Peripherally Acting Medications Orlistat (Xenical) is a synthetic hydrogenated derivative of a naturally occurring lipase inhibitor, lipostatin, produced by the mold Streptomyces toxytricini. Orlistat is a potent, slowly reversible inhibitor of pancreatic, gastric, and carboxylester lipases and phospholipase A2, which are required for the hydrolysis of dietary fat into fatty acids and monoacylglycerols. The drug acts in the lumen of the stomach and small intestine by forming a covalent bond with the active site of these lipases. Taken at a therapeutic dose of 120 mg tid, orlistat blocks the digestion and absorption of about 30% of dietary fat. After. | Chapter 075. Evaluation and Management of Obesity Part 6 Peripherally Acting Medications Orlistat Xenical is a synthetic hydrogenated derivative of a naturally occurring lipase inhibitor lipostatin produced by the mold Streptomyces toxytricini. Orlistat is a potent slowly reversible inhibitor of pancreatic gastric and carboxylester lipases and phospholipase A2 which are required for the hydrolysis of dietary fat into fatty acids and monoacylglycerols. The drug acts in the lumen of the stomach and small intestine by forming a covalent bond with the active site of these lipases. Taken at a therapeutic dose of 120 mg tid orlistat blocks the digestion and absorption of about 30 of dietary fat. After discontinuation of the drug fecal fat usually returns to normal concentrations within 48-72 h. Multiple randomized 1-2 year double-blind placebo-controlled studies have shown that after one year orlistat produces a weight loss of about 9-10 compared with a 4-6 weight loss in the placebo-treated groups. Because orlistat is minimally 1 absorbed from the GI tract it has no systemic side effects. Tolerability to the drug is related to the malabsorption of dietary fat and subsequent passage of fat in the feces. GI tract adverse effects are reported in at least 10 of orlistat-treated patients. These include flatus with discharge fecal urgency fatty oily stool and increased defecation. These side effects are generally experienced early diminish as patients control their dietary fat intake and infrequently cause patients to withdraw from clinical trials. Psyllium mucilloid is helpful in controlling the orlistat-induced GI side effects when taken concomitantly with the medication. Serum concentrations of the fat-soluble vitamins D and E and 0-carotene may be reduced and vitamin supplements are recommended to prevent potential deficiencies. Orlistat was approved for other-the-counter use in 2007. The Endocannabinoid System Cannabinoid receptors and their endogenous ligands have been
