Gastrointestinal tract fungal

For some substances, a wealth of genotoxicity data may be available from studies conducted in vitro and/or in vivo. In addition to studies conducted according to test guidehne methods, there may be nonstandard studies available in which first site of contact tissues, i.e., skin, epithelium of the respiratory or gastrointestinal tract, have been examined. In addition, data from plant, fungal, or insect Drosophila) systems may be available. Occasionally, studies of genotoxic effects in humans may also be available. The vahdity and usefulness of each of the data sets to the overall assessment... 

Combinations of amphotericin-B with flucytosine are sometimes used to reduce the occurrence of resistance. Amphotericin-B is not absorbed from the gastrointestinal tract which necessitates intravenous administration. It is 90% protein bound and widely distributed, except for the CNS. For the treatment of fungal meningitis therefore only intrathecal drug administrations can be effective. Amphotericin-B is eliminated very slowly in urine, mainly in an inactive form, with an elimination half-life of about 24 hours which can increase to up to 15 days with repeated doses. 

Fungal infections of the gastrointestinal tract can result in serious diarrhoea. The macrolides amphotericin B (51) and nystatin (52) are used to control this disease in pigs and poultry respectively. 

Absorption of a mycotoxin will occur when it crosses body membranes and enters the blood stream. The primary sites of mycotoxin absorption are the gastrointestinal tract (ingestion of contaminated food), lungs (inhalation of contaminated particles or toxin-containing fungal spores) and the skin (direct contact with contaminated materials or pure mycotoxins). When the mycotoxin enters the blood it is then available for distribution. Livers and kidneys have a high capacity to bind many mycotoxins while other mycotoxins are highly lipophilic and can concentrate in body fat. In the final outcome a toxic response by a mycotoxin will be critically influenced by the rate of absorption, distribution, biotransformation and excretion (Smith et al., 1994). 

Terbinafine interferes with ergosterol biosynthesis, and thereby with the formation of the fungal cell membrane. It is absorbed from the gastrointestinal tract and undergoes extensive metabolism in the liver (tj 14 h). Terbinafine is used topically for dermatophyte infections of the skin and orally for infections of hair and nails where the site (e.g. hair), severity or extent of the infection render topical use inappropriate (see p. 315). Treatment (250 mg/d) may need to continue for several weeks. It may cause nausea, diarrhoea, dyspepsia, abdominal pain, headaches and cutaneous reactions. 

A 16-year-old man with neurofibromatosis type 1, a malignant pheochromocytoma with lung and bone metastases, and candidiasis of the gastrointestinal tract with fungemia was taking nifedipine for arterial hjrper-tension. The fungal infection responded to fluconazole, but three attempts to withdraw the fluconazole resulted in recurrence of headache, palpitation, and increased blood pressure. 

Amphotericin B (Figure 11.2) is not well absorbed from the gastrointestinal tract and it is only used orally for local treatment for oral infections. It is used in veterinary medicine for systemic fungal infections and is usually given intravenously or by intrathecal administration. It is poorly soluble in water and so most formulations make use of sodium deoxycholate, which then permits the formation of a suspension. In human and veterinary medicine, the limiting factor to systemic treatment with amphotericin B is nephrotoxicity. ... 

Nosocomially acquired fungal infections may arise from either exogenous or endogenous flora. Endogenous flora may include normal commensals of the skin, gastrointestinal (GI), genitourinary, or respiratory tract. C. albicans is found as a normal commensal of the GI tract in 20% to 30% of humans. ... 

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