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1.
J Occup Rehabil ; 34(1): 157-168, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37040000

RESUMO

PURPOSE: Musculoskeletal (MSK) injuries are a major contributing factor for chronic pain. To date, little is known how pain medication use in MSK injuries has changed over time. We assessed pain medication prescription for MSK injuries in a representative sample of Swiss workers between 2008 and 2018. METHODS: Retrospective analysis of the Swiss Accident Insurance Fund (Suva) data. We calculated annual pain medication use, treatment days, and costs associated with pain medication use in minor and major MSK injuries. RESULTS: In total, 1,921,382 cases with MSK injuries with ≥ 1 pain medication were analyzed. Whereas MSK injuries with ≥ 1 pain medication increased by 9.4%, we observed a larger increase in metamizole (+ 254%), strong opioids (+ 88.4%), coxibs (+ 85.8%), and paracetamol (+ 28.1%). Strong opioids were increasingly used in minor (+ 91.4%) and major (+ 88.3%) injuries. The increase in metamizole (+ 390.6%) and coxibs (+ 115.5%) was larger in minor injuries compared to major injuries (+ 238.7% and + 80.6%, respectively). Medical expenses decreased in all medications except for strong opioids where a substantial increase was observed (+ 192.4% in minor; + 34% in major injuries). CONCLUSIONS: We observed a disproportionate increase in metamizole, strong opioids, coxibs, and paracetamol prescriptions even in minor MSK injuries between 2008 and 2018. Whereas treatment costs decreased for all pain medications, there was a substantial increase in strong opioids. A more liberal prescription practice of opioids conflict with current evidence-based practice recommendations and need to be addressed by physicians and policy makers.


Assuntos
Dor Crônica , Dipirona , Humanos , Dipirona/uso terapêutico , Analgésicos Opioides/uso terapêutico , Acetaminofen/uso terapêutico , Suíça/epidemiologia , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Estudos Retrospectivos
2.
Gastroenterol Hepatol ; 47(3): 230-235, 2024 Mar.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-37207963

RESUMO

INTRODUCTION: Acute pancreatitis is one of the main reasons for digestive admissions. Adequate pain treatment is crucial in its management. However, there are hardly any descriptions of the analgesic guidelines used in our setting. METHODS: On-line survey on analgesic management in acute pancreatitis, aimed at attending physicians and residents practising in Spain. RESULTS: Two hundred and nine physicians from 88 centres responded to the survey. Ninety percent were specialists in gastrointestinal medicine and 69% worked in a tertiary centre. The majority (64.4%) do not routinely use scales to measure pain. When choosing a drug, experience in its use was the most important factor. The most commonly prescribed initial treatments are: combination of paracetamol and metamizole (53.5%), paracetamol alone (19.1%) and metamizole alone (17.4%). As rescue: meperidine (54.8%), tramadol (17.8%), morphine chloride (17.8%) and metamizole (11.5%). Continuous perfusion is used in 8.2% of initial treatments. Physicians with >10 years of service use more metamizole as monotherapy (50%), while residents and attending physicians with <10 years of service prescribe it in combination with paracetamol (85%). If progression is needed, morphine chloride and meperidine are mainly used. The speciality of the respondent, the size of the work centre and the unit/service where the patients were admitted did not influence the analgesia prescribed. Satisfaction with pain management reached 7.8/10 (SD 0.98). CONCLUSION: In our setting, metamizole and paracetamol are the most commonly used analgesics as initial pain treatment in acute pancreatitis, and meperidine is the most commonly used rescue analgesic.


Assuntos
Analgesia , Pancreatite , Humanos , Manejo da Dor , Acetaminofen/uso terapêutico , Dipirona/uso terapêutico , Morfina , Doença Aguda , Pancreatite/tratamento farmacológico , Dor , Meperidina/uso terapêutico , Analgésicos/uso terapêutico
4.
Eur J Med Chem ; 265: 116044, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38145603

RESUMO

Ferroptosis is a form of non-apoptotic cell death, regulated by phospholipid hydroperoxide glutathione peroxidase 4 (GPX4), a selenoprotein with a selenocysteine residue (sec) in the active site. GPX4 is a promising target for cancer cells in therapy-resistant conditions via ferroptosis, which can reduce the level of lipid reactive oxygen species (ROS). So far, all existing GPX4 inhibitors covalently bind to GPX4 via a reactive alkyl chloride moiety or masked nitrile-oxide electrophiles with poor selectivity and pharmacokinetic properties and most were obtained by cell phenotype-based screening. Lacking of effective high-throughput screening methods for GPX4 protein limits the discovery of GPX4 inhibitors. Here, we report a fluorescence polarization (FP)-based high throughput screening (HTS) assay for GPX4-U46C-C10A-C66A in vitro, and found Metamizole sodium from our in-house compound library inhibits GPX4-U46C-C10A-C66A enzyme activity. Structure-activity relationships (SAR) demonstrated the importance of sulfonyl group on interaction between Metamizole sodium and GPX4-U46C-C10A-C66A. Our FP assay could be an effective tool for discovery of GPX4 inhibitors and Metamizole sodium was a potential inhibitor for GPX4 in vitro.


Assuntos
Dipirona , Ensaios de Triagem em Larga Escala , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Selenocisteína/metabolismo , Relação Estrutura-Atividade , Glutationa Peroxidase/metabolismo
5.
Infection ; 52(2): 685-690, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38133714

RESUMO

We report the case of a young female with steroid-dependent ulcerative colitis (UC) who developed a complex systemic infection with Aspergillus flavus. This occurred following a UC relapse while vacationing in the Middle East, leading to extended use of metamizole and subsequent agranulocytosis. On her return to Germany, she was hospitalized for neutropenic sepsis and later transferred to our hospital due to persistent cytopenia and suspected Hemophagocytic Lymphohistiocytosis (HLH). Despite initial stabilization with targeted treatment for pulmonary Aspergillus flavus infection, her condition rapidly deteriorated following the onset of an Immune Reconstitution Inflammatory Syndrome (IRIS), which manifested as skin necrosis and pneumothorax after the replenishment of neutrophil granulocytes. The patient eventually died from an unmanageable pulmonary hemorrhage. Microscopy of skin necroses showed a massive presence of Aspergillus flavus, but tissue culture remained negative, suggesting effective antifungal treatment yet delayed phagocytosis due to agranulocytosis. This case underscores the need to consider IRIS in immunosuppressed patients who worsen despite aggressive and appropriately targeted treatment, highlighting its potential beyond the commonly recognized context in HIV-positive patients.


Assuntos
Agranulocitose , Aspergilose , Pneumopatias , Linfo-Histiocitose Hemofagocítica , Pneumotórax , Sepse , Humanos , Feminino , Aspergillus flavus , Dipirona , Aspergilose/complicações , Aspergilose/tratamento farmacológico , Hemorragia , Necrose , Linfo-Histiocitose Hemofagocítica/microbiologia
6.
J Vet Intern Med ; 37(6): 2544-2551, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37882246

RESUMO

BACKGROUND: Treatment with phenylbutazone (nonselective COX inhibitor) decreases the diuretic and natriuretic effects of furosemide by nearly 30% but the effects of COX-2 specific inhibitors (firocoxib) and atypical NSAIDs (dipyrone) are unknown. HYPOTHESIS: Furosemide-induced diuresis after pretreatment with firocoxib or dipyrone is diminished to a lesser extent than after pretreatment with phenylbutazone. ANIMALS: Eight healthy mares. METHODS: Each mare received 4 treatments in a prospective experimental crossover study using a replicated 4 × 4 Latin Square design: furosemide alone (FU), furosemide and phenylbutazone (PB), furosemide and firocoxib (FX), and furosemide and dipyrone (DP). After 24 hours of NSAID treatment at recommended dosages, ureteral catheters were placed for continual urine collection. After a 30-minute baseline collection period, furosemide (1.0 mg/kg, IV) was administered, and urine and blood samples were collected for 4 hours. Data were assessed by repeated measures ANOVA. RESULTS: Four-hour urine volume was (mean ± SD) ~25% less (P < .001) after pretreatment with all NSAIDs (PB 19.1 ± 2.1 mL/kg, FX 17.7 ± 3.5 mL/kg, DP 19.1 ± 3.9 mL/kg), as compared to FU (23.4 ± 5.1 mL/kg) (P < .001), but there were no differences between PB, FX, or DP. Interindividual variability in furosemide diuresis after pretreatment with different NSAIDs was observed. CONCLUSIONS AND CLINICAL IMPORTANCE: Though COX-2 selective NSAIDs and dipyrone might have less severe or fever gastrointestinal adverse effects in horses, our data suggest minimal differences in effects on furosemide-induced diuresis, and possibly, risk of nephrotoxicosis.


Assuntos
Diuréticos , Furosemida , Animais , Cavalos , Feminino , Diuréticos/farmacologia , Furosemida/farmacologia , Dipirona/farmacologia , Estudos Cross-Over , Ciclo-Oxigenase 2 , Estudos Prospectivos , Fenilbutazona/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia
7.
Res Vet Sci ; 164: 105034, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37820460

RESUMO

This study aimed to monitor the effects of dipyrone following multiple administrations in northeastern donkeys. Ten castrated male donkeys, aged 6.4 ± 3 years and weighing 130.6 ± 9.8 kg, were administered dipyrone (25 mg/kg IV) every 12 h, resulting in six administrations (D1 to D6) per animal. Blood samples were collected over a 72 h monitoring period. A validated UHPLC-MS/MS method was employed to determine the plasma concentrations of the 4- methylaminoantipyrine (4-MAA) and 4-aminoantipyrine (4-AA). The calculated pharmacokinetic variables of 4-MAA after D1 and D6 were, respectively: Cmax (µg/mL) = 163.60 ± 179.72 and 178.79 ± 196.94; T1/2beta (h) = 2.65 ± 0.65 and 3.37 ± 1.03; and AUC0-t (µg/mL × h) = 240.38 ± 130.87 and 373.52 ± 78.85. The same variables for 4-AA were: Cmax, (µg/mL) = 0.44 ± 0.27 and 0.90 ± 0.31, T1/2beta (h) = 14.77 ± 13.13 and 35.97 and AUC0-t (µg/mL × h) = 3.20 ± 0.43 and 27.73 ± 11.99. Concentrations of 4-MAA exceeded the minimum concentration required for 50% inhibition of cyclooxygenases 1 and 2. However, an accumulation of 4-AA, was observed. Further clinical studies are necessary to ascertain the implications of these findings on the pharmacodynamic response to dipyrone in northeastern donkeys.


Assuntos
Dipirona , Equidae , Masculino , Animais , Dipirona/farmacocinética , Brasil , Espectrometria de Massas em Tandem/veterinária , Ampirona/farmacocinética
8.
BMC Emerg Med ; 23(1): 104, 2023 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-37710177

RESUMO

ABSTRAC: BACKGROUND: Treatment of acute pain is an essential element of pre-hospital care for injured and critically ill patients. Clinical studies indicate the need for improvement in the prehospital analgesia. OBJECTIVE: The aim of this study is to assess the current situation in out of hospital pain management in Germany regarding the substances, indications, dosage and the delegation of the use of analgesics to emergency medical service (EMS) staff. MATERIAL AND METHODS: A standardized survey of the medical directors of the emergency services (MDES) in Germany was carried out using an online questionnaire. The anonymous results were evaluated using the statistical software SPSS (Chi-squared test, Mann-Whitney-U test). RESULTS: Seventy-seven MDES responsible for 989 rescue stations and 397 EMS- physician bases in 15 federal states took part in this survey. Morphine (98.7%), Fentanyl (85.7%), Piritramide (61%), Sufentanil (18.2%) and Nalbuphine (14,3%) are provided as opioid analgesics. The non-opioid analgesics (NOA) including Ketamine/Esketamine (98,7%), Metamizole (88.3%), Paracetamol (66,2%), Ibuprofen (24,7%) and COX-2-inhibitors (7,8%) are most commonly available. The antispasmodic Butylscopolamine is available (81,8%) to most rescue stations. Fentanyl is the most commonly provided opioid analgesic for treatment of a traumatic pain (70.1%) and back pain (46.8%), Morphine for visceral colic-like (33.8%) and non-colic pain (53.2%). In cases of acute coronary syndrome is Morphine (85.7%) the leading analgesic substance. Among the non-opioid analgesics is Ketamine/Esketamine (90.9%) most frequently provided to treat traumatic pain, Metamizole for visceral colic-like (70.1%) and non-colic (68.6%) as well as back pain (41.6%). Butylscopolamine is the second most frequently provided medication after Metamizole for "visceral colic-like pain" (55.8%). EMS staff (with or without a request for presence of the EMS physician on site) are permitted to use the following: Morphine (16.9%), Piritramide (13.0%) and Nalbuphine (10.4%), and of NOAs for (Es)Ketamine (74.1%), Paracetamol (53.3%) and Metamizole (35.1%). The dosages of the most important and commonly provided analgesic substances permitted to independent treatment by the paramedics are often below the recommended range for adults (RDE). The majority of medical directors (78.4%) of the emergency services consider the independent application of analgesics by paramedics sensible. The reason for the relatively rare authorization of opioids for use by paramedics is mainly due to legal (in)certainty (53.2%). CONCLUSION: Effective analgesics are available for EMS staff in Germany, the approach to improvement lies in the area of application. For this purpose, the adaptations of the legal framework as well as the creation of a guideline for prehospital analgesia are useful.


Assuntos
Dor Aguda , Analgésicos não Narcóticos , Ketamina , Nalbufina , Diretores Médicos , Adulto , Humanos , Analgésicos não Narcóticos/uso terapêutico , Dipirona , Acetaminofen , Pirinitramida , Brometo de Butilescopolamônio , Analgésicos/uso terapêutico , Analgésicos Opioides/uso terapêutico , Fentanila , Alemanha , Derivados da Morfina
9.
J Agric Food Chem ; 71(28): 10841-10849, 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37406351

RESUMO

To avoid false-positive results in immunoassays due to cross-reactivity of antibodies with structural analogues, especially metabolites of target compounds, the preparation of highly specific antibodies is crucial. Preserving the characteristic structure of a target compound when designing a hapten is important when preparing highly specific antibodies. Here, we designed a novel hapten, 4-(((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4yl)amino)methyl)benzoic acid, named AA-BA, to improve the specificity of antibodies for detection of 4-methylaminoantipyrine (MAA), a residual marker of dipyrone, an important antipyretic-analgesic and anti-inflammatory drug. The structural features of the hapten remained almost the same as those of MAA. After experimental validation, monoclonal antibody 6A4 (mAb 6A4) was prepared with the half maximal inhibitory concentration (IC50) value of 4.03 ng/mL and negligible cross-reactivity with dipyrone metabolites and other antibiotics. In addition, a specific lateral flow immunoassay (LFA) strip based on colloidal gold was developed for screening MAA with a cutoff value of 25 ng/mL in milk. The developed LFA is a useful tool for rapid and accurate detection of MAA.


Assuntos
Anticorpos Monoclonais , Dipirona , Dipirona/farmacologia , Imunoensaio/métodos , Haptenos , Coloide de Ouro/química , Limite de Detecção
10.
Reprod Domest Anim ; 58(7): 972-981, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37151194

RESUMO

The aim of this study was to determine the effectiveness of meloxicam with or without dipyrone on the welfare of ewes subjected to non-surgical embryo recovery (NSER). Two studies were carried out using 51 multiparous Santa Inês ewes. All animals received a standard oestrous synchronization treatment and a superovulatory protocol. In Study 1, 12 ewes received meloxicam (GM) before cervical transposition (1 mg kg-1 , i.v.), repeated 24 h after (1 mg kg-1 , i.m.), while the other 10 received a saline solution, remaining as a control group (GC1). In Study 2, ewes were allocated into a group of 15 ewes treated as GM of Study 1 associated with dipyrone (GMD; 50 mg kg-1 , i.m.) before cervical transposition, 12 h, and 24 h after, or a control group (GC2) of 14 ewes treated with saline solution. In both studies, heart and respiratory rates (RR), cortisol, glucose, total proteins, albumin and globulins blood concentration were recorded before sedation (BS), after sedation (AS), after cervical transposition, immediately after collection (IAC), and 0.5, 1.5, 3, 6, 12, 24 and 48 h after embryo collection (hAC). In Study 1, RR tended to be greater in GC1 (p = .08), serum total proteins and globulins values were lower and serum albumin values were greater in this group than GM (p = .003, p < .0001, and p < .0001, respectively). In Study 2, treatment of GMD tended to reduce the glycaemia at AS (p = .052) and reduced it at 3hAC (p < .0001), and 6hAC (p = .03). It also tended to reduce cortisol concentrations (p = .10). The other variables varied with NSER without interaction with the experimental treatments. In conclusion, in this study condition, NSER in sheep induced transient changes indicative of stress and possibly pain, therefore, affecting animal welfare. The administration of meloxicam was ineffective to reduce those responses, and the association of dipyrone had only slight effects without modifying the main welfare indicative responses in ewes subjected to NSER.


Assuntos
Dipirona , Hidrocortisona , Ovinos , Feminino , Animais , Meloxicam/farmacologia , Solução Salina , Bem-Estar do Animal
11.
IET Nanobiotechnol ; 17(4): 360-367, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37095723

RESUMO

To assess and evaluate Chitosan-Metamizole nanoparticles for fracture healing and analgesic potential, nanoparticles were formulated using the ionotropic gelation method. The nanoparticles were evaluated for particle size, zeta potential, polydispersity index, loading efficiency, surface characteristics and drug release properties. The analgesic activity was determined in carrageenan-induced arthritic male Wister rats. Further fracture healing potency, mechanical testing, radiographic examination and bone histology of the femur were studied. The drug loading efficiency of 11.38%-17.45%, particle size of 140-220 nm, and zeta potential of 19.12-23.14 mV were observed with a spherical, smooth appearance. Nanoparticles showed sustained release behaviour over a longer period. Nearly 4-fold inhibition of oedema was observed in animals treated with nanoparticles with excellent fracture healing potential. The femurs treated with nanoparticles required greater force to fracture. Nanoparticles significantly improved the strength and healing process. Histopathological studies showed the potential of nanoparticles in the healing process. The study confirmed the potential of nanoparticles in fracture healing and enhancement of analgesic activity.


Assuntos
Quitosana , Nanopartículas , Ratos , Masculino , Animais , Quitosana/farmacologia , Consolidação da Fratura , Dipirona , Ratos Wistar , Tamanho da Partícula , Portadores de Fármacos
12.
Drugs R D ; 23(2): 93-98, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36988798

RESUMO

BACKGROUND AND OBJECTIVE: Metamizole is a non-opioid ampyrone sulfonate compound with potent analgesic, antipyretic, and spasmolytic effects. Agranulocytosis is a rare life-threatening complication of metamizole. CASE: Here, we present the case of a 62-year-old patient who developed agranulocytosis as well as hemolysis after a single administration of metamizole. CONCLUSION: This case illustrates the inherent allergic potential of metamizole and its effects on different hematopoietic cell types.


Assuntos
Agranulocitose , Neutropenia , Humanos , Pessoa de Meia-Idade , Dipirona/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Hemólise , Agranulocitose/induzido quimicamente
13.
Br J Clin Pharmacol ; 89(8): 2458-2464, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36946257

RESUMO

AIMS: In patients of all ages, metamizole is a frequently used analgesic. Recently, metamizole has been identified as an inducer of, among others, cytochrome P450 (CYP) 3A activity, but the time course of this interaction has not been evaluated. METHODS: Using repeated oral microdoses (30 µg) of the CYP3A index substrate midazolam, we assessed changes in midazolam pharmacokinetics (area under the concentration-time curve from 2-4 h: AUC2-4 and estimated partial metabolic clearance: eClmet ) before, at steady-state, and after discontinuation of 3 × 1000 mg metamizole/day orally for 8 days. RESULTS: Significant changes in pharmacokinetic parameters were detected already 3 days after start of metamizole treatment. At the steady-state of enzyme induction, the geometric mean ratio of midazolam AUC2-4 was substantially reduced to 0.18 (90% confidence interval: 0.14-0.24) with a corresponding 5.43-fold (4.15-7.10) increase of eClmet . After discontinuation of metamizole, the changes slowly recovered, but were still significant at the end of the observation period on the fifth day after discontinuation of metamizole therapy (AUC2-4 reduced to 0.50 [0.41-0.63] and eClmet 1.99-fold increased [1.60-2.47, P < 0.05]). CONCLUSION: Metamizole acts as a strong inducer of CYP3A already few days after start of metamizole administration and, thus, should be avoided in patients using drugs with narrow therapeutic index and major clearance via CYP3A. If their administration is essential, close monitoring and dose adjustment of comedication should be performed as early as the first week after the initiation and after discontinuation of metamizole therapy.


Assuntos
Dipirona , Midazolam , Humanos , Midazolam/farmacocinética , Dipirona/farmacologia , Citocromo P-450 CYP3A/metabolismo , Voluntários Saudáveis , Cinética , Área Sob a Curva , Interações Medicamentosas , Administração Oral
14.
Pharmacoepidemiol Drug Saf ; 32(8): 898-909, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36960493

RESUMO

PURPOSE: Concomitant use of diuretics, renin-angiotensin-aldosterone system (RAAS) inhibitors, and non-steroidal anti-inflammatory drugs (NSAIDs) or metamizole, known as 'triple whammy' (TW), has been associated with an increased risk of acute kidney injury (AKI). Nevertheless, there is still uncertainty on its impact in hospitalisation and mortality. The aim of the study was to analyse the association between exposure to TW and the risk of hospitalisation for AKI, all-cause mortality and the need for renal replacement therapy (RRT). METHODS: A case-control study nested in a cohort of adults exposed to at least one diuretic or RAAS inhibitor between 2009 and 2018 was carried out within the Pharmacoepidemiological Research Database for Public Health Systems (BIFAP). Patients hospitalised for AKI between 2010 and 2018 (cases) were matched with up to 10 patients of the same age, sex and region of Spain who had not been hospitalised for AKI as of the date of hospitalisation for AKI of the matching case (controls). The association between TW exposure versus non-exposure to TW and outcome variables was analysed using logistic regression models. RESULTS: A total of 480 537 participants (44 756 cases and 435 781 controls) were included (mean age: 79 years). The risk of hospitalisation for AKI was significantly higher amongst those exposed to TW [adjusted odds ratio (aOR) 1.36, 95% confidence interval (95%CI) 1.32-1.40], being higher with current (aOR 1.60, 95%CI 1.52-1.69) and prolonged exposure (aOR 1.65, 95%CI 1.55-1.75). No significant association was found with the need of RRT. Unexpectedly, mortality was lower in those exposed to TW (aOR 0.81, 95%CI 0.71-0.93), which may be influenced by other causes. CONCLUSION: Vigilance should be increased when diuretics, RAAS inhibitors, and NSAIDs or metamizole are used concomitantly, especially in patients at risk such as elderly patients.


Assuntos
Injúria Renal Aguda , Diuréticos , Adulto , Humanos , Idoso , Diuréticos/efeitos adversos , Sistema Renina-Angiotensina , Dipirona/efeitos adversos , Estudos de Casos e Controles , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Hospitalização
15.
Lab Anim ; 57(5): 529-540, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36960681

RESUMO

Application of dextran sodium sulfate (DSS) is often used to induce experimental colitis. Current state of the art is to refrain from the use of analgesics due to their possible interaction with the model. However, the use of analgesics would be beneficial to reduce the overall constraint imposed on the animals. Here, we analyzed the effect of the analgesics Dafalgan (paracetamol), Tramal (tramadol) and Novalgin (metamizole) on DSS-induced colitis. To study the effect of those analgesics in colitis mouse models, acute and chronic colitis was induced in female C57BL6 mice by DSS administration in the drinking water. Analgesics were added to the drinking water on days four to seven (acute colitis) or on days six to nine of each DSS cycle (chronic colitis). Tramadol and paracetamol had minor effects on colitis severity. Tramadol reduced water uptake and activity levels slightly, while mice receiving paracetamol presented with a better overall appearance. Metamizole, however, significantly reduced water uptake, resulting in pronounced weight loss. In conclusion, our experiments show that tramadol and paracetamol are viable options for the use in DSS-induced colitis models. However, paracetamol seems to be slightly more favorable since it promoted the overall wellbeing of the animals upon DSS administration without interfering with typical readouts of colitis severity.


Assuntos
Colite , Água Potável , Tramadol , Animais , Feminino , Camundongos , Tramadol/farmacologia , Dipirona/farmacologia , Acetaminofen/efeitos adversos , Água Potável/efeitos adversos , Sulfato de Dextrana/efeitos adversos , Camundongos Endogâmicos C57BL , Colite/induzido quimicamente , Colite/tratamento farmacológico , Analgésicos/efeitos adversos , Modelos Animais de Doenças
16.
Toxicon ; 226: 107083, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36898505

RESUMO

Phoneutrism (bites by wandering spiders of the genus Phoneutria) frequently results in local pain. We describe a retrospective cohort study of a case series of phoneutrism admitted to our Emergency Department (ED), in which we used the Numeric Pain Rating Scale (NPRS 0-10) to assess the intensity of local pain upon admission, and recorded the analgesic measures used to control this pain. Other criteria for inclusion were: (1) An age ≥8 years, (2) Treatment exclusively at our ED, and (3) Visualization or photographing the spider at the time of the bite and/or bringing the spider for identification. The patients were classified into three groups based on the intensity of pain at admission: group 1 - mild or no pain (NPRS: 0-3), group 2 - moderate pain (NPRS: 4-6), and group 3 - intense or severe pain (NPRS: 7-10). Fifty-two patients fulfilled the inclusion criteria (n = 11, 14 and 27 in groups 1, 2, and 3, respectively), with a median age of 37 years. The median NPRS upon admission was 7 (interquartile range: 5-8). In patients with an NPRS <7 (groups 1 and 2), only dipyrone was used to alleviate the pain, with six cases in group 1 requiring no analgesia. Most of the cases in group 3 (19/27) were treated with a local anesthetic infiltration (2% lidocaine), in association with analgesics given i.v. in 16 cases (dipyrone, 14; tramadol, 2); additional analgesic treatment was required in seven cases, six of which were treated with tramadol i.v. The median time spent in the ED was 18, 58 and 120 min for groups 1, 2 and 3, respectively. These findings show that most cases of envenoming by Phoneturia spp. involved intense local pain (NPRS ≥7), with local anesthetics being used only in these cases, often in association with dipyrone i.v.


Assuntos
Aranhas , Tramadol , Animais , Dipirona/uso terapêutico , Estudos Retrospectivos , Dor/tratamento farmacológico , Analgésicos/uso terapêutico
17.
Eur J Pharmacol ; 943: 175567, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36754194

RESUMO

INTRODUCTION: Dipyrone has been used as an analgesic for a century, but recently was proposed as a novel therapeutic strategy for the prevention and therapy of pulmonary hypertension (PH). The aim of this study was to analyze whether the risk for ventilation procedures and hospitalization was lower among patients with PH who used dipyrone compared to subjects who did not use dipyrone. MATERIALS AND METHODS: Initially, patients with PH were retrieved from the TriNetX database, whereby subjects who used dipyrone were assigned to cohort I, and cohort II was formed by those individuals who did not use dipyrone. Both cohorts were matched for several variables. The outcomes were requirement for ventilation procedures and hospital admission, whereby the time window to record events was 5 years after diagnosis of PH. Subsequently, risk analysis was carried out, and risk ratio (RR) and odds ratio (OR) were calculated. In addition, the risk of agranulocytosis was determined for both cohorts. RESULTS: Out of 741,875 individuals diagnosed with PH 4,282 and 737,593 patients were assigned to the cohorts I and II. After matching, each cohort accounted for 4,278 individuals. Among the cohorts I and II 10 and 187 individuals required ventilation procedures. The according risks of 0.2% vs. 4.4% were significantly different (p < 0.0001; Log-Rank test). RR and OR were 0.053 and 0.051. Within the cohorts I and II 10 and 1,195 subjects required hospital admission. The risks of hospitalization of 0,4% vs. 27.9% differed significantly (p < 0.0001). RR and OR were 0.016 and 0.012. Among the cohorts I and II 47 and 66 individuals were diagnosed with agranulocytosis, whereby no significance was found (p > 0.05). CONCLUSIONS: The risk for ventilation measures and hospitalization among patients with PH was found to be significantly lower when dipyrone was used. Even though the underlying mechanisms remain unknown to date, they are supposedly mediated by an active metabolite of dipyrone. The obtained results appear to be promising for patients suffering from PH. Hence, the present study may encourage further research.


Assuntos
Agranulocitose , Hipertensão Pulmonar , Humanos , Dipirona/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/induzido quimicamente , Hospitalização , Agranulocitose/tratamento farmacológico , Agranulocitose/induzido quimicamente , Agranulocitose/diagnóstico
18.
Bratisl Lek Listy ; 124(4): 320-329, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36598328

RESUMO

BACKGRAUND: There is evidence that the adverse effects of metamizole occur due to the effect of the drug on the hematopoietic stem/progenitor cells, and therefore, the disruption of hematopoiesis. Therefore, our study aimed to evaluate the effects of metamizole on hematopoietic stem/progenitor cells using cell culture techniques. MATERIAL AND METHODS: In our study, samples were taken from stem cell products of healthy allogeneic stem cell transplant donors. The colony-forming unit (CFU) assay was used for the cells obtained from these samples. In addition, the drug effects on cell proliferation were evaluated with the MTT. Furthermore, the cell colonies were labelled with immunofluorescent antibodies and the effects of metamizole on cell types formed in culture were evaluated. RESULTS: We determined that metamizole negatively affects the proliferation of cells, especially starting from 10 µM. As a result of the evaluation of colonization, we saw that the number of colonies decreased with increasing concentrations. Granulocyte-macrophage colonies were more affected at increasing concentrations than other colonies. As a result of the evaluations of our in vitro study, it was also shown as an important finding that the individual effects of the drug were highly variable. CONCLUSION: CFU method can be used as a suitable method to investigate the effects of drugs and toxic substances on hematopoiesis. We also think it may be suitable for pre-analysing hematopoietic side effects in new drug research. In addition, using stem cell samples in studies may contribute more easily to the in vitro simulation of hematopoietic differentiations (Fig. 7, Ref. 29). Text in PDF www.elis.sk Keywords: metamizole, hematopoietic progenitor cells, hematopoiesis, CFU assay, adverse effect.


Assuntos
Dipirona , Células-Tronco Hematopoéticas , Dipirona/farmacologia , Células-Tronco Hematopoéticas/fisiologia , Hematopoese , Ensaio de Unidades Formadoras de Colônias , Diferenciação Celular , Células Cultivadas
19.
Eur J Anaesthesiol ; 40(3): 171-178, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36632758

RESUMO

BACKGROUND: There is growing evidence that the analgesic effect of metamizole is mediated at least partly by central mechanisms, including the endocannabinoid/endovanilloid system. Consequently, metamizole may have additive or even synergistic analgesic effects with paracetamol and nonsteroidal anti-inflammatory drugs (NSAID). OBJECTIVE: This study aimed to assess if triple therapy with metamizole, ibuprofen and paracetamol (MIP) is superior to double therapy with ibuprofen and paracetamol (i.p.) in treating pain at home after ambulatory arthroscopic shoulder surgery. DESIGN/SETTING/PATIENTS/INTERVENTION: In this double-blind, controlled, high-volume single centre, superiority trial, 110 patients undergoing elective ambulatory arthroscopic shoulder surgery were randomised to receive either MIP ( n  = 55) or i.p. ( n  = 55) orally for 4 days between December 2019 and November 2021. Pain intensity at movement and rest, using a numeric rating scale (NRS), perceived pain relief, use of rescue medication and adverse effects of study medication were recorded at the post-anaesthesia care unit (PACU) and on postoperative day (POD) 1 to 4 and 7. Quality of Recovery (QoR) and satisfaction with study medication were measured at POD 7 with telephone follow-up. MAIN OUTCOME MEASURE: The primary outcome measure was postoperative pain intensity on movement measured by an 11-point NRS (where 0 = no pain and 10 = worst pain imaginable) on POD 1. RESULTS: For the primary outcome, superiority of MIP in reducing postoperative pain at movement on POD 1 was not confirmed: mean difference NRS [95% confidence interval (CI), -0.08 (-1.00 to 0.84)]. For pain on movement and at rest, no significant differences were found between groups in the PACU nor on POD 1 to 4 or day 7. Nausea was reported significantly more frequently in the metamizole group (22.6 vs. 58.5; P  < 0.001). Other adverse effects of study medication, rescue opioid consumption, perceived pain relief, QoR at POD 7, and overall patient satisfaction were similar in both groups. CONCLUSION: Clinically, triple oral treatment with metamizole, paracetamol and ibuprofen is not superior to oral paracetamol and ibuprofen in multimodal pain treatment at home after ambulatory arthroscopic shoulder surgery. TRIAL REGISTRATION: European Union Clinical Trials Register 2019-002801-23 and Clinicaltrials.gov NCT04082728.


Assuntos
Dipirona , Ibuprofeno , Humanos , Dipirona/efeitos adversos , Acetaminofen , Ombro , Anti-Inflamatórios não Esteroides/uso terapêutico , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia
20.
Otolaryngol Pol ; 77(2): 1-5, 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36718573

RESUMO

SummaryIntroduction. . The aim of the study was the analysis of reasons for the occurrence and treatment results of chronic inflammation of the paranasal sinuses in own materail. MATERIAL AND METHODS: The study was performed on 520 women aged 18 - 87 and 789 men aged 19-85, diagnosed and treated for the chronic inflammation of the paranasal sinuses in 2016 - 2020. The analysis was based on disease medical history, taking into account: gender; age of patients; type of symptoms; allergy diagnosis; probable cause of inflammation; type of anatomical anomalies; assessment of the advancement of lesions based on CT images in the Lund- Mackay scale; number of operations; histopathological result of the removed lesions; complications that occured after surgical treatment.ResultsThe study showed that the hospitalized patients were most often aged 41-50, 51-60 and 31-40 among women and men aged 51-60, 41-50 and 31- 40 . The results of allergological diagnostics among patients with chronic inflammation of the paranasal sinuses showed that women were most often allergic to pyralgin + ketonal + paracetamol + ibuprofen in 4.50 % , to penicillins in 1.07 % and to house dust saprophytes in 0.92%, while among men, positive reactions were found in 3.36 % for pyralgin + ketonal + paracetamol + ibuprofen, 0.99% for house dust saprophytes and 0.92% for cats and dogs fur. Absence of anatomical anomalies was found among 20.75 % of woman and 26.36 % of men, but most often they occurred in the form of nasal septal curvature and excessively dilated middle nasal turbinate. In the histopathological examination of the lesions from the paranasal sinuses, the following were found: chronicinflammation of mucous membrane, chronic polypoid inflammation, chronic cystic inflammation and chronic allergic inflammation. CONCLUSIONS: The main symptoms among patients with chronic inflammation of paranasal sinuses were: nasal congestion + rhinorrhea, nasal congestion + rhinorrhea + smell impairment and nasal congestion + rhinorrhea+ headache. The most common probable causes for chronic inflammation of nasal sinuses among the examined patients were: anatomical anomalies, allergies, irritant factors, including tobacco smoke. Depending on the assessment of the severity of changes in the paranasal sinuses according to the Lund- Mackay scale, it appears that medium and large inflammatory lesions prevailed in the examined patients. KEY WORDS: reason/cause, occurrence, treatment results, chronic inflammation of the paranasal sinuses.


Assuntos
Ibuprofeno , Seios Paranasais , Humanos , Feminino , Animais , Gatos , Cães , Acetaminofen , Dipirona , Seios Paranasais/diagnóstico por imagem , Seios Paranasais/cirurgia , Seios Paranasais/patologia , Inflamação/patologia , Rinorreia/patologia
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