RESUMO
ABSTRACT Objective: The advent of multikinase inhibitor (MKI) therapy has led to a radical change in the treatment of patients with advanced thyroid carcinoma. The aim of this manuscript is to communicate rare adverse events that occurred in less than 5% of patients in clinical trials in a subset of patients treated in our hospital. Subjects and methods: Out of 760 patients with thyroid cancer followed up with in our Division of Endocrinology, 29 (3.8%) received treatment with MKIs. The median age at diagnosis of these patients was 53 years (range 20-70), and 75.9% of them were women. Sorafenib was prescribed as first-line treatment to 23 patients with differentiated thyroid cancer and as second-line treatment to one patient with advanced medullary thyroid cancer (MTC). Vandetanib was indicated as first-line treatment in 6 patients with MTC and lenvatinib as second-line treatment in two patients with progressive disease under sorafenib treatment. Results: During the follow-up of treatment (mean 13.7 ± 7 months, median 12 months, range 6-32), 5/29 (17.2%) patients presented rare adverse events. These rare adverse effects were: heart failure, thrombocytopenia, and squamous cell carcinoma during sorafenib therapy and squamous cell carcinoma and oophoritis with intestinal perforation during vandetanib treatment. Conclusions: About 3 to 5 years after the approval of MKI therapy, we learned that MKIs usually lead to adverse effects in the majority of patients. Although most of them are manageable, we still need to be aware of potentially serious and rare or unreported adverse effects that can be life-threatening.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Piperidinas/efeitos adversos , Quinazolinas/efeitos adversos , Carcinoma/tratamento farmacológico , Carcinoma Medular/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Antineoplásicos/efeitos adversos , Ooforite/induzido quimicamente , Compostos de Fenilureia/efeitos adversos , Quinolinas/efeitos adversos , Trombocitopenia/induzido quimicamente , Fatores de Tempo , Neoplasias da Glândula Tireoide/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco , Seguimentos , Estimativa de Kaplan-Meier , Sorafenibe/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Perfuração Intestinal/induzido quimicamenteRESUMO
ABSTRACT Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating from parafollicular C cells of the thyroid and associated with mutations in the proto-oncogene REarranged during Transfection (RET). The prognosis of MTC depends on clinical stage, with a 95.6% 10-year survival rate among patients with localized disease and 40% among patients with advanced disease. Standard chemotherapy and radiotherapy have no significant impact on the overall survival of these patients and two tyrosine kinase receptor inhibitors (TKIs), vandetanib and cabozantinib, have been recently approved for the systemic treatment of locally advanced or metastatic MTC. However, since patients with MTC and residual or recurrent disease may have an indolent course with no need for systemic treatment, and since these drugs are highly toxic, it is extremely important to select the patients who will receive these drugs in a correct manner. It is also essential to carefully monitor patients using TKI regarding possible adverse effects, which should be properly managed when occurring.
Assuntos
Humanos , Piperidinas/uso terapêutico , Piridinas/uso terapêutico , Quinazolinas/uso terapêutico , Carcinoma Neuroendócrino/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Anilidas/uso terapêutico , Piperidinas/efeitos adversos , Piridinas/efeitos adversos , Quinazolinas/efeitos adversos , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/tratamento farmacológico , Carcinoma Neuroendócrino/metabolismo , Medição de Risco , Inibidores de Proteínas Quinases/efeitos adversos , Anilidas/efeitos adversosRESUMO
OBJECTIVE: This study sought to describe and analyze ocular findings associated with nonocular surgery in patients who underwent general anesthesia. METHODS: The authors retrospectively collected a series of 39,431 surgeries using standardized data forms. RESULTS: Ocular findings were reported in 9 cases (2.3:10,000), which involved patients with a mean age of 58.9±19.5 years. These cases involved patients classified as ASA I (33%), ASA II (55%) or ASA III (11%). General anesthesia with propofol and remifentanil was used in 4 cases, balanced general anesthesia was used in 4 cases, and regional block was used in combination with balanced general anesthesia in one case. Five patients (55%) underwent surgery in the supine position, one patient (11%) underwent surgery in the lithotomy position, two patients (22%) underwent surgery in the prone position, and one patient (11%) underwent surgery in the lateral position. Ocular hyperemia was detected in most (77%) of the 9 cases with ocular findings; pain/burning of the eyes, visual impairment, eye discharge and photophobia were observed in 55%, 11%, 11% and 11%, respectively, of these 9 cases. No cases involved permanent ocular injury or vision loss. CONCLUSION: Ophthalmological findings after surgeries were uncommon, and most of the included patients were relatively healthy. Minor complications, such as dehydration or superficial ocular trauma, should be prevented by following systematic protocols that provide appropriate ocular occlusion with a lubricating ointment and protect the eye with an acrylic occluder. These procedures will refine the quality of anesthesia services and avoid discomfort among patients, surgeons and anesthesia staff. .
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Anestesia Geral/efeitos adversos , Oftalmopatias/etiologia , Oftalmopatias/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Anestésicos Intravenosos/efeitos adversos , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Lubrificantes Oftálmicos/uso terapêutico , Posicionamento do Paciente/efeitos adversos , Piperidinas/efeitos adversos , Propofol/efeitos adversos , Estudos Retrospectivos , Fatores de RiscoRESUMO
Association between postoperative nausea and vomiting (PONV) and micro-opioid receptor A118G single nucleotide polymorphism (SNP) is undefined and might underlie inconsistent results of studies on PONV occurrence in patients undergoing general anesthesia with the opioid, remifentanil. Four hundred and sixteen Korean women undergoing breast surgery with general anesthesia were randomized to receive remifentanil 10 ng/mL (plasma-site, Minto model) using a target-controlled infusion device and either propofol for total intravenous anesthesia (T group) or sevoflurane for inhalation anesthesia (I group) with bispectral index values maintained between 40 and 60. Blood specimens were collected after anesthesia induction for A118G SNP analysis. PONV and postoperative pain were evaluated. A118G SNP type distribution among Korean female adults studied was AG (n=195)>AA (n=158)>GG (n=63). Regardless of anesthetic technique, patients with GG types had lower PONV scale on arrival at postoperative care unit (PACU) (P=0.002), while T group showed lower PONV scale than I group up to 6 hr after PACU discharge in AA and AG types. No differences were apparent for postoperative pain among opioid receptor polymorphism. PONV occurrence differs according to opioid receptor polymorphism and anesthetic technique in patients undergoing general anesthesia with remifentanil.
Assuntos
Adulto , Feminino , Humanos , Analgésicos Opioides/efeitos adversos , Anestesia Geral/efeitos adversos , Doenças Mamárias/cirurgia , Demografia , Método Duplo-Cego , Éteres Metílicos/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Piperidinas/efeitos adversos , Polimorfismo de Nucleotídeo Único , Náusea e Vômito Pós-Operatórios/etiologia , Receptores Opioides mu/genéticaRESUMO
OBJECTIVE: Laryngoscopy and stimuli inside the trachea cause an intense sympatho-adrenal response. Remifentanil seems to be the optimal opioid for rigid bronchoscopy due to its potent and short-acting properties. The purpose of this study was to compare bolus propofol and ketamine as an adjuvant to remifentanil-based total intravenous anesthesia for pediatric rigid bronchoscopy. MATERIALS AND METHODS: Forty children under 12 years of age who had been scheduled for a rigid bronchoscopy were included in this study. After midazolam premedication, a 1 µg/kg/min remifentanil infusion was started, and patients were randomly allocated to receive either propofol (Group P) or ketamine (Group K) as well as mivacurium for muscle relaxation. Anesthesia was maintained with a 1 µg/kg/min remifentanil infusion and bolus doses of propofol or ketamine. After the rigid bronchoscopy, 0.05 µg/kg/min of remifentanil was maintained until extubation. Hemodynamic parameters, emergence characteristics, and adverse events were evaluated. RESULTS: The demographic variables were comparable between the two groups. The decrease in mean arterial pressure from baseline values to the lowest values during rigid bronchoscopy was greater in Group P (p = 0.049), while the reduction in the other parameters and the incidence of adverse events were comparable between the two groups. The need for assisted or controlled mask ventilation after extubation was higher in Group K. CONCLUSION: Remifentanil-based total intravenous anesthesia with propofol or ketamine as an adjuvant drug along with controlled ventilation is a viable technique for pediatric rigid bronchoscopy. Ketamine does not provide a definite advantage over propofol with respect to hemodynamic stability during rigid bronchoscopy, while propofol seems more suitable during the recovery period. .
Assuntos
Criança , Pré-Escolar , Feminino , Humanos , Masculino , Anestésicos Combinados/administração & dosagem , Anestésicos Intravenosos/administração & dosagem , Broncoscopia/métodos , Ketamina/administração & dosagem , Piperidinas/administração & dosagem , Propofol/administração & dosagem , Anestesia Intravenosa/métodos , Anestésicos Combinados/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Esquema de Medicação , Frequência Cardíaca/efeitos dos fármacos , Ketamina/efeitos adversos , Piperidinas/efeitos adversos , Propofol/efeitos adversosRESUMO
PURPOSE: We evaluated the incidence and risk factors of postoperative nausea and vomiting (PONV) in patients with fentanyl-based intravenous patient-controlled analgesia (IV-PCA) and single antiemetic prophylaxis of 5-hydroxytryptamine type 3 (5 HT3)-receptor antagonist after the general anesthesia. MATERIALS AND METHODS: In this retrospective study, incidence and risk factors for PONV were evaluated with fentanyl IV-PCA during postoperative 48 hours after various surgeries. RESULTS: Four hundred-forty patients (23%) of 1878 had showed PONV. PCA was discontinued temporarily in 268 patients (14%), mostly due to PONV (88% of 268 patients). In multivariate analysis, female, non-smoker, history of motion sickness or PONV, long duration of anesthesia (>180 min), use of desflurane and intraoperative remifentanil infusion were independent risk factors for PONV. If one, two, three, four, five, or six of these risk factors were present, the incidences of PONV were 18%, 19%, 22%, 31%, 42%, or 50%. Laparoscopic surgery and higher dose of fentanyl were not risk factors for PONV. CONCLUSION: Despite antiemetic prophylaxis with 5 HT3-receptor antagonist, 23% of patients with fentanyl-based IV-PCA after general anesthesia showed PONV. Long duration of anesthesia and use of desflurane were identified as risk factors, in addition to risk factors of Apfel's score (female, non-smoker, history of motion sickness or PONV). Also, intraoperative remifentanil infusion was risk factor independent of postoperative opioid use. As the incidence of PONV was up to 50% according to the number of risk factors, risk-adapted, multimodal or combination therapy should be applied.
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Analgesia Controlada pelo Paciente/efeitos adversos , Analgésicos Opioides/efeitos adversos , Antieméticos/administração & dosagem , Fentanila/efeitos adversos , Incidência , Isoflurano/efeitos adversos , Piperidinas/efeitos adversos , Náusea e Vômito Pós-Operatórios/induzido quimicamente , Estudos Retrospectivos , Fatores de RiscoRESUMO
Introducción: El objetivo fue comprobar si los sistemas de perfusión guiados por ordenador TCI (Target Control Infusion) estimando concentraciones plasmáticas (Cp), modulan condiciones hemodinámicas, consumo de remifentanil y concentraciones sitio efecto (Ce), en colecistectomía videolaparoscópica (CVL). Material y Métodos: Estudio clínico prospectivo, aleatorizado en pacientes ASA I, dos grupos: GRUPO PC (n = 12) remifentanil 0.5 mcg x kg-1 x min-1 y GRUPO TCI (n = 12) TCI remifentanil Cp 4 ng x ml-1 (Modelo Minto, Ke sub 0 0,595/min). Ambas perfusiones disminuidas 50% posintubación. Se registraron Tensión Arterial Sistólica (TAS), Tensión Arterial Diastólica (TAD) y Frecuencia Cardíaca (FC), remifentanil consumido y Ce, basal, posintubación, posincisión y finalización cirugía. Resultados: Sin diferencias entre grupos variables antropométricas, tiempos quirúrgico y de anestesia. Se halló diferencia G PC vs G TCI en FC (X ± de) posintubación 63,2 ± 12,2 vs 76,6 ± 13 (p = 0,014). Dentro grupos, G PC posintubación TAS 96,9 ± 18,5 (p = 0,0009), TAD 57,7 ± 15,2 (p = 0,0006) y FC 63,2 ± 12,2 (p = 0,010). Consumo de remifentanil G PC vs G TCI posintubación 216,2 ± 91,6 vs 102,4 ± 14,8 (p < 0,0001), posincisión 381,4 ± 185,4 vs 184,1 ± 39,6 (p = 0,0002) y fin de cirugía 2310 ± 912,8 vs 1642,4 ± 607,8 (p = ,028). Ce remifentanil posintubación 7,4 ± 1,6 vs 3,6 ± 0,2 (p < 0,0001), posincisión 6,1 ± 1,7 vs 2,2 ± 0,3 (p < 0,0001). Hipotensión G PC posintubación (50% p < 0,007), posincisión (33,3% p < 0,047), necesidad de efedrina dos pacientes G PC. Conclusión: La perfusión de remifentanil controlada por ordenador Cp de 4 ng/ml produjo en nuestro grupo de pacientes mejores condiciones hemodinámicas durante el intraoperatorio, comparada con perfusión continua de 0.5 mcg x kg-1 x min-1, en CVL. La mejoría se atribuiría a la adecuada concentración de remifentanil en sitio de efecto, permitiendo además disminuir el consumo de la droga.
Assuntos
Humanos , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Anestesia Intravenosa/instrumentação , Anestesia Intravenosa/métodos , Piperidinas/administração & dosagem , Piperidinas/efeitos adversos , Anestesia Geral/métodos , Colecistectomia Laparoscópica , Hemodinâmica , Bombas de Infusão , Monitorização Intraoperatória , Propofol/administração & dosagemRESUMO
PURPOSE: Although the presence of cannabinoid type 1 (CB1) receptor in islets has been reported, the major contributor to the protective effect of rimonabant on islet morphology is unknown. We determined whether the protective effect of rimonabant on pancreatic islet morphology is valid in established diabetes and also whether any effect was independent of decreased food intake. MATERIALS AND METHODS: After diabetes was confirmed, Otsuka Long-Evans Tokushima Fatty rats, aged 32 weeks, were treated with rimonabant (30 mg/kg/d, rimonabant group) for 6 weeks. Metabolic profiles and islet morphology of rats treated with rimonabant were compared with those of controls without treatment (control group), a pair-fed control group, and rats treated with rosiglitazone (4 mg/kg/d, rosiglitazone group). RESULTS: Compared to the control group, rats treated with rimonabant exhibited reduced glycated albumin levels (p<0.001), islet fibrosis (p<0.01), and improved glucose tolerance (p<0.05), with no differences from the pair-fed control group. The retroperitoneal adipose tissue mass was lower in the rimonabant group than those of the pair-fed control and rosiglitazone groups (p<0.05). Rimonabant, pair-fed control, and rosiglitazone groups showed decreased insulin resistance and increased adiponectin, with no differences between the rimonabant and pair-fed control groups. CONCLUSION: Rimonabant had a protective effect on islet morphology in vivo even in established diabetes. However, the protective effect was also reproduced by pair-feeding. Thus, the results of this study did not support the significance of islet CB1 receptors in islet protection with rimonabant in established obesity-associated type 2 diabetes.
Assuntos
Animais , Masculino , Ratos , Adiponectina/metabolismo , Adiposidade/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Diabetes Mellitus Tipo 2/dietoterapia , Ingestão de Alimentos/efeitos dos fármacos , Intolerância à Glucose/dietoterapia , Resistência à Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Piperidinas/efeitos adversos , Pirazóis/efeitos adversos , Ratos Endogâmicos OLETF , Receptor CB1 de Canabinoide/fisiologia , Tiazolidinedionas/uso terapêuticoRESUMO
PURPOSE: This study aims to investigate the most appropriate effect-site concentration of remifentanil to minimize cardiovascular changes during inhalation of high concentration desflurane. MATERIALS AND METHODS: Sixty-nine American Society of Anesthesiologists physical status class I patients aged 20-65 years were randomly allocated into one of three groups. Anesthesia was induced with etomidate and rocuronium. Remifentanil was infused at effect-site concentrations of 2, 4 and 6 ng/mL in groups R2, R4 and R6, respectively. After target concentrations of remifentanil were reached, desflurane was inhaled to maintain the end-tidal concentration of 1.7 minimum alveolar concentrations for 5 minutes (over-pressure paradigm). The systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR) and end-tidal concentration of desflurane were measured for 5 minutes. RESULTS: The end-tidal concentration of desflurane increased similarly in all groups. The SBP, DBP, MAP and HR within group R4 were not significantly different as compared with baseline values. However, measured parameters within group R2 increased significantly 1-3 minutes after desflurane inhalation. The MAP within group R6 decreased significantly at 1, 2, 4, and 5 minutes (p<0.05). There were significant differences in SBP, DBP, MAP and HR among the three groups 1-3 minutes after inhalation (p<0.05). The incidence of side effects such as hyper- or hypo-tension, and tachy- or brady-cardia in group R4 was 4.8% compared with 21.8% in group R2 and 15.0% in group R6. CONCLUSION: The most appropriate effect-site concentration of remifentanil for blunting hemodynamic responses by inhalation of high concentration desflurane is 4 ng/mL.
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Androstanóis/efeitos adversos , Anestésicos/efeitos adversos , Anestésicos Inalatórios/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Etomidato/efeitos adversos , Coração/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Isoflurano/efeitos adversos , Piperidinas/efeitos adversos , Substâncias Protetoras/efeitos adversosRESUMO
The recent availability of molecular targeted therapies leads to a reconsideration of the treatment strategy for patients with distant metastases from medullary thyroid carcinoma. In patients with progressive disease, treatment with kinase inhibitors should be offered.
Assuntos
Humanos , Antineoplásicos/uso terapêutico , Carcinoma Medular/tratamento farmacológico , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Antineoplásicos/efeitos adversos , Carcinoma Medular/patologia , Ensaios Clínicos como Assunto/normas , Terapia de Alvo Molecular , Seleção de Pacientes , Piperidinas/efeitos adversos , Quinazolinas/efeitos adversos , Neoplasias da Glândula Tireoide/secundárioRESUMO
Remifentanil has a unique pharmacokinetic profile, with a rapid onset and offset of action and a plasmatic metabolism. Its use can be recommended even in patients with renal impairment, hepatic dysfunction or poor cardiovascular function. A potential protective cardiac preconditioning effect has been suggested. Drug-related adverse effects seem to be comparable with other opioids. In cardiac surgery, many randomized controlled trials demonstrated that the potential benefits of the use of remifentanil not only include a profound protection against intraoperative stressful stimuli, but also rapid postoperative recovery, early weaning from mechanical ventilation, and extubation. Remifentanil shows ideal properties of sedative agents being often employed for minimally invasive cardiologic techniques, such as transcatheter aortic valve implantation and radio frequency treatment of atrial flutter, or diagnostic procedures such as transesophageal echocardiography. In intensive care units remifentanil is associated with a reduction in the time to tracheal extubation after cessation of the continuous infusion; other advantages could be more evident in patients with organ dysfunction. Effective and safe analgesia can be provided in case of short and painful procedures (i.e. chest drain removal). In conclusion, thanks to its peculiar properties, remifentanil will probably play a major role in critically ill cardiac patients.
Assuntos
Analgésicos Opioides/farmacologia , Anestesia/métodos , Anestésicos Intravenosos/farmacologia , Procedimentos Cirúrgicos Cardíacos , Estado Terminal , Humanos , Hipnóticos e Sedativos/farmacologia , Unidades de Terapia Intensiva , Piperidinas/efeitos adversos , Piperidinas/farmacocinética , Piperidinas/farmacologiaRESUMO
OBJECTIVE: To evaluate the effects of three different target-controlled remifentanil infusion rates during target-controlled propofol infusion on hemodynamic parameters, pain, sedation, and recovery score during oocyte retrieval. METHODS: Sixty-nine women were scheduled for oocyte retrieval. Target-controlled propofol infusion at an effectsite concentration of 1.5 μg/mL was instituted. The patients were randomly allocated to receive remifentanil at an effect-site concentration of either 1.5 (group I, n = 23), 2 (group II, n = 23) or 2.5 ng/mL (group III, n = 23). Hemodynamic variables, sedation, pain, the Aldrete recovery score, and side effects were recorded. RESULTS: Hemodynamic variables, sedation and pain scores and the number of patients with the maximum Aldrete recovery score 10 min after the procedure were comparable among the groups. The number of patients in group III with the maximum Aldrete recovery score 5 min after the procedure was significantly lower than that in groups I and II. One patient in group II and one patient in group III suffered from nausea. CONCLUSION: Similar pain-free conscious sedation conditions without significant changes in hemodynamic parameters were provided by all three protocols. However, target controlled infusion of remifentanil at 1.5 or 2 ng/mL proved superior at providing early recovery compared to 2.5 ng/mL.
Assuntos
Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Anestésicos Intravenosos/administração & dosagem , Recuperação de Oócitos/métodos , Piperidinas/administração & dosagem , Propofol/administração & dosagem , Período de Recuperação da Anestesia , Anestésicos Intravenosos/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Infusões Intravenosas , Dor Pós-Operatória , Náusea e Vômito Pós-Operatórios , Piperidinas/efeitos adversos , Propofol/efeitos adversosRESUMO
Succinylcholine is a popular muscle relaxant and one of its most common side effects is muscle fasciculation. The purpose of this study was to evaluate the efficacy of remifentanil in preventing succinylcholine-induced fasciculation in patients undergoing general anesthesia. In aprospective, double blind study, 60 ASA I and II patients were randomly assigned into two groups [30 each] to receive either remifentanil 1 micro g/kg [Group R], or saline 3 ml [Group S] as a pretreatment agent, one minute before induction of general anesthesia by propofol, fentanyl, and 1.5 mg/kg succinylcholine. The duration and the intensity of fasciculation were assessed using a four-point rating scale. Data were analyzed by Mann-Whitney U-test, Fisher exact test and Student-t-test using SPSS software. In the remifentanil group the duration [p<0.001] and the intensity [p<0.001] of fasciculation were lower compared to the saline group. However the incidence of bradycardia was higher in the remifentanil group in comparison to the group which received normal saline. Our findings indicate that remifentanil can reduce the duration and the intensity of succinylcholine induced fasciculation. However, it induces greater bradycardia
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Piperidinas/efeitos adversos , Succinilcolina/efeitos adversos , /tratamento farmacológico , Estudos Prospectivos , Método Duplo-Cego , Resultado do TratamentoRESUMO
OBJECTIVE: Experimental evidence has suggested that drugs that enhance cannabinoid type-1 (CB1) receptor activity may induce anxiolytic and antidepressant effects, whilst the opposite has been reported with antagonists. Thus, the objective of the present review is to discuss the potential psychiatric side-effects of CB1 receptor antagonists, such as rimonabant, which has been recently marketed in several countries for the treatment of smoking cessation, obesity and associated metabolic disorders. METHOD: Literature searches were performed in PubMed and SciELO databases up to February 2009. The terms searched were "obesity", "rimonabant", "cannabinoids", "unwanted effects", "diabetes", "smoking cessation" and "side-effects". RESULTS: Clinical trials have revealed that rimonabant may promote weight loss in obese patients, although it may also induce symptoms of anxiety and depression. DISCUSSION: Patients taking CB1 receptor antagonists should be carefully investigated for psychiatric side-effects. These drugs should not be prescribed for those already suffering from mental disorders. Nevertheless, the development of new compounds targeting the endocannabinoid system for the treatment of several conditions would be necessary and opportune.
OBJETIVO: Evidência experimental sugere que drogas que aumentam a atividade dos receptores canabinóides tipo 1 (CB1) podem induzir efeitos ansiolíticos ou antidepressivos, enquanto que o oposto tem sido relatado com antagonistas. Assim, o objetivo da presente revisão é discutir os potenciais efeitos-colaterais psiquiátricos de antagonistas do receptor CB1, como o rimonabanto, que foi recentemente liberado para comercialização em diversos países para o tratamento do tabagismo, obesidade e de desordens metabólicas associadas. MÉTODO: Foi realizada uma busca na literatura no PubMed e Scielo até fevereiro de 2009, com os termos "obesity", "rimonabant", "cannabinoids", "unwanted effects", "diabetes" , "smoking cessation" e "side effects". RESULTADOS: Ensaios clínicos revelaram que o rimonabanto pode produzir perda de peso em pacientes obesos, embora também possa induzir sintomas de ansiedade e depressão. DISCUSSÃO: Pacientes tomando antagonistas do receptor CB1 devem ser cuidadosamente examinados quanto aos efeitos-colaterais psiquiátricos. Estas drogas não devem ser prescritas a indivíduos que já sofrem de transtornos mentais. Entretanto, o desenvolvimento de novos compostos que atuem no sistema endocanabinóide para o tratamento das mais diversas condições parece necessário e oportuno.
Assuntos
Humanos , Transtornos de Ansiedade/induzido quimicamente , Depressores do Apetite/efeitos adversos , Transtorno Depressivo/induzido quimicamente , Obesidade/tratamento farmacológico , Piperidinas/efeitos adversos , Pirazóis/efeitos adversos , Fumar/tratamento farmacológico , Endocanabinoides/fisiologia , Doenças Metabólicas/tratamento farmacológico , Efeito Placebo , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptor CB1 de Canabinoide/antagonistas & inibidores , Receptor CB1 de Canabinoide/fisiologia , Abandono do Hábito de Fumar/métodosRESUMO
OBJETIVOS: Este estudo teve por objetivo avaliar a eficácia da efedrina na prevenção dos efeitos hemodinâmicos induzidos pela associação do propofol e do remifentanil, assim como os efeitos sobre o tempo de latência do cisatracúrio. MÉTODOS: Sessenta pacientes com idade entre 18 e 52 anos, estado físico ASA I ou II, foram divididos em três grupos, aleatoriamente: G I - propofol 1 por cento; G II - propofol 1 por cento + efedrina 0,5 mg.ml-1 e G III - propofol 1 por cento + efedrina 1,0 mg.ml-1 (velocidade de infusão igual a 180 ml.h-1), até a perda da consciência. Administrou-se remifentanil (0,5 mg.kg-1.min-1) e cisatracúrio na dose de 0,15 mg.kg-1. Foram registrados os dados demográficos, os sinais vitais (PAS, PAM, PAD, FC e SpO2) e o tempo de latência do cisatracúrio. RESULTADOS: Os grupos foram homogêneos com relação aos dados demográficos. Houve diminuição estatisticamente significativa dos valores de PAS, PAM, PAD e FC, um e três minutos após a administração do propofol, porém sem significado clínico importante e sem diferença entre os grupos. As medianas para os tempos de latência do cisatracúrio foram: 178 s (G2 e G3) e 183 s (G1), mas sem diferença significante entre os grupos. CONCLUSÃO: Não houve diminuição clinicamente importante dos parâmetros hemodinâmicos avaliados nos grupos que receberam ou não a efedrina e o tempo de latência do cisatracúrio foi o mesmo para os diferentes grupos.
OBJECTIVE: The onset time of neuromuscular blocking drugs is partially determined by circulatory factors, including muscle blood flow and cardiac output. The aim of the present paper was to: 1) compare the haemodynamic effects of adding different doses of ephedrine to an induction dose of propofol and remifentanil. 2) onset time of cisatracurium. METHODS: Sixty patients were randomly allocated into three groups: G1 - 1 percent propofol; G2 - 1 percent propofol + 0.5 mg.ml-1 ephedrine and G3 - 1 percent propofol + 1.0 mg.ml-1 ephedrine. All patients received continuous infusion of remifentanil (0.5 mg.kg-1.min-1). The rate of propofol infusion was 180 ml.h-1 until loss of consciousness and a loading dose of cisatracurium (0.15 mg.kg-1) was then given. After induction of anesthesia, the ulnar nerve was stimulated supramaximally every 10s, and the evoked twitch response of the adductor pollicis was recorded by accelerometry. RESULTS: There was no statistical difference between groups with respect to age, weight, dose of propofol administered and onset time of cisatracurium (tables 1, 2). Heart rate, SpO2, systolic, diastolic and mean blood pressures were compared at 1 and 3 min post-induction. There were statistical differences in HR, SAP, DAP and MAP, without significant adverse clinical effects. CONCLUSIONS: There were no clinically important decreases in the hemodynamic parameters evaluated in the groups receiving ephedrine or not, and the onset time of cisatracurium was the same for all groups.
Assuntos
Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adrenérgicos/uso terapêutico , Anestésicos Intravenosos/efeitos adversos , Atracúrio/análogos & derivados , Efedrina/uso terapêutico , Hipotensão/prevenção & controle , Bloqueadores Neuromusculares/farmacologia , Anestesia Geral , Anestésicos Intravenosos/administração & dosagem , Atracúrio/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Hipotensão/induzido quimicamente , Piperidinas/administração & dosagem , Piperidinas/efeitos adversos , Propofol/administração & dosagem , Propofol/efeitos adversos , Fatores de Tempo , Vasoconstritores/uso terapêuticoRESUMO
OBJETIVO: Avaliar criticamente os mais novos anti-histamínicos anti-H1 e os diferentes termos utilizados para denominá-los, com base na revisão de evidências sobre o papel dos anti-H1 no tratamento das doenças alérgicas. FONTES DOS DADOS: Artigos originais, revisões e consensos indexados nos bancos de dados MEDLINE e PUBMED de 1998 a 2006. Palavra chave: anti-histamínicos. SíNTESE DOS DADOS: Os anti-histamínicos de segunda geração diferenciam-se dos de primeira geração por sua elevada especificidade e afinidade pelos receptores H1 periféricos e pela menor penetração no sistema nervoso central (SNC), com conseqüente redução dos efeitos sedativos. Embora os anti-histamínicos de segunda geração sejam, geralmente, melhor tolerados do que seus predecessores, alguns efeitos adversos, principalmente cardiotoxicidade, surgiram com alguns deles. Nos últimos 20 anos, novos compostos, com diferentes farmacocinéticas, foram sintetizados. A maioria deles manifesta propriedades antiinflamatórias que independem de sua atividade no receptor H1. Aprimoramentos mais recentes, geralmente na forma de metabólitos ativos, levaram ao uso do termo anti-histamínico de terceira geração. Esse termo surgiu espontaneamente, sem uma descrição clara de seu significado e implicações clínicas, criando grande confusão entre os profissionais da saúde. CONCLUSÕES: Com base nas evidências sobre anti-histamínicos anti-H1, nenhum deles pode ser considerado como "anti-histamínico de terceira geração". Para tanto, seria preciso comprovar que a nova classe de anti-histamínicos possui vantagens clínicas distintas sobre os compostos existentes e preenche pelo menos três pré-requisitos: ausência de cardiotoxicidade, de interações medicamentosas e de efeitos sobre o SNC.
OBJECTIVE: To perform a critical evaluation of the more recent H1 antihistamines and the various terms used to describe them, based on a review of evidence on their role in the treatment of allergic disorders. SOURCES: Original articles, reviews and consensus documents published from 1998 to 2006 and indexed in the MEDLINE and PubMed databases. Keyword: antihistamines. SUMMARY OF THE FINDINGS: Second-generation antihistamines differ from first-generation ones because of their elevated specificity and affinity for peripheral H1 receptors and because of their lower penetration of the central nervous system (CNS), having fewer sedative effects as a result. Whilst second-generation antihistamines are in general better tolerated than their predecessors, some adverse effects, principally cardiotoxicity, have been observed with some of them. Over the last 20 years, new compounds with different pharmacokinetic properties have been synthesized. The majority of these exhibit anti-inflammatory properties that are independent of their action on the H1 receptor. More recent improvements, generally in the form of active metabolites, led to the use of the term third-generation antihistamines. This term emerged spontaneously, with no clear definition of its meaning or clinical implications, creating great confusion among healthcare professionals. CONCLUSIONS: On the basis of the evidence on H1 antihistamines, none of them deserve the title"third-generation antihistamine." As the Consensus Group on New Generation Antihistamines concluded, to merit this definition, a new class of antihistamines would have to demonstrate distinct clinical advantages over existing compounds and fulfill at least three prerequisites: they should be free from cardiotoxicity, drug interactions and effects on the CNS.