OBESITY

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:

• Nonselective 5-HT 2 agonists: Fenfluramine and dexfenfluramine. Combined with

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 However, these drugs were found to cause pulmonary hypertension and cardiac valve defects and were withdrawn.

• The other drugs include methamphetamine, phenylpropanolamine, diethylpropion, benzphetamine, amphetamine, phentermine, mazindol, and phendimetrazine. These drugs are all amphetamine mimics and are central nervous system appetite suppressants, generally helpful only during the first few weeks of therapy and the toxicity are significant and include hypertension and addiction liability.
• Phentermine: [FEN-ter-meen] exerts its pharmacologic action by increasing release of nor epinephrine and dopamine from the nerve terminals and by inhibiting reuptake of these neurotransmitters, thereby increasing levels of neurotransmitters in the brain.

• Orlistat is the only non-amphetamine drug. Orlistat is the first drug in a class of antiobesity drugs known as lipase inhibitors. Orlistat is a pentanoic acid ester that inhibits gastric and pancreatic lipases, thus decreasing the breakdown of dietary fat into smaller molecules that can be absorbed. Fat absorption is decreased by about 30 percent. The loss of calories is the main cause of weight loss, but adverse gastrointestinal effects associated with the drug may also contribute to a decreased intake of food.

Adverse effects: Gastrointestinal symptoms, such as oily spotting, fecal urgency, flatulence with discharge, and increased defecation.

• Siburtramine: It inhibits the reuptake of 5HT and noradrenalin at the hypothalamic sites that regulate food intake. Sibutramine [si-BYOO-tra-meen] inhibits central reuptake of nor epinephrine, serotonin, and to a lesser extent, dopamine. Unlike the other agents, sibutramine does not cause the release of neurotransmitters.

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