Special considerations

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Target specificity

Many drugs bind to cellular receptors or proteins selectively. By mimicking the structure of the naturally occurring chemical, its effect is either replicated (agonist) or blocked (antagonist). An example is the group of histamine H2 receptor antagonists that block acid secretion by parietal cells. With advancing scientific knowledge, greater specificity can be achieved: for example different serotonin (5-hydroxytryptamine, 5HT) receptor subtypes are now being selectively targeted.

Selective release and topical treatment

Another way of achieving selective effects is to only apply the medication where it can reach the target tissue. In the gastrointestinal system, this can be achieved by oral administration of non-absorbed drugs that then act locally. The 5-aminosalicylic acid (5ASA, mesalazine) drugs used to treat inflammatory bowel disease (IBD) are delivered this way, either as slow-release preparations that dissolve in the distal intestine or as pro-drugs that are activated by bacterial metabolism in the colon.

Some drugs are significantly absorbed through the rectal mucosa, such as diazepam, used to treat active epileptic fitting, while others, such as rectal 5ASA compounds, act locally.

Hepatic first pass effect

Enterically administered drugs that are rapidly and completely metabolized by the liver are said to have high hepatic first pass metabolism. This allows high doses to be delivered to the intestine, with fewer systemic side-effects. An example is the synthetic corticosteroid, budesonide, used to treat IBD.

Augmenting or inhibiting intestinal function

Pancreatic enzyme supplements and lactase can be taken by mouth to correct the effects of pancreatic failure and intestinal hypolactasia, respectively. The enzyme supplements act locally in the intestine. Orlistat, which is designed to reduce fat absorption, acts by inhibiting pancreatic lipase in the intestine.

Oral tolerance, immunotherapy and vaccination

Orally administered antigens stimulate a strong secretory immune response with immunoglobulin A (IgA) and IgM antibodies, while the systemic immune response is inhibited. Thus the live polio vaccine and vaccines against salmonellae and Vibrio cholera are administered orally. Orally administered autoantigens may induce selective immunological tolerance and could be used to treat autoimmune diseases, such as multiple sclerosis, although results of clinical trials have so far been discouraging.

Antibiotics and probiotics

Some intestinal symptoms may be due to a proliferation of abnormal intestinal bacteria or reduced normal commensals, and oral or rectal administration of live commensal bacteria is currently being investigated, particularly in the treatment of IBD. This is a counterpart to the administration of antibiotics to selectively decontaminate the intestinal lumen, for example, before abdominal surgery or in chronic liver disease.

Food as therapy

Intolerance to various food elements occurs, for example, in coeliac disease, lactose intolerance, cow's milk protein, peanut and other food allergies.

A totally bland, antigen-free diet comprising monomers or short oligomers of carbohydrate, fat and protein is apparently effective in treating Crohn's disease, although the mechanism of action is unknown.

Enteral feeding

Enteral, as opposed to parenteral, feeding, even in severely ill patients is critically important, as the food-free intestine atrophies, increasing the risk of bacterial translocation and systemic sepsis.

Pharmacotherapy 105

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