Functional Interactions

Functional Interactions in the Gastrointestinal Tract

Functional interactions in the GI tract are particularly significant because alterations in GI function are likely to affect the digestion and absorption both of the drug and of a number of nutrients. The most common GI functional effects are as follows.

Changes in GI motility A reduction in transit time may lead to decreased absorption. There are a large number of drugs that affect gut motility, whether this is their primary therapeutic effect or not. Conversely, food composition also affects motility. Dietary fiber not only increases motility but also may trap other nutrients and drugs and reduce their bioavailability.

Changes in gastric-acid output Reduced production of chloride with a subsequent increase in gastric pH retards gastric emptying and may alter the balance between ionized and nonionized forms of therapeutic agents.

Reduction in the concentration of bile acids A reduction in the concentration of bile acids will affect the absorption of most fat-soluble compounds. Lower bile-acid concentration may result from increased binding and excretion or from decreased production. For example, the antibiotic neomycin binds to bile acids and increases their faecal excretion, thus reducing their luminal concentration and, in this fashion, decreasing the absorption of fat-soluble vitamins. This interaction, like many others, can be used ther-apeutically to reduce bile-acid turnover in patients with certain liver diseases and to lower cholesterol levels by reducing their reabsorption.

Alterations in the GI microflora Alterations in the GI microflora may affect the availability of nutrients produced by the normal gut flora, such as vitamin B12'. Since many drugs are susceptible to bacterial metabolism, changes in the gut flora may also affect drug bioavailability. In certain cases, drug cleavage by intestinal microorganisms is an expected and necessary step for adequate drug action. For example, the anti-inflammatory agent 5-aminosalicylic acid is given as its precursor sulfasalazine, which is converted into the active compound by colonic bacteria. An altered colonic flora will affect the production of the active compound. Drugs can also affect nutrient absorption by directly inhibiting protein synthesis in the enterocyte. Since most transport systems require active protein synthesis and turnover, such inhibition results in a decreased rate of nutrient absorption. Furthermore, certain drugs undergo initial metabolism in the enterocyte, before reaching the bloodstream. Alterations in protein synthesis in the enterocyte, or an impaired turnover of the intestinal epithelia, will also affect this process.

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