Allopurinol
Allopurinol attenuates left ventricular remodeling and dysfunction after experimental myocardial infarction: a new action for an old drug?

Engberding N, Spiekermann S, Schaefer A, Heineke A, Wiencke A, Muller M, Fuchs M, Hilfiker-Kleiner D, Hornig B, Drexler H, Landmesser U.

Abteilung Kardiologie und Angiologie, Medizinische Hochschule Hannover, Hannover, Germany.

BACKGROUND: Accumulating evidence suggests a critical role for increased reactive oxygen species (ROS) production in left ventricular (LV) remodeling and dysfunction after myocardial infarction (MI). Increased expression of xanthine oxidase (XO), a major source of ROS, has recently been demonstrated in experimental and clinical heart failure; however, a potential role for LV remodeling processes remains unclear. We therefore studied the effect of long-term treatment with allopurinol, a potent XO inhibitor, on myocardial ROS production and LV remodeling and dysfunction after MI. METHODS AND RESULTS: Mice with extensive anterior MI (n=105) were randomized to treatment with either vehicle or allopurinol (20 mg x kg(-1) x d(-1) by gavage) for 4 weeks starting on day 1 after surgery. Infarct size was similar among the groups. XO expression and activity were markedly increased in the remote myocardium of mice after MI, as determined by electron spin resonance spectroscopy. Myocardial ROS production was increased after MI but markedly reduced after allopurinol treatment. Importantly, allopurinol treatment substantially attenuated LV cavity dilatation and dysfunction after MI, as assessed by echocardiography, and markedly reduced myocardial hypertrophy and interstitial fibrosis. CONCLUSIONS: The present study reveals a novel beneficial effect of treatment with allopurinol, ie, a marked attenuation of LV remodeling processes and dysfunction after experimental MI. Allopurinol treatment therefore represents a potential novel strategy to prevent LV remodeling and dysfunction after MI.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15466649&dopt=Abstract allopurinol Zyloprim



Allopurinol
[Life-threatening adverse effects of pharmacologic antihyperuricemic therapy]

[Article in German]

Russmann S, Lauterburg B.

Institut fur Klinische Pharmakologie, Universitat Bern, Inselspital, Bern.

Minor hypersensitivity reactions to allopurinol presenting as skin rash occur in approximately 2% of patients. A more severe, albeit rare, hypersensitivity reaction with fever, eosinophilia, dermatitis, renal failure, vasculitis and hepatic dysfunction carries a mortality of up to 20%. The incidence of this severe reaction can probably be reduced by adjusting the dose of allopurinol in patients with impaired renal function. Azathioprine and mercaptopurine are metabolised by xanthine oxidase, the enzyme that is inhibited by allopurinol. Concomitant administration can result in life-threatening neutropenia unless the dose of allopurinol is reduced by approximately 75%. The uricosuric agent benzbromarone has recently been withdrawn from the market because of several cases of fulminant hepatic failure with subsequent death of the patient or liver transplantation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15493119&dopt=Abstract allopurinol Zyloprim



Allopurinol
Chronic treatment with allopurinol boosts survival and cardiac contractility in murine postischemic cardiomyopathy.

Stull LB, Leppo MK, Szweda L, Gao WD, Marban E.

Institute of Molecular Cardiobiology, Johns Hopkins University School of Medicine, Baltimore, Md, USA.

Oxidative stress is a hallmark of systemic illnesses, including heart failure. Nevertheless, the overall importance of radical production in the heart remains conjectural; is it merely a marker of illness, or can intervention alter the progression of disease? This question was addressed by blocking xanthine oxidase (XO), a superoxide-generating enzyme that is upregulated in animal models of heart failure. In a randomized prospective trial design, we administered the XO inhibitor allopurinol orally to mice that had undergone massive myocardial infarction (MI). Cardiac XO activity was elevated in untreated mice after MI; allopurinol suppressed the XO activity to levels comparable to those in sham-operated mice. Eighty-one percent of untreated mice died of advanced heart failure over 2 to 4 weeks of follow-up. Survival doubled in the allopurinol-treated mice, whereas cardiac contractile function (both in vivo and in isolated muscle) was markedly improved. Response to isoproterenol was restored to near-normal levels in the allopurinol group but was attenuated in untreated mice. Oxidative modifications to proteins were prevented in the allopurinol-treated mice. Our findings indicate that targeted blockade of just one source of oxidants, XO, impacts dramatically on the progression of postischemic cardiomyopathy in mice and prevents oxidative protein modifications.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15499028&dopt=Abstract allopurinol Zyloprim



Allopurinol
The efficacy of combined low dose of Allopurinol and benzbromarone compared to standard dose of Allopurinol in hyperuricemia.

Akkasilpa S, Osiri M, Deesomchok U, Avihingsanon Y.

Department of Medicine, Faculty of Medicine, Chulalongkorn University, Thailand.

OBJECTIVE: To compare the efficacy of combined low dose of hypouricemic drugs (Allopurinol 100 mg and benzbromarone 20 mg; Allomaron) and standard dose 300 mg of allopurinol in hyperuricemia. MATERIAL AND METHOD: A prospective, open study of 94 hyperuricemic patients was done at King Chulalongkorn Memorial Hospital. Each group of 47 patients was given a combined low dose of hypouricemic drugs (Allopurinol 100 mg and benzbromarone 20 mg; Allomaron) and a standard dose 300 mg of allopurinol. Serum uric acid was measured before and 4 weeks after receiving the drugs. The efficacy was measured from the difference of the level of serum uric acid before and after receiving the drugs. RESULTS: The patients receiving the combined low dose of hypouricemic drugs and standard dose of allopurinol showed a mean reduction of serum uric acid of 2.5+/-3.4 mg/dl and 4.1+/-2.7 mg/dl consecutively. There was a statistically significant difference between the 2 groups (P = 0.010). CONCLUSION: This study demonstrates that the efficacy of standard dose 300 mg of allopurinol is superior to a combined low dose of allopurinol and benzbromarone in lowering the level of serum uric acid level.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15516011&dopt=Abstract allopurinol Zyloprim



Allopurinol
Colchicine for prophylaxis of acute flares when initiating allopurinol for chronic gouty arthritis.

Borstad GC, Bryant LR, Abel MP, Scroggie DA, Harris MD, Alloway JA.

Department of Rheumatology, Wilford Hall US Air Force Medical Center, Lackland AFB, San Antonio, Texas, USA.

OBJECTIVE: The use of colchicine to prevent acute gout flares during initiation of allopurinol therapy is widely practiced despite lack of proven benefit. We investigated if colchicine administration during initiation of allopurinol for chronic gouty arthritis reduces the frequency and/or severity of acute gout flares. METHODS: Patients starting allopurinol for crystal-proven chronic gouty arthritis were randomized to receive colchicine 0.6 mg po bid or placebo in a randomized, prospective, double blind, placebo controlled trial. Subjects were followed for evidence of acute gout flares and remained on study drug for 3 months beyond attaining a serum urate concentration < 6.5 mg/dl. Treatment arms were analyzed regarding frequency of flares, likelihood of any flare or multiple flares, severity of flares on the visual analog scale (VAS), and length of flares in days. RESULTS: Forty-three subjects were studied. Subjects treated with colchicine experienced fewer total flares (0.52 vs 2.91, p = 0.008), fewer flares from 0 to 3 months (0.57 vs 1.91, p = 0.022), fewer flares 3-6 months (0 vs 1.05, p = 0.033), less severe flares as reported on VAS (3.64 vs 5.08, p = 0.018), and fewer recurrent gout flares (p = 0.001). Colchicine was well tolerated. CONCLUSION: Colchicine prophylaxis during initiation of allopurinol for chronic gouty arthritis reduces the frequency and severity of acute flares, and reduces the likelihood of recurrent flares. Treating patients with colchicine during initiation of allopurinol therapy for 6 months is supported by our data.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15570646&dopt=Abstract allopurinol Zyloprim



Allopurinol
Ineffectiveness of allopurinol in reduction of oxidative stress in diabetic patients; a randomized, double-blind placebo-controlled clinical trial.

Afshari M, Larijani B, Rezaie A, Mojtahedi A, Zamani MJ, Astanehi-Asghari F, Mostafalou S, Hosseinnezhad A, Heshmat R, Abdollahi M.

Endocrine and Metabolism Research Center, Tehran University of Medical Sciences, Tehran, Iran.

The objective of this randomized, double-blind placebo-controlled clinical trial was to evaluate the value of allopurinol treatment on reduction of oxidative stress in patients with diabetes type II patients. Forty-one diabetic type II subjects were randomly assigned to two groups. One group (n = 20) received 100 mg allopurinol three times a day for 14 days and the other group (n = 21) received a placebo. Blood and saliva samples were collected before and after intervention for analysis of lipid peroxidation level and total antioxidant power as indices of oxidative stress. At the beginning of the study, the groups were similar based upon age, duration of diabetes, fasting glucose, and HbA1c. Both allopurinol and placebo were effective in reduction of lipid peroxidation and total antioxidant power whether in saliva or plasma in a similar extent. HbA1c and FBS levels did not change through the study neither in case or placebo group. It is concluded that allopurinol therapy is not more effective than placebo in reduction of oxidative stress in diabetic patients. The same trend of changes in blood and saliva shown for oxidative stress indices was interesting and suggests a chance for saliva to be valuable in diagnosis of oxidative stress. However, to elaborate the exact role of allopurinol in diabetes, further large randomized clinical trials are needed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15589061&dopt=Abstract allopurinol Zyloprim