RESUMEN
BACKGROUND: Opioids are frequently prescribed for moderate to severe pain. A side effect of opioid usage is the inhibition of gastrointestinal (GI) motility, known as opioid-induced bowel dysfunction (OBD). OBD is typically treated prophylactically with laxatives and/or acid suppressants. AIM: The present study describes the prevalence of outpatient opioid dispensing, opioid patient demographics, and concomitant dispensing of opioids and GI medications in the Quebec Public Prescription Drug Insurance Plan in 2005. METHODS: Using a retrospective cohort design, opioid dispensings were identified using claims and reimbursement data. Laxative and acid suppressant dispensings were also identified. Concurrent use was defined as having at least one 'GI medication-exposed day' overlapping an 'opioid-exposed day'. RESULTS: More than 11% of the drug plan population was dispensed an opioid in 2005, and dispensings increased with age. Approximately two-thirds of patients who received an opioid were given codeine. Approximately one-third of opioid patients were concomitantly dispensed a GI medication, yet only 2% were dispensed a laxative. CONCLUSIONS: Although the GI side effects of opioids are well known, these side effects appear to increase with age and duration of opioid use. Opioid-related side effects, particularly OBD, should be effectively managed so as not to lead to the cessation of opioid therapy.
Asunto(s)
Analgésicos Opioides , Prescripciones de Medicamentos/estadística & datos numéricos , Fármacos Gastrointestinales , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Analgésicos Opioides/efectos adversos , Antiácidos/uso terapéutico , Codeína/uso terapéutico , Estudios de Cohortes , Utilización de Medicamentos , Femenino , Enfermedades Gastrointestinales/inducido químicamente , Enfermedades Gastrointestinales/tratamiento farmacológico , Enfermedades Gastrointestinales/epidemiología , Motilidad Gastrointestinal/efectos de los fármacos , Humanos , Reembolso de Seguro de Salud/estadística & datos numéricos , Seguro de Servicios Farmacéuticos/estadística & datos numéricos , Laxativos/uso terapéutico , Masculino , Persona de Mediana Edad , Medicamentos sin Prescripción , Pacientes Ambulatorios/estadística & datos numéricos , Quebec/epidemiología , Estudios Retrospectivos , Factores Socioeconómicos , Adulto JovenRESUMEN
OBJECTIVE: To describe characteristics of vasomotor symptoms, specifically daily frequency and severity, among women 40-65 years old in the United States (US). DESIGN: A survey was completed by a nationally representative sample of 4402 US women aged 40-65 years old. A questionnaire focusing on menopausal symptoms was administered online in April 2005. RESULTS: The prevalence of vasomotor symptoms was 79% in peri- and 65% in postmenopausal women. Women with daily vasomotor symptoms had an average of 2.5 very mild/mild, 2.6 moderate, 2.5 severe, and 1.4 very severe daytime hot flushes in a typical day. Women with night sweats every night had an average of 2.4 moderate, 3.2 severe, and 2.7 very severe night sweats in a typical night. Overall, 9% of peri- and 7% of postmenopausal women reported 7+ moderate to very severe vasomotor symptoms in a typical day. Although some women reported that symptoms were worse in the evening and in the summer, many women reported they were consistent, both throughout the day and throughout the seasons of the year. CONCLUSIONS: The Menopause Epidemiology Study builds upon existing literature by providing data on daily frequency and severity of vasomotor symptoms. There are many women with frequent and severe vasomotor symptoms who may benefit from treatment.
Asunto(s)
Sofocos/epidemiología , Sofocos/patología , Perimenopausia/fisiología , Posmenopausia/fisiología , Sistema Vasomotor/fisiopatología , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Calidad de Vida , Estaciones del Año , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Sudoración , Estados Unidos/epidemiologíaRESUMEN
At any instant, the human erythrocyte sugar transporter presents at least one sugar export site but multiple sugar import sites. The present study asks whether the transporter also presents more than one sugar exit site. We approached this question by analysis of binding of [3H]cytochalasin B (an export conformer ligand) to the human erythrocyte sugar transporter and by analysis of cytochalasin B modulation of human red blood cell sugar uptake. Phloretin-inhibitable cytochalasin B binding to human red blood cells, to human red blood cell integral membrane proteins, and to purified human red blood cell glucose transport protein (GluT1) displays positive cooperativity at very low cytochalasin B levels. Cooperativity between sites and K(d(app)) for cytochalasin B binding are reduced in the presence of intracellular ATP. Red cell sugar uptake at subsaturating sugar levels is inhibited by high concentrations of cytochalasin B but is stimulated by lower (<20 nM) concentrations. Increasing concentrations of the e1 ligand forskolin also first stimulate then inhibit sugar uptake. Cytochalasin D (a cytochalasin B analogue that does not interact with GluT1) is without effect on sugar transport over the same concentration range. Cytochalasin B and ATP binding are synergistic. ATP (but not AMP) enhances [3H]cytochalasin B photoincorporation into GluT1 while cytochalasin B (but not cytochalasin D) enhances [gamma-32P]azidoATP photoincorporation into GluT1. We propose that the red blood cell glucose transporter is a cooperative tetramer of GluT1 proteins in which each protein presents a translocation pathway that alternates between uptake (e2) and export (e1) states but where, at any instant, two subunits must present uptake (e2) and two subunits must present exit (e1) states.
Asunto(s)
Adenosina Trifosfato/metabolismo , Metabolismo de los Hidratos de Carbono , Eritrocitos/metabolismo , Proteínas de Transporte de Monosacáridos/metabolismo , 3-O-Metilglucosa/metabolismo , Adenosina Trifosfato/química , Carbohidratos/química , Citocalasina B/metabolismo , Eritrocitos/química , Transportador de Glucosa de Tipo 1 , Humanos , Cinética , Maltosa/metabolismo , Modelos Químicos , Proteínas de Transporte de Monosacáridos/química , Unión Proteica , Estructura Cuaternaria de Proteína , Transporte de ProteínasRESUMEN
Human erythrocyte sugar transport is mediated by the integral membrane protein GLUT1 and is regulated by cytosolic ATP [Carruthers, A., and Helgerson, A. L. (1989) Biochemistry 28, 8337-8346]. This study asks the following questions. (1) Where is the GLUT1 ATP binding site? (2) Is ATP-GLUT1 interaction sufficient for sugar transport regulation? (3) Is ATP modulation of transport subject to metabolic control? GLUT1 residues 301-364 were identified as one element of the GLUT1 ATP binding domain by peptide mapping and N-terminal sequence analysis of proteolytic fragments of azidoATP-photolabeled GLUT1. Nucleotide binding and sugar transport experiments undertaken with dimeric and tetrameric forms of GLUT1 indicate that only tetrameric GLUT1 binds and is subject to modulation by ATP. Reconstitution experiments indicate that nucleotide and tetrameric GLUT1 are sufficient for ATP modulation of sugar transport. Feedback control of GLUT1 regulation by ATP was investigated by measuring sugar uptake into erythrocyte ghosts containing or lacking ATP and glycolytic intermediates. Only AMP and ADP modulate ATP regulation of transport. Reduced cytosolic pH inhibits ATP modulation of GLUT1-mediated 3OMG uptake and increases Kd(app) for ATP interaction with GLUT1. We conclude that tetrameric but not dimeric GLUT1 is subject to direct regulation by cytosolic ATP and that this regulation is antagonized by intracellular AMP and acidification.