1. The four main members of Nitrofurans are Nitrofurantoin, Nitrofurazone, Furazolidone, and Nifuroxazide.
2. Nitrofurans work by being reduced in bacterial cells through an enzymatic reaction, forming highly reactive intermediates that damage bacterial DNA.
3. Nitrofurantoin is rapidly and completely absorbed from the GI tract, but does not achieve antibacterial concentrations in plasma or tissues. It reaches bactericidal concentrations in the urine and is eliminated through tubular secretion, coloring the urine brown.
3. INTRODUCTION
Nitrofurans
Nitrofurans are a class of drugs typically used as
antibiotics or antimicrobials.
Members of this class of drugs include:
Antibacterials (antibiotics) Difurazone (also known
as Nitrovin) — an antibacterial growth promoter
used in the animal feeds.
Since the first reports of the antibacterial action
of nitrofuran derivatives in the 1940s (DODD and
STILLMAN, 1944; DANN and MOLLER, 1947)
4. Chemistry of
Nitrofurans
Nitrofurans are a class of drugs typically used as
antibiotics or antimicrobials.
Members of this class of drugs include:
Antibacterials (antibiotics) Difurazone (also known
as Nitrovin) — an antibacterial growth promoter
used in the animal feeds.
Nitrofurans
5. Mechanism of
Nitrofurans
It is reduced by bacterial flavoproteins to reactive
intermediates that inhibit bacterial ribosomes and
other macromolecules. Protein synthesis, aerobic
energy metabolism, DNA and RNA synthesis, and
cell wall synthesis are inhibited.
Since the first reports of the antibacterial action
of nitrofuran derivatives in the 1940s (DODD and
STILLMAN, 1944; DANN and MOLLER, 1947)
6. Antimicrobial
activity of
Nitrofurans
Bacteria - Gram positive , Gram negative some
protozoa and fungi
Moderate -anaerobes, Resistance-
Pseudomonas. Activity more in PH < 5.5 and well
absorbed after oral administration
Toxic signs seen with excessive doses
of nitrofuran derivatives include CNS
involvement (excitement, tremors,
convulsions, peripheral neuritis), GI
disturbances, poor weight gain, and
depression of spermatogenesis.
7. Nitrofurans
Member of class drugs
Antibacterials (antibiotics)
●Difurazone (also known as Nitrovin) — an antibacterial growth promoter used in the animal feeds
● Furazolidone
● Nifurfoline
● Nifuroxazide
● Nifurquinazol
● Nifurtoinol
● Nifurzide
● Nitrofural (also known as nitrofurazone)
● Nitrofurantoin — a drug used to treat urinary tract infections[
● Ranbezolid — technically an oxazolidinone antibiotic bearing a nitrofuran group
8. Antimicrobials
● Furaltadone — an antiprotozoal
● Furazidine — an antibacterial and antiprotozoal
● Furylfuramide — a formerly used food preservative
● Nifuratel — an antiprotozoal and antifungal
● Nifurtimox — an antiprotozoal
● FANFT, a potent nitrofuran derivative tumor initiator. It causes bladder tumors in all animals
studied and is mutagenic to many bacteria.
9. Resistance & Drug
interaction of
Nitrofurans
Chromosomal mutation - Permeability
absence of intracellular reductase enzyme.
Drug interaction
Antagonistic – Nalidixic acid
10. Pharmacokinetics
& toxicity of
Nitrofurans
It is Well absorbed orally , short t½, elimination
through kidney. No nitrofuran is effective
systemically.
Toxicity
Peripheral neuritis, GI irritation, Haemorrhagic
diathesis, poor weight gain, mutagenic and
procarcinogenic effect. CNS involvment
(excitement, tremors, convulsions peripheral
neuritis) , various hypersensitive reactions,
depression of spermatogenesis.
12. NITROFURANTOIN
●To treat UTI by E.coli, S.aureus, S. pyogenes, and
A. aergenes.
●After administration PO, nitrofurantoin is rapidly and
completely absorbed( the microcrystal form takes
longer) and is swiftly eliminated by the kidneys
●when the PH reaches =5, the drug becomes
supersaturated without precipitation and its antibacterial
action is maximal.
●can be administered PO or parenteral. The dosage for
dogs and cats is 4.4 mg /kg, TID for 4- 10 days
●cause nausea, vomition, and diarrhea etc,
polyneropathy is a serious effect seen in humans
Animals with decreased renal function have a
predisposition for polyneuritis.
●yellow discoloration of teeth occasionally has been
reported in very young animals
13. NITROIMIDAZOLES
Heterocyclic, compounds with 5
membered nucleus similar to
nitrofurans
Mechanism of action
●After entry into the cell it undergoes reduction
under anaerobic condition to produce unstable
intermediates which is responsible for antibacterial
activity.
● It causes excessive breakage of DNA strand and
inhibit DNA repair enzyme DNA ase - bactericidal
Reduction system is low in aerobes
● Resistance is rare.
● It involves reduced intracellular drug activation.
Cross resistance between nitroimidazole is
complete and some with nitrofurans.
14. Pharmacokinetics
NITROIMIDAZOLES
● It is well absorbed in monogastrics and horses
from GIT.
●Highly lipophilic and excellent tissue penetration
(even into blood brain barrier), oxidised and
conjugated in the liver and 2/3 excreted unchanged in
urine.
15. Pharmacokinetics & Drug interaction
NITROIMIDAZOLES
● It is well absorbed in monogastrics and horses
from GIT.
●Highly lipophilic and excellent tissue
penetration (even into blood brain barrier),
oxidised and conjugated in the liver and 2/3
excreted unchanged in urine.
Drug interaction
●No interference with penicillin G, Amoxcillin+Cloxacillin,
cefoxitin, clindamycin, erythromycin.
16. TOXICITY AND CLINICAL APPLICATION
NITROIMIDAZOLES
● High dose- neurotoxicity and reversible bone
marrow suppression
●Carcinogenic- not used in food producing
animals in US and not approved by FDA for use
in cattle.
●Teratogenic not used in first trimester of
pregnancy
●Dog- nausea, retching and uneasiness
17. CLINICAL APPLICATION
NITROIMIDAZOLES
● Amoebiasis, Trichomoniasis, Giardiasis,
Anaerobic bacterial infection, abdominal
abscess, peritonitis, empyema, genital tract
infection, meningitis and necrotic tissue.
● Cattle- urethral douche in trichomoniasis
● Pyometra- mixed infection
● Swine dysentery - Dimetridazole in feed /
water
● Horses- anaerobic pleuropnemonia,mixed
infection of gastrointestinal tract
● Dogs and cats- acute gingivitis, periodantal
disease, Giardiasis, anal sac infection and
clostridium difficult enteritis
18. SUMMARY
1.What are the 4 members of Nitrofurans?
(i).Nitrofurantoin
- (ii)Nitrofurazone
(iii)Furazolidone
(iv) Nifuroxazide
2.What is Mechanism of action Nitrofurans?
(i) Reduction of nitrofurans in bacteria's cells- reaction is enzymatically controlled
(ii) Highly reactive intermediated are formed - they are responsible for the capacity of the
drug to damage bacterial DNA
3.What is Pharmacokinetic properties of Nitrofurantoin?
(i) Absorbed rapidly and completely from GI-tract
(ii)Antibacterial concentration is not achieved in plasma and tissues
(iii)Bactericidal concentration is reached in the urine
(iv)Eliminated by tubular secretion
(v)colors urine brown
19. 4. What are the toxicity and adverse effects Nitrofurans ?
(i) Mutagenic, carcinogenic potential
(ii)Nausea, vomiting, diarrhea
(iii)Allergy
(iv)Bleeding from GI tract
(v)Visual disturbances
(vi)Peripheral neuritis
(vii)Spermatogenesis reduction
5. What are the members of Nitroimidazoles?
(i) Metronidazole
(ii) Ronidazole
(iii)Dimetronidazole
(iv)Tinidazole
(v) Ipronidazole
20. 6. What are the clinical applications of Nitroimidazoles in different animals?
(i) Horses - anaerobic infections; pleuropneumonia, lung abscesses and
Clostridial enterocolitis
(ii)Small animals - anaerobic infections; bacterial stomatitis, osteomyelitis,
hepatitis +++
(iii)Cattle - trichomonasis in bulls
7. What are the route of administration Nitroimidazoles?
(i)Oral
(ii)Per rectum
(iii)Intravenous
(iii)Topical
8. What is route of nitrofuratoin elimination?
(i)urinary biliary elimination
9.In what P
H
poor activity of nitrofuratoin?
(i) Alkaline
