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)

Tuberculosis is a growing international health concern; it is the leading infectious cause of death in the world today. The fluoroquinolones are the most recent class of drugs offering hope in the fight against this disease. Ciprofloxacin, ofloxacin, levofloxacin and sparfloxacin are currently the most commonly used agents used against Mycobacterium tuberculosis (TB), with in vitro minimum inhibitory concentrations (MICs) of 0.1 to 4 mcg/ml. Resistance in TB to fluoroquinolones may occur spontaneously or may be acquired, especially when these agents are used inappropriately. Cross-resistance among the fluoroquinolones has been shown in TB. The fluoroquinolones offer a favourable pharmacokinetic profile for the treatment of TB. Most demonstrate excellent oral bioavailability and achieve maximum (peak) serum concentrations well above the MIC. They are also distributed widely, including intracellularly. The fluoroquinolones are cleared renally and/or hepatically, with varying serum half-lives. Fluoroquinolones are most effective when the peak concentration (Cmax) to MIC ratio is maximised. Fluoroquinolones such as ciprofloxacin and ofloxacin have been used in regimens for the prevention of TB, but have been poorly tolerated when used in combination with pyrazinamide. Favourable responses with fluoroquinolones in regimens used in the treatment of clinical TB disease have been seen. They, however, are not to be considered as equal replacements for isoniazid or rifampicin (rifampin) and should be used with at least 2 other antituberculous agents. Therapeutic drug monitoring of fluoroquinolones is beneficial in assuring that maximum Cmax to MIC ratios are being achieved, especially in patients at risk for malabsorption, such as those infected with HIV. Higher, once-daily doses of most fluoroquinolones are becoming more common in treating TB. Fluoroquinolones are generally well tolerated with long term use in treating TB, but rare, serious adverse effects have been reported with general fluoroquinolone use. The most common drug interactions with fluoroquinolones in TB therapy include the malabsorption interactions associated with multivalent cations and cytochrome P450 interactions with ciprofloxacin. An increased risk of central nervous system effects with concomitant cycloserine has been reported and seen clinically. When using fluoroquinolones to treat TB, careful consideration of individual susceptibility patterns, pharmacokinetic and toxicity profiles should be taken. The aid of a TB expert may also be warranted. The exact role of the fluoroquinolones in treating TB remains to be determined.
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PMID:The role of fluoroquinolones in tuberculosis today. 1121 74

Weight loss in the HIV patient appears to result from the interplay of poor nutritional intake, altered metabolism, and malabsorption. Rapid weight loss, defined as greater than 4 kg in four months or less, is associated with non-gastrointestinal secondary infection; and slower weight loss is typically associated with diarrheal disorders, malabsorption and villous atrophy. Non-infectious causes of HIV-associated diarrhea may include hyperosmolar tubal feedings, antibiotics, magnesium-containing antacids and supplements, Vitamin C, or sorbitol-containing liquid medications. Antidiarrheal agents fall into three categories: antimotility agents, agents acting directly in the intestinal lumen, and hormonal agents such as octreotide. In one study, 41 percent of the subjects experienced a reduction in diarrhea when treated with octreotide. Nutritional deficits may be associated with painful symptoms of opportunistic infections, side effects of medications, lifestyle issues or psychological issues related to drug treatment. Such deficits can be treated with nutritional supplements, megestrol acetate (Megace), dronabinol (Marinol) and testosterone therapy. One study compared Advera, a recently-released peptide-based nutritional supplement, with a standard formulation, Ensure. It was found to result in better maintenance of body weight with significantly fewer hospitalizations. Recombinant human erythropoietin has been shown to reduce the number of transfusions required in patients receiving zidovudine with low endogenous erythropoietin levels (<500 IU/L). Where it fails to increase the serum hematocrit, iron deficiency is often present. Supplemental iron, given orally as a tablet or liquid, or intravenously as iron dextran, can help resolve this problem.
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PMID:Pharmacologic agents used for nutritional disorders of HIV/AIDS. 1136 99

Nutritional adequacy is essential in treating HIV/AIDS, where gastrointestinal problems are common. Patients need to consider taking nutritional supplements if their appetite diminishes or mouth sores create a special difficulty in maintaining an adequate diet. All parts of the digestive tract are affected by HIV/AIDS, causing pain and malabsorption of nutrients and drugs. Patients are cautioned to monitor and control their diets to insure that they are not becoming malnourished.
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PMID:Nutrition Power. Gut drama: malabsorption. 1136 91

Chronic diarrhea is a major contributor to malabsorption and malnutrition in people with HIV, and damage to the intestines from diarrhea can lead to a worsening of the condition. Patients need to protect themselves against acquiring new pathogens via food-borne sources, unsanitary practices, or unsafe anal sex. Dietary modifications can be helpful in managing diarrhea. Starches with insoluble starches should be avoided, and lactose-intolerant patients should use lactase enzyme tablets. Reducing fat content in the diet, and using only well-cooked fruits and vegetables may help. Dietary supplements that contain high calories and high protein may help patients with chronic diarrhea to ingest adequate nutrients.
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PMID:Nutritional management of diarrhea in HIV disease. 1136 27

Highly elevated triglyceride levels being reported in HIV-infected people are a concern because they can contribute to heart disease, stroke, and pancreatitis. The elevated levels may be the result of medication on the liver, dietary habits, or malabsorption of key nutrients. Preliminary studies have shown that dietary and vitamin supplements may help lower the levels to a more normal and safe range. Strategies to reduce triglyceride levels are described.
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PMID:High triglyceride levels: their danger and what can be done. 1136 11

Wasting occurs in approximately 20 percent of people with AIDS and is associated with higher mortality rates and diminished quality of life. Weight loss in HIV-positive patients targets lean body mass or muscle rather than fat. Wasting syndrome is currently defined as a 10 percent loss in body weight accompanied by 30 days of fever and/or diarrhea. Many physicians find the definition too limiting and are modifying the criteria to make it more inclusive of earlier forms of the disease. Wasting is caused by inadequate calorie intake, malabsorption of nutrients, an altered metabolic rate, and hormone deficiency. Physicians need to monitor body composition of people with HIV to prevent and reverse the loss of lean body mass.
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PMID:How to recognize wasting syndrome. 1136 21

Weight loss is a significant problem with HIV and AIDS patients. The definition of wasting syndrome is provided. Men and women do not lose weight and body mass in the same way; the differences between the genders are reviewed. Treatment includes insuring an adequate oral intake of calories, correcting malabsorption problems, and using anabolic steroids to rebuild body mass. Resistance exercises may also be helpful.
Hopkins HIV Rep 1999 Jan
PMID:Treatment of HIV related weight loss. 1136 64

Severe lactic acidosis has been increasingly reported as a potentially fatal complication of HIV treatment. We report on an asymptomatic HIV-infected woman treated with stavudine, lamivudine and indinavir for one year. She was hospitalized because of progressive dispnoea, oedema, cyanosis and severe lactic acidosis. Arterial blood pH was 6.98, bicarbonate 4.4 mmol/l (normal value 22-26), blood lactate: 29.7 mmol/l (normal value <2.2). Hepatic function was normal. She had an impressively rapid response (within a few hours) to empirical treatment with thiamine (100 mg i.v.). No evidence of sepsis or malabsorption were identified and vitamin B1 level was not tested before thiamine infusion. Three months later she was re-started successfully on nelfinavir plus nevirapine. The rapid response to thiamine infusion deserves a careful attention and such an approach should be considered in similar cases as a support treatment of this potentially life-threatening complication of HIV therapy.
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PMID:Severe lactic acidosis and thiamine administration in an HIV-infected patient on HAART. 1136 26

In the developed world, a significant increase in the incidence of protozoan diarrhoea was observed following the AIDS epidemic. The profound immunodeficiency associated with advanced HIV disease produced increased susceptibility to opportunistic protozoan infections. The resultant profuse diarrhoea, malabsorption and weight loss contributed to the high morbidity and mortality rates associated with the epidemic. The success of highly active antiretroviral therapy (HAART) in suppressing viral replication has led to a reduced incidence of AIDS-related opportunistic infections and this has contributed to decreased morbidity and mortality. In this review, we examine current management practices for HIV-related opportunistic protozoan diarrhoea
J HIV Ther 2002 Feb
PMID:Opportunistic protozoan diarrhoea. 1195

Therapeutic drug monitoring (TDM) is a standard clinical technique used for many disease states, including many infectious diseases. As for these other conditions, the use of TDM in the setting of tuberculosis (TB) allows the clinician to make informed decisions regarding the timely adjustment of drug therapy. Such adjustments may not be required for otherwise healthy individuals who are responding to the standard, four-drug TB regimens. However, some patients are slow to respond to treatment, have drug-resistant TB, are at risk of drug-drug interactions or have concurrent disease states that significantly complicate the clinical situation. Such patients may benefit from TDM and early interventions may preclude the development of further drug resistance. It is not possible to collect multiple blood samples in the clinical setting for logistical and financial reasons. Therefore, one typically is limited to one or two time points. When only one sample can be obtained, the 2-hour post-dose concentrations of isoniazid, rifampin, pyrazinamide and ethambutol are usually most informative. Unfortunately, low 2-hour values do not distinguish between delayed absorption (late peak, close to normal range) and malabsorption (low concentrations at all time points). A second sample, often collected at 6-hour post-dose, can differentiate between these two scenarios. The second time point can also provide some information about clearance and half-life, assuming that drug absorption was nearly completed by 2 hours. 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. Rifampin is stable for more than 6 hours under these conditions. During TB treatment, isoniazid causes the greatest early reduction in organisms and is considered to be one of the two most important TB drugs, along with rifampin. Although isoniazid is highly active against TB, low isoniazid concentrations were associated with poorer clinical and bacteriological outcomes in US Public Health Services (USPHS) TB Trial 22. Several earlier trials showed a clear dose-response for rifampin and pyrazinamide, so low concentrations for those two drugs also may correlate with poorer treatment outcomes. At least in USPHS TB Trial 22, the rifampin pharmacokinetic parameters were not predictive of the outcome variables. In contrast, low concentrations of unbound rifapentine may have been responsible, in part, for the worse-than-anticipated performance of this drug in clinical trials. The 'second-line' TB drugs, including p-aminosalicylic acid, cycloserine and ethionamide, are relatively weak TB drugs. Under the best conditions, treatment with these drugs takes over 2 years, as opposed to 6 to 9 months with isoniazid- and rifampin-containing regimens. Therefore, TB centres such as National Jewish Medical and Research Center in Denver, CO, USA, measure serum concentrations of the 'second-line' TB drugs early in the course of treatment. That way, poor drug absorption can be dealt with in a timely manner. This helps to minimise the time that patients are sputum smear- and culture-positive with multidrug-resistant TB, and may prevent the need for even longer treatment durations. Patients with HIV are at particular risk for drug-drug interactions. Because the published guidelines typically reflect interactions only between two drugs, these guidelines are of limited value when the patient is treated with three or more interacting drugs. Under such complicated circumstances, TDM often is the best available tool for sorting out these interactions and placing the patient the necessary doses that they require. TDM is only one part of the care of patients with TB. In isolation, it is of limited value. However, combined with clinical and bacteriological data, it can be a decisive tool, allowing the clinician to successfully treat even the most complicated TB patients.
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PMID:Therapeutic drug monitoring in the treatment of tuberculosis. 1238 Dec 17


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