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Central and Peripheral Modulators of Appetite and Satiety
Published in Emmanuel C. Opara, Sam Dagogo-Jack, Nutrition and Diabetes, 2019
Gabrielle Page-Wilson, Sam Dagogo-Jack
The amino acid derivative 5-hydroxytryptamine (serotonin, 5-HT) has ubiquitous neurotransmitter functions on numerous central nervous system (CNS) targets (Blundell 1984). Receptors for 5-HT are widely expressed in regions including the limbic system, raphe nucleus, and the hypothalamus. Activation of 5-HT receptors (especially the 5-HT2c subtype) is associated with inhibition of food intake. A similar anorexigenic effect is observed following augmentation of serotonin abundance through inhibition of its re-uptake. Conversely, studies in rodents have shown that deletion of the serotonin 5-HT2c gene results in marked hyperphagia (Tecott et al. 1995). Unfortunately, clinical experience with selective serotonin reuptake inhibitors shows modest and inconsistent effects on body weight, which indicates that the serotonergic pathway is overridden by more powerful orexigenic impulses under normal physiological conditions. Nonetheless, sibutramine, a selective agonist of the serotonin 2C receptor, is an effective weight-loss medication. (Sibutramine was withdrawn from use in 2010 because of increase risk of cardiovascular events.)
Current Trends in Performance- and Image-Enhancing Substance Use Among Gym Goers, Exercisers, and Athletes
Published in Ornella Corazza, Andres Roman-Urrestarazu, Handbook of Novel Psychoactive Substances, 2018
Neha P. Ainsworth, Jake Shelley, Andrea Petróczi
Sibutramine is another common appetite suppressant that was used widely as an adjunct in the treatment of obesity. In 2010, it was withdrawn from the market in several countries because of concerns it caused an increased risk of heart attacks and strokes. Sibutramine is a monoamine reuptake inhibitor that reduces the reuptake of norepinephrine, serotonin, and dopamine, thereby increasing the levels of these substances in synaptic clefts and helping to decrease appetite. Sibutramine is still available on the black market and may be taken by bodybuilders, in the form of a 15 mg tablet, to decrease appetite and lose weight.
Psychotropic-Induced Weight Gain: Liability, Mechanisms and Treatment Approaches
Published in Susan L. McElroy, David B. Allison, George A. Bray, Obesity and Mental Disorders, 2006
Roger S. McIntyre, Jakub Z. Konarski, Paul E. Keck
Sibutramine treatment has been demonstrated to achieve and maintain weight loss over a period of 18 months (243). Henderson et al. conducted a 12-week double-blind placebo controlled trial with adjunctive sibutramine (10–15 mg) in olanzapine-treated schizophrenic and schizoaffective patients (n = 37). All patients were previously stabilized on olanzapine, reported a history of weight gain, and had a BMI > 30 kg/m2 or BMI 27 kg/m2 plus another cardiovascular risk factor. In addition, all patients were offered group support and behavioral interventions (244).
Severe lactic acidosis due to excessive consumption of Cellucor C4 exercise supplement
Published in Canadian Journal of Respiratory, Critical Care, and Sleep Medicine, 2021
Jason Rajchgot, Mika Hamilton, David K. Wong, Sandra Fischer, Aleksandra Leligdowicz
The disclosure rates of herbal and dietary supplement use to health care providers is as low as 33%, yet as many as 19% of adults in the United States admit to using one of these products in the past year.9 Dietary supplements are not necessarily benign, leading to approximately 23,000 emergency department visits in the United States annually.10 Contamination and product substitution are widely reported. In a study of 44 herbal products available in North America, more than half contained DNA from plant species not listed on the label.11 Modern pharmaceuticals have also been reported as unlisted ingredients. For example, supposedly natural products for erectile dysfunction have been found to contain PDE-5 inhibitors like sildenafil.12 Sibutramine, an appetite suppressant withdrawn from many countries due to risk of cardiovascular events, has been found in numerous products marketed for weight loss.12 In 1997, two cases of digitalis toxicity were reported in the United States after ingestion of a contaminated herbal supplement marketed as a cleanse.13
The risk of cardiovascular complications with current obesity drugs
Published in Expert Opinion on Drug Safety, 2020
Ariana M. Chao, Thomas A. Wadden, Robert I. Berkowitz, Kerry Quigley, Frank Silvestry
The Sibutramine Cardiovascular Outcomes (SCOUT) trial was a 5-year, randomized, double blind, placebo-controlled study of over 10,000 patients with overweight or obesity and: preexisting cardiovascular disease; type 2 diabetes with at least one other cardiovascular risk factor; or both [14]. The risk of the primary outcome (a composite of nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death) occurred in 11.4% of the sibutramine group which was significantly greater than the 10.0% in the placebo group (hazard ratio (HR) = 1.16, 95% confidence interval (CI) = 1.03–1.31). The rates of nonfatal myocardial infarction and nonfatal stroke were significantly different between groups, but those for cardiovascular and all-cause mortality were not. Based on these results, the EMA recommended suspension of marketing authorization for sibutramine across Europe. The FDA initially requested that healthcare professionals be notified that sibutramine should not be used in patients with known cardiovascular disease and required stronger product label warning. However, the FDA ultimately concluded that sibutramine posed undue cardiovascular risks and recommended withdrawal of the medication from the US market in 2010.
Drug-induced arterial hypertension – a frequently ignored cause of secondary hypertension: a review
Published in Acta Cardiologica, 2018
Camelia Cristina Diaconu, Giorgiana Nicoleta Dediu, Mihaela Adela Iancu
Sibutramine, a serotonin-norepinephrine reuptake inhibitor used for the treatment of obesity, can increase the blood pressure and the heart rate, by activating the sympathetic nervous system, increasing the levels of norepinephrine and noradrenergic neurotransmission. The blood pressure must be monitored in obese patients treated with sibutramine. Also, the use of sibutramine must be limited to patients without cardiovascular diseases. Antiemetic agents (metoclopramide, prochlorperazine) may induce transient elevations of blood pressure in patients treated with cisplatin [14,15]. Physostigmine and levo-dopa increase the blood pressure by activation of the sympathetic system [16,17]. One double-blind placebo controlled trial has found that 5–10% of patients with rheumatoid arthritis treated with leflunomide developped hypertension [18]. Growth hormone and thyroid hormones increase the blood pressure, the heart rate and the cardiac contractility [19].