity.
Nitrofurantoin and the quinolone antibiotics are mutually antagonistic in vitro. It is not known whether this is of clinical significance, but the combination should be avoided.
Resistance to nitrofurantoin may be chromosomal or plasmid mediated and involves inhibition of nitrofuran reductase.[2] Acquired resistance in E. coli continues to be rare.
Nitrofurantoin and its metabolites are excreted mainly by the kidneys. In renal impairment, the concentration achieved in urine may be subtherapeutic. Nitrofurantoin should not be used in patients with a creatinine clearance of 60 ml/min or less.
Uses
The normal adult dose of nitrofurantoin is 50 to 100 mg four times daily for seven days. If a long-acting preparation (e.g., Macrobid) is used then the dose is 100mg twice daily. The pediatric dose is 3mg/kg/day in four divided doses. Nitrofurantoin should be taken with food, as this improves the absorption of the drug by 45%.
Nitrofurantoin is only clinically proven for use against E. coli or Staph. saprophyticus. It may also have in vitro activity against:
- Coagulase-negative staphylococci
- Enterococcus faecalis,
- Staphylococcus aureus,
- Streptococcus agalactiae,
- Citrobacter species,
- Klebsiella species,
and is used in the treatment of infections caused by these organisms. Only a minority of Enterobacter species and Klebsiella species are sensitive to nitrofurantoin; nitrofurantoin has no activity against
- Acinetobacter species,
- Morganella species,
- Proteus species,
- Providentia species,
- Serratia species, or
- Pseudomonas species.
Nitrofurantoin must never be used to treat pyelonephritis,[3] renal abscess, and pyeloempyema because of extremely poor tissue penetration and low blood levels. Urinary catheter infections may be treated with nitrofurantoin if there are no systemic features; the catheter must be changed after 48 hours of antibiotics and treatment is ineffective if the catheter is not replaced or removed.
Adverse effects
Nitrofuratoin can cause nausea and vomiting, fever, rash, hypersensitivity pneumonitis. When given for long periods of time, nitrofurantoin can cause progressive pulmonary interstitial fibrosis. All these side effects are much more common in the elderly.
Patients should be informed that nitrofurantoin colours urine a dark orange-brown; this is completely harmless.
Neonates (babies up to the age of one month) have immature enzyme systems in their red blood cells (glutathione instability) and nitrofurantoin must therefore not be used because it can cause haemolytic anaemia. For the same reason, nitrofurantoin should not be given to pregnant women after 38 weeks of pregnancy, or who are about to give birth.
Nitrofurantoin is contraindicated in patients with decreased renal function (CrCl < 60ml/min) due to systemic accumulation and subtherapeutic levels reached in the urinary tract.
Banned usage in Foods
Nitrofuratoin residues from the breakdown of Nitrofurans have been found in Vietnam, China, Brazil, and Thailand chicken used as veterinary antibiotics, see FAO: Nitrofuran study The European Union banned the use of nitrofurans in food producing animals by classifying it in ANNEX IV (list of pharmacologically active substances for which no maximum residue limits can be fixed) of the Council Regulation 2377/90. The Food and Drug Administration (FDA) of the United States of America prohibited furaltadone since February 1985 and withdrew the approval for the other nitrofuran drugs (except some topical uses) in January 1992. The topical use of furazolidone and nitrofurazone was prohibited in 2002. Australia prohibited the use of nitrofurans in food production in late 1992. Japan did not allocate MRLs for nitrofurans leading to the implementation of a "zero tolerance or no residue standard". In Thailand, the Ministry of Health issued in 2001 Proclamation No. 231 MRL of veterinary drug in food which did not allocate MRL for nitrofurans. The Ministry of Agriculture and Cooperatives had already prohibited importation and use of furazolidone and nitrofurazone in animal feed in 1999 which was extended to all nitrofurans in 2002. Several metabolites of Nitrofurans, such as Furazolidone, Furaltadone and Nitrofurazone cause cancer or genetic damage in rats. (see study)
Precautions
Nitrofurantoin must be taken with food and can cause bleeding in the stomach, vomiting and other gastrointestinal disruptions if these warnings are not adhered to. Nitrofurantoin is contraindicated in patients with glucose-6-phosphate dehydrogenase deficiency because of risk of extravascular hemolysis resulting in anemia.
Trade names
- Furadantin (U.S., UK)
- Macrobid (long acting preparation for twice daily dosing available in U.S., Canada, and UK)
- Macrodantin (U.S., UK)
- furatin( inda medica INDIA)
References
- ^ Tu Y, McCalla DR (1975). "Effect of activated nitrofurans on DNA,". Biochem Biophys Acta 402: 142–49.
- ^ McCalla DR, Kaiser C, Green MHL (1978). "Genetics of nitrofurazone resistance in Escherichia coli". J Bacteriol 133: 10–16.
- ^ Richards WA, et al. (1955). "Nitrofurantoin: Clinical and laboratory studies in urinary tract infections". Arch Intern Med 96: 437–50.
- drugs.com for Macrodantin
- Meds-Help.com for Nitrofurantoin side effects, interactions and information
- RxList for Macrobid (Nitrofurantoin)
|
|||||||||||||||||||||||||||||||||||
Wikipedia content modification information:
- This page was last modified on 10 October 2008, at 11:19.
Wikipedia Authorship and Review
Wikipedia content provided here is not reviewed directly by MedLibrary.org. Wikipedia content is authored by an open community of volunteers and is not produced by or in any way affiliated with MedLibrary.org.
Wikipedia Usage Guidelines
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article on "Nitrofurantoin".
The URL for this specific entry is:
All Wikipedia text is available under the terms of the GNU Free Documentation License. (See Copyrights for details). Wikipedia® is a registered trademark of the Wikimedia Foundation, Inc.