INDEX gastrointestinal effects

JL Madsen. Effects of gender, age, and body mass index on gastrointestinal transit times. Digest Dis Sci 37 1548-1553, 1992. 

Such requirements are expected to assure that the dosage form is formulated and manufactured appropriately to ensure that the index or marker ingredients are uniformly distributed and will dissolve in the gastrointestinal tract and be available for absorption. No assumption is made that the marker or index compound selected for demonstration of dissolution is responsible for the purported effect. The test is valuable in that it assures that the formulation technology used is reflective of the state-of-the-art technology, provides a means to evaluate lot-to-lot performance over a product s shelf-life and that excipients used to facilitate transfer of the index or marker ingredients of the botanical to the human system are appropriate. 

Therapy is perfectly adequate with simple iron salts (Table 2). In adults ferrous gluconate, fumarate or sulphate are all of proven equal efficiency. Approximately 50 mg of iron is present in each tablet with the remaining 300 mg made up with an inert filler. These are given on an empty stomach at least twice a day but should nausea prevail they can be taken with food. Absorption of slow release preparations is not recommended since iron is detached from the carrier beyond the main areas of absorption in the duodenum or jejunum. Stools turn black in all cases and this is a useful index of patient compliance. In 25% of individuals gastrointestinal tract side effects are encountered in the form of diarrhoea or constipation and patients will often spontaneously discontinue medication. It is therefore essential that a tablet-count be carried out on a regular basis with a substitute being provided when this first-line medication is intolerable. In children the same preparations are favoured as syrups these are given twice... 

Consequently, antineoplastic drugs typically have a very low therapeutic index compared with drugs that are used to treat less serious disorders (see Chapter 1). Considering that cancer is usually life threatening, these toxic effects must be expected and tolerated during chemotherapeutic treatments. Some side effects, however, can be treated with other drugs. In particular, gastrointestinal disturbances (e.g., nausea,... 

All NSAIDs, including aspirin, are about equally efficacious with a few exceptions—tolmetin seems not to be effective for gout, and aspirin is less effective than other NSAIDs (eg, indomethacin) for ankylosing spondylitis. Thus, NSAIDs tend to be differentiated on the basis of toxicity and cost-effectiveness. For example, the gastrointestinal and renal side effects of ketorolac limit its use. Fries et al (1993), using a toxicity index, estimated that indomethacin, tolmetin, and meclofenamate were associated with the greatest toxicity, while salsalate, aspirin, and ibuprofen were least toxic. The selective COX-2 inhibitors were not included in this analysis. 

Absorption of theophylline from the gastrointestinal tract is usually rapid and complete. Some 90% is metabolised by the liver and there is evidence that the process is saturable at therapeutic doses. The tis 8 h, with substantial variation, and it is prolonged in patients with severe cardiopulmonary disease and cirrhosis. Obesity and prematurity are associated with reduced rates of elimination, whereas tobacco smoking enhances theophylline clearance by inducing hepatic P450 enzymes. Because of these pharmacokinetic factors and low therapeutic index, monitoring of the plasma theophylline concentration is necessary to optimise its therapeutic effect and minimise the risk of adverse reactions the optimum concentration range is 10-20 mg/1 (55-110 mmol/1). 

As a therapeutic agent, mechlorethamine has many toxic effects. Acutely, it causes nausea and vomiting, skin blistering, and ulceration. After a week or two, it causes leukopenia, lymphopenia, anemia, thrombocytopenia, diarrhea, oral ulcers, and hyperuricemia. It can cause sterility and after a few years, leukemia. The most susceptible tissues are those with renewable cell populations, bone marrow, lymphoid tissues, and gastrointestinal (GI) epithelium. The therapeutic dose of mechlorethamine and most of the cytotoxic chemotherapy drugs is very close to the toxic dose. The therapeutic index (ratio of beneficial effect to toxic effect) is small. 

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