肥胖的药物治疗原则_培训课件.pptVIP

* Sibutramine blocks neuronal monoamine (serotonin, norepinephrine, dopamine) reuptake Sibutramine is a derivative of the amphetamine precursor β-phenylethylamine that has been chemically modified to eliminate its abuse potential. Sibutramine enhances satiation (level of fullness during a meal), by blocking the reuptake of monoamine neurotransmitters (serotonin, norepinephrine, and to a lesser extent, dopamine) in the hypothalamus. Monoamines, synthesized by presynaptic neurons, are stored in granules that release their contents into the cleft between pre- and postsynaptic nerves. Most of the monoamines released into the interneuronal cleft are taken back up by the presynaptic nerve, where they are either degraded or repackaged into new granules. A small portion of released monoamines bind to postsynaptic receptors, which transmits a signal from one nerve to the other. Blocking monoamine reuptake increases the signal transmitted to the postsynaptic nerve. * Effect of continuous vs intermittent sibutramine therapy on body weight The effectiveness of continuous versus intermittent sibutramine therapy in achieving weight loss was evaluated in a 48-week randomized, controlled trial in 1102 obese subjects [1]. Subjects entered a 4-week open-label run-in period during which they received 15 mg of sibutramine daily. Patients with a weight loss of at least 2% or 2 kg were randomized to receive sibutramine continuously (15 mg daily for 44 weeks), sibutramine intermittently (15 mg from weeks 1 through 12, 19 through 30, and 37 through 48, and placebo during the off-sibutramine weeks), or placebo. During the 44-week treatment period, overall weight loss was similar in patients receiving either continuous (3.8 kg; 4.0%) or intermittent therapy (3.3 kg; 3.5%) (P=0.28 continuous vs intermittent), whereas the placebo group gained weight (0.2 kg; 0.2%) (P0.001 placebo vs either treatment group). Overall weight loss during the 48-week period was 7.9 kg and 7.8 kg in the con