A case report of colchicine-induced myopathy in a patient with chronic kidney disease / 北京大学学报(医学版)

Colchicine plays an important role in the treatment of gout and some other diseases. Besides gastrointestinal symptoms, myopathy has been reported as a rare side effect of colchicine in some patients. We report a case of myopathy in a patient with chronic kidney disease caused by high-dose colchicine, and then review literature on colchicine-induced myopathy, so as to provide some experience for the clinical diagnosis, treatment and medication safety. A 51-year-old male patient with 10 years of gout and 5 years of chronic kidney disease history and irregular treatment was admitted to the hospital with complaint of recurrent left wrist arthralgia and emerging lower extremities myalgia after intake of 40-50 mg colchicine in total within 20 days. Laboratory examinations showed significantly increased creatine kinase (CK) and then colchicine-induced myopathy was diagnosed preliminarily. After withdrawl of colchicine and implementation of hydration, alkalization and intramuscular injection of compound betamethasone, the symptoms of arthralgia and myalgia were relieved within 3 days and CK decreased to normal range gradually. According to literature reports, colchicine related myopathy was mostly characterized by proximal myasthenia and myalgia, accompanied by elevated CK level, which usually occurred days to weeks after initial administration of colchicine at the usual dosage in patients with renal impairment or a change in the underlying disease state in those receiving long-term therapy, and the features might remit within three to four weeks after the drug was discontinued. Electromyography of proximal muscles showed myopathy marked by abnormal spontaneous activity and muscle pathology waa marked by accumulation of lysosomes and autophagic vacuoles. Chronic kidney disease, liver cirrhosis, higher colchicine dose and concomitant cytochrome P450 3A4 (CYP3A4) inhibitors were associated with increased risk of myo-pathy. Based on the similar efficacy and lower adverse reaction rate compared with larger dosage, small dose of colchicine was recommended by many important current guidelines and recommendations in the treatment of gout. In consideration of potential risks, colchicine should be used with caution in patients with kidney or liver impairment, and in those taking CYP3A4 or P-glycoprotein inhibitors. For those patients, the drug dose should be adjusted and the latent adverse reactions should be monitored carefully.

Benzbromarone in the treatment of gout

Abstract Background Benzbromarone is a uricosuric drug that has been used in the treatment of gout over the last 30 years. Due to its potent inhibition of the dominant apical (luminal) urate exchanger in the human proximal tubule URAT1, it reduces the urate reabsorption, diminishing serum urate levels and therefore preventing gout flares. Main body of the abstract Through several clinical trials, Benzbromarone has been proved effective and safe, inclusive in patients with chronic kidney disease and as combination therapy with allopurinol. Due to hepatotoxicity reports, it was withdrawn from the European market by the manufacturer, however many authors have questioned the product's withdrawal due to a lack of clinical evidence in order to support its hepatotoxicity. Benzbromarone is still available in several European countries, New Zealand, Brazil and several other countries. Despite the product's marketing over more than 20 years after the first hepatotoxicity reports, we have found only five reports in our literature search, and no prospective or retrospective study correlating hepatotoxicity with benzbromarone use. Short conclusion Benzbromarone is a safe and effective molecule for the treatment of gout. However, due to in vitro and in vivo data related to hepatotoxicity, it is prudent to prescribe it with some caution, especially for patients with an already known liver condition.

Critical revision of the medical treatment of gout in Brazil / Revisão crítica do tratamento medicamentoso da gota no Brasil

ABSTRACT Gout is considered the most common form of inflammatory arthritis in men over 40 years. The authors present a brief review of the current treatment of gout and discuss the existing pharmacological limitations in Brazil for the treatment of this disease. Although allopurinol is still the main drug administered for decreasing serum levels of uric acid in gout patients in this country, the authors also present data that show a great opportunity for the Brazilian drug market for the treatment of hyperuricemia and gout and especially for patients using private and public (SUS) health care systems.

RESUMO A gota é considerada a forma mais comum de artrite inflamatória em homens acima de 40 anos. Os autores apresentam uma breve revisão sobre o tratamento atual da gota e discutem as limitações farmacológicas existentes no Brasil para o tratamento dessa enfermidade. Apesar de o alopurinol ainda ser a principal medicação para a redução dos níveis de uricemia de pacientes com gota no país, os autores também apresentam dados que apontam para uma grande oportunidade para o mercado farmacológico brasileiro em relação ao tratamento da hiperuricemia e da artrite gotosa e especialmente para pacientes usuários de sistemas privados de saúde e do SUS (Sistema Único de Saúde).

Prevention of Comorbidity and Acute Attack of Gout by Uric Acid Lowering Therapy

The object of this study was to evaluate the effect of uric acid lowering therapy in reducing the new development of comorbidities and the frequency of acute attacks in gout patients. We retrospectively reviewed patients who were diagnosed to have gout with at least 3 yr of follow up. They were divided into 2 groups; 53 patients with mean serum uric acid level (sUA) or =6 mg/dL. Comorbidities of gout such as hypertension (HTN), type II diabetes mellitus (DM), chronic kidney disease, cardiovascular disease (CVD) and urolithiasis were compared in each group at baseline and at last follow-up visit. Frequency of acute gout attacks were also compared between the groups. During the mean follow up period of 7.6 yr, the yearly rate of acute attack and the new development of HTN, DM, CVD and urolithiasis was lower in the adequately treated group compared to the inadequately treated group. Tight control of uric acid decreases the incidence of acute gout attacks and comorbidities of gout such as HTN, DM, CVD and urolithiasis.

Four-Week Effects of Allopurinol and Febuxostat Treatments on Blood Pressure and Serum Creatinine Level in Gouty Men

The aim of this study was to observe the effects of uric acid lowering therapy (UALT), febuxostat and allopurinol, on blood pressure (BP) and serum creatinine level. Post-hoc data were derived from a phase-III, randomised, double-blind, 4-week trial of male gouty patients that compared the safety and efficacy of febuxostat and allopurinol in adults with gout. The subjects were randomly assigned to one of five groups, 35-37 in each group (febuxostat: 40, 80, 120 mg/d; allopurinol: 300 mg/d; control group: placebo). Blood pressure and serum creatinine level were measured at baseline and at weeks 2 and 4. Diastolic BP and creatinine level had decreased significantly in the UALT groups compared to the control group at week 4. Diastolic BP had decreased significantly in the allopurinol group and serum creatinine level had decreased significantly in the febuxostat groups at week 4. After adjusting for confounding variables, serum uric acid changes were found to be significantly correlated with changes in serum creatinine level but were not associated with changes in systolic or diastolic BP. UALT in gouty subjects significantly decreased diastolic BP and serum creatinine level. Changes in uric acid were significantly correlated with those in serum creatinine level, suggesting the feasibility of renal function improvement through UALT in gouty men.

Virtual screening analysis and in-vitro xanthine oxidase inhibitory activity of some commercially available flavonoids

Allopurinol, the xanthine oxidase inhibitor, is the only drug available for the treatment of gout. We examined the xanthine oxidase inhibitory activity of some commercially available flavonoids such asepigallocatechin, acacatechin, myricetin, naringenin, daidzein and glycitein by virtual screening and in-vitro studies. The interacting residues within the complex model and their contact types were identified. The virtual screening analysis were carried out using AutoDock 4.2 and in-vitro xanthine oxidase inhibitory activity was carried out using xanthine as the substrate. In addition, enzyme kinetics was performed using LineweaverBurkplot analysis. Allopurinol, a known xanthine oxidase inhibitor was used as the standard. The docking energy of glycitein was found to be -8.49 kcal/mol which was less than that of the standard [-4.47 kcal/mol]. All the selected flavonoids were found to exhibit lower binding energy [-8.08 to -6.03 kcal/mol] than allopurinol. The docking results confirm that flavonoids showed greater inhibition of xanthine oxidase due to their active binding sites and lesser binding energies compared to allopurinol. This may be attributed to the presence of benzopyran ring in the flavonoids. In the xanthine oxidase assay, IC[50] value of glycitein was found to be 12 +/- 0.86 micro g/mL, whereas that of allopurinol was 24 +/- 0.28 micro g/mL. All the remaining compounds exhibited IC[50] values ranging between 22 +/- 0.64 to 62 +/- 1.18 micro g/mL. In the enzyme kinetic studies, flavonoids showed competitive type of enzyme inhibition. It can be concluded that flavonoids could be a promising remedy for the treatment of gout and related inflammatory disorders. Further in-vivo studies are required to develop potential compounds with lesser side effects

Inmunopatogenia de la gota / Immunopathogenesis of gout

La gota es un tipo de artritis gatillada por la cristalización de ácido úrico dentro de las articulaciones. Múltiples factores están involucrados en su desarrollo, constituyendo actualmente la hiperuricemia una condición estrechamente relacionada con el síndrome metabólico. Los humanos carecen de una enzima que degrada el ácido úrico llamada uricasa, lo que les confiere niveles de urato más elevados que otras especies animales. Se cree que esto sería un mecanismo adaptativo que entrega protección contra diversas noxas, dadas sus propiedades antioxidantes. Los cristales de urato monosódico pueden directamente iniciar la cascada inflamatoria a través de la activación del complemento y de diversos tipos celulares. Esto genera a nivel intracelular una cascada de transducción de señales que activarán un complejo catalítico multiproteico llamado inflamasoma, el cual es clave en la activación de caspasas inflamatorias, con el consecuente clivaje proteolítico de la pro-ILl en ILl , que junto a otras citoquinas y mediadores tendrán un rol fundamental en la patogénesis de esta enfermedad. Avances en el conocimiento de esta patología han permitido identificar nuevos targets terapéuticos y desarrollar nuevas terapias que han mostrado resultados favorables en pacientes con fracaso a los tratamientos convencionales.

Gout is a type of arthritis triggered by the crystallization of uric acid in the joints. Multiple factors are involved in its development, hyperuricemia currently constitutes a condition which is closely related to the metabolic syndrome. Humans lack an enzyme that degrades uric acid called uricase, which gives us urate levels higher than other animal species. It is believed that this is an adaptive mechanism that confers protection against various noxa, given its antioxidant properties. Monosodium urate crystals can directly start the infiammatory cascade through the activation of the complement and of various cell types. This leads to a cascade of intracellular signal transduction that will activate a multiprotein catalytic complex called infiammasome, which is key in the activation of infiamatory caspases and the consequent proteolytic cleavaje of the pro-ILl in ILl, which together with other cytokines and mediators have a fundamental role in the pathogenesis of this disease. Advances in the understanding of this condition have allowed us to identify new therapeutic targets and develop new therapies that have shown favorable results in patients that do not respond to conventional treatments.

Consumo de medicamentos em adolescentes escolares: uma preocupação / Consumption of medicines among adolescent students: a concern

OBJETIVO: Estudar a prevalência de consumo de medicamentos em adolescentes escolares e correlacioná-la com tipo de escola (pública ou particular), série e turno de estudo, idade e sexo dos alunos, escolaridade dos pais e hábito de consumo familiar de medicamentos. MÉTODOS: Estudo transversal com amostra representativa da população de escolares do ensino médio de Porto Alegre - 1.281 alunos de 58 turmas, distribuídos em estratos proporcionais de escolas públicas e particulares. O questionário foi respondido, de forma individual e anônima, pelos alunos dentro da sala de aula, que informaram o consumo de medicamentos nos últimos 7 dias, especificando o fármaco utilizado. Foram realizados análise descritiva das variáveis, testes de associação linear e regressão logística múltipla. RESULTADOS: O uso de medicamentos ocorreu em 49,5 por cento da amostra. Os grandes grupos farmacológicos mais consumidos foram analgésicos/antiinflamatórios e antigotosos (32,5 por cento do consumo) e hormônios e análogos (12,1 por cento). Os analgésicos/antipiréticos/antiinflamatórios e os estrógenos/progestágenos foram, respectivamente, os mais utilizados nos grupos farmacológicos citados anteriormente. O ácido acetilsalicílico foi a substância analgésica mais consumida. Os alunos do sexo feminino (RC = 2,24), com 17 anos ou mais (RC = 1,41), com menor escolaridade materna (RC = 1,40) e cujos familiares tinham o hábito de consumir medicamentos (RC = 1,39) apresentaram risco aumentado para o consumo de medicamentos. CONCLUSÕES: Houve um elevado consumo de medicamentos entre adolescentes escolares, em especial entre as meninas e os alunos com mais idade. O hábito familiar de consumo e a baixa escolaridade materna também favorecem o uso de medicamentos.

Microcrystalline arthritis and acute gout; current therapy

Nonsteroidal anti-inflammatory drugs [NSAIDs] are currently the most fivored treatment of acute microcrystalline arthritis: acute gout, acute pyrophosphate arthritis [acute pseudogout], and acute calcific periarthritis. Although coichicine has been widely used for a long time with considerable efficacy, its therapeutic utility is limited by its narrow benefit-to-toxicity ratio. The management of acute microcrystalline events can be difficult in aged patients, and in those with medical illnesses contraindicating therapy with either NSATDs or colchicine. Intraarticular corticosteroid therapy is particularly useful for the treatment of acute mono- or oligo-articular microcrystalline synovitis in these patients. Oral prednisone and both parenteral corticotropin [ACTI-l] and corticosteroids [triamcinolone acetonide and methylprednisolone acetate] are useful alternate therapeutic modalities in those with acute polyarticular microcrystalline attacks. Although ACTH has demonstrated comparable clinical efficacy to corticosteroids, its use is limited by a number of factors: need for parenteral administration, difficulty delivering a precise dose, dependence of therapeutic effects on adrenocortical responsiveness, a relatively short duration of action and a higher incidence of hypertension and fluid overload

Effect of suranjan [colchicum luteum] in Niqris [Gout]

Niqris [gout] is a condition characterised by recurrent attacks of acute pain and swelling at first affecting only one joint, usually the metatarso-phalangeal joint of the big toe, later becoming polyarticular. Since ancient times it is believed that an excessive intake of baadi ghiza [food containing high purine contents] is the primary and essential cause of gout which results in deposition of Maddah-e-nigris [urates of tophi] in the articular and periarticular tissues. Although several potent and effective drugs like Allopurinol [Zyloric] and Sulphinpyrazone [Artiran] are available in modern medical treatment, they are not without side effects like gastritis, peptic ulcers, tolerance and dependence. Among several useful Unani drugs, Suranjan [Colchium luteum] is one which is claimed to be effective in this ailment. On an average the oral use of Suranjan Showed relief in symptoms in 94.3% of cases in 30 days without any side effect. Our study included 20 cases of chronic gout

Gota e hiperuricemia / Gout and hyperuricemia

La lesión articular por microcristales de urato monosódico es la artritis mas frecuente en el sexo masculino entre los 40 y 60 años. Su presentación clínica clásica esta precedida por un estado morbido de hiperuricemia que debe ser adecuadamente reconocido y manejado. Una vez la gota se presenta clínicamente el papel del médico consiste no solo en tratar el episodio agudo sino en realizar un enfoque diagnóstico y terapéutico acorde con los parámetros internacionales, buscando un control sintomático rápido y seguro. Esta revisiàn incluye conceptos sobre la etiopatogenia, presentación clínica, criterios de diagnóstico y las diferentes opciones terapéuticas disponibles hoy en dia.