Drug Topics - November 10, 2008 - (Page 45)

CONTINUING EDUCATION Moreover, dietary fat content inﬂuences de novo synthesis of gallstones during weight loss induced by a VLCD. Consuming a meal with minimal fat does not stimulate the gallbladder to empty, whereas a meal with a higher amount of fat prompts gallbladder contraction. Furthermore, increasing dietary fat content may not be as important in preventing gallstones in patients consuming an LCD compared with those consuming a VLCD. Moreover, the use of bile acids, such as ursodeoxycholic acid, may be beneﬁcial if the risk of gallstone formation is thought to be increased. Liver Disease Obesity is associated with a spectrum of liver abnormalities known as nonalcoholic fatty liver disease (NAFLD).31 NAFLD is manifested by alterations in liver histology including steatosis, steatohepatitis, ﬁbrosis, and cirrhosis in addition to hepatomegaly and abnormal liver biochemistry. Available data suggest that steatosis affects approximately 75% of obese patients, whereas 20% experience steatohepatitis, and cirrhosis is prevalent in approximately 2%.32 The reasons NAFLD develops in obese patients are ambiguous. However, it is recognized that NAFLD is associated with abdominal obesity and the metabolic syndrome. Losing excess weight through diet and exercise is the cornerstone of treatment of NAFLD. Gout Gout is a type of inﬂammatory arthritis triggered by the crystallization of uric acid within the joints and is often associated with hyperuricemia. Both hyperuricemia and gout are highly associated with overweight and obesity. A 12year prospective study done by Choi et al. evaluated the relationship between obesity and weight change and the incidence of gout in men.33 They determined that a BMI of 25 or more was consistently associated with an increased risk of gout. The degree of the association became larger with increasing BMI. Their ﬁnding also suggested that risk of gout is more strongly inﬂuenced by current BMI than by BMI earlier in life. Osteoarthritis The risk of osteoarthritis, particularly of the weight-bearing joints, is increased in overweight and obese individuals. The knees are most often involved because more weight is exerted on these joints during activity than on others. The excess weight places pressure on the joint and wears away the protective cartilage, resulting in joint pain and stiffness. The relationship between BMI and osteoarthritis is stronger in women than in men, and obesity often precedes osteoarthritis by decades. Even small increases in body weight in women can promote osteoarthritis.34 There is some evidence to suggest that increased load on a joint may not be the only factor associated with joint disease in the obese, and studies have demonstrated an association between obesity and osteoarthritis of the hand.35,36 W W W.D R U GTO P I C S .C O M Cancer Overweight and obesity are associated with an increased risk of certain forms of cancer.37 The mechanism by which obesity confers risk for cancer is still unclear, though there are several proposed processes. The conventional view considers adipose tissue as an active metabolic entity that may promote the genesis and progression of cancer. A more recent hypothesis suggests adipose tissue as a reservoir for lipophilic environmental carcinogens, which are then released into the bloodstream over time.37 Available data indicate that men are at an increased risk for cancers of the colon, rectum, and prostate.37 In women, a substantial risk for neoplasms of the reproductive system and gallbladder are plausible. The Million Women Study found that increasing BMI is associated with a signiﬁcant increase in the risk of cancer for 10 out of 17 speciﬁc types investigated. The study demonstrated that menopausal status is a key factor in the relationship between BMI and cancer risk for women.38 This is true not only of hormonally related cancers, but also for cancers that are not ordinarily associated with hormone levels, such as colorectal cancer. For endometrial and esophageal cancer, BMI represents a major modiﬁable risk factor, and about half of all cases in postmenopausal women are attributable to overweight or obesity. Polycystic ovarian syndrome Polycystic ovarian syndrome (PCOS) is associated with incompletely developed ovarian follicles and irregular menses. Most often caused by insulin resistance, it is the leading cause of infertility and increases the risk of diabetes development. Nearly half of all women with PCOS have abdominal obesity.39 Medications such as TZDs and biguanides are often employed to restore fertility and treat the hyperinsulinemicproducing hormone dysregulation.40 Pharmacotherapy for obesity management When considering pharmacologic therapy, it is essential to be cautious when recommending treatment to patients. Alternatively, some clinicians are quite hesitant to advocate pharmacotherapy due to the history of weight-loss agents being withdrawn from the market.41 Fenfluramine and dexfenﬂuramine, two appetite-suppressant medications, were withdrawn from the market in 1997. These agents were marketed and used individually and in combination with phentermine (often referred to as “fen/phen”). The withdrawal of these drugs was triggered when they were linked to the development of valvular heart disease and primary pulmonary hypertension (PPH).41 Although the relation between PPH and phentermine use is not deﬁnitive, there have been a few case reports, and the possibility that phentermine alone is associated with PPH cannot be overlooked.5,6,42 Prior to 1996, all anti-obesity agents were approved for short-term use (<12 weeks). Medications that are currently approved in the U.S. for managing obesity can be divided N OV. 10, 2008 DRUG TOPICS 45 http://WWW.DRUGTOPICS.COM

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Drug Topics - November 10, 2008 Contents Up Front Up Front in Depth Letters Rx Care Government Community Practice First Responders Clinical Practice Self-Care FDA Safety Page Weighing the Complications of Obesity New Products Viewpoint

Drug Topics - November 10, 2008

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