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1.
Obesity (Silver Spring) ; 28(6): 1023-1030, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32441476

RESUMO

OBJECTIVE: Weight regain (WR) after Roux-en-Y gastric bypass surgery (RYGB) starts to occur 2 years after surgery, ultimately affecting at least 25% of patients. A limited number of studies have evaluated the impact of antiobesity medications (AOMs) on this phenomenon. METHODS: This study reviewed the electronic medical records of 1,196 patients who underwent RYGB between 2004 and 2015. WR was evaluated by comparing each patient's weight during subsequent postoperative office visits to nadir weight (lowest weight after RYGB, n = 760), taking into consideration the interval during which WR occurred. Patients who were prescribed AOMs and came to follow-up visits were classified as adherent users, whereas those who missed their follow-up visits were considered nonadherent. This study used a linear mixed model, Cox regression, and generalized equation estimator to determine the impact of AOMs on WR trajectory, hazard ratio for time to event, and odds ratio for repeated event occurrence, respectively. RESULTS: Despite the lack of a unified protocol for using AOMs, the three statistical models converged to show that phentermine and topiramate, used individually or in combination, can significantly reduce WR after RYGB. CONCLUSIONS: Phentermine and topiramate are effective in mitigating WR after RYGB. Further studies are needed to help ascertain optimal use of AOMs after bariatric surgery.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Derivação Gástrica/métodos , Fentermina/uso terapêutico , Topiramato/uso terapêutico , Ganho de Peso/efeitos dos fármacos , Adulto , Fármacos Antiobesidade/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fentermina/farmacologia , Período Pós-Operatório , Estudos Retrospectivos , Topiramato/farmacologia
2.
Diabetes ; 68(4): 683-695, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30674622

RESUMO

Liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, and phentermine, a psychostimulant structurally related to amphetamine, are drugs approved for the treatment of obesity and hyperphagia. There is significant interest in combination use of liraglutide and phentermine for weight loss; however, both drugs have been reported to induce systemic hemodynamic changes, and as such the therapeutic window for this drug combination needs to be determined. To understand their impact on metabolic and cardiovascular physiology, we tested the effects of these drugs alone and in combination for 21 days in lean and obese male mice. The combination of liraglutide and phentermine, at 100 µg/kg/day and 10 mg/kg/day, respectively, produced the largest reduction in body weight in both lean and diet-induced obese (DIO) mice, when compared with both vehicle and monotherapy-treated mice. In lean mice, combination treatment at the aforementioned doses significantly increased heart rate and reduced blood pressure, whereas in DIO mice, combination therapy induced a transient increase in heart rate and decreased blood pressure. These studies demonstrate that in obese mice, the combination of liraglutide and phentermine may reduce body weight but only induce modest improvements in cardiovascular functions. Conversely, in lean mice, the additional weight loss from combination therapy does not improve cardiovascular parameters.


Assuntos
Fármacos Antiobesidade/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Liraglutida/farmacologia , Fentermina/farmacologia , Animais , Fármacos Antiobesidade/uso terapêutico , Quimioterapia Combinada , Liraglutida/uso terapêutico , Masculino , Camundongos , Obesidade/tratamento farmacológico , Fentermina/uso terapêutico , Resultado do Tratamento , Perda de Peso/efeitos dos fármacos
4.
J Psychopharmacol ; 32(12): 1351-1361, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30269642

RESUMO

BACKGROUND: This study evaluated the human abuse potential of solriamfetol (formerly JZP-110), a selective dopamine and norepinephrine reuptake inhibitor with robust wake-promoting effects. METHODS: Adults with a recent history of recreational polydrug use, including stimulants, and who met criteria in a Qualification Phase were randomized to one of six sequences in a Test Phase. Each Test Phase sequence included a single administration of placebo, solriamfetol (300, 600, and 1200 mg), and phentermine (45 and 90 mg), with a two-day washout between periods. The primary endpoint was peak rating ( Emax) of Liking at the Moment across the first 12 h on a liking/disliking visual analog scale; key secondary endpoints were Next Day Overall Drug Liking, how much the participant would like to Take the Drug Again, and positive and negative subjective effects. Safety was also assessed throughout the study. RESULTS: Of 43 participants (74.4% male; mean age 29.3 years), 37 completed the study. Peak Emax Liking at the Moment for all solriamfetol doses was significantly greater than placebo and significantly less than phentermine 90 mg ( p < 0.05). Overall Next Day Drug Liking was greater than placebo for solriamfetol 300 mg and phentermine 45 and 90 mg ( p < 0.05). Willingness to Take the Drug Again was significantly greater than placebo and significantly less than both doses of phentermine for all doses of solriamfetol ( p < 0.05). Ratings of negative subjective effects (bad effects, disliking, anxiety, agitation) were higher with solriamfetol 600 and 1200 mg relative to phentermine. The most common treatment-emergent adverse events with solriamfetol were hypervigilance, elevated mood, dry mouth, hyperhidrosis, and insomnia. CONCLUSION: Solriamfetol appears to have abuse potential similar to or lower than phentermine.


Assuntos
Inibidores da Captação Adrenérgica/administração & dosagem , Carbamatos/administração & dosagem , Inibidores da Captação de Dopamina/administração & dosagem , Transtornos Relacionados ao Uso de Substâncias/psicologia , Inibidores da Captação Adrenérgica/efeitos adversos , Inibidores da Captação Adrenérgica/farmacologia , Adulto , Carbamatos/efeitos adversos , Carbamatos/farmacologia , Estudos Cross-Over , Inibidores da Captação de Dopamina/efeitos adversos , Inibidores da Captação de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Fentermina/administração & dosagem , Fentermina/efeitos adversos , Fentermina/farmacologia , Adulto Jovem
5.
Ann Plast Surg ; 81(4): 503-507, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30204622

RESUMO

PURPOSE: Phentermine is the most prescribed antiobesity drug in America, with 2.43 million prescriptions written in 2011. Case reports suggest there are anesthetic risks, such as refractory hypotension, involved with its perioperative use. Despite these risks and the frequency of phentermine use among plastic surgery patients, there are no published guidelines for the perioperative management of phentermine use in the plastic surgery literature. To address this patient safety issue, we performed a systematic review and provide management recommendations. METHODS: A systematic review of the pharmacology of phentermine and the anesthetic risks involved with its perioperative use was undertaken using the search engines PubMed/MEDLINE, EMBASE, and Scopus. RESULTS: A total of 251 citations were reviewed, yielding 4 articles that discussed perioperative phentermine use and complications with anesthesia. One was a review article, 2 were case reports, and 1 was a letter. Complications included hypotension, hypertension, hypoglycemia, hyperthermia, bradycardia, cardiac depression, and acute pulmonary edema. CONCLUSIONS: The relationship between phentermine and anesthesia, if any, is unclear. Hypotension on induction of general anesthesia is the most reported complication of perioperative phentermine use. Specifically, phentermine-induced hypotension may be unresponsive to vasopressors that rely on catecholamine release, such as ephedrine. Therefore, the decision to perform surgery, especially elective surgery, in a patient taking phentermine should be made with caution. Because of the half-life of phentermine, we recommend discontinuing phentermine for at least 4 days prior to surgery. This differs from the classic 2-week discontinuation period recommended for "fen-phen." The patient should be made aware of the increased risk of surgery, and a skilled anesthesiologist should monitor intraoperative blood pressure and body temperature for signs of autonomic derailment.


Assuntos
Anestesia , Anestésicos/farmacologia , Depressores do Apetite/farmacologia , Fentermina/farmacologia , Procedimentos Cirúrgicos Reconstrutivos , Anestésicos/efeitos adversos , Depressores do Apetite/efeitos adversos , Interações Medicamentosas , Humanos , Fentermina/efeitos adversos
6.
Obesity (Silver Spring) ; 26(2): 332-339, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29363287

RESUMO

OBJECTIVE: This study evaluated the effect of lorcaserin 10 mg twice daily (LOR BID), or with phentermine 15 mg once daily (LOR BID + PHEN QD) and 15 mg twice daily (LOR BID + PHEN BID), in conjunction with energy restriction on food cravings. METHODS: Two hundred and thirty-five patients without diabetes but with obesity or overweight and ≥ 1 comorbidity received LOR BID, LOR BID + PHEN QD, or LOR BID + PHEN BID for 12 weeks in a randomized double-blind study. The Food Craving Inventory (FCI) and the Control of Eating Questionnaire (COEQ) were administered over 12 weeks. RESULTS: The FCI total score and the subscale scores reduced from baseline in all groups. The least squares means (95% confidence intervals) for the total scores were -0.65 (-0.75 to -0.55), -0.75 (-0.84 to -0.65), and -0.84 (-0.95 to -0.74) in the LOR BID, LOR BID + PHEN QD, and LOR BID + PHEN BID groups, respectively. Cravings assessed by COEQ reduced from baseline in all groups. In general, the combination treatments were more effective than lorcaserin alone. At week 12, except for fruit juice and dairy products, general and specific cravings reduced in LOR BID + PHEN BID compared with LOR BID (P < 0.05). CONCLUSIONS: Lorcaserin in combination with phentermine improves control of food cravings during short-term energy restriction.


Assuntos
Benzazepinas/uso terapêutico , Fissura/efeitos dos fármacos , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Fentermina/uso terapêutico , Adolescente , Adulto , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/uso terapêutico , Benzazepinas/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fentermina/farmacologia , Adulto Jovem
7.
Expert Opin Pharmacother ; 19(3): 223-231, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29376439

RESUMO

INTRODUCTION: Type 2 diabetes (T2DM) is associated with significant morbidity and mortality. Obesity is one of the main risk factors for T2DM and its management requires a multidisciplinary approach, which may include pharmacotherapy. AREAS COVERED: In this paper, data on efficacy, tolerability and safety of FDA-approved pharmacotherapies for obesity (orlistat, phentermine/topiramate extended-release, lorcaserin, bupropion sustained release/naltrexone sustained release and liraglutide) are reviewed, focusing on individuals with type 2 diabetes. EXPERT OPINION: Obesity is the major pathophysiologic driver of T2DM; conversely 5-10% weight loss leads to significant improvement in glycemic control, lipids and blood pressure. Weight loss maintenance is difficult with lifestyle interventions alone and may require adjunctive therapies. There is good evidence for the efficacy and tolerability of approved anti-obesity pharmacotherapies in individuals with T2DM, with current cardiovascular safety data being most favorable for liraglutide, orlistat and lorcaserin. Given the link between obesity and T2DM, a weight-centric therapeutic approach including use of weight reducing anti-diabetic therapies, and anti-obesity pharmacotherapies is both intuitive and rational to improve glycemic and other metabolic outcomes in patients with T2DM.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Obesidade/tratamento farmacológico , Fármacos Antiobesidade/química , Fármacos Antiobesidade/farmacologia , Benzazepinas/química , Benzazepinas/farmacologia , Benzazepinas/uso terapêutico , Ensaios Clínicos como Assunto , Composição de Medicamentos , Humanos , Lactonas/química , Lactonas/farmacologia , Lactonas/uso terapêutico , Liraglutida/química , Liraglutida/farmacologia , Liraglutida/uso terapêutico , Orlistate , Fentermina/química , Fentermina/farmacologia , Fentermina/uso terapêutico , Perda de Peso/efeitos dos fármacos
8.
J Am Assoc Nurse Pract ; 29(S1): S43-S52, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29024552

RESUMO

BACKGROUND AND PURPOSE: To review the currently available pharmacotherapies for obesity management with a particular focus on the United States. METHODS: Narrative review based on literature searches and the latest prescribing information (up to July 2017). CONCLUSIONS: Obesity pharmacotherapies may assist those individuals who have obesity, or overweight with comorbidities, who have failed to maintain weight loss with lifestyle modifications alone (caloric restriction and increased physical activity). Currently approved options in the United States include phentermine for short-term use and five obesity pharmacotherapies that can be used long-term (orlistat, lorcaserin, phentermine-topiramate, naltrexone-bupropion, and liraglutide 3.0 mg). If the use of an obesity pharmacotherapy is indicated, treatment should be selected to provide the most appropriate option for each individual and their circumstances. Variables such as contraindications, individual comorbidities, patient choice, patient readiness to incorporate additional behavioral changes (e.g., alcohol prohibition), and cost should guide choices. IMPLICATIONS FOR PRACTICE: Each of the obesity pharmacotherapies has advantages and disadvantages that can help guide treatment choice. Those receiving treatment may also have individual preferences based on factors such as administration route, frequency of dosing, and/or safety profile. In addition, some options may be particularly appropriate for patients with common obesity-related complications such as depression or diabetes.


Assuntos
Fármacos Antiobesidade/efeitos adversos , Fármacos Antiobesidade/farmacologia , Obesidade/tratamento farmacológico , Adulto , Fármacos Antiobesidade/uso terapêutico , Benzazepinas/efeitos adversos , Benzazepinas/farmacologia , Benzazepinas/uso terapêutico , Feminino , Humanos , Lactonas/efeitos adversos , Lactonas/farmacologia , Lactonas/uso terapêutico , Liraglutida/efeitos adversos , Liraglutida/farmacologia , Liraglutida/uso terapêutico , Pessoa de Meia-Idade , Naltrexona/efeitos adversos , Naltrexona/farmacologia , Naltrexona/uso terapêutico , Orlistate , Fentermina/efeitos adversos , Fentermina/farmacologia , Fentermina/uso terapêutico , Comportamento de Redução do Risco , Estados Unidos
9.
Aust Fam Physician ; 46(7): 472-477, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28697290

RESUMO

BACKGROUND: Obesity is a serious, chronic, relapsing disease of energy regulation, with strong genetic and early-life environmental determinants. Pharmacotherapy can be a useful adjunct to lifestyle intervention in effecting and maintaining clinically meaningful weight loss. OBJECTIVE: The aim of this article is to discuss the role of pharmacotherapy in obesity management. The efficacy, side effects and contraindications of available weight-loss medications are reviewed. DISCUSSION: Long-term pharmacotherapy options, which can be effective in providing moderate weight loss, are available to treat obesity. Pharma-cotherapy should be considered an adjunct to lifestyle intervention in those with a body mass index (BMI) >30 kg/m30 kg/m2, or in those with a BMI of 27-30 kg/m2 and obesity-related complications. Safety and efficacy should be monitored closely on commencement, and the medication should be discontinued if there are safety or tolerability issues, or if.


Assuntos
Tratamento Farmacológico/métodos , Tratamento Farmacológico/normas , Obesidade/tratamento farmacológico , Fármacos Antiobesidade/efeitos adversos , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/uso terapêutico , Depressores do Apetite/efeitos adversos , Depressores do Apetite/farmacologia , Depressores do Apetite/uso terapêutico , Índice de Massa Corporal , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/normas , Frutose/efeitos adversos , Frutose/análogos & derivados , Frutose/farmacologia , Frutose/uso terapêutico , Humanos , Incretinas/efeitos adversos , Incretinas/farmacologia , Incretinas/uso terapêutico , Lactonas/efeitos adversos , Lactonas/farmacologia , Lactonas/uso terapêutico , Liraglutida/efeitos adversos , Liraglutida/farmacologia , Liraglutida/uso terapêutico , Orlistate , Fentermina/efeitos adversos , Fentermina/farmacologia , Fentermina/uso terapêutico , Topiramato
10.
Obesity (Silver Spring) ; 25(5): 857-865, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28440045

RESUMO

OBJECTIVE: To assess the short-term tolerability of lorcaserin alone or with two dose regimens of phentermine. METHODS: This was a 12-week, randomized, double-blind, pilot safety study of N = 238 nondiabetic patients with obesity or overweight with ≥1 comorbidity randomized to lorcaserin 10 mg twice daily (BID; LOR BID) alone or with phentermine 15 mg once daily (QD; LOR BID+PHEN QD) or 15 mg twice daily (LOR BID+PHEN BID). Patients reporting ≥ 1 of 9 potentially serotonergic adverse events (AEs), mean weight loss (WL), and ≥5% WL are reported. RESULTS: N = 238 were randomized, and N = 235 were treated. N = 94 reported potentially serotonergic AEs: 37.2% LOR BID, 42.3% LOR BID+PHEN QD, and 40.5% LOR BID+PHEN BID. AEs leading to discontinuation were reported approximately twice as often in the LOR BID+PHEN BID group versus the LOR BID group. Mean WL was 3.5 kg/3.3%, 7.0 kg/6.7%, and 7.6 kg/7.2% for LOR BID, LOR BID+PHEN QD, and LOR BID+PHEN BID, respectively. At least 5% WL was achieved by 28.2% LOR BID, 59.0% LOR BID+PHEN QD (P = 0.0002 vs. LOR BID), and 70.9% LOR BID+PHEN BID (P < 0.0001 vs. LOR BID) patients. CONCLUSIONS: Phentermine added to lorcaserin enhanced short-term weight loss but did not increase incidence of potentially serotonergic AEs; however, phentermine twice daily increased discontinuation compared to both lorcaserin alone and lorcaserin plus phentermine once daily.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Benzazepinas/uso terapêutico , Fentermina/uso terapêutico , Perda de Peso/efeitos dos fármacos , Adolescente , Adulto , Fármacos Antiobesidade/administração & dosagem , Fármacos Antiobesidade/farmacologia , Benzazepinas/administração & dosagem , Benzazepinas/farmacologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fentermina/administração & dosagem , Fentermina/farmacologia , Projetos Piloto , Adulto Jovem
12.
Psychopharmacology (Berl) ; 233(8): 1405-13, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26887589

RESUMO

RATIONALE: Phentermine is structurally similar to methamphetamine and is widely used as an anti-obesity drug in the USA and many other countries. The potential for reward of phentermine has been noted; however, the mechanisms of phentermine dependence have not been established. OBJECTIVES: Here, we investigated the rewarding and dopaminergic behavioral responses to phentermine in mice and found that phentermine produced conditioned rewarding effects through the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway in the nucleus accumbens (NAc). METHODS: The impact of phentermine was assessed using conditioned place preference (CPP) test, climbing behavior test, and western blot analysis. RESULTS: Phentermine 1 and 3 mg/kg (i.p.) significantly increased CPP. Phentermine, a known dopamine releaser, boosted apomorphine-induced climbing behavior in mice, and methamphetamine (i.p.) also increased apomorphine-induced dopaminergic behavior. Phentermine and methamphetamine increased the level of expression of the dopamine transporter (DAT) and phospho-Akt proteins to a similar degree in the NAc of CPP mice. To determine whether the conditioned rewarding effects of phentermine were mediated through the PI3K/Akt pathway, we assessed the effects of the Akt inhibitor LY294002 on phentermine-induced place preference and climbing behavior. LY294002 (1 and 3 µg/site, i.c.v.) reduced phentermine-induced CPP and phentermine-increased climbing behavior. However, LY294002 did not change CPP and climbing behavior itself and also did not decrease apomorphine-induced climbing behavior in mice. Further, LY294002 decreased the phentermine-increased levels of DAT protein and phosphorylation of Akt in the NAc of CPP mice. CONCLUSIONS: Thus, these findings suggest that phentermine induces conditioned rewarding effects via activation of the PI3K/Akt signaling pathway in the NAc.


Assuntos
Condicionamento Psicológico/fisiologia , Núcleo Accumbens/metabolismo , Proteína Oncogênica v-akt/metabolismo , Fentermina/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Recompensa , Animais , Fármacos Antiobesidade/farmacologia , Apomorfina/farmacologia , Condicionamento Psicológico/efeitos dos fármacos , Dopamina/metabolismo , Relação Dose-Resposta a Droga , Masculino , Metanfetamina/farmacologia , Camundongos , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Núcleo Accumbens/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
13.
J Am Assoc Nurse Pract ; 28(2): 107-15, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26119641

RESUMO

PURPOSE: To highlight the prevalence and impact of obesity in the United States and provide nurse practitioners (NPs) with an overview of pharmacotherapy options for treatment of overweight and obese individuals. DATA SOURCE: A comprehensive review of the literature was conducted using multiple databases, including PubMed, MEDLINE, and Ovid. Keywords used to obtain relevant articles included obesity and drug, or orlistat, topiramate/phentermine, lorcaserin, bupropion/naltrexone, and liraglutide. CONCLUSIONS: Obesity is a prevalent disease with more than two thirds of Americans being considered overweight and one third being obese. Obesity places patients at an increased risk for many comorbidities that impact patient health as well as public health. There are currently five approved medications for the chronic management of obesity, two of which were approved in 2014. These pharmacological therapies are options to aid weight loss in patients that are obese or those who are overweight with additional risk factors. IMPLICATIONS FOR PRACTICE: NPs can assist patients struggling with their weight. With new pharmacotherapy options, there is an opportunity to add to diet and exercise in order to achieve increased weight loss. A decrease in obesity would potentially alleviate the burden on the healthcare system, both socially and economically, and improve patient quality of life.


Assuntos
Gerenciamento Clínico , Obesidade/tratamento farmacológico , Benzazepinas/efeitos adversos , Benzazepinas/farmacologia , Benzazepinas/uso terapêutico , Bupropiona/efeitos adversos , Bupropiona/farmacologia , Bupropiona/uso terapêutico , Frutose/efeitos adversos , Frutose/análogos & derivados , Frutose/farmacologia , Frutose/uso terapêutico , Humanos , Lactonas/efeitos adversos , Lactonas/farmacologia , Lactonas/uso terapêutico , Liraglutida/efeitos adversos , Liraglutida/farmacologia , Liraglutida/uso terapêutico , Naltrexona/efeitos adversos , Naltrexona/farmacologia , Naltrexona/uso terapêutico , Orlistate , Fentermina/efeitos adversos , Fentermina/farmacologia , Fentermina/uso terapêutico , Topiramato , Estados Unidos
14.
Expert Opin Pharmacother ; 16(8): 1263-74, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25958964

RESUMO

INTRODUCTION: Losing ≥ 5% of initial weight improves quality of life and risk factors for cardiovascular disease (CVD) in obese individuals. Lifestyle modification, the cornerstone of weight reduction, may be complemented by pharmacotherapy. In 2012, the FDA approved the combination of phentermine and topiramate extended release (ER) for chronic weight management, as an adjunct to lifestyle modification. AREAS COVERED: This review examines the safety and efficacy of phentermine-topiramate ER, as determined by randomized controlled trials (RCTs). A preliminary study confirmed the benefit of combining the two medications for improving weight loss and reducing adverse effects, as compared to using equivalent-dose monotherapy alone. EXPERT OPINION: Across RCTs, groups prescribed phentermine 15 mg/topiramate ER 92 mg lost an average of 10% of initial weight, ∼ 8% more than placebo and 2% more than phentermine 7.5 mg/topiramate 46 mg. Weight loss reduced the risk of developing type 2 diabetes and improved CVD risk factors. Phentermine-topiramate ER, however, was associated with increased heart rate, the clinical significance of which is being investigated in an FDA-required CVD outcomes study. The medication also must be used with caution in women of child-bearing age because of an increased risk to infants of oral cleft.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Frutose/análogos & derivados , Obesidade/tratamento farmacológico , Fentermina/uso terapêutico , Fármacos Antiobesidade/farmacologia , Doenças Cardiovasculares/prevenção & controle , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Preparações de Ação Retardada , Diabetes Mellitus Tipo 2/prevenção & controle , Gerenciamento Clínico , Combinação de Medicamentos , Frutose/farmacologia , Frutose/uso terapêutico , Humanos , Estilo de Vida , Fentermina/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Topiramato , Perda de Peso
15.
J Neurophysiol ; 114(1): 585-607, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25972577

RESUMO

Obesity is a worldwide health problem that has reached epidemic proportions. To ameliorate this problem, one approach is the use of appetite suppressants. These compounds are frequently amphetamine congeners such as diethylpropion (DEP), phentermine (PHEN), and bupropion (BUP), whose effects are mediated through serotonin, norepinephrine, and dopaminergic pathways. The nucleus accumbens (NAc) shell receives dopaminergic inputs and is involved in feeding and motor activity. However, little is known about how appetite suppressants modulate its activity. Therefore, we characterized behavioral and neuronal NAc shell responses to short-term treatments of DEP, PHEN, and BUP. These compounds caused a transient decrease in weight and food intake while increasing locomotion, stereotypy, and insomnia. They evoked a large inhibitory imbalance in NAc shell spiking activity that correlated with the onset of locomotion and stereotypy. Analysis of the local field potentials (LFPs) showed that all three drugs modulated beta, theta, and delta oscillations. These oscillations do not reflect an aversive-malaise brain state, as ascertained from taste aversion experiments, but tracked both the initial decrease in weight and food intake and the subsequent tolerance to these drugs. Importantly, the appetite suppressant-induced weight loss and locomotion were markedly reduced by intragastric (and intra-NAc shell) infusions of dopamine antagonists SCH-23390 (D1 receptor) or raclopride (D2 receptor). Furthermore, both antagonists attenuated appetite suppressant-induced LFP oscillations and partially restored the imbalance in NAc shell activity. These data reveal that appetite suppressant-induced behavioral and neuronal activity recorded in the NAc shell depend, to various extents, on dopaminergic activation and thus point to an important role for D1/D2-like receptors (in the NAc shell) in the mechanism of action for these anorexic compounds.


Assuntos
Depressores do Apetite/farmacologia , Antagonistas dos Receptores de Dopamina D2/farmacologia , Núcleo Accumbens/efeitos dos fármacos , Receptores de Dopamina D1/antagonistas & inibidores , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Depressores do Apetite/efeitos adversos , Benzazepinas/farmacologia , Bupropiona/efeitos adversos , Bupropiona/farmacologia , Dietilpropiona/efeitos adversos , Dietilpropiona/farmacologia , Interações Medicamentosas , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Masculino , Núcleo Accumbens/fisiologia , Fentermina/efeitos adversos , Fentermina/farmacologia , Racloprida/farmacologia , Distribuição Aleatória , Ratos Sprague-Dawley , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Comportamento Estereotipado/efeitos dos fármacos , Comportamento Estereotipado/fisiologia , Perda de Peso/efeitos dos fármacos , Perda de Peso/fisiologia
16.
Psychopharmacology (Berl) ; 232(11): 1973-82, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25524140

RESUMO

RATIONALE: Synergistic or supra-additive interactions between the anorectics (dex)fenfluramine and phentermine have been reported previously in the rat and in the clinic. Studies with 5-HT2C antagonists and 5-HT2C knockouts have demonstrated dexfenfluramine hypophagia in the rodent to be mediated by actions at the 5-HT2C receptor. Given the recent FDA approval of the selective 5-HT2C agonist lorcaserin (BELVIQ®) for weight management, we investigated the interaction between phentermine and 5-HT2C agonists on food intake. OBJECTIVES: This study aims to confirm dexfenfluramine-phentermine (dex-phen) synergy in a rat food intake assay, to extend these findings to other 5-HT2C agonists, and to determine whether pharmacokinetic interactions could explain synergistic findings with particular drug combinations. METHODS: Isobolographic analyses were performed in which phentermine was paired with either dexfenfluramine, the 5-HT2C agonist AR630, or the 5-HT2C agonist lorcaserin, and inhibition of food intake measured in the rat. Subsequent studies assessed these same phentermine-drug pair combinations spanning both the full effect range and a range of fixed ratio drug combinations. Satellite groups received single doses of each drug either alone or in combination with phentermine, and free brain concentrations were measured. RESULTS: Dex-phen synergy was confirmed in the rat and extended to the 5-HT2C agonist AR630. In contrast, although some synergistic interactions between lorcaserin and phentermine were observed, these combinations were largely additive. Synergistic interactions between phentermine and dexfenfluramine or AR630 were accompanied by combination-induced increases in brain levels of phentermine. CONCLUSIONS: Dex-phen synergy in the rat is caused by a pharmacokinetic interaction, resulting in increased central concentrations of phentermine.


Assuntos
Depressores do Apetite/farmacologia , Dexfenfluramina/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Fenfluramina/farmacologia , Fentermina/farmacologia , Receptor 5-HT2C de Serotonina/efeitos dos fármacos , Animais , Depressores do Apetite/farmacocinética , Dexfenfluramina/farmacocinética , Sinergismo Farmacológico , Fenfluramina/farmacocinética , Masculino , Fentermina/farmacocinética , Ratos , Ratos Sprague-Dawley , Agonistas do Receptor 5-HT2 de Serotonina/farmacocinética , Agonistas do Receptor 5-HT2 de Serotonina/farmacologia
17.
Food Drug Law J ; 69(1): 87-111, ii-iii, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24772687

RESUMO

As obesity rates continue to rise in the United States, both physicians and patients have demanded more safe and effective drug treatment options. However, following the fen-phen/Redux and sibutramine failures, the FDA has been hesitant to approve any anti-obesity drugs, despite the magnitude of the epidemic. Some have argued that these public embarrassments have led the FDA to overestimate the risks and underestimate the benefits when deciding whether to approve new anti-obesity drugs. On June 27, 2012, the FDA approved Belviq for chronic weight management, making it the first anti-obesity drug approved by the FDA in thirteen years. Less than one month later, the FDA approved Qsymia for the treatment of obesity. Both drugs had been denied FDA approval less than two years earlier. In this paper, I will first review the obesity crisis and discuss the high-profile market withdrawals of fenfluramine, dexfenfluramine, and sibutramine. Second, I will explain the FDA's drug approval process with a focus on the FDA's risk/benefit calculus. Third, I will compare the FDA's risk/benefit analysis for Qsymia and Belviq in 2010 with the agency's risk/benefit analysis in 2012 to determine what caused the agency to grant approval in 2012 while denying it in 2010. Finally, I will analyze what these drug approvals may mean for the future of other anti-obesity drugs.


Assuntos
Fármacos Antiobesidade/farmacologia , Aprovação de Drogas , Obesidade/tratamento farmacológico , Benzazepinas/farmacologia , Combinação de Medicamentos , Frutose/análogos & derivados , Frutose/farmacologia , Humanos , Fentermina/farmacologia , Medição de Risco , Estados Unidos , United States Food and Drug Administration
18.
Nurs Womens Health ; 17(1): 53-62, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23399013

RESUMO

Obesity, defined as a body mass index (BMI, kg/m(2) ) >30, is a significant public health problem. It's estimated that 50 percent of the U.S. population will be classified as obese by the year 2030. Due to associated health complications and rising health care costs related to obesity, new treatment options are being explored. For people who need additional treatment beyond lifestyle modification, new pharmacologic options have been developed that may assist in reducing BMI. Health care providers and patients should consider each person's individual health history and consider both the potential risks and benefits of these therapies.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Benzazepinas/uso terapêutico , Frutose/análogos & derivados , Obesidade/tratamento farmacológico , Fentermina/uso terapêutico , Fármacos Antiobesidade/farmacologia , Benzazepinas/farmacologia , Índice de Massa Corporal , Combinação de Medicamentos , Feminino , Frutose/farmacologia , Frutose/uso terapêutico , Humanos , Estilo de Vida , Obesidade/enfermagem , Fentermina/farmacologia , Gravidez , Medição de Risco , Estados Unidos
20.
Hormones (Athens) ; 12(4): 507-16, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24457398

RESUMO

BACKGROUND AND OBJECTIVE: Very few drugs are approved for obesity treatment by regulatory agencies. Very recently phentermine/topiramate controlled-release [PHEN/TPM CR; (Qsymia®)] obtained Food and Drug Administration (FDA) approval as an addition to a reduced-calorie diet and exercise for chronic weight management. Our aim was to review the available clinical evidence on weight loss, metabolic effects and adverse events associated with use of this product. METHODS: Randomized controlled trials with phentermine/topiramate controlled-release were selected through a Medline search using the terms: phentermine and topiramate, phentermine and controlled release topiramate, new anti-obesity drugs and phentermine/topiramate, recent combinations of anti-obesity drugs and Qnexa®. RESULTS: PHEN/TPM CR was associated with a weight loss of 8.1-10.9 % (mid and high dose, respectively), while patients in placebo groups lost 1.4-1.8 % of their initial weight. PHEN/TPM CR also resulted in a significant decrease of waist circumference. Weight loss with PHEN/TPM CR was associated with a decrease in blood pressure but with a slight increase in the heart rate. Furthermore, in all trials it exerted favorable effects on lipid profile, especially on triglycerides and high-density lipopoprotein (HDL) cholesterol. PHEN/TPM CR treatment also improved insulin sensitivity and glycemia. Moreover, it decreased significantly progression to type 2 diabetes. In all of the studies the severe adverse events were similar between the control groups and the groups of PHEN/TPM CR. The most frequent side-effects observed in the active treatment group were paresthesia, dysgeusia, dry mouth, constipation and insomnia. WHAT IS NEW AND CONCLUSION: PHEN/TPM CR combined with lifestyle modification may be an effective and well-tolerated treatment for obesity and weight-related metabolic complications. Its long-term efficacy and safety have yet to be defined.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Frutose/análogos & derivados , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Fentermina/uso terapêutico , Fármacos Antiobesidade/farmacologia , Preparações de Ação Retardada , Dieta Redutora , Quimioterapia Combinada , Exercício Físico , Frutose/farmacologia , Frutose/uso terapêutico , Humanos , Estilo de Vida , Fentermina/farmacologia , Topiramato , Resultado do Tratamento , Perda de Peso/efeitos dos fármacos
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