-
The Israel Medical Association Journal... Oct 2005Hyperuricemia is present in approximately 5% of the population, the vast majority of whom are asymptomatic and at no clinical risk. Complications, including renal... (Review)
Review
Hyperuricemia is present in approximately 5% of the population, the vast majority of whom are asymptomatic and at no clinical risk. Complications, including renal calculi, uric acid nephropathy and gout, occur in a small proportion of patients. Allopurinol, an analog of hypoxanthine, has been widely used in clinical practice for over 30 years for the treatment of hyperuricemia and gout. Two percent of patients taking this medication develop a mild exanthema. A syndrome characterized by exfoliative dermatitis, hepatitis, interstitial nephritis and eosinophilia has been described previously. Termed allopurinol hypersensitivity syndrome, its etiology is related to the accumulation of one of the allopurinol metabolites, oxypurinol; clearance of oxypurinol is decreased in the setting of renal insufficiency and the use of thiazide diuretics. The term DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms) was recently introduced to describe a disorder associated with various drugs or viral infections and characterized by similar features. The pathophysiology of allopurinol-induced hypersensitivity, clinical presentation and treatment are reviewed.
Topics: Allopurinol; Drug Hypersensitivity; Gout; Gout Suppressants; Humans
PubMed: 16259349
DOI: No ID Found -
Rheumatology (Oxford, England) Jan 2018Allopurinol hypersensitivity syndrome (AHS) is a severe and sometimes life-threatening adverse drug reaction. Although AHS is rare, the number of patients with gout... (Review)
Review
Allopurinol hypersensitivity syndrome (AHS) is a severe and sometimes life-threatening adverse drug reaction. Although AHS is rare, the number of patients with gout requiring allopurinol is high, and there are sufficient overall cases of AHS to warrant consideration of preventive measures. Most cases occur within 8-9 weeks of commencing allopurinol, and good patient education at initiation may lead to rapid drug cessation at onset of symptoms. Pretreatment testing for HLA-B*5801 and avoidance of allopurinol when positive reduces the risk of AHS and is cost-effective in some ethnic groups. A low starting allopurinol dose may reduce AHS risk, but the relationship between maintenance dose and AHS is more controversial. Chronic kidney disease increases AHS risk, but slowly increasing the allopurinol dose in chronic kidney disease has not been associated with AHS. Alternative newer treatments are available for patients at risk of AHS, but similar adverse reactions can also occur with these.
Topics: Allopurinol; Dose-Response Relationship, Drug; Drug Hypersensitivity; Gout; Gout Suppressants; Humans
PubMed: 29272508
DOI: 10.1093/rheumatology/kex422 -
Efficacy of Allopurinol in Improving Endothelial Dysfunction: A Systematic Review and Meta-Analysis.High Blood Pressure & Cardiovascular... Nov 2023Endothelial dysfunction has been implicated in various cardiovascular disorders as the initial pathology. Allopurinol has been shown to improve endothelial dysfunction... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Endothelial dysfunction has been implicated in various cardiovascular disorders as the initial pathology. Allopurinol has been shown to improve endothelial dysfunction in patients with gout, but its effect on cardiovascular patients is unclear.
AIMS
We aim to assess allopurinol efficacy in improving endothelial dysfunction overall and in different disease states including but not limited to heart failure, chronic kidney disease, ischemic heart disease METHODS: We conducted a literature search of PubMed, Cochrane's Central Library, and Scopus until December 2022, including randomized controlled trials and double-arm observational studies. The primary outcome measure was endothelial function assessed by change in flow mediated dilation (FMD) RESULTS: Our meta-analysis included 22 studies with a total of 1472 patients. Our pooled analysis shows that allopurinol significantly improved FMD (WMD = 1.46%, 95% CI [0.70, 2.22], p < 0.01) compared to control. However, there was no significant difference between allopurinol and control for endothelial-independent vasodilation measured by forearm blood flow (WMD = 0.10%, 95% CI [- 0.89, 0.69], p = 0.80). Subgroup analysis indicated that the effect of allopurinol on FMD was more significant in diabetic and congestive heart failure patients.
CONCLUSION
While allopurinol may improve endothelial function in various patient populations, further high-quality randomized controlled trials are needed to determine its efficacy in preventing cardiovascular disease exacerbation.
Topics: Humans; Allopurinol; Endothelium, Vascular; Vascular Diseases; Vasodilation; Cardiovascular Diseases
PubMed: 38070035
DOI: 10.1007/s40292-023-00615-z -
Joint Bone Spine Jan 2016Allopurinol is the most commonly used urate lowering therapy in the management of gout. Despite the fact that it has been available for over 40 years there is ongoing... (Review)
Review
Allopurinol is the most commonly used urate lowering therapy in the management of gout. Despite the fact that it has been available for over 40 years there is ongoing debate about optimal allopurinol dosing in gout patients with chronic kidney disease. Given that gout is common in patients with renal impairment, clinicians need to be aware of the relationships between serum urate and kidney function as well as the effects of allopurinol on kidney function and vice versa. The use of allopurinol in patients on dialysis is an understudied area. Dialysis reduces plasma oxypurinol concentrations, therefore the dose and time of administration in relationship to dialysis need to be carefully considered. Recently, it has been suggested that there may be a role for allopurinol in patients with chronic kidney disease without gout. Observational studies have reported an association between serum urate and chronic kidney disease and end stage renal failure. The effect of urate lowering therapy with allopurinol on progression of kidney disease has been examined in small studies with varying results. Larger clinical trials are currently underway. This review will examine the relationships between allopurinol and kidney function in adults with and without renal disease and address allopurinol dosing in gout patients with impaired kidney function.
Topics: Allopurinol; Creatinine; Dose-Response Relationship, Drug; Glomerular Filtration Rate; Gout; Gout Suppressants; Humans; Kidney; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 26453097
DOI: 10.1016/j.jbspin.2015.03.013 -
The Cochrane Database of Systematic... 2000To determine the effects of allopurinol in the treatment of chronic prostatitis (Review)
Review
OBJECTIVES
To determine the effects of allopurinol in the treatment of chronic prostatitis
SEARCH STRATEGY
Trials were searched in computerized general and specialized databases (MEDLINE, Cochrane Library, Cochrane Prostate Group database), bibliographies of obtained articles, and direct contact with authors.
SELECTION CRITERIA
All randomized trials of allopurinol versus placebo used to treat patients with chronic prostatitis. Acute prostatitis, bacterial prostatitis, and asymptomatic prostatitis were excluded. The main outcome measure was the change in patient-reported discomfort.
DATA COLLECTION AND ANALYSIS
The reviewers extracted the data independently for the outcomes of change in patient-reported discomfort, investigator graded prostate pain, leukocyte counts, and biochemical indices.
MAIN RESULTS
Only one trial with 54 men lasting 240 days (with 330 days of follow-up) met study inclusion criteria. There was a statistically significant change favoring allopurinol in patient-reported discomfort between the study and control groups at follow-up. Between days 45-225, the mean score was -0.95 (s.d. 0.19) for the allopurinol group (7 men), compared with -0.47 (s.d. 0.21) for the placebo group (7 men). The weighted mean difference (WMD) was -0.48 (95%CI -0.690, -0.270). The mean score between days 45-135 was -1.08 (s.d. 1.29) for the 25 men in the allopurinol group, compared with -0.21 (sd 0.97) for the 14 men in the control group. The WMD was -0.87 (95%CI -1.587, -0.153). The allopurinol group had significantly less investigator graded prostate pain and had lower levels of serum urate, urine urate, and expressed prostatic secretion urate and xanthine. No significant differences between the two groups regarding leukocyte counts were found. No patient receiving allopurinol had any significant side effects. Three patients in the placebo group dropped out because of side effects.
REVIEWER'S CONCLUSIONS
One small trial of allopurinol for treating chronic prostatitis showed improvements in patient-reported symptom improvement, investigator-graded prostate pain, and biochemical parameters. However, the data provided, the measures used, and the statistics presented do not make these findings convincing that changes in urine and prostatic secretion composition regarding purine and pyrimidine bases resulted in the relief of symptoms. Further studies of allopurinol treatment using standardized and validated outcomes measures and analyses are necessary to determine whether allopurinol is effective.
Topics: Allopurinol; Antimetabolites; Chronic Disease; Humans; Male; Prostatitis
PubMed: 10796738
DOI: 10.1002/14651858.CD001041 -
Cardiology in Review 2011Cardiovascular disease (CVD) remains the leading cause of death in the United States. There is evidence that shows a direct relationship between an elevated uric acid... (Review)
Review
Cardiovascular disease (CVD) remains the leading cause of death in the United States. There is evidence that shows a direct relationship between an elevated uric acid level and an increased risk of cardiovascular (CV) events, which has set the foundation for the investigation of uric acid-lowering drugs for the treatment of CVD. Although traditionally the cornerstone therapy for gout, allopurinol's ability to be a competitive inhibitor of the key enzyme, xanthine oxidase, needed for uric acid formation, has prompted recent clinical research evaluating allopurinol as a CV drug. Epidemiologic and biochemical studies on uric acid formation have shown that it is not only uric acid itself that leads to worsening prognosis and increased CV events, but also the free radicals and superoxides formed during xanthine oxidase activity. The combination of uric acid formation and formed free radicals could ultimately lead to coronary endothelial dysfunction and worsening of myocardial oxidative stress. Along with preventing uric acid formation, allopurinol also has the ability to behave as a free radical scavenger of the superoxide anions and free radicals released during uric acid formation.Clinical studies have shown that allopurinol improves endothelial dysfunction and subsequently improves the exercise capacity in patients diagnosed with angina pectoris. Allopurinol has also been shown to decrease oxidative stress and ameliorate the morbidity and mortality of congestive heart failure patients by possibly improving mechanoenergetic uncoupling, with the enhancement of myocardial contractility and the left ventricular ejection fraction. This review presents the pharmacologic action of allopurinol on the CV system and describes the effectiveness of allopurinol as a potential drug to treat 2 CVD morbidities: ischemic heart disease and congestive heart failure.
Topics: Allopurinol; Cardiovascular Diseases; Free Radical Scavengers; Humans; Uric Acid; Xanthine Oxidase
PubMed: 21983313
DOI: 10.1097/CRD.0b013e318229a908 -
Transplant Immunology Dec 2022
Topics: Humans; Allopurinol; Kidney Transplantation; Kidney
PubMed: 36049719
DOI: 10.1016/j.trim.2022.101700 -
British Medical Journal Feb 1967
Topics: Allopurinol; Animals; Enzyme Therapy; Gout; Humans
PubMed: 6017531
DOI: No ID Found -
Hormones (Athens, Greece) Dec 2022Cardiovascular disease (CVD) remains the main cause of death in patients with type 2 diabetes (T2D). Although hyperuricemia has been associated with multiple CV... (Review)
Review
BACKGROUND
Cardiovascular disease (CVD) remains the main cause of death in patients with type 2 diabetes (T2D). Although hyperuricemia has been associated with multiple CV complications, it is not officially recognized as a target parameter for CVD risk reduction.
AIM
To systematically review the literature in order to determine whether treating hyperuricemia with allopurinol in patients with T2D reduces CVD risk.
METHODS
A thorough literature search in the PubMed, CENTRAL, and EMBASE databases from inception to August 2022 was performed. After application of selection criteria, 6 appropriate studies were identified.
RESULTS
Detailed analysis of the data derived indicated that there is an association between allopurinol treatment and CV benefits, resulting in a reduced risk of CVD events and mortality rates. This association can be attributed mainly to the reduction of inflammation and oxidative burden, as well as to the improvement of glycemic and lipid profiles.
CONCLUSIONS
This systematic review provides evidence that allopurinol may reduce CVD risk in patients with T2D. Randomized, placebo-controlled trials should be performed in order to confirm these findings and identify specific subgroups of patients who will benefit most.
Topics: Humans; Allopurinol; Diabetes Mellitus, Type 2; Hyperuricemia; Cardiovascular Diseases; Blood Glucose
PubMed: 36197637
DOI: 10.1007/s42000-022-00403-9 -
Clinical Pharmacology and Therapeutics May 1978A spectrophotometric assay for measuring allopurinol and oxipurinol has been developed which can detect as little as 5 X 10(-8) M of each in serum and urine. With this...
A spectrophotometric assay for measuring allopurinol and oxipurinol has been developed which can detect as little as 5 X 10(-8) M of each in serum and urine. With this assay, serum disappearance characteristics of intravenous and orally administered allopurinol have been investigated in man. Serum concentrations of both allopurinol and oxipurinol reach levels above 1 X 10(-5) M within minutes of intravenous administration and within 1 or 2 hr of oral administration of 300 mg allopurinol. Patients receiving 300 mg allopurinol daily show a mean serum concentration of 3 X 10(-5) M oxipurinol (range, 0.9 to 9 X 10(-5) M). Serum half-lives of allopurinol and oxipurinol were 39 +/- 11 min and 13.6 +/- 2.8 hr, respectively. Estimates of renal clearance were 13.6 and 18.9 ml/min for allopurinol and 23.2 and 30.6 ml/min for oxipurinol in 2 patients studied. The metabolic conversion of allopurinol to oxipurinol in man does not appear to be altered by long-term therapy with allopurinol, which suggests that this conversion takes place by way of an enzymatic reaction not strongly inhibited by either substrate or product. These results suggest the possibility of a nonxanthine oxidase enzymatic pathway for this conversion.
Topics: Administration, Oral; Allopurinol; Humans; Infusions, Parenteral; Kidney; Kinetics; Lymphoma; Oxypurinol; Time Factors
PubMed: 639435
DOI: 10.1002/cpt1978235598