Current Concepts in the Pharmacological Management of Obesity

Abstract

The pharmacological management of obesity has gained increasing attention as new weight loss treatments are approved and a significant proportion of the public strives to lose weight. Obesity is associated with a high mortality rate, multiple chronic medical conditions, and carries an enormous financial burden. Obesity is a multifactorial condition, most often due to an imbalance in energy intake and expenditure. Despite the greater focus on management of obesity, weight loss remains a difficult goal to achieve. Obesity is a chronic medical condition that may require long term treatment, therefore the risks and benefits of all pharmacological agents must be carefully considered. Noradrenergic appetite suppressants (ie. phenyl-propanolamine, phentermine) result in weight loss but stimulatory effects limit their use. The serotonergic agents (fenfluramine, dexfenfluramine) were effective weight loss drugs, but were voluntarily withdrawn from the US market last year because of cardiovascular and pulmonary complications. The combination noradrenergic/serotonergic agent sibutramine is indicated for the management of obesity, particularly in the presence of other cardiovascular risk factors. Modest weight loss is achieved with sibutramine, although weight gain is significant after discontinuation. In addition, long term safety data are not yet available. The thermogenic combination of ephedrine plus caffeine is minimally effective, and adverse effects are usually transient. Other thermogenic agents, such as beta3-agonists, are still under investigation. Agents may alter digestion through lipase inhibition (orlistat) or fat substitution (olestra). Orlistat decreases systemic absorption of dietary fat, decreasing body weight and cholesterol. Olestra is a fat substitute that has been incorporated into snack foods. Olestra substitution for dietary fat has not been studied as a weight loss strategy, although olestra has no caloric value and may be beneficial. The use of orlistat and olestra may be limited by gastrointestinal adverse effects. Finally, the manipulation of leptin and neuropeptide Y are under investigation for the treatment of obesity. Pharmacological agents should be used as an aid to a structured diet and exercise regimen in the treatment of obesity. Weight loss agents may result in initial weight loss, but sustained weight loss is not always achieved even with continuation of treatment. The effect of weight loss obtained while using pharmacotherapeutic agents on morbidity and mortality has not been established. Therefore, diet and exercise should be the focus of any weight loss programme. There is a continued need for safe and effective pharmacotherapeutic agents for the treatment of obesity.

The Effect of Sibutramine, a Serotonin-Norepinephrine Reuptake Inhibitor, on Platelets and Fibrin Networks of Male Sprague-Dawley Rats: A Descriptive Study

“…Sibutramine's therapeutic effects are mostly attributed to serotonin (5-HT) and norepinephrine (NE) transporter inhibition (SERT and NET, respectively) by its potent metabolites monodesmethylsibutramine (M1) and di-desmethylsibutramine (M2) at neuronal synapse sites centrally (CNS) and peripherally [1,[7][8][9][10]. This inhibition ultimately leads to an increase in satiety mediated centrally by the b 1 -adrenergic and 5-HT 2A/2C receptors and peripherally by an increase in energy expenditure by enhancing the function of NE through b 3 -adrenoceptors [3,8,11,12].…”

Antidepressivos e alterações no peso corporal

“…Nos Estados Unidos, essas drogas ainda não foram aprovadas pela Food and Drug Administration (FDA) para o uso na perda de peso 14 .…”

“…Baixos níveis de 5HT neste local produzem aumento do apetite e preferência por hidratos de carbono 21 . Por isso, ela tem sido postulada como agente anorexígeno, embora seu efeito na perda de peso a longo prazo não tenha sido demonstrado 14 .…”

Cardiac valve evaluation and adipokine levels in obese women treated with sibutramine

“…Pharmacological agents are often useful adjuncts to dietary therapy in causing weight loss. The prolonged use of adrenergic or serotoninergic anorectic drugs induce several adverse effects (4,12). Previously, severe heart valve disorders have been reported in patients receiving a combination of the anorectic drugs such as fenfluramine and phentermine (8,9).…”