Nitrofurantoin

Structural formula
General
Non-proprietary name	Nitrofurantoin
other names	( E ) -1 - [(5-nitrofurfurylidene) amino] imidazolidine-2,4-dione; Furadoxyl; ( E ) - N - (5-nitro-2-furfurylidene) -1-aminohydantoin;
Molecular formula	C 8 H 6 N 4 O 5
Brief description	yellow solid
External identifiers / databases
EC number	200-646-5
ECHA InfoCard	100,000,587
PubChem	6604200
ChemSpider	4510228
DrugBank	DB00698
Wikidata	Q422669
Drug information
ATC code	J01 XE01
Drug class	Antibiotics , urinary tract anti-infectives
Mechanism of action	Bacteriostasis
properties
Molar mass	238.16 g mol −1
Physical state	firmly
Melting point	268 ° C
pK s value	7.2
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
H and P phrases	H: 302-317-334
	P: 261-280-342 + 311
Toxicological data	604 mg kg −1 ( LD 50 , rat , oral )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Nitrofurantoin is an antibiotic drug used to treat urinary tract infections .

Structurally, a synthetic nitrofuran - derivative . It is a chemotherapeutic agent used to treat bacterial diseases of the urinary tract. The drug has a wide spectrum of activity. In the treatment of uncomplicated urinary tract infections in particular, it is the agent of first choice, but it can cause serious side effects if used long-term and in high doses. Nitrofurantoin requires a prescription.

Mechanism of action

Nitrofurantoin induces DNA strand breaks in the prokaryotic cells and thus has a bacteriostatic effect.

application

So far, the active ingredient has mostly been used as a reserve antibiotic for the treatment of urinary tract infections if these cannot be treated with another antibiotic or other antibiotics cannot be used (e.g. in the case of intolerance). In the current S3 guideline for the treatment of uncomplicated urinary tract infections, however, it is recommended as the first choice for the treatment of uncomplicated cystitis due to the favorable resistance situation. The capsules are swallowed whole with sufficient liquid with meals .

Spectrum of activity

Nitrofurantoin only develops its full effect in the urine. It works against:

The following bacteria have a natural resistance to nitrofurantoin, so that this antibiotic is not effective in infections caused by these pathogens:

frequent side effects

nausea
Vomit
Loss of appetite
fatigue

Occasional side effects

allergic reactions of the lungs
Cough, fever, chills
Chest pain
Shortness of breath
Eye tremors
Drowsiness
dizziness
Powerlessness
a headache
sleepiness
Pulmonary fibrosis

Rare side effects

Inflammation of the liver
Feeling down (depression)
Happiness
confusion
benign increase in intracranial pressure
Changes in the blood count (see the package insert)

Side effects in patients with impaired kidney function, anemia or diabetes as well as with vitamin B deficiency:

Disorder of the nervous system (tingling sensation) in the hands and feet
Inflammation of the optic nerve

Described side effects

Itching of the skin
Hives
various rashes
Flaking
Blistering
temporary hair loss

Others

Nitrofurantoin has also been causally linked to pleural effusion .

Contraindications

Do not take nitrofurantoin:

In patients with known hypersensitivity to nitrofurantoin or other nitrofurans
In patients with renal dysfunction with creatinine clearance below 60 ml / min or with increased creatinine plasma levels.
With glucose-6-phosphate dehydrogenase deficiency (see «Pregnancy / Breastfeeding» in the package insert).
For acute porphyria.
In infants under 3 months of age and at the end of pregnancy (during labor and delivery) because of the theoretical possibility of haemolytic anemia in the fetus or newborns (under 3 months) as a result of the immature erythrocyte enzyme system.

Oliguria, anuria. Polyneuropathy, neuritis. Pulmonary fibrosis.

Special warnings and precautions for use

Because of the alcohol intolerance, alcohol consumption should be completely avoided during therapy with the active ingredient nitrofurantoin. Regular blood counts, liver and kidney values should be checked, especially with long-term therapy. For short-term therapy, a doctor's visit is required after 3 days. Here the urine is checked again.

Children should not take the drug if possible. The drug must not be used in severe renal impairment.

The drug should be discontinued immediately if any of the following symptoms occur:

Coughing fits
Shortness of breath
Chest pain
fever
Allergic reaction
Cholestasis
Signs of polyneuropathy

synthesis

The synthesis of nitrofurantoin can be done in two steps. First, the hydantoin derivative 3 is synthesized starting from chloroacetic acid and hydrazine :

Here, chloroacetic acid and hydrazine react in a nucleophilic substitution to form aminoglycine ( 1 ). Subsequently, with the addition of potassium cyanate, N- amino- N -carbamoylglycine ( 2 ) is formed, which then forms aminohydantoin ( 3 ) in an intramolecular dehydration . In the second step, ( 3 ) reacts in a further dehydration with nitrofuran, resulting in the desired nitrofurantoin ( 4 ):

Trade names

Monopreparations

Furadantin (D, A, CH), Nifurantin (D), Nifuretten (D), Urodin (CH), Uro-Tablinen (D), Uvamin (CH), as well as generic (D, A)

Combination preparations

Nifurantin B6 (D)

literature

W. Forth, D. Henschler, W. Rummel: General and special pharmacology and toxicology . 9th edition. Urban & Fischer, Munich 2005, ISBN 3-437-42521-8 .
Recurring bladder infections: When every toilet is on fire. In: Spiegel online. February 25, 2014

Individual evidence

↑ ^a ^b ^c ^d ^e data sheet nitrofurantoin from Sigma-Aldrich , accessed on May 14, 2017 ( PDF ).
↑ Entry on nitrofurantoin. In: Römpp Online . Georg Thieme Verlag, accessed on July 19, 2019.
↑ K. Gupta, TM Hooton, PL Roberts, WE Stamm: Short-course nitrofurantoin for the treatment of acute uncomplicated cystitis in women. In: Archives of internal medicine. Volume 167, Number 20, November 2007, pp. 2207-2212, doi : 10.1001 / archinte.167.20.2207 , PMID 17998493 .
↑ Thomas Herdegen, Vicki Wätzig: short textbook pharmacology . 3. Edition. Thieme, Stuttgart 2013, ISBN 978-3-13-142293-4 , pp. 592 .
↑ Florian ME Wagenlehner, Udo Hoyme, Martin Kaase, Reinhard Fünfstück, Kurt G. Naber, Guido Schmiemann: Clinical guidelines for uncomplicated urinary tract infections (2011) . In: Dtsch Arztebl Int . tape 108 , no. 24 , 2011, p. 415-423 ( aerzteblatt.de [accessed June 20, 2011]).
↑ Jürgen Freyschmidt: manual diagnostic radiology. Volume 3, Springer, 2003, ISBN 3-540-41421-5 , p. 591.
↑ Berthold Jany, Tobias Welte: Pleural effusion in adults - causes, diagnosis and therapy. In: Deutsches Ärzteblatt. Volume 116, No. 21, (May) 2019, pp. 377-385, here: p. 380.
↑ ^a ^b Axel Kleemann ; Jürgen Engel; Bernhard Kutscher; Dietmar Reichert: Pharmaceutical Substances - Syntheses, Patents and Applications of the most relevant APIs. , 5th edition, Georg Thieme Verlag KG, 2009, ISBN 978-3-13-558405-8 , p. 981.

[sigma-1] ↑ ^a ^b ^c ^d ^e data sheet nitrofurantoin from Sigma-Aldrich , accessed on May 14, 2017 ( PDF ).

[römpp-2] Entry on nitrofurantoin. In: Römpp Online . Georg Thieme Verlag, accessed on July 19, 2019.

[3] K. Gupta, TM Hooton, PL Roberts, WE Stamm: Short-course nitrofurantoin for the treatment of acute uncomplicated cystitis in women. In: Archives of internal medicine. Volume 167, Number 20, November 2007, pp. 2207-2212, doi : 10.1001 / archinte.167.20.2207 , PMID 17998493 .

[4] Thomas Herdegen, Vicki Wätzig: short textbook pharmacology . 3. Edition. Thieme, Stuttgart 2013, ISBN 978-3-13-142293-4 , pp. 592 .

[5] Florian ME Wagenlehner, Udo Hoyme, Martin Kaase, Reinhard Fünfstück, Kurt G. Naber, Guido Schmiemann: Clinical guidelines for uncomplicated urinary tract infections (2011) . In: Dtsch Arztebl Int . tape 108 , no. 24 , 2011, p. 415-423 ( aerzteblatt.de [accessed June 20, 2011]).

[6] Jürgen Freyschmidt: manual diagnostic radiology. Volume 3, Springer, 2003, ISBN 3-540-41421-5 , p. 591.

[7] Berthold Jany, Tobias Welte: Pleural effusion in adults - causes, diagnosis and therapy. In: Deutsches Ärzteblatt. Volume 116, No. 21, (May) 2019, pp. 377-385, here: p. 380.

[Kleemann1-8] Axel Kleemann ; Jürgen Engel; Bernhard Kutscher; Dietmar Reichert: Pharmaceutical Substances - Syntheses, Patents and Applications of the most relevant APIs. , 5th edition, Georg Thieme Verlag KG, 2009, ISBN 978-3-13-558405-8 , p. 981.