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1.
Lancet Haematol ; 7(2): e168-e176, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32004486

RESUMO

Tumour lysis syndrome is a complication of chemotherapy for haematological malignancies; in particular, aggressive leukaemias and lymphomas. For haematological malignancies, targeted therapies, such as small molecule inhibitors and monoclonal antibodies, have a high anti-tumour activity, are well tolerated, and have a low incidence of associated tumour lysis syndrome. The BCL-2 inhibitor venetoclax has a high anti-tumour activity in chronic lymphocytic leukaemia, achieving deep remissions by potently inducing apoptosis and increasing the risk for tumour lysis syndrome. In this Viewpoint, we discuss the pathophysiology, risk factors, monitoring, changes in laboratory parameters, and clinical manifestations of tumour lysis syndrome, and the prophylaxis and treatments available for this complication. Prophylaxis and treatment strategies have been implemented as standard of care in patients receiving venetoclax to minimise the risk of both laboratory and clinical manifestations of tumour lysis syndrome.


Assuntos
Antineoplásicos/efeitos adversos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Terapia de Alvo Molecular/efeitos adversos , Proteínas de Neoplasias/antagonistas & inibidores , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Síndrome de Lise Tumoral/etiologia , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/terapia , Alopurinol/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/etiologia , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Sinergismo Farmacológico , Humanos , Hiperfosfatemia/etiologia , Hiperfosfatemia/terapia , Hiperuricemia/tratamento farmacológico , Hiperuricemia/etiologia , Leucemia Linfocítica Crônica de Células B/enzimologia , Diálise Renal , Fatores de Risco , Índice de Gravidade de Doença , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Síndrome de Lise Tumoral/diagnóstico , Síndrome de Lise Tumoral/tratamento farmacológico , Síndrome de Lise Tumoral/prevenção & controle , Urato Oxidase/uso terapêutico
2.
Angiology ; 71(4): 315-323, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32000517

RESUMO

Several trials have been completed in patients with heart failure (HF) treated with uric acid (UA)-lowering agents with inconsistent results. We aimed to investigate whether lowering UA would have an effect on mortality and cardiovascular (CV) events in patients with HF in a systematic review and meta-analysis. The primary outcome measures were all-cause mortality, CV mortality, CV events, and CV hospitalization in patients with HF. We included 11 studies in our final analysis. Overall, allopurinol treatment was associated with a significant increase in the risk for all-cause mortality (hazard ratio [HR]: 1.24, 95% confidence interval [CI]: 1.04-1.49, P = .02). The trial heterogeneity is high (heterogeneity χ2 = 37.3, I2 = 73%, P < .001). With regard to CV mortality, allopurinol treatment was associated with a 42% increased risk of CV mortality (HR: 1.42, 95% CI: 1.11-1.81, P = .005). There was a trend toward increased CV hospitalization in the same group (HR: 1.21, 95% CI: 0.95-1.53, P = .12). Uric acid-lowering treatments increase all-cause and CV mortality but did not increase CV hospitalization significantly in this study.


Assuntos
Inibidores Enzimáticos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Xantina Oxidase/antagonistas & inibidores , Alopurinol/uso terapêutico , Febuxostat/uso terapêutico , Insuficiência Cardíaca/mortalidade , Humanos , Oxipurinol/uso terapêutico , Ácido Úrico
3.
Int J Clin Pharmacol Ther ; 58(1): 21-28, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31657714

RESUMO

OBJECTIVE: Febuxostat, a novel non-purine selective xanthine oxidase inhibitor, is a recommended treatment option for patients with chronic kidney disease (CKD) and hyperuricemia. There are only a few trials on the long-term use of allopurinol and febuxostat for CKD. In this study, we compared the efficacy of allopurinol and febuxostat and their effects on renal function in patients with CKD and hyperuricemia. MATERIALS AND METHODS: This was a retrospective study of adult patients with hyperuricemia and CKD (estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73m2) treated with febuxostat or allopurinol. The proportion of patients who achieved the treatment goal and the difference in efficacy between different drug doses were evaluated. Further, the effects on cardiovascular and renal functions were assessed. Cardiovascular risk is defined as cardiovascular events occurring after treatment initiation. RESULTS: We enrolled 316 patients in the study, with 83 and 233 patients in the allopurinol and febuxostat groups, respectively. The application of linear mixed model for analysis revealed that febuxostat 40 mg was more effective than allopurinol 100 mg in reducing the serum uric acid level. The results indicated that the long-term eGFR slope of the febuxostat group was positive, whereas that of the allopurinol group was negative. CONCLUSION: The results showed that, in patients with CKD and hyperuricemia, febuxostat can be used to reduce the serum uric acid level. The long-term use of febuxostat may exert a protective effect on the kidneys. Moreover, there were no obvious adverse reactions and the patients tolerated the drug well.


Assuntos
Alopurinol/uso terapêutico , Febuxostat/uso terapêutico , Supressores da Gota/uso terapêutico , Hiperuricemia/tratamento farmacológico , Insuficiência Renal Crônica/tratamento farmacológico , Adulto , Alopurinol/efeitos adversos , Febuxostat/efeitos adversos , Supressores da Gota/efeitos adversos , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Ácido Úrico/sangue
4.
Clin Nephrol ; 93(1): 24-33, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31661061

RESUMO

BACKGROUND: Treatment with allopurinol has been suggested to reduce the incidence of contrast-induced acute kidney injury (CI-AKI). However, results of previous randomized controlled trials (RCTs) are not consistent. We performed a meta-analysis to evaluate the influence of allopurinol on the risk of CI-AKI. MATERIALS AND METHODS: Related RCTs were identified via systematic search of electronic databases including PubMed, Embase, and Cochrane's Library. The influence of allopurinol on the incidence of CI-AKI was defined as the primary outcome. Results were pooled using a random-effects model or a fixed-effects model according to the heterogeneity. RESULTS: Five RCTs with 754 patients who underwent percutaneous coronary intervention (PCI) were included. All patients received preprocedural hydration therapy with intravenous normal saline. Pooled results showed that allopurinol significantly reduced the incidence of CI-AKI (risk ratio (RR): 0.37, p = 0.01). Subgroup analyses demonstrated that allopurinol significantly reduced the incidence of CI-AKI in high-risk patients (incidence of CI-AKI ≥ 30%, RR: 0.10, p = 0.04) but not in low-risk patients (incidence of CI-AKI < 30%, RR: 0.67, p = 0.14). Moreover, allopurinol significantly prevented the increment of serum creatinine (weighted mean difference (WMD): -0.13 mg/dL, p < 0.001) and attenuated the loss of estimated glomerular filtration rate (WMD: 4.78 mL/min, p = 0.04). However, serum uric acids were not significantly affected (WMD: -0.26 mg/dL, p = 0.72). CONCLUSION: Pretreatment with allopurinol reduces the incidence of CI-AKI in patients undergoing contrast exposure in PCI. The benefits of allopurinol on CI-AKI may be more remarkable in high-risk patients.


Assuntos
Lesão Renal Aguda/prevenção & controle , Alopurinol/uso terapêutico , Meios de Contraste/efeitos adversos , Inibidores Enzimáticos/uso terapêutico , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/fisiopatologia , Angiografia Coronária , Creatinina/sangue , Taxa de Filtração Glomerular , Humanos , Intervenção Coronária Percutânea , Cuidados Pré-Operatórios , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Ácido Úrico/sangue
5.
Vasc Health Risk Manag ; 15: 539-550, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827327

RESUMO

Background: Left ventricular hypertrophy (LVH), as assessed by measurement of left ventricular mass (LVM), is one of the most important cardiovascular risk factors. It is commonly present in patients with ischemic heart disease (IHD), irrespective of the level of blood pressure; recently, oxidative stress has been shown to be an important factor in its development. The question then arises: can this risk factor be modified by antioxidant treatment (e.g., with allopurinol, a xanthine oxidase inhibitor)? Methods: This is an observational study with a cross-sectional design which explored the association between long-term (>12 months) allopurinol therapy and LV mass index (LVMI) as well as geometry in patients generally receiving standard treatments for IHD. The primary endpoint was LVMI measurement (by 2D-echocardiography) and secondary endpoints included the association of allopurinol use with LV function (ejection fraction), blood pressure, glycemic control, and lipid profile. Results: Ninety-six patients on standard anti-ischemic drug treatment (control group) and 96 patients who were additionally taking allopurinol (minimum dose 100 mg/day) were enrolled. Both groups were matched for age, sex, height, and co-morbidities, but poorer kidney function in the allopurinol group required further sub-group analysis based on renal function. Allopurinol treatment was associated with the lowest LVMI in the patients with normal serum creatinine (median LVMI; 70.5 g/m2): corresponding values were 76.0 and 87.0 in the control group with, respectively, normal and elevated serum creatinine, and 89.5 in the allopurinol group with elevated serum creatinine (P=0.027). In addition, allopurinol was associated with better glycemic control (HbA1c) with a difference of 0.8% (95% CI; 1.3, 0.2) (P=0.004) as compared with control patients. Conclusion: In our population, treatment with allopurinol (presumably because of its anti-oxidant properties) has shown a tendency to be associated with smaller LVM in IHD patients with normal serum creatinine, along with better glycemic control.


Assuntos
Alopurinol/uso terapêutico , Antioxidantes/uso terapêutico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Isquemia Miocárdica/tratamento farmacológico , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Alopurinol/efeitos adversos , Antioxidantes/efeitos adversos , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Estudos de Casos e Controles , Creatinina/sangue , Estudos Transversais , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/sangue , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
7.
Exp Parasitol ; 206: 107768, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31539540

RESUMO

Canine leishmaniosis due to Leishmania infantum is a widespread zoonotic disease. Although aminosidine can be an effective treatment, current therapeutic recommendations do not advocate its use, mainly due to concerns regarding the potential nephrotoxicity and ototoxicity of this drug. The aim of this randomized, blinded, controlled study was to evaluate the nephrotoxicity and ototoxicity of aminosidine-allopurinol combination and compare it with that of meglumine antimonate-allopurinol combination in non-azotemic dogs with leishmaniosis. Forty dogs with leishmaniosis were randomly assigned to be treated with either aminosidine at 15 mg/kg, subcutaneously, once daily for 28 days (group A) or with meglumine antimonate at 100 mg/kg, subcutaneously, once daily for 28 days (group B). In addition to either drug, dogs in both groups were administered allopurinol at 10 mg/kg per os twice daily for 2 months. Kidney function was evaluated through measurement of serum creatinine, urea nitrogen, inorganic phosphorus, and cystatin-c concentrations and complete urinalysis, including protein-to-creatinine ratio, at baseline and after 14, 28, and 60 days from the beginning of the treatment. At the same time points, vestibular and auditory functions were evaluated through neurological examination and brainstem auditory evoked response (BAER) recordings of wave I, wave V, inter-wave I-V latencies, and minimum hearing thresholds. None of the dogs developed clinicopathological evidence of kidney disease during the study. Serum creatinine concentration increased >0.3 mg/dl over baseline in 2 dogs in group A and in 5 dogs in group B. Parameters of kidney function were not significantly different or were improved compared to baseline and the only difference between the two groups was the lower concentration of serum creatinine in group A. None of the dogs developed peripheral vestibular syndrome or hearing impairment. At the end of the study, parameters of auditory function were not significantly different or were improved compared to baseline and there were no differences between the two groups. The results of this study show that the nephrotoxicity and ototoxicity of aminosidine, when administered to non-azotemic dogs with leishmaniosis at 15 mg/kg subcutaneously once daily for 28 days along with allopurinol, is minimal and does not differ from that of meglumine antimonate.


Assuntos
Alopurinol/efeitos adversos , Doenças do Cão/tratamento farmacológico , Audição/efeitos dos fármacos , Rim/efeitos dos fármacos , Leishmaniose Visceral/veterinária , Paromomicina/efeitos adversos , Alopurinol/administração & dosagem , Alopurinol/uso terapêutico , Animais , Cóclea/efeitos dos fármacos , Creatinina/sangue , Doenças do Cão/parasitologia , Cães , Método Duplo-Cego , Combinação de Medicamentos , Potenciais Evocados Auditivos do Tronco Encefálico , Feminino , Perda Auditiva/induzido quimicamente , Perda Auditiva/veterinária , Injeções Subcutâneas/veterinária , Leishmania infantum , Leishmaniose Visceral/tratamento farmacológico , Masculino , Antimoniato de Meglumina/administração & dosagem , Antimoniato de Meglumina/efeitos adversos , Antimoniato de Meglumina/uso terapêutico , Exame Neurológico/veterinária , Paromomicina/administração & dosagem , Paromomicina/uso terapêutico , Distribuição Aleatória , Vestíbulo do Labirinto/efeitos dos fármacos
8.
Nutr Metab Cardiovasc Dis ; 29(10): 1011-1022, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31378626

RESUMO

BACKGROUND AND AIMS: Systemic reviews and meta-analyses suggest hyperuricemia is a cardiovascular risk factor. The effects of xanthine oxidase inhibitors on cardiac outcomes remain unclear. We assessed the effects of febuxostat and allopurinol on mortality and adverse reactions in adult patients with hyperuricemia. METHODS AND RESULTS: PubMed and EMBASE were searched to retrieve randomized controlled trials of febuxostat and allopurinol from January 2005 to July 2018. The meta-analysis consisted of 13 randomized controlled trials with a combined sample size of 13,539 patients. Febuxostat vs. allopurinol was not associated with an increased risk of cardiac-related mortality in the overall population (OR: 0.72, 95% CI: 0.24-2.13, P = 0.55). Regarding adverse skin reactions, the patients receiving febuxostat had significantly fewer adverse skin reactions than those receiving allopurinol treatment (OR: 0.50, 95% CI: 0.30-085, P = 0.01). Compared with allopurinol, febuxostat was associated with an improved safety outcome of cardiac-related mortality and adverse skin reactions (OR: 0.72, 95% CI: 0.55-0.96, P = 0.02). The net clinical outcome, composite of incident gout and the safety outcome, was not different significantly in the patients receiving febuxostat or allopurinol (OR: 1.04, 95% CI: 0.76-0.1.42, P = 0.79). In sensitivity analyses, a borderline significance was found in the patients randomized to febuxostat vs. allopurinol regarding cardiac-related mortality (OR: 1.29, 95% CI: 1.00-1.67, P = 0.05) after the CARES study was included. CONCLUSION: Febuxostat vs. allopurinol was associated with the improved safety outcome and have comparable mortality and net clinical outcome in patients with hyperuricemia. REGISTRATION NUMBER: PROSPERO(CRD42018091657).


Assuntos
Alopurinol/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Febuxostat/uso terapêutico , Supressores da Gota/uso terapêutico , Gota/tratamento farmacológico , Hiperuricemia/tratamento farmacológico , Ácido Úrico/sangue , Idoso , Alopurinol/efeitos adversos , Doenças Assintomáticas , Biomarcadores/sangue , Inibidores Enzimáticos/efeitos adversos , Febuxostat/efeitos adversos , Feminino , Gota/sangue , Gota/enzimologia , Gota/mortalidade , Supressores da Gota/efeitos adversos , Humanos , Hiperuricemia/sangue , Hiperuricemia/enzimologia , Hiperuricemia/mortalidade , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Xantina Oxidase/antagonistas & inibidores
9.
Med Hypotheses ; 131: 109314, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31443750

RESUMO

Metabolic targeting of liver 5-aminolevulinate synthase (5-ALAS) by inhibition of heme utilisation by tryptophan (Trp) 2,3-dioxygenase (TDO) or the use of tryptophan is proposed as a therapy of acute hepatic porphyrias. 5-ALAS, the rate-limiting enzyme of heme biosynthesis, is under negative feedback control by a small regulatory heme pool in the hepatic cytosol. Acute porphyric attacks, precipitated by fasting, certain hormones and some drugs, involve induction of 5-ALAS secondarily to depletion of the above pool, and the resultant elevation of 5-ALA levels initiates the abdominal and neurological symptoms of attacks. By utilising the regulatory heme, cytosolic TDO undermines the feedback control, thus allowing 5-ALAS induction to occur, e.g. upon glucocorticoid induction of TDO during fasting (starvation) and exogenous glucocorticoid administration. Currently, glucose therapy is the preferred strategy for reversing moderate attacks induced by fasting (calorie restriction), with more severe attacks being treated by intravenous heme preparations. Reversal of fasting-induced attacks by glucose is explained by the previously demonstrated reversal of increased heme utilisation by TDO. Inhibitors of this utilisation are therefore potential therapeutic targets in acute attacks and also for maintenance of a symptomless state. Existing TDO inhibitors other than glucose include allopurinol, nicotinamide and recently developed potent inhibitors such as LM10 used in cancer therapy. Based on studies in rats, the hypothesis predicts that the safety or otherwise of drugs in the hepatic porphyrias is determined by their ability to inhibit TDO utilisation of heme under basal conditions or after glucocorticoid induction or heme activation of TDO, in parallel with reciprocal changes in 5-ALAS induction. Tryptophan is also proposed as a potential therapy of acute attacks either alone or as an adjunct to the recently proposed 5-ALAS1 gene silencing. Trp increases heme biosynthesis by enhancing 5-ALA dehydratase activity and, based on a Trp-5-ALA model presented herein, Trp offers several advantages over heme therapy, namely rapid conversion of 5-ALA into heme, a greatly enhanced heme availability, a near complete inhibition of 5-ALAS induction, assumed rapid clearance of 5-ALA and hence accelerated resolution of symptoms of attacks, and finally provision of the neuroprotective metabolite kynurenic acid to neutralise the neurological symptoms. The hypothesis also addresses heme regulation in species lacking the TDO free apoenzyme and its glucocorticoid induction mechanism and proposes detailed assessment of heme biosynthesis in these species. Detailed proposals for testing the hypothesis are presented.


Assuntos
5-Aminolevulinato Sintetase/antagonistas & inibidores , Inibidores Enzimáticos/uso terapêutico , Heme/metabolismo , Terapia de Alvo Molecular , Porfirias Hepáticas/tratamento farmacológico , Triptofano Oxigenase/antagonistas & inibidores , Triptofano/uso terapêutico , 5-Aminolevulinato Sintetase/genética , Alopurinol/farmacologia , Alopurinol/uso terapêutico , Animais , Indução Enzimática/efeitos dos fármacos , Jejum/metabolismo , Retroalimentação Fisiológica , Inativação Gênica , Glucose/metabolismo , Glucose/uso terapêutico , Cobaias , Heme/uso terapêutico , Humanos , Cinurenina/metabolismo , Fígado/efeitos dos fármacos , Fígado/enzimologia , Modelos Biológicos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/fisiologia , Porfirias Hepáticas/induzido quimicamente , Porfirias Hepáticas/genética , Porfirias Hepáticas/metabolismo , Roedores , Especificidade da Espécie , Triptofano/efeitos adversos , Triptofano/farmacologia
10.
Hereditas ; 156: 26, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31367212

RESUMO

Background: One common ATP-binding cassette subfamily G member 2 (ABCG2) gene variant, which is encoded by the single nucleotide polymorphism (SNP) rs2231142, was identified to take an essential part in gouty arthritis. However, the relationship between rs2231142, gout comorbidities and therapeutic effect of allopurinol in Chinese Han male population is still unclear. Wherefore, this study explored into the association between ABCG2 SNP rs2231142 affecting common comorbidities and the therapeutic effect of allopurinol in Chinese Han male gout patients. Results: ABCG2 SNP rs2231142 and the gout comorbidities including nephrolithiasis and CKD were associated (P = 0.014 and P = 0.026). Group CKD stage = 1 were significantly different from those in group CKD stage≥2 regarding genotypes of ABCG2 gene polymorphism, while they were not significantly different from those in group CKD stage≥3. Meanwhile, the genotypes of rs2231142 and allopurinol response were not significantly associated (P = 0.588). Conclusions: ABCG2 rs2231142 may predict the risk of kidney comorbidities for Chinese Han male gout patients, but not allopurinol response.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Alelos , Predisposição Genética para Doença , Gota/genética , Proteínas de Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Alopurinol/uso terapêutico , Grupo com Ancestrais do Continente Asiático/genética , China , Comorbidade , Genótipo , Gota/tratamento farmacológico , Gota/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade
11.
Transplant Proc ; 51(6): 1816-1821, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31256872

RESUMO

PURPOSE: This retrospective analysis of medical chart data was performed to compare severity and treatment of gout in patients with or without a history of kidney transplantation (KT). METHODS: Via an online survey, a panel of board-certified US nephrologists (N = 104) provided the following deidentified chart data for their 3 most recent patients with gout: age, sex, serum uric acid, numbers of swollen or tender joints, visible tophi, gout flare events (prior 12 months), gout drug treatment history, and KT history. The presence of "severe, uncontrolled gout" was defined as: serum uric acid ≥ 7.0 mg/dL, ≥1 tophi and ≥2 flares in the last 12 months, and history of xanthine oxidase inhibitor treatment. RESULTS: Twenty-five out of 312 (8.0%) gout patients had a history of KT. Univariate analysis found that patients with gout and history of kidney transplants had: greater prevalence of severe uncontrolled gout (27% vs 8%, P = .007) and tophi (36% vs 17%, P = .030), and higher rates of failure or physician perceived contraindication to allopurinol (44% vs 23%, P = .028). CONCLUSION: This study provides preliminary evidence that gout in patients with history of KT is more severe and poses greater challenges to pharmacologic management. Although gout has been linked to worse outcomes among kidney recipients in the literature, there are presently no publications on gout severity among patients with KT in comparison to other patients with gout. Further investigation of disease severity and appropriate, effective treatment options in recipients of kidney transplant with a diagnosis of gout, especially prior to the transplant, is warranted.


Assuntos
Gota/sangue , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/sangue , Índice de Gravidade de Doença , Idoso , Alopurinol/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Feminino , Gota/tratamento farmacológico , Gota/epidemiologia , Supressores da Gota/uso terapêutico , Humanos , Rim , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/epidemiologia , Prevalência , Estudos Retrospectivos , Inquéritos e Questionários , Resultado do Tratamento , Ácido Úrico/sangue
12.
Mayo Clin Proc ; 94(7): 1147-1157, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31272565

RESUMO

OBJECTIVE: To determine and compare the risk of cardiovascular events and mortality of febuxostat and allopurinol use. PATIENTS AND METHODS: We conducted a cohort study using the Taiwan National Health Insurance Research Database. New users of febuxostat and allopurinol between April 1, 2012 and December 31, 2015 were identified, and the two groups were 1:1 matched by propensity score, benzbromarone use history, renal impairment, and time of drug initiation. The risk of major adverse cardiovascular events (MACEs), venous thromboembolism (VTE), heart failure (HF) hospitalization, atrial fibrillation hospitalization, cardiovascular (CV) death, and all-cause mortality was assessed using Cox proportional hazards models. The dose-response relationship between xanthine oxidase inhibitor use and adverse CV outcomes were also determined. RESULTS: A total of 44,111 patients were included for each group, and all baseline covariates were well matched. Febuxostat users were at a significantly higher risk for HF hospitalization (hazard ratio [HR], 1.22; 95% CI, 1.13-1.33), atrial fibrillation hospitalization (HR, 1.19; 95% CI, 1.05-1.36), and CV death (HR, 1.19; 95% CI, 1.03-1.36) than allopurinol users, whereas no difference was found for the major adverse cardiac events composite endpoint, venous thromboembolism, myocardial infarction, ischemic stroke, and all-cause mortality. The elevated risk of HF hospitalization was consistent throughout the primary and sensitivity analyses. In addition, febuxostat increased the risk of adverse CV outcomes in a dose-dependent manner. CONCLUSION: The use of febuxostat, compared with allopurinol, was associated with a significantly increased risk of adverse CV events. Higher febuxostat doses had a greater impact. Further studies are needed to investigate the mechanisms linking febuxostat to adverse CV outcomes.


Assuntos
Alopurinol/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Febuxostat/uso terapêutico , Supressores da Gota/uso terapêutico , Gota/tratamento farmacológico , Idoso , Alopurinol/efeitos adversos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Bases de Dados Factuais , Febuxostat/efeitos adversos , Feminino , Gota/mortalidade , Hospitalização , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia
13.
Int J Rheum Dis ; 22(8): 1445-1451, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31317680

RESUMO

AIM: To investigate the effects on hypercholesterolemia and hypertriglyceridemia in gouty patients receiving uric acid-lowering therapy (UALT). METHODS: A retrospective study was performed from January 2015 to December 2017 in gouty patients receiving UALT. A total of 124 gouty patients with hypercholesterolemia or hypertriglyceridemia who were administered UALT were monitored. Of the 124 patients with gout, 52 were treated with febuxostat, 29 were treated with allopurinol, and 43 were treated with benzbromarone. Cholesterol and triglyceride levels were recorded and analyzed following treatment for 8-10 weeks. RESULTS: We compared the efficacy of febuxostat, allopurinol, and benzbromarone. All therapies mildly influenced serum cholesterol and triglyceride levels. Febuxostat significantly decreased cholesterol and triglyceride levels in patients who did not receive lipid-lowering therapy. Allopurinol and benzbromarone modestly decreased triglyceride levels, but cholesterol levels were unaffected. CONCLUSION: Uric acid-lowering therapy benefits hyperlipidemia in gouty patients. Febuxostat effectively improved serum cholesterol and triglyceride levels compared to allopurinol and benzbromarone in patients with gout.


Assuntos
Colesterol/sangue , Supressores da Gota/uso terapêutico , Gota/tratamento farmacológico , Hipercolesterolemia/sangue , Hipertrigliceridemia/sangue , Triglicerídeos/sangue , Ácido Úrico/sangue , Adulto , Alopurinol/uso terapêutico , Benzobromarona/uso terapêutico , Biomarcadores/sangue , Febuxostat/uso terapêutico , Feminino , Gota/sangue , Gota/diagnóstico , Humanos , Hipercolesterolemia/diagnóstico , Hipertrigliceridemia/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Uricosúricos/uso terapêutico
14.
Medicine (Baltimore) ; 98(25): e16078, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31232948

RESUMO

RATIONALE: Toxic epidermal necrolysis (TEN) is a life-threatening, immunologically mediated, and usually drug-induced disease. Rarely, clinical pharmacists participating in finding the etiology have been reported. PATIENTS CONCERNS: A 33-year-old male presented to the emergency department with a 1-day history of fever and rash. The patient, being newly diagnosed with gout 10 days ago, received allopurinol at a dose of 250 mg by mouth daily. After 10 days' exposure to allopurinol, the patient manifested with an "influenza-like" prodromal phase (fever of 38°C, throat pains), which was treated with amoxicillin and nonsteroidal anti-inflammatory drugs of the oxicam type. The next day, he developed a worsening fever of 39.5°C, accompanied by a pruriginous rash all over his body. DIAGNOSIS: On physical examination, we observed coalescing dusky red macules over >60% of his body surface area, with blisters and detachment of large sheets of necrolytic epidermis all over his chest and face. The diagnosis of TEN was confirmed. INTERVENTIONS: The patient recovered following treatment with short-term high-dose methylprednisolone sodium succinate, immunoglobulin therapy, topical medication, and supportive therapy. OUTCOMES: He showed a slow but progressive improvement both in symptoms and cutaneous manifestations. Reepithelization of the skin was achieved after 3 weeks. LESSONS: Drug-induced-TEN is potentially fatal. This case underlines the necessity of asking medication history in detail and detecting related drug gene to correctly identify the cause of TEN.


Assuntos
Alopurinol/toxicidade , Síndrome de Stevens-Johnson/etiologia , Adulto , Alopurinol/uso terapêutico , Serviço Hospitalar de Emergência/organização & administração , Supressores da Gota/uso terapêutico , Supressores da Gota/toxicidade , Humanos , Masculino
15.
Saudi J Kidney Dis Transpl ; 30(3): 723-725, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31249241

RESUMO

Adenine phosphoribosyltransferase deficiency is an inherited condition presenting from infancy to late adulthood. The common features are recurrent kidney and urinary tract stones and obstructive symptoms. The stones are characteristically radiolucent. 2, 8-Dihydroxyadenine (2, 8-DHA) formation is blocked by xanthine oxidase blocker allopurinol. Here, we report the case of an eight-month-old baby girl who presented with obstructive acute kidney injury secondary to calculi which was treated with surgical removal of stone. The analysis of the calculi revealed 2, 8-DHA crystals.


Assuntos
Lesão Renal Aguda/etiologia , Adenina Fosforribosiltransferase/deficiência , Adenina/análogos & derivados , Cálculos Renais/etiologia , Erros Inatos do Metabolismo/complicações , Urolitíase/complicações , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/cirurgia , Adenina/metabolismo , Alopurinol/uso terapêutico , Cristalização , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Lactente , Cálculos Renais/diagnóstico , Cálculos Renais/metabolismo , Cálculos Renais/cirurgia , Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo/tratamento farmacológico , Resultado do Tratamento , Urolitíase/diagnóstico , Urolitíase/tratamento farmacológico , Xantina Oxidase/antagonistas & inibidores , Xantina Oxidase/metabolismo
16.
Regul Toxicol Pharmacol ; 107: 104400, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31152858

RESUMO

Fipronil (FPN) can induce oxidative tissue damage and may be contemplated as an apoptosis inducer. Our aim is to investigate the possible hepatoprotective roles of garlic or allopurinol (ALP) against fipronil subacute toxicity. Thirty-six mature male albino rats were randomly divided into six groups; the first group was saved as control (C), the 2nd (G) was orally intubated with 500 mg/kg aqueous garlic extract, and the 3rd (A) received 150 mg/L allopurinol in their drinking water. The 4th group (F) was administered 13.277 mg/kg fipronil by gavage, while the 5th (G + F) and 6th (A + F) groups received the same doses of garlic and allopurinol, respectively two hours before fipronil intoxication. Our results revealed that FPN significantly increased the hepatic malondialdehyde, protein carbonyl levels, and the enzymatic activities of superoxide dismutase, catalase, glutathione peroxidase, and xanthine oxidase, but it decreased glutathione-S-transferase compared to the control group. Moreover, FPN exhibited significant up-regulation in the hepatic pro-apoptotic (Bax) and caspase-3 genes expression, down-regulation in the anti-apoptotic (Bcl-2) mRNA gene expression and induced DNA fragmentation. Surprisingly, garlic or allopurinol co-treatment ameliorated the hepatic lipid peroxidation, antioxidants disruption, and apoptosis induced by FPN. In conclusion, garlic and allopurinol relieved the oxidative injury and reduced the fipronil-induced apoptosis probably by improving the tissue antioxidant defense system.


Assuntos
Alopurinol/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Alho , Inseticidas/toxicidade , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/uso terapêutico , Pirazóis/toxicidade , Alopurinol/farmacologia , Animais , Apoptose/efeitos dos fármacos , Caspase 3/genética , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Glutationa/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Malondialdeído/metabolismo , Oxirredutases/metabolismo , Extratos Vegetais/farmacologia , Raízes de Plantas , Substâncias Protetoras/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Ratos
17.
J Vet Cardiol ; 23: 32-37, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31174727

RESUMO

A 4-year-old crossbreed dog presented with a two-day history of lethargy and abdominal effusion. Physical examination and echocardiography revealed pericardial effusion with cardiac tamponade. Pericardiocentesis was performed. Intracytoplasmic Leishmania amastigotes were found on cytological examination of the pericardial fluid. The animal was treated with N-methylglucamine antimoniate and allopurinol. After an initial favorable response, cardiac tamponade reoccurred one month later. The dog died during a pericardiectomy four months after the initial diagnosis. Histology confirmed the presence of chronic pericarditis. The presence of Leishmania amastigotes on cytological examination of pericardial effusion suggests a possible association between canine leishmaniasis and chronic pericarditis. This finding also supports the importance of cytological examination of pericardial fluid in areas endemic for canine leishmaniasis.


Assuntos
Doenças do Cão/parasitologia , Leishmaniose/veterinária , Derrame Pericárdico/veterinária , Alopurinol/uso terapêutico , Animais , Antiprotozoários/uso terapêutico , Tamponamento Cardíaco/veterinária , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/fisiopatologia , Cães , Ecocardiografia/veterinária , Leishmania/isolamento & purificação , Leishmaniose/complicações , Leishmaniose/tratamento farmacológico , Antimoniato de Meglumina/uso terapêutico , Derrame Pericárdico/diagnóstico por imagem , Derrame Pericárdico/parasitologia , Líquido Pericárdico/parasitologia
18.
Parasitol Int ; 72: 101934, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31129197

RESUMO

This report describes the first case of visceral leishmaniasis (VL) resistant to pentavalent antimonials and also the first use of combinational therapy in Iran. The patient was a two-year old boy, from a non-endemic area for leishmaniasis in northern Iran, presenting with pentavalent antimonial resistant VL. Additional treatment with conventional and liposomal amphotericin B was not effective. A complete cure was achieved following a three week treatment with liposomal amphotericin B (5 mg/kg/day for 5 days, then on the 14th and 21st days), allopurinol (25 mg/day for 5 days, then on the 14th and 21st days) and interferon gamma (50 µg/m2 subcutaneously three times weekly). Our results suggest a need for further studies to identify resistant Leishmania species and their susceptibility to different treatment regimens.


Assuntos
Alopurinol/uso terapêutico , Anfotericina B/uso terapêutico , Antiprotozoários/uso terapêutico , Interferon gama/uso terapêutico , Leishmaniose Visceral/tratamento farmacológico , Anfotericina B/administração & dosagem , Antiprotozoários/administração & dosagem , Pré-Escolar , Resistência a Múltiplos Medicamentos , Quimioterapia Combinada , Humanos , Interferon gama/administração & dosagem , Irã (Geográfico) , Leishmaniose Visceral/diagnóstico , Resultado do Tratamento
20.
Clin Perinatol ; 46(2): 311-325, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31010562

RESUMO

Neonatal brain injury (NBI) remains a major contributor to neonatal mortality and long-term neurodevelopmental morbidity. Although therapeutic hypothermia is the only proven treatment to minimize brain injury caused by neonatal encephalopathy in term neonates, it provides incomplete neuroprotection. There are no specific drugs yet proven to prevent NBI in preterm neonates. This review discusses the scientific and emerging clinical trial data for several neuroprotective drugs in development, examining potential efficacy and safety concerns. Drugs with the highest likelihood of success and closest to clinical application include erythropoietin for term and preterm neonates and antenatal magnesium for preterm neonates.


Assuntos
Hemorragia Cerebral Intraventricular/prevenção & controle , Hipóxia-Isquemia Encefálica/prevenção & controle , Leucomalácia Periventricular/prevenção & controle , Neuroproteção , Corticosteroides/uso terapêutico , Alopurinol/uso terapêutico , Anestésicos Inalatórios/uso terapêutico , Anticonvulsivantes/uso terapêutico , Antioxidantes/uso terapêutico , Hemorragia Cerebral Intraventricular/tratamento farmacológico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Darbepoetina alfa/uso terapêutico , Eritropoetina/uso terapêutico , Depuradores de Radicais Livres/uso terapêutico , Hematínicos/uso terapêutico , Humanos , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Indometacina/uso terapêutico , Recém-Nascido , Leucomalácia Periventricular/tratamento farmacológico , Magnésio/uso terapêutico , Melatonina/uso terapêutico , Cuidado Pré-Natal , Topiramato/uso terapêutico , Xenônio/uso terapêutico
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