Extensión de tiempo QT
Efectos adversos de las drogas
|Fosfatasa alcalina elevada|
Variantes ✨Para la evaluación computacionalmente intensiva de las variantes, elija la suscripción estándar paga.
Áreas de aplicación
El alopurinol se usa para prevenir y tratar los niveles altos de ácido úrico y sus depósitos (uratos) y para tratar los ataques agudos de gota. El ácido úrico se produce mediante la descomposición de las purinas de los alimentos, que se encuentran en la carne, los embutidos, el pescado, los guisantes y las lentejas, por ejemplo. Un nivel elevado de ácido úrico puede ser problemático porque si la concentración es demasiado alta, el ácido úrico se cristaliza y, debido a su forma de aguja, puede provocar deformaciones (nódulos de gota) e inflamaciones muy dolorosas en las articulaciones o desarrollar cálculos renales. El alopurinol inhibe la enzima xantina oxidasa y por tanto inhibe la formación de ácido úrico. Además, promueve la eliminación de los depósitos de ácido úrico de la piel, huesos, articulaciones y riñones. Es esencial una cantidad suficiente de líquidos. El alopurinol se ha utilizado desde la década de 1960.
Dado que solo se introdujo alopurinol sin otras sustancias, no se pueden detectar interacciones farmacocinéticas.
Los parámetros farmacocinéticos de la población media se utilizan como punto de partida para calcular los cambios individuales en la exposición debidos a las interacciones.
La alopurinol tiene una biodisponibilidad oral media [ F ] del 79%, por lo que los niveles plasmáticos máximos [Cmax] tienden a cambiar con una interacción. La vida media terminal [ t12 ] es bastante corta a las 1.5 horas y se alcanzan rápidamente niveles plasmáticos constantes [ Css ]. La unión a proteínas [ Pb ] es muy débil al 0% y el volumen de distribución [ Vd ] es muy grande a 112 litros. El metabolismo no tiene lugar a través de los citocromos comunes..
|Efectos serotoninérgicos a||0||Ø|
Clasificación: Según nuestro conocimiento, la alopurinol no aumenta la actividad serotoninérgica.
Clasificación: Según nuestros hallazgos, la alopurinol no aumenta la actividad anticolinérgica.
Extensión de tiempo QT
No conocemos ningún potencial de prolongación del intervalo QT para la alopurinol.
Efectos secundarios generales
|Efectos secundarios||∑ frecuencia||alo|
|Fosfatasa alcalina elevada||1.0 %||+|
|Síndrome de Stevens-Johnson||0.9 %||0.9|
|Necrolisis epidérmica toxica||0.9 %||0.9|
|Insuficiencia hepática||0.9 %||0.9|
|Anemia aplásica||0.0 %||0.0|
Reacción de hipersensibilidad: alopurinol
Insuficiencia renal: alopurinol
Con base en sus
Referencias de literatura
Abstract: Allopurinol is the mainstay of urate-lowering therapy for patients with gout and impaired renal function. Although rare, a life-threatening hypersensitivity syndrome may occur with this drug. The risk of this allopurinol hypersensitivity syndrome (AHS) is increased in renal impairment. The recognition that AHS may be because of delayed-type hypersensitivity to oxypurinol, the main metabolite of allopurinol, and that oxypurinol concentrations are frequently elevated in patients with renal impairment prescribed standard doses of allopurinol has led to the widespread adoption of allopurinol-dosing guidelines. These guidelines advocate allopurinol dose reduction according to creatinine clearance in patients with renal impairment. However, recent studies have challenged the role of these guidelines, suggesting that AHS may occur even at low doses of allopurinol, and that these guidelines lead to under-treatment of hyperuricemia, a key therapeutic target in gout. Based on current data, we advocate gradual introduction of allopurinol according to current treatment guidelines, with close monitoring of serum uric acid concentrations. In patients with severe disease and persistent hyperuricemia, allopurinol dose escalation above those recommended by the guidelines should be considered, with careful evaluation of the benefits and risks of therapy. Further work is needed to clarify the safety and efficacy of allopurinol dose escalation, particularly in patients with renal impairment.
Abstract: BACKGROUND: The term chronic kidney disease (CKD) is used to describe abnormal kidney function (or structure). People with CKD have an increased prevalence of cardiovascular disease (CVD). Evidence is emerging that allopurinol may have a role to play in slowing down the progression of CKD and reducing the risk of CVD. OBJECTIVES: This systematic review addresses the research question: does allopurinol reduce mortality, the progression of chronic kidney disease or cardiovascular risk in people with CKD? DATA SOURCES: The following databases were searched on 7 January 2013: MEDLINE (1946 to 7 January 2013), EMBASE (1974 to 28 December 2012), The Cochrane Library (Issue 1, 2013) and ClinicalTrials.gov. Bibliographies of retrieved citations were also examined and two manufacturers of allopurinol were approached for data. REVIEW METHODS: Two reviewers independently screened all titles and abstracts to identify potentially relevant studies for inclusion in the review. Full-text copies were assessed independently by two reviewers. Data were extracted and assessed for risk of bias by one reviewer and independently checked for accuracy by a second. Summary statistics were extracted for each outcome and, where possible, data were pooled. Meta-analysis was carried out using fixed-effects models. RESULTS: Efficacy evidence was derived solely from four randomised controlled trials (RCTs). Adverse event (AE) data were derived from the RCTs and 21 observational studies. Progression of CKD was measured by estimated glomerular filtration rate (eGFR) in three trials and by changes in serum creatinine in the other. No significant differences in eGFR over time were reported. The only significant difference between groups was reported in one trial at 24 months favouring allopurinol [eGFR: 42.2 ml/minute/1.73 m(2), standard deviation (SD) 13.2 vs. 35.9 ml/minute/1.73 m(2), SD 12.3 ml/minute/1.73 m(2); p < 0.001]. In this same trial, there were twice as many cardiovascular events in the control arm (27%) as in the allopurinol arm (12%). Another trial reported an improvement in CKD progression as measured by serum creatinine in the allopurinol arm. No significant differences were reported in blood pressure between treatment groups in the meta-analyses. The incidence of AEs was estimated to be around 9% from all studies. The incidence of severe cutaneous adverse reactions (SCARs), which typically occurred within the first 2 months after allopurinol commencement, was reported to be 2% in two studies. Evidence for whether or not AEs and SCARs were dose related was conflicting. Not all patients had CKD in these studies. LIMITATIONS: None of the included studies reported concealment of allocation, one of the greatest risks to study validity. Relatively few (< 115) patients were enrolled in any RCT. For studies reporting AEs, the main limitation is the heterogeneity across studies. No studies examining quality-of-life measures were identified. CONCLUSIONS: There is limited evidence that allopurinol reduces CKD progression or cardiovascular events. It appears that AEs and in particular serious adverse events attributable to allopurinol are rare. However, the exact incidence of AEs in patients with CKD is unknown. Direct evidence for the impact of allopurinol on quality of life is lacking. Given the uncertainties in the evidence base, additional RCT evidence comparing allopurinol with usual care is required, accompanied by supporting data from observational studies of patients with CKD and using allopurinol. STUDY REGISTRATION: The study is registered as PROSPERO CRD42013003642. FUNDING: The National Institute for Health Research Health Technology Assessment programme.
Abstract: Transporters in proximal renal tubules contribute to the disposition of numerous drugs. Furthermore, the molecular mechanisms of tubular secretion have been progressively elucidated during the past decades. Organic anions tend to be secreted by the transport proteins OAT1, OAT3 and OATP4C1 on the basolateral side of tubular cells, and multidrug resistance protein (MRP) 2, MRP4, OATP1A2 and breast cancer resistance protein (BCRP) on the apical side. Organic cations are secreted by organic cation transporter (OCT) 2 on the basolateral side, and multidrug and toxic compound extrusion (MATE) proteins MATE1, MATE2/2-K, P-glycoprotein, organic cation and carnitine transporter (OCTN) 1 and OCTN2 on the apical side. Significant drug-drug interactions (DDIs) may affect any of these transporters, altering the clearance and, consequently, the efficacy and/or toxicity of substrate drugs. Interactions at the level of basolateral transporters typically decrease the clearance of the victim drug, causing higher systemic exposure. Interactions at the apical level can also lower drug clearance, but may be associated with higher renal toxicity, due to intracellular accumulation. Whereas the importance of glomerular filtration in drug disposition is largely appreciated among clinicians, DDIs involving renal transporters are less well recognized. This review summarizes current knowledge on the roles, quantitative importance and clinical relevance of these transporters in drug therapy. It proposes an approach based on substrate-inhibitor associations for predicting potential tubular-based DDIs and preventing their adverse consequences. We provide a comprehensive list of known drug interactions with renally-expressed transporters. While many of these interactions have limited clinical consequences, some involving high-risk drugs (e.g. methotrexate) definitely deserve the attention of prescribers.