The document discusses nitrofuran compounds used in chemotherapy for bacterial and protozoal infections, focusing on nitrofurazone, furazolidone, nitrofurantoin, and methenamine. It details the mechanisms of action, uses, chemical stability, and common side effects of these drugs, highlighting their effectiveness against various pathogens. Additionally, it mentions methenamine derivatives and fosfomycin, emphasizing their roles in urinary tract infections and their interactions with urine acidity.

1. NITROFURANS
Dr. Shilpa Sudhakar Harak
Asst. Prof., Pharm. Chem.,
GES Sir Dr. M. S. Gosavi College of Pharmaceutical Education and Research, Nasik

2. Introduction
• first Nitro-heterocyclic compounds to be introduced into chemotherapy
• 3 compounds used for the treatment of bacterial infections vastly for nearly 50
years:
i. Nitrofurazone,
ii. Furazolidone, and
iii. Nitrofurantoin
• Fourth nitrofuran is nifurtimox - used as an antiprotozoal agent to treat
trypanosomiasis and leishmaniasis.
• 5th Metronidazole, which is an amebicide (a trichomonicide) and is used for
the treatment of systemic infections caused by anaerobic bacteria.

3. Chemistry
• Derivatives of 5-nitro-2-furaldehyde,
• Formed on reaction with the appropriate hydrazine or amine derivative.
• Antimicrobial activity is present only when the nitro group is in the 5-position
• Nitrofurantoin inhibits DNA and RNA functions through mechanisms that are
not well understood, although bioreductive activation is most possible
mechanism.
Nitrofurazone Furanzolidone Nitrofurantoin

4. Nitrofurazone
• 5-Nitro-2-furaldehyde semicarbazone
• Chemically stable, but moderately light sensitive.
• Used topically in the treatment of burns, in antibiotic resistance bacteria.
• Used to prevent bacterial infection associated with skin grafts.
• Broad spectrum (Gram +ve & Gram –ve)
• Inactive against fungi
• Bactericidal against most bacteria commonly causing surface infections, including S.
aureus, Streptococcus spp., E. coli, Clostridium perfringens, Enterobacter (Aerobacter)
aerogenes, and Proteus spp.;
• Resistant : P. aeruginosa strains

5. Furazolidone
• 3-[(5-Nitrofurylidene)amino]-2-oxazolidinone (Furoxone)
• Bactericidal activity against a relatively broad range of intestinal pathogens,
including S. aureus, E. coli, Salmonella, Shigella, Proteus spp., Enterobacter,
and Vibrio cholerae.
• It is also active against the protozoan Giardia lamblia.
• Oral treatment of bacterial or protozoal diarrhea caused by susceptible
organisms.
• Approximately 5% of the oral dose is detectable in the urine in the form of
several metabolites.
• Contra-indicated with Alcohol as it can inhibit aldehyde dehydrogenase.

6. Nitrofurantoin
• 1-(5-nitro-2-furfurylidene)-1-aminohydantoin
• Oral
• Used in urinary tract infections caused by susceptible strains of E. coli,
enterococci, S. aureus, Klebsiella, Enterobacter, and Proteus spp.
• The most common side effects are gastrointestinal
• Norexia, nausea, and vomiting
• Hypersensitivity reactions (pneumonitis, rashes, hepatitis, and hemolytic
anemia) have occasionally been observed.
• A macrocrystalline form (Macrodantin) is claimed to improve gastrointestinal
tolerance without interfering with oral absorption.

7. Methenamine
• Chemically Hexamethylenetetramine
• Methenamine is a prodrug that can be used for the disinfection of acidic urine.
• Structurally it is polymer of ammonia and formaldehyde which reverts to its
components under mildly acid conditions.
• Formaldehyde is the active antimicrobial component.
• The activity depends on the liberation of formaldehyde.
• The compound is prepared by evaporating a solution of formaldehyde and strong
ammonia water to dryness.

8. Methenamine
• In acidic pH, methenamine is converted to formaldehyde, which acts as an
antibacterial agent.
• Tablets of methenamine are often enteric coated to prevent conversion to
formaldehyde in the stomach.
• Methenamine is cleared intact from the kidney into the urine, where it is
hydrolyzed to formaldehyde if the pH is less than 6.5.
• The rate of hydrolysis is controlled by the urinary pH.

9. Methenamine
• To optimize the antibacterial effect, an acidifying agent such as sodium
biphosphate or ammonium chloride generally accompanies the administration
of methenamine.
• Certain bacterial strains are resistant to the action of methenamine because
they elaborate urease, an enzyme that hydrolyzes urea to form ammonia.
• The resultant high urinary pH prevents the activation of methenamine,
rendering it ineffective.
• This problem can be overcome by the coadministration of the urease inhibitor
acetohydroxamic acid (Lithostat).

10. Methenamine Mandelate
• Hexamethylenetetramine mandelate (Mandelamine) is a white crystalline powder with a sour
taste and practically no odor.
• It is very soluble in water and has the advantage of providing its own acidity, although in its
use, the custom is to carry out a preliminary acidification of the urine for 24 to 36 hours before
administration.

11. Methenamine Hippurate
• Methenamine hippurate (Hiprex) is the hippuric acid salt of methenamine.
• It is readily absorbed after oral administration and is concentrated in the
urinary bladder, where it exerts its antibacterial activity.
• Its activity is increased in acid urine.

12. FOSFOMYCIN
• Fosfomycin (also known as phosphomycin) inhibits enolpyruvial transferase,
an enzyme catalyzing an early step in bacterial cell wall biosynthesis.
• Inhibition results in reduced synthesis of peptidoglycan, an important
component in the bacterial cell wall.
• Fosfomycin is bactericidal against Escherichia coli and Enterobacter faecalis
infections.
• It is used for treatment of uncomplicated urinary tract infections by
susceptible organisms.

13. Phenazopyridine
• 2,6-diamino-3-phenylazopyridine
• Urinary antiseptic
• Active in vitro against staphylococci, streptococci, gonococci, and E. coli, it
has no useful antibacterial activity in the urine.
• Present utility lies in its local analgesic effect on the mucosa of the urinary
tract.
• Usually, phenazopyridine is given in combination with urinary antiseptics.
• Azo-Gantrisin, a fixed-dose combination with the sulfisoxazole, and
• Urobiotic, a combination with the antibiotic oxytetracycline and
sulfamethizole
• The drug is rapidly excreted in the urine, to which it gives an orange-red color.