Flora drugs altering

Drugs that alter the Gl flora Drugs that alter the Gl flora may interact with mycophenolate by leading to less MPA available for absorption. 

The effectiveness of an OC is sometimes limited by drug interactions that interfere with gastrointestinal absorption, increase intestinal motihty by altering gut bacteriologic flora, and alter the metabolism, excretion, or binding of the OC 12,13,18,24,57 77 6). 

In subacute toxicity studies only the highest rifaximin dose (i.e. 100 mg/kg, corresponding to 25 times the therapeutic dose in humans) induced mild toxic effects (like, for instance, acute gastroenteritis) connected to the topical GI action of the drug [59, 255], A dose-dependent increase of the total cholesterol value was recorded in female animals [255], most likely due to an alteration of biliary acid metabolism consequent to the antibiotic effect on gut flora [256]. 

Drugs that affect transit time would be expected to alter the normal flora and metabolic activity of the colonic lumen. Oufir et al. (45) investigated the effects of treatment with cisapride and loperamide on fecal flora and SCFA production. By doubling the transit time with loperamide, the concentration of SCFAs was markedly increased whereas by reducing the transit time with cisapride, pH was elevated and the concentration of SCFAs was significantly reduced. 

Nitrofurantoin is administered orally and is rapidly and almost completely absorbed from the small intestine only low levels of activity are achieved in serum because the drug is rapidly metabolized. Relatively high protein binding (about 70%) also affects serum levels, reducing potential for systemic toxicity and alteration of intestinal flora. Relative tissue penetration is much lower than other antimicrobials for UTIs, and therefore, nitrofurantoin is not indicated in the therapy of infections such as pyelonephritis and renal cortical or perinephric abscesses. Nitrofurantoin is rapidly excreted by glomerular filtration and tubular secretion to yield effective urinary levels. In moderate to severe renal dysfunction, toxic blood levels may occur while urinary levels may be inadequate. The drug is inactivated in the liver. 

These antibiotics are partially absorbed from the stomach and upper gastrointestinal tract. Food impairs absorption of all tetracyclines except doxycycline and minocycline. Absorption of doxycycline and minocy-cbne is improved with food. Since the tetracyclines form insoluble chelates with calcium (such as are found in many antacids), magnesium, and other metal ions, their simultaneous administration with milk (calcium), magnesium hydroxide, aluminum hydroxide, or iron will interfere with absorption. Because some of the tetracyclines are not completely absorbed, any drug remaining in the intestine may inhibit sensitive intestinal microorganisms and alter the normal intestinal flora. 

Hypersensitivity reactions (drug fever, skin rashes) to tetracyclines are uncommon. Most adverse effects are due to direct toxicity of the drug or to alteration of microbial flora. 

Drug Interactions Acyclovir Antacids with magnesium and aluminum hydroxides Cholestyramine Drugs that alter gastrointestinal flora may interact with mycophenolate mofetil by disrupting enterohepatic recirculation Probenecid... 

Drugs such as tetracycline and chloramphenicol affect a wide variety of microbial species and are referred to as broad spectrum antibiotics (Figure 28.6C). Administration of broad spectrum antibiotics can drastically alter the nature of the normal bacterial flora and can precipitate a superinfection of an organism, such as Candida whose growth is normally kept in check by the presence of other microorganisms. 

Drug therapy, particularly with broad spectrum antimicrobials or combinations of agents, can lead to alterations of the normal microbial flora of the upper respiratory, intestinal and genitourinary tracts, permitting the overgrowth of opportunistic organisms, especially fungi or resistant bacteria. These infections are often difficult to treat. 

The gastrointestinal tract is the main site of action of acarbose, which is metabolized exclusively within the gastrointestinal tract, principally by intestinal bacteria this process may be adversely affected by antibiotics that alter the intestinal bacterial flora. Acarbose affects the absorption of some drugs (e.g. digoxin). 

METRONIDAZOLE MYCOPHENOLATE Likely 1 in plasma concentration of mycophenolate Theoretically, drugs that alter gastrointestinal flora may 1 oral bioavailability of mycophenolic acid products by 1 bacterial hydrolytic enzymes that are responsible for regenerating mycophenolic acid from its glu-curonide metabolites following first-pass metabolism Avoid co-administration... 

Alteration of normal gut flora has been proposed as a mechanism to explain alterations in the concentrations of several drugs, including digoxin, oral contraceptives, and warfarin, during antibiotic... 

Antimicrobials are the commonest drugs that cause diarrhoea, probably due to alteration of bowel flora. It may range from a mild inconvenience to life-threatening antibiotic-associated (pseudomembranous colitis), due to colonisation of the bowel with Clostridium difficile. The condition particularly affects... 

The most prominent adverse reaction of the lincosamides is diarrhea, which varies from mildly loose bowel movements to life-threatening pseudomembranous colitis (see monograph on Beta-lactam antibiotics). Almost all antimicrobial drugs have been associated with severe diarrhea and colitis however, lincomycin and clindamycin have been particularly incriminated. The incidence of clindamycin-induced diarrhea in hospital is 23%. Diarrhea resolves promptly after withdrawal in most cases. It seems to be dose-related and may result from a direct action on the intestinal mucosa. Severe colitis due to C. difficile is not dose-related and occurs in 0.01-10% of recipients. Clustering of cases in time and place suggests the possibility of cross-infection. Even low doses of clindamycin, in some cases after topical administration, can cause marked alterations in several intestinal functions related to bowel flora (23). There was reduced susceptibility of C. difficile to clindamycin in 80% of French isolates in 1997 (24). Lincomycin was among the antibiotics that were most often associated with the development of antibiotic-associated diarrhea in a Turkish study of 154 patients other associated antibiotics were azithromycin and ampicillin (25). 

Controversy over alteration of the microbial flora of the skin flared in the FDA Over-the-Counter (OTC) Review of Antimicrobial Drugs, especially with reference to total body exposure to antimicrobial/deodorant soaps. The relationship of routine bathing (rinsing) with these soaps with infection was implied in several studies [43-45] and shown conclusively in the study by Taplin [46] in Costa Rica in a population with a high infection rate utilizing a 2% solution of chlorhexidine in water (therefore, 2% available chlorhexidine). 

Oral aminoglycosides reduce the activity of the gut flora, which metabo-lise methotrexate so that more is available for absorption. However, paromomycin and neomycin, in common with other oral aminoglycosides, can cause a malabsorption syndrome, which reduces drug absorption and presumably negates any effect altering the gut flora has. Kanamycin may possibly be different because it causes less malabsorption. 

Neomycin is used to alter the intestinal flora in preparation of the bowel for surgery and in hepatic coma. In patients with allergic contact dermatitis to neomycin it may cause a flare of the skin lesions (Pirila and Rantanen 1960 Ekelund and Moller 1969). Nystatin is effective in eliminating moniliasis. Side effects are rare. A case of fixed drug eruption has been reported (Kandil 1969). 

Limitation of cholesterol absorption either by removal of bile acids or by competitive Inhibition continued to be investigated. Cholestyramine was found to consistently reduce the LDL cholesterol with a possible offsetting of this action by a slight rise in the VLDL cholesterol . Over-all, cholestyramine had a definite hypocholesteremic action. A new copolymer of tetraethylenepentamine and epichlorohydrin, U-26597A, may be somewhat more effective than cholestyramine . The mechanism for the decreased cholesterol absorption following neomycin administration was reported to be due to the drug s ability to increase bile acid secretion as well as its known alteration of intestinal flora . The inhibition of cholesterol esterification was suggested as the mechanism for the cholesterol absorption reduction induced by cholestane-5P,5a,6p triol . 

Vitamin K may be synthesized by intestinal bacteria, and this explains why it is so diflScult to produce vitamin K deficiency by dietary restriction. It has never been produced in man by this means. A change in intestinal flora, such as may be produced by the use of sulfa drugs or antibiotics, often alters the amount of vitamin K avaUahle to the organism (Nutrition Foundation, 1953). 

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