OBESITY
Obesity can be defined as excess adipose tissue; it is currently quantitated by means of the body mass index (BMI), calculated from BMI = weight (in kilograms)/height2 (in meters).
Using this measure, a normal BMI is defined as 18.5–24.9; overweight, 25–29.9; obese, 30–39.9; and morbidly obese (i.e., at very high risk), ≥ 40. Some extremely muscular individuals may have a BMI higher than 25 and no excess fat; however, the BMI scale generally correlates with the degree of obesity and with risk.
Causes of obesity: energy intake (dietary calories) exceeding energy output (resting metabolism plus exercise), the actual physiology of weight control is extremely complex.
Pathophysiology of obesity: Many hormones and neuronal mechanisms regulate intake (appetite, satiety), processing (absorption, conversion to fat, glycogen, etc), and output (thermogenesis, muscle work.
Management: The social and psychological aspects of eating are powerful influences that are independent of or only partially dependent on the physiologic control mechanisms. In contrast, bariatric (weight-reducing) surgery readily achieves a sustained weight loss of 10–40%. Furthermore, surgery that bypasses the stomach and upper small intestine (but not simple restrictive banding) rapidly reverses some aspects of the metabolic syndrome even before significant weight is lost. However, even a 5–10% loss of weight is associated with a reduction in blood pressure and improved glycemic control.
Treatment:
Phentermine as Fen-Phen and Dex-Phen, they were moderately effective. However, these drugs were found to cause pulmonary hypertension and cardiac valve defects and were withdrawn.
Adverse effects: Gastrointestinal symptoms, such as oily spotting, fecal urgency, flatulence with discharge, and increased defecation.
Pharmacokinetics: Sibutramine undergoes first-pass demethylation to active metabolites, which are primarily responsible for its pharmacologic effects. The active metabolites are biotransformed further in the liver and excreted primarily in the urine. The half-life of the active metabolites is about 15 hours.
Adverse effects and contraindication: Sibutramine should also be avoided in patients who are taking selective serotonin inhibitors such as fluoxetine, serotonin agonists for migraine such as sumatriptan, as well as lithium, dextromethorphan, or pentazocine. Drug interactions can occur when sibutramine is administered with drugs that inhibit CYP3A4, such as ketoconazole, erythromycin, and cimetidine.
Obesity, body mass index