NAME:Tone Tedjere Oristesholayemi DEPARTMENT: PHARMACOLOGY MATRIC NO:17/MHS02/089 COURSE CODE:PHA 306 NITROFURANTOIN Nitrofurantoin is an antibiotic that fights bacteria in the body. Nitrofurantoin is used to treat urinary tract infections. Antibacterial activity Nitrofurantoin has been shown to have good activity against: • E. coli • Staphylococcus saprophyticus • Coagulase negative staphylococci • Enterococcus faecalis • Staphylococcus aureus • Streptococcus agalactiae • Citrobacter species MECHANISM OF ACTION The mechanism of action 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, respiration, pyruvate metabolism and other macromolecules within the cell. Nitrofurantoin exerts greater effects on bacterial cells than mammalian cells because bacterial cells activate the drug more rapidly. It is not known which of the actions of nitrofurantoin is primarily responsible for its bactericidal activity. The broad mechanism of action for this drug likely is responsible for the low development of resistance to its effects, as the drug affects many different processes important to the bacterial cell. Pharmacokinetics, Route of Administration and Dosage Nitrofurantoin was initially produced in microcrystalline form (nitrofurantoin monohydrate); a macrocrystalline for­mulation with a slower absorption rate and thus improved gastrointestinal tolerance was later introduced. Currently most formulations are either purely macrocrystalline or mixed (25% macrocrystalline/75% microcrystalline). Bioavailability is 80%, with roughly 25% of nitrofurantoin excreted in the urine unchanged. Except in patients with severe renal failure, serum concentrations are almost undetectable, with peak levels of 1 µg/mL. This is because of destruction of nitrofurantoin in the tissues and, in particular, a very rapid renal elimination by glomerular filtration (20%) and tubular secretion, resulting in a serum half-life of only 20 minutes in patients with normal renal function. Excretion is complete within 6 hours after intake and urine concentrations of 200–400 µg/mL are achieved after a dose of 100 mg q8h. Nitrofurantoin achieves therapeutically active concentrations only in the lower urinary tract; it does not penetrate other body sites in therapeutic concentrations.13 Nitrofurantoin's use in most stages of pregnancy appears to be safe. However, some authorities advise avoidance in pregnant women at term (38–42 weeks' gestation) due to the possible risk of hemolytic anemia in the newborn. NOTE Nitrofurantoin should not be taken if you have severe kidney disease, urination problems, or a history of jaundice or liver problems caused by nitrofurantoin. ADVERSE EFFECTS Along with its needed effects, nitrofurantoin may cause some unwanted effects. Although not all of these side effects may occur: More common: • Changes in facial skin color • chest pain • chills • cough • fever • general feeling of discomfort or illness • hives • hoarseness • itching • joint or muscle pain • shortness of breath • skin rash • sudden trouble in swallowing or breathing • swelling of the face, mouth, hands, or feet • troubled breathing   Rare: • general tiredness and weakness • light-colored stools • loss of appetite • loss of heat from the body • mental depression • mood or mental changes • nausea or vomiting • pale skin • pale stools • red skin lesions, often with a purple center • red, irritated eyes • red, swollen skin • red, thickened, or scaly skin • skin rash • sores, ulcers, or white spots on the lips or in the mouth • swollen or painful glands • tenderness of salivary glands • unpleasant breath odor • upper right abdominal pain • visual changes • vomiting of blood • wheezing or tightness in the chest • yellow eyes or skin