Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of chronic alcohol consumption on vitamin A metabolism was investigated in male rats. Liquid diets containing five times the NRC requirement for vitamin A and varied levels of ethanol were fed. The vitamin A content of the liver was decreased in rats receiving alcohol. Liver lipids were only slightly elevated in alcohol-fed rats. Hepatic vitamin A storage was also decreased in rats fed 30% calories as alcohol and beta-carotene or vitamin A at the NRC requirement level, but not in rats fed one-sixth the NRC requirement as vitamin A. The activities of alcohol dehydrogenase, NADPH cytochrome c reductase, and retinol dehydrogenase were not altered in hepatic or testicular tissue by the vitamin A or alcohol content of the diet. When an intragastric dose of [3H]retinyl acetate or [14C]beta-carotene was administered, fecal excretion of radioactivity was lower than controls in rats receiving 30% ethanol in the diet for a total of 4 weeks, for 1 week following 7 weeks of control diet consumption, and after an acute dose of ethanol. Recovery of the 3H label was greater in the testes of rats chronically consuming ethanol. When a solution containing [3H]retinyl acetate or [3H]beta-carotene with or without ethanol was injected into intestinal segments, no alterations in absorption of retinyl acetate or beta-carotene due to ethanol occurred. It is concluded that alcohol consumption results in decreased hepatic vitamin A storage, which is not due to the malabsorption of either retinyl acetate or beta-carotene, or to altered activities of several enzymes involved in ethanol and vitamin A metabolism.
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PMID:Effect of chronic alcohol consumption and moderate fat diet on vitamin A status in rats fed either vitamin a or beta-carotene. 668 29

The management of MDR-TB requires that the clinician become familiar with the "second-line" antimycobacterial agents. These drugs are generally less potent and frequently more toxic than isoniazid and rifampin. Because they are less active, innovative dosing schedules may allow us to take advantage of the few strengths that they possess. This approach will require further research into the dose-response relationships for each agent. Based on our current knowledge of these drugs, practical guidelines for their use have been described. These guidelines include the gradual escalation of the oral doses of PAS, cycloserine, and ethionamide over several days, and the intravenous administration of streptomycin and capreomycin. Both ciprofloxacin and ofloxacin may be used for the treatment of MDR-TB, but data from clinical trials are currently lacking. Finally, because patients with AIDS appear to develop antimycobacterial drug malabsorption over the course of their HIV infection, therapeutic drug monitoring can be used to verify drug absorption in the individual patient. This approach may improve therapy for that patient and prevent the selection of additional drug resistance.
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PMID:Pharmacology of the antimycobacterial drugs. 823 10

Tuberculosis (TB) is the world's second leading infectious killer. Cases of multidrug-resistant (MDR-TB) and extremely drug-resistant (XDR-TB) have increased globally. Therapeutic drug monitoring (TDM) remains a standard clinical technique for using plasma drug concentrations to determine dose. For TB patients, TDM provides objective information for the clinician to make informed dosing decisions. Some patients are slow to respond to treatment, and TDM can shorten the time to response and to treatment completion. Normal plasma concentration ranges for the TB drugs have been defined. For practical reasons, only one or two samples are collected post-dose. A 2-h post-dose sample approximates the peak serum drug concentration (Cmax) for most TB drugs. Adding a 6-h sample allows the clinician to distinguish between delayed absorption and malabsorption. TDM requires that samples are promptly centrifuged, and that the serum is promptly harvested and frozen. Isoniazid and ethionamide, in particular, are not stable in human serum at room temperature. Rifampicin is stable for more than 6 h under these conditions. Since our 2002 review, several papers regarding TB drug pharmacokinetics, pharmacodynamics, and TDM have been published. Thus, we have better information regarding the concentrations required for effective TB therapy. In vitro and animal model data clearly show concentration responses for most TB drugs. Recent studies emphasize the importance of rifamycins and pyrazinamide as sterilizing agents. A strong argument can be made for maximizing patient exposure to these drugs, short of toxicity. Further, the very concept behind 'minimal inhibitory concentration' (MIC) implies that one should achieve concentrations above the minimum in order to maximize response. Some, but not all clinical data are consistent with the utility of this approach. The low ends of the TB drug normal ranges set reasonable 'floors' above which plasma concentrations should be maintained. Patients with diabetes and those infected with HIV have a particular risk for poor drug absorption, and for drug-drug interactions. Published guidelines typically describe interactions between two drugs, whereas the clinical situation often is considerably more complex. Under 'real-life' circumstances, TDM often is the best available tool for sorting out these multi-drug interactions, and for providing the patient safe and adequate doses. Plasma concentrations cannot explain all of the variability in patient responses to TB treatment, and cannot guarantee patient outcomes. However, combined with clinical and bacteriological data, TDM can be a decisive tool, allowing clinicians to successfully treat even the most complicated TB patients.
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PMID:Therapeutic drug monitoring in the treatment of tuberculosis: an update. 2484 78