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Xenical Review Article

 

The amount of our body fat is important to how we look and how we feelXenical (generic name: Orlistat) is a drug that promotes loss of weight by preventing the digestion and absorption of dietary fat. In the intestine, an enzyme called lipase (produced primarily by the pancreas) breaks apart dietary fat so that the fat can be absorbed into the body. Orlistat blocks the action of lipase and thereby prevents the breakup and absorption of fat. The unabsorbed fat is excreted in the stool. Orlistat was approved by the FDA in 1999. Weight and Fat Our society is very critical with appearance - everyone is conscious of how they look, paying attention to every detail, especially their weight. Most people, if not everyone, equate having a low body weight to looking good. There are very few exceptions, women and men alike desire to look and feel good by achieving their desired weight. Aside from the aesthetic aspect of the weight issue, most people are conscious of their weight because it as a big factor to consider in health. However, body weight does not bear much significance, as it tells nothing about body composition, which is more important. Continue reading...

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Take for example two persons who look exactly the same, have the same height and body surface area. They may look the same and hypothetically, weigh the same, but surprisingly they may weigh differently. That is because weight depends on the composition of the body – the bone density, muscle mass and fat content all play a factor in determining one’s weight. In health, the amount of body fat (often misinterpreted as higher body weight) is a more significant factor than total weight. Total body fat is determined through Body Mass Index or BMI.

Body mass index or BMI is the official medical measure of body fatness. It is an index of the body’s weight relative to height. The formula for BMI is:

BMI=(weight in kg)/〖(height in m)〗^2

The World Health Organization (WHO) has provided an international standard category for BMI values.

A BMI value of <18.5 is interpreted as "Underweight"
A BMI value of 18.5-24.5 is interpreted as "Normal"
A BMI value of >25 is interpreted as "Overweight"
A BMI value of >30 is interpreted as "Obese"

Excessive fat accumulation is seen in people with BMI values of greater than 25. Being an overweight or obese predisposes a person to several adverse health consequences and serious long term diseases. If not treated or managed early, being overweight or obese can lead to life threatening diseases.

Obesity

According to the WHO, being an overweight or obese means having an abnormal or excessive fat accumulation in the body. Basically, this excess fat is caused by an imbalance between one’s caloric intake and expenditure. Increased intake of energy-rich foods (high fat and sugar content) combined with a sedentary lifestyle increases fat stores.

Being overweight or obese is already a major risk factor for many serious conditions, such as cardiovascular diseases (like arteriosclerosis, hypertension, and coronary artery disease), musculoskeletal disorders (like osteoarthritis), some types of cancers (breast, colon and endometrial cancer), dyslipidemia, and diabetes mellitus.

Obesity is a serious global burden. It is the most common health problem in the United States today, with adult prevalence of 28% in men and 34% in women. In Europe, prevalence is about 10 – 20% in men and 15 – 25% in women (Hainer, Toplak & Mitrakou, 2008). According to WHO, almost 1.5 billion adults worldwide aged 20 or older is overweight. Obesity and overweight is already the fifth leading risk for death worldwide, with around 2.8 million mortalities each year.

Sadly, these morbidities and mortalities could have been avoided, as obesity and overweight is preventable and treatable. Using appropriate lifestyle changes and drug therapy, if necessary, can reduce the number of obese and overweight patients worldwide.

Several lifestyle changes can be made by an individual to reduce his or her BMI value. Generally, making healthier food choices (being conscious of the caloric intake by observing sugar and fat content and increasing fruit and vegetable consumption) and engaging in regular physical activity is the easiest and most recommended way to deal with obesity. However, when non pharmacological approaches are not enough or when the patient is morbidly obese, the addition of drug therapy is recommended. Xenical is a drug used for the management of obesity (Ellrichmann, et al., 2008).

Excess weight due to fat may be lost through proper diet and exercise

Xenical (Orlistat)

Xenical (Orlistat), or tetrahydrolipstatin, is an anti-obesity drug approved for use in 1999. It is used in the treatment of obese patients in combination with a strict caloric diet, as well as of overweight patients who have other health conditions (high blood pressure, diabetes and hyperlipidemia). Among the different anti-obesity drugs, it is the only one approved for use in adolescents as well as children. Its molecular formula is C29H53NO.

Because fat is the highest source of excess calories that is stored in the body, a good approach to medical treatment of obesity is to reduce the amount of fat being absorbed in the body and increase its excretion. Xenical is a weight loss drug that works by blocking the digestion and absorption of fat in the body, leading to its excretion.

Xenical acts on an intestinal enzyme called lipase. Fats are too big to be absorbed in the body; thus breaking them down to smaller compounds is necessary for them to be absorbed. Lipase is an enzyme that breaks down lipids or fats into much smaller compounds called fatty acids, which are easily absorbed in the body. By inhibiting lipase, fat absorption is inhibited, and thus eliminated in the body, which is manifested as oily stools or steatorrhea.

Aside from the blocking of lipase, Xenical also reduces gastric emptying time and pyloric pressure, and increases motility (Ellrichmann, et al., 2008), all leading to faster excretion and elimination of fats and other gastric contents that may lead to higher caloric storage when absorbed.

Xenical is a prescription drug that may be used for inducing weight loss. However, pharmacotherapy using Xenical is meant to supplement the non-pharmacological therapy (diet and exercise), not as a substitute to it . It is not useful when used alone for reducing weight.

Effectiveness of Xenical

Xenical has been proven effective as approved by Food and Drugs Administration (FDA). When followed at its recommended dosage level, it cuts down fat absorption by as much as 30%. However, as stated, it only works if coupled with a strict caloric diet and regular exercise.

Several clinical trials have been made to prove its effectiveness for use in weight loss. In a study made by Padwal, Li & Lau (2003), they found that weight loss through Xenical is “certain ”. The drug can reduce as much as 2 to 3 kilos of weight more than those not using the drug within one year of therapy.

Obesity and overweight are significant risk factors for several chronic diseases. As such, managing these two risk factors will greatly reduce the morbidities and mortalities associated with it. Some of these diseases are diabetes mellitus type 2 (Non – insulin dependent) and cardiovascular diseases.

The Xenical in the prevention of diabetes in obese subjects, or Xendos (2004), is a study done to determine the incidence of diabetes type 2 in obese patients followed for four years. It was found that Xenical, combined with lifestyle changes, achieved a significant reduction in the incidence of diabetes type 2. The X-PERT study (2005) also supports the findings from these two studies.

Three different meta-analyses made by O’meara et al. (2004), Padwal, Li & Lau (2003) and Hutton & Furgosson (2004) have found that Xenical has beneficial effects in blood pressure reduction, as well as lipid metabolism. Triglycerides and LDL are significant factors for the development of cardiovascular disease, as well as hypertension. In a review made by Siebenhofer et al., it was found that long term use of Xenical can produce a slight reduction in blood pressure. In another study by Mittendorfer et al. (2001), they have found that there is a reduction of triglycerides and low density lipoprotein (LDL) levels when Xenical is used. Reduction of blood pressure and LDL and triglyceride levels all contribute to a lower morbidity of cardiovascular diseases associated with obesity (Rubio et al., 2007).

Xenical and drug interactions

Because Xenical prevents the absorption of fats in the body, the absorption of drugs which are highly lipid soluble are affected. Some of these drugs are the fat soluble vitamins A, D, E, and K (XENDOS study); the immunosuppressive drug Cyclosporin (Le Beller et al., 2000; Nagele, et al., 1999; Asberg, 2003); antiarrhythmic drug amiodarone (Zhi et al., 2003); anticoagulant Warfarin due to decreased vitamin K (Kiortsis, Filippatos & Elisaf, 2005); anti epileptic drug Lamotrigine, Valproic acid, Vigabatrin and Gabapentin (Beigham, McGuigan & MacDonald, 2006); and Thyroxine (Madhava & Hartley, 2005). Patients taking these drugs should be closely monitored for possible suboptimal treatment.


Bibliography

ASBERG, A. 2002. Interactions between cyclosporine and lipid lowering drugs: implications for organ transplant recipients. Drugs 63(4): 367-378

BEIGHAM, S., MCGUIGAN, C., & MACDONALD, B.K. 2006. Reduced absorption of lipophilic anti-epileptic medications when used concomitantly with the anti-obesity drug orlistat. Epilepsia 47(12) 2207

ELLRICHMANN, M., KAPELLE, M., RITTER, P.R., ET AL. 2008. Orlistat inhibition of intestinal lipase acutely increases appetite and attenuates postprandial glucagon-like peptide-1-(7–36)-amide-1, cholecystokinin, and peptide YY concentrations. Retrieved from
http://jcem.endojournals.org/content/93/10/3995.full.pdf+html

HAINER, V., FINER, N., TSIGOS, C., ET AL. 2004. Management of obesity in adults: profect for European primary care. Int J Obes 28

HAINER, V., TOPLAK, H., MITRAKOU, A. Treatment modalities of obesity: what fits whom? Retrieved from
http://care.diabetesjournals.org/content/31/Supplement_2/S269.full.pdf+html

HUTTON, B., FERGUSSON, D. 2004. Changes in body weight and serum lipid profile in obese patients treated with orlistat in addition to a hypocaloric diet: a systematic review of randomized clinical trials. American Journal of Clinical Nutrition 80: 1461-1468

KIORTOSIS, D.N., FILIPPATOS, T.D., & ELISAF, M.S. 2005. The effects of orlistat on the metabolic parameters and other cardiovascular risk factors. Diabetes Metab 31 (1): 15-22

LE BELLER, C., BEZIE, Y., CHABETTE, C., ET AL. 2000. Co-administration of orlistat and cyclosporine in heart transplant recipient. Transplantation 27:70 1541-1542

MADHAVA, K., & HARTLEY, A. 2005. Hypothyroidsism in thyroid carcinoma follow-up: orlistat may inhibit the absorption of thyroxine. Clin Oncol 17(6)

MITTENDORFER, B., OSLUND, R.E., PATTERSON, B.W., ET AL. 2001. Orlistat inhibits dietary cholesterol absorption. Obesity Research 7:699-708

NAGELE, H., PETESEN, B., BONACKER, U. ET AL. 1999. Effect of orlistat on blood cyclosporine concentration in an obese heart transplant patient. Eur J Clin Pharmacol 55(9): 667-669

O’MEARA, S., RIEMSMA, R., SHIRRAN, I., ET AL. 2004. A systematic review of clinical effectiveness of orlistat used for the management of obesity. Obesity Reviews 5:51-68.

PADWAL, R., LI, S.K., LAU, D.C.W. 2003. Long term pharmacotherapy for overweight and obesity: a systematic review and meta-analysis of randomized controlled trials. International Journal of Obesity 27:1437-1446

RUBIO, M.A., GARGALLO, M., MILLAN, A.I., ET AL. 2007. Drugs in the treatment of obesity: sibutramine, orlistat and rimonabant. Retrieved from
http://journals.cambridge.org/download.php?file=%2FPHN%2FPHN10_10A%2FS1368980007000717a.pdf&code=104dd213e6b315b4a239898b8d35813a

TOPLAK, H., ZIEGLER, O., KELLER, U., ET AL. 2005. X-PERT: weight reduction with orlistat in obese subjects receiving a mildly or moderately reduced – energy diet: early response to treatment predicts weight maintenance. Diabetes Obes Metab 7:699-708

TORGERSON, J.S., HAUPTMAN, J., BOLDRIN, M.N., SJOSTROM, L. 2004. Xenical in the prevention of diabetes in obese subjects (XENDOS) study: randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care 27:155-161

SIEBENHOFER, A., HORVATH, K., JEITLER, K., ET AL. Long-term effects of weight reducing drugs in hypertensive patients. Retrieved from
http://www.ncbi.nlm.nih.gov/pubmed/19588440

ZHI, J., MOORE, R., KANITRA, L., ET AL. 2003. Effects of orlistat, a lipase inhibitor, on the pharmacokinetics of three highly lipophilic drugs (amiodarone, fluoxetine and simvastatin) in healthy volunteers. J Clin Pharmacol: 43(4): 428-435


 

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