Orlistat action

Exhibit 2.11 shows two selected drugs, celecoxib (a COX-2 inhibitor) and orlistat (a lipase inhibitor), and their actions on disease targets. 

Cholecalciferol [Vitamin D3] (Delta D) [Vitamin/Dietary Supplement] Uses Dietary supl to Rx vit D deficiency Action T Intestinal Ca2+ absorption Dose 400-1000 Int Units/d PO Caution [A (D doses above the RDA), +] Contra T Ca2+, hypervitaminosis, allergy Disp Tabs SE Vit D tox Interactions T Risk of arrhythmias w/ cardiac glycosides X effects w/ cholestyramine, colestipol, mineral oil, orlistat, phenobarbital, phenytoin EMS Can cause vit D tox (Tin serum Ca2+ weakness, AMS, Gl upset and cardiac arrhythmias) OD May cause T risk of vitD tox give IV fluids... 

Regrettably, the pharmacologist must confess that no drugs exist that can be recommended for the purpose of weight reduction. The so-called appetite suppressants (anorexiants) act only, if at all, for a limited period and are fraught with side effects. Most anorexiants are derivatives of metham-phetamine that have been withdrawn from the market. A different mechanism of action is involved in the case of an inhibitor of pancreatic lipase, which is required in the intestines for fat absorption. This inhibitor (orlistat) diminishes fat absorption so that fats reach the lower bowel, where they can cause disturbances flatulence, steatorrhea, and frequent need to relieve the bowels occur in about 30% of affected subjects. These symptoms correspond exactly to those seen in pancreatic hypofunction which are then usually treated with pancreatic lipase. Before an obese person submits to treatment with orlistat, he or she should voluntarily reduce the food fat content by one half to live free of such unpleasant adverse effects. 

Orlistat (Xenical) inhibits the action of the enzyme lipase in the intestine, thereby inhibiting the digestion and absorption of fats. This can lead to significant weight loss, but is often accompanied by flatulence, diarrhoea and oily stools. Its clinical application is described in Chapter 8. 

With the solid test meal, the overall level of lipolysis was highly and significantly reduced by the double action of orlistat on the gastric and duodenal lipolysis (28.8% of controls for Xenical pellets, p<0.005 33.4% of controls for micronized orlistat powder in butter, p<0.001 Tab. 10.6). The difference between the two treated groups was not significant. 

Orlistat binds to intestinal and pancreatic lipases, inhibiting their action and reduces dietary fat absorption by about 30%. The typical dose of orlistat is 120 mg three times per day with meals. Less than 1% of the drug is taken up. Thus, most of the drug is excreted unchanged in faeces. 

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