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1.
Pediatr Blood Cancer ; 68(5): e28947, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33686754

RESUMO

This 2021 clinical practice guideline update provides recommendations for preventing anticipatory chemotherapy-induced nausea and vomiting (CINV) in pediatric patients. Recommendations are based on systematic reviews that identified (1) if a history of acute or delayed CINV is a risk factor for anticipatory CINV, and (2) interventions for anticipatory CINV prevention and treatment. A strong recommendation to optimize acute and delayed CINV control in order to prevent anticipatory CINV is made. Conditional recommendations are made for hypnosis, systematic desensitization, relaxation techniques, and lorazepam for the secondary prevention of anticipatory CINV. No recommendation for the treatment of anticipatory CINV can be made.


Assuntos
Antineoplásicos/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Náusea/prevenção & controle , Neoplasias/tratamento farmacológico , Vômito Precoce/prevenção & controle , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Náusea/induzido quimicamente , Vômito Precoce/psicologia
2.
Rheumatology (Oxford) ; 59(7): 1482-1488, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32259834

RESUMO

MTX is the medication most commonly used for antirheumatic treatment in juvenile idiopathic arthritis. It has high efficacy, is usually well tolerated and has an excellent safety profile. However, frequently intolerance symptoms develop that manifest as nausea, feelings of disgust or abdominal complaints prior to or directly after administration of the medication. No obvious toxicity is causing these intolerance symptoms, but symptoms are strictly limited to MTX and not transferred to other medications. MTX intolerance causes a significant reduction of quality of life in affected patients, frequently puts the treating physician in difficult situations regarding treatment choice, and may lead to uncomfortable decisions whether or not to stop an otherwise effective drug. Conventional countermeasures such as antiemetics, change of route from subcutaneous to oral or vice versa, or taste masking usually have only a limited effect. In this review, we present the current knowledge on MTX intolerance, its clinical picture and commonly employed strategies. We also consider newer behavioural treatment strategies that may offer a more effective symptom control.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Metotrexato/uso terapêutico , Náusea/etiologia , Efeito Nocebo , Vômito Precoce/etiologia , Adolescente , Criança , Condicionamento Clássico , Asco , Vias de Administração de Medicamentos , Gastroenteropatias/etiologia , Humanos
3.
Cancer Med ; 9(5): 1733-1740, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31957269

RESUMO

PURPOSE: Chemotherapy side effects diminish quality of life and can lead to treatment delay. Nausea and vomiting can occur prior to chemotherapy because of classical conditioning. We studied the effects of 20-minute behavioral interventions, administered by oncology nurses, of higher intensity (mindfulness relaxation-MR) or lower intensity (relaxing music-RM), on anticipatory nausea and vomiting (ANV). PATIENTS AND METHODS: Patients undergoing chemotherapy for solid tumors were randomized to MR (N = 160), RM (N = 159), or standard care SC (N = 155). Subjects were mostly female (91.8%) and white (86.1%) with breast cancer (85%). Most patients had early stage disease (Stage I: 26%; II: 52.9%; III: 19%; IV: 0.1%). Anticipatory nausea and vomiting were assessed at the midpoint and end of the chemotherapy course using the Morrow Assessment of Nausea and Emesis (MANE). RESULTS: Compared to SC, there was reduced anticipatory nausea at the midpoint of chemotherapy in those receiving MR (OR 0.44, 95% CI 0.20-0.93) and RM (OR 0.40, 95% CI 0.20-0.93), controlling for age, sex, cancer stage, and emetogenic level of chemotherapy. There was no difference between treatment groups in anticipatory nausea at the end of chemotherapy or in anticipatory vomiting and postchemotherapy nausea and vomiting at either time point. CONCLUSION: A brief nurse-delivered behavioral intervention can reduce midpoint ANV associated with chemotherapy.


Assuntos
Antineoplásicos/efeitos adversos , Atenção Plena/métodos , Náusea/prevenção & controle , Neoplasias/tratamento farmacológico , Cuidados de Enfermagem/métodos , Vômito Precoce/prevenção & controle , Adulto , Condicionamento Clássico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/epidemiologia , Náusea/psicologia , Estadiamento de Neoplasias , Neoplasias/diagnóstico , Neoplasias/psicologia , Qualidade de Vida , Resultado do Tratamento , Vômito Precoce/epidemiologia , Vômito Precoce/psicologia , Adulto Jovem
4.
Br J Pharmacol ; 174(21): 3837-3847, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28805944

RESUMO

BACKGROUND AND PURPOSE: Effective treatments of nausea are limited. In this study we evaluated the ability of the peripherally restricted fatty acid amide hydrolase (FAAH) inhibitor, URB937, to suppress acute and anticipatory nausea in rats and examined the pharmacological mechanism of this effect. EXPERIMENTAL APPROACH: We investigated the potential of URB937 (administered i.p.) to reduce the establishment of lithium chloride-induced conditioned gaping (model of acute nausea) and to reduce the expression of contextually-elicited conditioned gaping (model of anticipatory nausea) in rats. The role of CB1 receptors, CB2 receptors and PPARα in the anti-nausea effect of URB937 was examined. The potential of URB937 to suppress FAAH activity in tissue collected from the area postrema (AP), prefrontal cortex (PFC), liver and duodenum and to elevate levels of FAAH substrates - anandamide (AEA), N-oleoylethanolamide (OEO) and N-palmitoylethanolamide (PEA) - in the AP was also evaluated. KEY RESULTS: URB937 reduced acute nausea by a PPARα-dependent mechanism and reduced anticipatory nausea by a CB1 receptor-dependent mechanism. The PPARα agonist, GW7647, similarly attenuated acute nausea. URB937 reduced FAAH activity in the liver and the duodenum but not in the PFC. In addition, URB937 reduced FAAH activity and elevated levels of fatty-acid ethanolamides in the AP, a brain region that is not protected by the blood-brain barrier. CONCLUSIONS AND IMPLICATIONS: The anti-nausea action of URB937 may occur in the AP and may involve PPARα to suppress acute nausea and CB1 receptors to suppress anticipatory nausea.


Assuntos
Amidoidrolases/antagonistas & inibidores , Canabinoides/farmacologia , Náusea/prevenção & controle , Vômito Precoce/prevenção & controle , Doença Aguda , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Butiratos/farmacologia , Modelos Animais de Doenças , Injeções Intraperitoneais , Masculino , PPAR alfa/metabolismo , Compostos de Fenilureia/farmacologia , Ratos Sprague-Dawley , Receptor CB1 de Canabinoide/metabolismo
6.
Support Care Cancer ; 25(1): 317-321, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27510314

RESUMO

PURPOSE: We aimed to update the 2011 recommendations for the prevention and treatment of anticipatory nausea and vomiting in children and adults receiving chemotherapy. METHODS: The original systematic literature search was updated. Randomized studies were included in the evidence to support this guideline if they as follows: were primary studies published in a journal in full text (i.e., abstracts, letters, book chapters, and dissertations were excluded); published in English; evaluated an intervention for the prevention or treatment of anticipatory nausea and vomiting; reported the proportion of patients experiencing complete control of anticipatory nausea and vomiting consistently and; included at least ten participants per study arm for comparative studies and at least ten participants overall for noncomparative studies. RESULTS: Eighty-eight new citations were identified. Of these, nine were brought to full-text screening; none met inclusion criteria. The guideline panel continues to recommend that anticipatory nausea and vomiting are best prevented through optimization of acute and delayed phase chemotherapy-induced nausea and vomiting control. Benzodiazepines and behavioral therapies, in particular progressive muscle relaxation training, systematic desensitization and hypnosis, continue to be recommended for the treatment of anticipatory nausea and vomiting. CONCLUSIONS: No new information regarding interventions aimed at treating or preventing ANV that met criteria for inclusion in this systematic review was identified. The 2015 MASCC recommendations affirm the content of the 2009 MASCC recommendations for the prevention and treatment of anticipatory nausea and vomiting.


Assuntos
Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Náusea/induzido quimicamente , Vômito Precoce/induzido quimicamente , Vômito/induzido quimicamente , Adulto , Antineoplásicos/administração & dosagem , Criança , Consenso , Humanos , Quimioterapia de Indução/efeitos adversos , Quimioterapia de Indução/métodos , Guias de Prática Clínica como Assunto
7.
Behav Pharmacol ; 27(8): 718-725, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27740965

RESUMO

Disgust has been proposed to have evolved as a means to rid the body and mouth of noxious substances and toxins, as well as to motivate and facilitate avoidance of contact with disease-causing organisms and infectious materials. Nonemetic species, such as the rat, show distinctive facial expressions, including the gaping reaction, indicative of nausea-based disgust. These conditioned disgust responses can be used to model anticipatory nausea in humans, which is a learned response observed following chemotherapy treatment. As social factors play a role in the modulation and expression of conditioned disgust responses in rats, and the nonapeptide, oxytocin (OT), is involved in the modulation of social behavior, the present study examined the effects of an OT antagonist, L-368 899, on the development and expression of socially mediated conditioned disgust in male rats. When administered 10 min before testing in a distinct context (different from the original conditioning context), L-368 899 (5 mg/kg) significantly decreased gaping behavior in rats that were conditioned with a social partner. LiCl-treated rats administered L-368 899 before testing also showed decreased social initiations toward their social partner. These findings suggest that OT may play a role in the modulation and expression of socially mediated conditioned disgust in rats.


Assuntos
Canfanos/farmacologia , Condicionamento Psicológico/fisiologia , Ocitocina/metabolismo , Piperazinas/farmacologia , Vômito Precoce/psicologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Expressão Facial , Cloreto de Lítio/toxicidade , Masculino , Náusea/psicologia , Ratos , Ratos Long-Evans , Comportamento Social
8.
Psychopharmacology (Berl) ; 233(12): 2265-75, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27048155

RESUMO

RATIONALE: Drugs that block fatty acid amide hydrolase (FAAH, which elevates anandamide [AEA]) and drugs which block monoacylglycerol (MAGL, which elevates 2-arachidonyl glycerol [2-AG]) have promise in treating both acute and anticipatory nausea in human patients. OBJECTIVE: This study aims to evaluate the relative effectiveness of dual MAGL/FAAH inhibition with either alone to reduce acute and anticipatory nausea in rat models. MATERIALS AND METHODS: AM4302, a new dual MAGL/FAAH inhibitor, was compared with a new selective MAGL inhibitor, AM4301, and new selective FAAH inhibitor, AM4303, for their potential to reduce acute nausea (gaping in taste reactivity) and anticipatory nausea (contextually elicited conditioned gaping) in two rat models. RESULTS: Our in vitro studies indicate that AM4302 blocks human and rat FAAH: IC50 60 and 31 nM, respectively, with comparable potencies against human MAGL (IC50 41 nM) and rat MAGL (IC50 200 nM). AM4301 selectively blocks human and rat MAGL (IC50 8.9 and 36 nM, respectively), while AM4303 selectively inhibits human and rat FAAH (IC50 2 and 1.9 nM), respectively. Our in vivo studies show that the MAGL inhibitor, AM4301, suppressed acute nausea in a CB1-mediated manner, when delivered systemically or into the interoceptive insular cortex. Although the dual FAAH/MAGL inhibitor, AM4302, was equally effective as the FAAH inhibitor or MAGL inhibitor in reducing acute nausea, it was more effective than both in suppressing anticipatory nausea. CONCLUSIONS: Dual FAAH and MAGL inhibition with AM4302 may be an especially effective treatment for the very difficult to treat symptom of anticipatory nausea.


Assuntos
Amidoidrolases/antagonistas & inibidores , Monoacilglicerol Lipases/antagonistas & inibidores , Náusea/tratamento farmacológico , Náusea/enzimologia , Vômito Precoce/tratamento farmacológico , Vômito Precoce/enzimologia , Doença Aguda , Amidoidrolases/metabolismo , Animais , Córtex Cerebral/efeitos dos fármacos , Modelos Animais de Doenças , Endocanabinoides/farmacologia , Inibidores Enzimáticos/farmacologia , Masculino , Monoacilglicerol Lipases/metabolismo , Ratos , Ratos Sprague-Dawley
9.
Behav Neurosci ; 130(2): 261-6, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26974857

RESUMO

Anticipatory nausea (AN) is a conditioned nausea reaction experienced by chemotherapy patients upon returning to the clinic. Currently, there are no specific treatments for this phenomenon, with the classic antiemetic treatments (e.g., ondansetron) providing no relief. The rat model of AN, contextually elicited conditioned gaping reactions in rats, provides a tool for assessing potential treatments for this difficult to treat disorder. Systemically administered drugs which elevate the endocannabinoids, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), by interfering with their respective degrading enzymes, fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL) interfere with AN in the rat model. We have shown that MAGL inhibition within the visceral insular cortex (VIC) interferes with acute nausea in the gaping model (Sticht et al., 2015). Here we report that bilateral infusion of the MAGL inhibitor, MJN110 (but neither the FAAH inhibitor, PF3845, nor ondansetron) into the VIC suppressed contextually elicited conditioned gaping, and this effect was reversed by coadministration of the CB1 antagonist, AM251. These findings suggest that 2-AG within the VIC plays a critical role in the regulation of both acute nausea and AN. Because there are currently no specific therapeutics for chemotherapy patients that develop anticipatory nausea, MAGL inhibition by MJN110 may be a candidate treatment. (PsycINFO Database Record


Assuntos
Ácidos Araquidônicos/metabolismo , Córtex Cerebral/efeitos dos fármacos , Endocanabinoides/metabolismo , Glicerídeos/metabolismo , Monoacilglicerol Lipases/efeitos dos fármacos , Amidoidrolases , Animais , Ácidos Araquidônicos/uso terapêutico , Endocanabinoides/uso terapêutico , Glicerídeos/uso terapêutico , Cloreto de Lítio/farmacologia , Modelos Animais , Monoacilglicerol Lipases/metabolismo , Náusea , Alcamidas Poli-Insaturadas , Ratos , Ratos Sprague-Dawley , Serotonina , Vômito Precoce/terapia
10.
J Pain Symptom Manage ; 51(6): 987-93, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26891606

RESUMO

CONTEXT: Anticipatory (prechemotherapy) nausea (AN) is a classic conditioned symptom not responding well to current antiemetics. Minimal work has been done to assess its risk factors and impact on chemotherapy-induced nausea and vomiting (CINV). OBJECTIVES: To evaluate risk factors for AN and assess its impact on CINV development. METHODS: We analyzed data (n = 991) from a prospective observational multisite study in eight European countries over three cycles of chemotherapy. Patient/treatment characteristics were collected before chemotherapy. History of nausea/vomiting (yes/no), patient expectation of CINV (0-100 mm visual analog scale, [VAS]), and prechemotherapy anxiety (0-100 mm VAS) also were collected before chemotherapy. A patient-completed diary during each chemotherapy cycle obtained information on AN in the 24 hours before chemotherapy administration and nausea and vomiting (episodes of vomiting and severity of nausea) daily for five days after administration of chemotherapy (0-100 mm VAS). RESULTS: AN was reported by 8.3%-13.8% of patients, increasing in frequency and intensity over each cycle. Every 1 mm increase in AN on the VAS was significantly associated with 2%-13% of increase in the likelihood of CINV (all P-values <0.05). Key predictors of AN in Cycle 1 included metastatic disease and prechemotherapy anxiety. However, predictors of AN in subsequent cycles included prechemotherapy anxiety and AN and CINV experience in the previous cycle, the latter being the strongest predictor (odds ratio = 3.30-4.09 for CINV outcomes over the cycles). CONCLUSION: AN is a challenging symptom, and its prevention needs to consider better CINV prevention in the previous cycles as well as managing prechemotherapy anxiety.


Assuntos
Antineoplásicos/efeitos adversos , Náusea/etiologia , Neoplasias/tratamento farmacológico , Antecipação Psicológica , Antineoplásicos/uso terapêutico , Europa (Continente) , Feminino , Humanos , Funções Verossimilhança , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Náusea/epidemiologia , Neoplasias/epidemiologia , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Vômito Precoce/epidemiologia , Vômito Precoce/etiologia
11.
Support Care Cancer ; 23(1): 283-91, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25112561

RESUMO

PURPOSE: Some patients experience nausea and/or vomiting (NV) before receipt of chemotherapy. Our objective was to evaluate the impact of prior chemotherapy-induced NV (CINV) on the incidence of anticipatory NV in later cycles. METHODS: This multicenter, prospective non-interventional study enrolled chemotherapy-naïve adults scheduled to receive highly or moderately emetogenic chemotherapy (HEC/MEC) for cancer in six Asia Pacific countries, excluding those with emesis within 24 h before cycle 1 chemotherapy. On day 1 before chemotherapy, patients answered four questions regarding emesis in the past 24 h, nausea, expectation of post-chemotherapy nausea, and anxiety in the past 24 h, the latter three scored from 0-10 (none-maximum). Multivariate logistic regression was used to assess the impact of prior CINV on anticipatory NV in cycles 2 and 3. RESULTS: Five hundred ninety-eight patients (59% female) were evaluable in cycle 2 (49% HEC, 51% MEC). The incidence of anticipatory emesis was low before cycles 2 and 3 (1.5-2.3%). The incidence of clinically significant anticipatory nausea (score of ≥3) was 4.8, 7.9, and 8.3% before cycles 1, 2, and 3, respectively, with adjusted odds ratio (OR), 3.95 (95% confidence interval (CI), 2.23-7.00; p < 0.001) for patients with clinically significant nausea in prior cycles, compared with none. The adjusted ORs for other anticipatory NV endpoints ranged from 4.54-4.74 for patients with prior CINV. The occurrence of clinically significant anxiety in the prior cycle also resulted in a significantly increased likelihood of anticipatory nausea. CONCLUSIONS: These findings highlight the importance of preventing CINV in cycle 1 to reduce anticipatory NV in subsequent cycles.


Assuntos
Antineoplásicos/efeitos adversos , Náusea/epidemiologia , Vômito Precoce/epidemiologia , Vômito/epidemiologia , Idoso , Antieméticos/uso terapêutico , Antineoplásicos/uso terapêutico , Ásia/epidemiologia , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Neoplasias/tratamento farmacológico , Estudos Prospectivos , Inquéritos e Questionários , Vômito/induzido quimicamente , Vômito/tratamento farmacológico , Vômito Precoce/tratamento farmacológico , Vômito Precoce/prevenção & controle
12.
Eur J Pharmacol ; 722: 172-9, 2014 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-24157982

RESUMO

As a specific variation of chemotherapy-induced nausea and vomiting, anticipatory nausea and vomiting (ANV) appears particularly linked to psychological processes. The three predominant factors related to ANV are classical conditioning; demographic and treatment-related factors; and anxiety or negative expectancies. Laboratory models have provided some support for these underlying mechanisms for ANV. ANV may be treated with medical or pharmacological interventions, including benzodiazepines and other psychotropic medications. However, behavioral treatments, including systematic desensitization, remain first line options for addressing ANV. Some complementary treatment approaches have shown promise in reducing ANV symptoms. Additional research into these approaches is needed. This review will address the underlying models of ANV and provide a discussion of these various treatment options.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/psicologia , Náusea/induzido quimicamente , Náusea/psicologia , Vômito Precoce/induzido quimicamente , Vômito Precoce/psicologia , Animais , Terapias Complementares , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/terapia , Humanos , Náusea/tratamento farmacológico , Náusea/terapia , Vômito Precoce/tratamento farmacológico , Vômito Precoce/terapia
13.
Trials ; 14: 103, 2013 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-23782493

RESUMO

BACKGROUND: Emesis and nausea are side effects induced by chemotherapy. These effects lead to enormous stress and strain on cancer patients. Further consequences may include restrictions in quality of life, cachexia or therapy avoidance. Evidence suggests that cancer patients develop the side effects of nausea and vomiting in anticipation of chemotherapy. Contextual cues such as smell, sounds or even the sight of the clinic may evoke anticipatory nausea and vomiting prior to infusion. Anticipatory nausea and vomiting are problems that cannot be solved by administration of antiemetica alone.The purpose of the proposed randomized placebo-controlled trial is to use an overshadowing technique to prevent anticipatory nausea and vomiting and to decrease the intensity and duration of post-treatment nausea and vomiting. Furthermore, the effect on anxiety, adherence and quality of life will be evaluated. METHODS/DESIGN: Fifty-two pediatric cancer patients will be evenly assigned to two groups: an experimental group and a control group. The participants, hospital staff and data analysts will be kept blinded towards group allocation. The experimental group will receive during three chemotherapy cycles a salient piece of candy prior to every infusion, whereas the control group will receive flavorless placebo tablets. DISCUSSION: If an effectiveness of the overshadowing technique is proven, implementation of this treatment into the hospitals' daily routine will follow. The use of this efficient and economic procedure should aid a reduced need for antiemetics. TRIAL REGISTRATION: Current Controlled Trials ISRCTN30242271/


Assuntos
Antineoplásicos/administração & dosagem , Doces , Condicionamento Clássico , Sinais (Psicologia) , Aprendizagem por Discriminação , Náusea/prevenção & controle , Projetos de Pesquisa , Vômito Precoce/prevenção & controle , Adolescente , Comportamento do Adolescente , Fatores Etários , Antieméticos/uso terapêutico , Ansiedade/etiologia , Ansiedade/prevenção & controle , Ansiedade/psicologia , Criança , Comportamento Infantil , Pré-Escolar , Protocolos Clínicos , Alemanha , Humanos , Adesão à Medicação , Náusea/etiologia , Náusea/psicologia , Qualidade de Vida , Fatores de Tempo , Resultado do Tratamento , Vômito Precoce/etiologia , Vômito Precoce/psicologia
14.
Brain Behav Immun ; 27(1): 123-32, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23064080

RESUMO

Anticipatory nausea is a classically conditioned response to a context that has been previously paired with toxin-induced nausea and/or vomiting. When injected with a nausea-inducing drug, such as lithium chloride (LiCl), rats will show a distinctive conditioned gaping response that has been suggested to be an index of nausea. Previous studies have found that immune system activation with an endotoxin, such as lipopolysaccharide (LPS), attenuates LiCl-induced conditioned gaping in rats. The present study examined the acquisition of LiCl-induced conditioned gaping in rats that were either LPS tolerant or LPS non-tolerant, as little is known about the effects of endotoxin tolerance on learning and memory. Male Long-Evan rats were given four systemic injections of LPS (200 µg/kg) or isotonic saline (NaCl) to induce LPS tolerance, indexed with 24 h changes in body weight following treatment. The animals were then given 4 acquisition trials in a LiCl-induced conditioned gaping paradigm. On conditioning days animals were treated with LPS (200 µg/kg) or saline followed 90 min later by injection of LiCl (127 mg/kg) or saline and then placed in a distinctive context for 30 min and their behavior video-recorded. On a drug free test day all animals were again placed in the distinctive context for 10 min and behavior was video-recorded. Gaping responses were scored for all acquisition days and the test day. Spleen and body weights were also obtained for all rats at the end of the experiment. Gaping responses were attenuated in rats treated with LPS in both the LPS tolerant and LPS non-tolerant groups. There were significant negative correlations between spleen weight as well as spleen/body weight ratios, and levels of conditioned gaping responses in LiCl treated rats, but not control rats. These results show that LPS interferes with learning/memory in the anticipatory nausea paradigm in rats that are both LPS tolerant and LPS non-tolerant.


Assuntos
Adjuvantes Imunológicos/farmacologia , Condicionamento Clássico , Endotoxinas/farmacologia , Lipopolissacarídeos/farmacologia , Cloreto de Lítio/farmacologia , Náusea , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Condicionamento Clássico/efeitos dos fármacos , Condicionamento Clássico/fisiologia , Tolerância a Medicamentos/fisiologia , Masculino , Memória/efeitos dos fármacos , Memória/fisiologia , Tamanho do Órgão , Ratos , Ratos Long-Evans , Baço/efeitos dos fármacos , Baço/patologia , Vômito Precoce/psicologia
15.
Support Care Cancer ; 20(7): 1479-89, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21818642

RESUMO

PURPOSE: Despite the widespread use of antiemetics, nausea continues to be reported by over 70% of patients receiving chemotherapy. METHODS: In this double blind, multicenter trial, we randomly assigned 744 cancer patients to four arms: 1) placebo, 2) 0.5 g ginger, 3) 1.0 g ginger, or 4) 1.5 g ginger. Nausea occurrence and severity were assessed at a baseline cycle and the two following cycles during which patients were taking their assigned study medication. All patients received a 5-HT(3) receptor antagonist antiemetic on Day 1 of all cycles. Patients took three capsules of ginger (250 mg) or placebo twice daily for 6 days starting 3 days before the first day of chemotherapy. Patients reported the severity of nausea on a 7-point rating scale ("1" = "Not at all Nauseated" and "7" = "Extremely Nauseated") for Days 1-4 of each cycle. The primary outcomes were to determine the dose and efficacy of ginger at reducing the severity of chemotherapy-induced nausea on Day 1 of chemotherapy. RESULTS: A total of 576 patients were included in final analysis (91% female, mean age = 53). Mixed model analyses demonstrated that all doses of ginger significantly reduced acute nausea severity compared to placebo on Day 1 of chemotherapy (p = 0.003). The largest reduction in nausea intensity occurred with 0.5 g and 1.0 g of ginger (p = 0.017 and p = 0.036, respectively). Anticipatory nausea was a key factor in acute chemotherapy-induced nausea (p < 0.0001). CONCLUSIONS: Ginger supplementation at a daily dose of 0.5 g-1.0 g significantly aids in reduction of the severity of acute chemotherapy-induced nausea in adult cancer patients.


Assuntos
Antieméticos/uso terapêutico , Náusea/prevenção & controle , Fitoterapia , Vômito/prevenção & controle , /química , Antieméticos/administração & dosagem , Antieméticos/isolamento & purificação , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Neoplasias/tratamento farmacológico , Antagonistas do Receptor 5-HT3 de Serotonina/uso terapêutico , Índice de Gravidade de Doença , Resultado do Tratamento , Vômito/induzido quimicamente , Vômito Precoce/prevenção & controle
16.
Support Care Cancer ; 19(10): 1549-63, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20811914

RESUMO

PURPOSE: Despite significant advances in antiemetic management, almost 50% of cancer patients still experience nausea and vomiting during treatment. The goal of antiemetic therapy is complete prevention of treatment-induced nausea and/or vomiting (TINV); however, realisation of this goal remains elusive, thus supplementary strategies identifying patients at high risk must be employed in the interim. Consequently, we examined TINV incidence and its risk factors, including patient, clinical and pretreatment quality of life (QOL)/psychological factors. METHODS: Two hundred newly diagnosed cancer patients beginning combined treatment participated in this prospective, longitudinal, observational study. QOL (including TINV), psychological adjustment, and patient/clinical characteristics were examined at pretreatment, on-treatment (8 weeks ± 1 week) and post-treatment. RESULTS: Overall, 62% of patients experienced TINV, with TIN incidence (60%) doubling that of TIV (27%). Eight independent risk factors predicted 73% of TIN incidence: high premorbid/anticipatory NV, moderately/highly emetogenic chemotherapy (M/HEC), longer treatment (>3 months), female gender, surgery prior to adjuvant chemotherapy ± radiotherapy, private health insurance and low emotional functioning (pretreatment). Six independent risk factors predicted 77% of TIV incidence: premorbid/anticipatory vomiting, M/HEC, female gender, cancer resection and low role functioning (pretreatment). CONCLUSIONS: TINV still represents a very major concern for patients. Several pretreatment risk factors for the development of TIN and TIV, respectively, were identified. Patients about to undergo cancer treatment, particularly combined treatment involving emetogenic chemotherapy and surgery, should be screened for these factors with a view to modifying standard pretreatment/maintenance antiemetic therapy. Furthermore, and consistent with recent research, it is recommended that more comprehensive interventions combining antiemetics with other effective pharmacological (e.g. anxiolytics) and non-pharmacological approaches (e.g. acupuncture, relaxation techniques) be considered by clinicians in attempts to improve control of TIN and TIV (and overall QOL) for their patients. In this way, optimal holistic care will be ensured for cancer patients by clinicians providing conventional oncology treatment.


Assuntos
Antineoplásicos/efeitos adversos , Náusea/induzido quimicamente , Neoplasias/tratamento farmacológico , Qualidade de Vida , Vômito/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Austrália , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Náusea/epidemiologia , Neoplasias/terapia , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Vômito/epidemiologia , Vômito Precoce/psicologia , Adulto Jovem
17.
Support Care Cancer ; 19(10): 1533-8, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20803345

RESUMO

A commonly reported consequence of post-treatment nausea or vomiting is the development of anticipatory nausea and vomiting (ANV). In most published work, nausea is reported to occur before chemotherapy drugs are administered by approximately 20% of patients at any one chemotherapy cycle and by 25-30% of patients by their fourth chemotherapy cycle. Most studies in adult patients strongly support the view that the development of ANV involves elements of classical conditioning. The best method to avoid development of ANV is to adequately prevent both vomiting and nausea from the first exposure to chemotherapy. If anticipatory side effects develop, behavioral treatment techniques, such as systematic desensitization, have been shown effective. Benzodiazepines used in combination with behavioral techniques or antiemetics may also be useful. The evidence on which these conclusions are based is reviewed in this article.


Assuntos
Antineoplásicos/efeitos adversos , Náusea/psicologia , Vômito Precoce/psicologia , Adulto , Animais , Antieméticos/uso terapêutico , Antineoplásicos/uso terapêutico , Terapia Comportamental/métodos , Benzodiazepinas/uso terapêutico , Condicionamento Clássico , Humanos , Náusea/induzido quimicamente , Náusea/terapia , Neoplasias/tratamento farmacológico , Vômito Precoce/etiologia , Vômito Precoce/terapia
19.
Neurosci Lett ; 450(3): 301-5, 2009 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-19059465

RESUMO

The effects of systemic treatment with lipopolysaccharide (LPS) on conditioned gaping in a rodent model of anticipatory nausea were examined. Stimulation of the immune system has been found to enhance, impair, or have no effect on various learning and memory tasks. The development of anticipatory nausea is formed through a classically conditioned response to a context that has been paired previously with toxin-induced nausea and/or vomiting. Rats display a distinctive conditioned gaping response when injected with a nausea-inducing drug such as LiCl. In the present study, male Long-Evans rats were injected intraperitoneally with LPS (200microg/kg) or saline (NaCl) followed 90min later by an injection of the toxin LiCl or saline before being placed in a distinctive context on four conditioning days (72h apart). On the condition test day, rats (n=6/group) were placed in the distinctive context in a drug-free state and behavioral responses were videotaped. Rats given LPS followed by LiCl were found to have significantly fewer gaping responses when compared to rats given NaCl followed by LiCl. All groups were also found to have similar levels of spontaneous ingestive behaviors suggesting that the decrease in gaping was not due to motor impairment. The present results suggest that activation of the immune system with LPS administration significantly impairs the acquisition of anticipatory nausea.


Assuntos
Aprendizagem por Associação/fisiologia , Condicionamento Psicológico/fisiologia , Fenômenos do Sistema Imunitário/fisiologia , Náusea/imunologia , Vômito Precoce/imunologia , Animais , Aprendizagem por Associação/efeitos dos fármacos , Condicionamento Psicológico/efeitos dos fármacos , Modelos Animais de Doenças , Fenômenos do Sistema Imunitário/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Cloreto de Lítio/antagonistas & inibidores , Masculino , Memória/efeitos dos fármacos , Memória/fisiologia , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/imunologia , Náusea/induzido quimicamente , Ponte/anatomia & histologia , Ponte/efeitos dos fármacos , Ponte/imunologia , Ratos , Ratos Long-Evans , Vômito Precoce/induzido quimicamente
20.
Behav Brain Res ; 187(1): 33-40, 2008 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-17897732

RESUMO

Following one or more chemotherapy treatments, many patients report that they experience anticipatory nausea. This phase of nausea has been interpreted as a classically conditioned response where a conditional association develops between the contextual clinic cues and the nausea and/or vomiting that developed following treatment. Although rats do not vomit, they display a distinctive gaping reaction when exposed a flavored solution previously paired with a toxin. Here we report that, even in the absence of a flavored solution, rats display conditioned gaping reactions during exposure to a distinctive context previously paired with a high dose of lithium (Experiment 1 with a distinctive odor and Experiment 3 without a distinctive odor), a low dose of lithium (Experiment 2) or provocative vestibular stimulation (Experiment 2). These results suggest that the conditioned gaping reaction in rats is selectively elicited by nausea-paired contextual stimuli, as well as flavors. This rat model of anticipatory nausea may serve as a valuable preclinical tool to evaluate the effectiveness of anti-nausea treatments and the side effect of nausea produced by newly developed pharmaceutical compounds intended for other clinical treatments.


Assuntos
Comportamento Animal/fisiologia , Condicionamento Clássico/fisiologia , Náusea/psicologia , Vômito Precoce/psicologia , Animais , Sinais (Psicologia) , Interpretação Estatística de Dados , Cloreto de Lítio/efeitos adversos , Masculino , Enjoo devido ao Movimento/psicologia , Odorantes , Estimulação Física , Ratos , Ratos Sprague-Dawley , Rotação , Paladar/efeitos dos fármacos , Vestíbulo do Labirinto/fisiologia
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