MedWorm: Allopurinol

The pharmacokinetics of oxypurinol in people with gout

British Journal of Clinical Pharmacology — Thu, 02 Feb 2012 05:00:00 +0100

Conclusions: In conclusion, this first established pharmacokinetic model provides a tool to achieve target oxypurinol plasma concentrations, thereby optimizing the effectiveness and safety of allopurinol therapy in gouty patients with various degree of renal impairment.© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society (Source: British Journal of Clinical Pharmacology)

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Women with gout: Efficacy and safety of urate‐lowering with febuxostat and allopurinol

Arthritis Care and Research — Fri, 27 Jan 2012 10:29:27 +0100

ConclusionThese data suggest that febuxostat 80 mg may be more efficacious than commonly prescribed doses of allopurinol in female gout subjects with high rates of comorbidities. (Source: Arthritis Care and Research)

Gout and Organ Transplantation

Current Rheumatology Reports — Thu, 19 Jan 2012 06:55:35 +0100

Abstract Acute and chronic gout are common complications following organ transplantation. Risk factors include those shared with the general population (eg, diuretic use) and transplant-specific risk factors (eg, cyclosporine). Clinical features of gout are similar to those seen in the general population, although tophi may be more common. A definitive diagnosis requires demonstration of monosodium urate crystals within synovial fluid or tophi. Treatment is often empiric, although a poor response should prompt joint aspiration to exclude septic arthritis. Corticosteroids are commonly used to treat acute gout due to the adverse profile and drug interactions with NSAIDs and colchicine. Sustained reduction of serum urate (≤6 mg/dL) is critical in long-term management. ...

A new lupane triterpene from Tetracera scandens L., xanthine oxidase inhibitor.

Natural Product Research — Thu, 19 Jan 2012 05:00:00 +0100

Authors: Nguyen MT, Nguyen NT Abstract From the MeOH extract of the stem of Tetracera scandens L., a new nor-lupane triterpene, 28-O-β-D-glucopyranosyl ester of platanic acid (1), has been isolated together with six known compounds. Their structures were elucidated on the basis of spectroscopic data. Compounds 1-6 displayed significant xanthine oxidase inhibitory activity in a concentration-dependent manner, and compound 4 showed more potent inhibitory activity with an IC(50) value of 1.9 µM than that of a positive control allopurinol (IC(50) 2.5 µM). PMID: 22260251 [PubMed - as supplied by publisher] (Source: Natural Product Research)

Allopurinol-induced palisaded neutrophilic and granulomatous dermatitis.

Cutaneous and Ocular Toxicology — Wed, 18 Jan 2012 05:00:00 +0100

We describe a 64-year-old man with past chronic myeloid leukemia. Palisading neutrophilic granulomatous dermatitis of the hands was diagnosed and related to recent allopurinol intake. Allopurinol is known to rarely cause granulomatous reactions, but this appears to be the first case of palisading neutrophilic granulomatous dermatitis induction. Possible mechanisms include immune complex deposition, an immune response directed against the metabolites of allopurinol, or allopurinol hypersensitivity exclusively localized to the skin. PMID: 22250812 [PubMed - as supplied by publisher] (Source: Cutaneous and Ocular Toxicology)

Allopurinol: DRESS syndrome: case report

Reactions — Tue, 17 Jan 2012 19:08:18 +0100

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Allopurinol: Stevens Johnson syndrome, drug hypersensitivity and rash: 16 case reports

Reactions — Tue, 17 Jan 2012 19:08:18 +0100

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Xanthine oxidase‐generated hydrogen peroxide is a consequence, not a mediator of cell death

FEBS Journal — Tue, 10 Jan 2012 05:00:00 +0100

SummaryOxidative stress has been associated with a wide range of diseases including atherosclerosis, cancer, and Alzheimer’s disease. When present in excessive concentrations, reactive oxygen species (ROS) can cause deleterious effects. This has led to the notion that the anticancer effects of various chemotherapeutics may be mediated, at least in part, by an increase in ROS. To investigate the role of xanthine oxidase (XO), a source of hydrogen peroxide, in cell death, MCF7, HeLa and 293T cells were treated with various cell death‐inducing drugs in the presence and absence of allopurinol, a specific inhibitor of XO. In the absence of allopurinol, each drug led to a time and concentration‐dependent increase in percent DNA fragmentation and ROS levels, regardless of the mechanism of c...

BioCryst reports long-term results of BCX4208 therapy

Drug Development Technology — Tue, 10 Jan 2012 00:00:00 +0100

BioCryst Pharmaceuticals has reported positive results from the extension phase of its randomised Phase 2b study of BCX4208 added to allopurinol in patients with gout. (Source: Drug Development Technology)

Pioglitazone treatment increases COX‐2 derived PGI2 production and reduces oxidative stress in hypertensive rats. Role on vascular function

British Journal of Pharmacology — Thu, 05 Jan 2012 05:00:00 +0100

Conclusions and implications: Pioglitazone treatment, although did not reduce blood pressure in SHR, increased COX‐2‐derived PGI2 production, reduced oxidative stress, and increased NO bioavailability, all of them involved on vasoconstrictor responses in resistance arteries. These effects would contribute to the cardioprotective effect of glitazones reported in several pathologies. (Source: British Journal of Pharmacology)

Xanthine Oxidase Inhibitors from Vietnamese Blumea balsamifera L.

Phytotherapy Research — Wed, 04 Jan 2012 05:00:00 +0100

From the MeOH extract of the aerial part of Blumea balsamifera L., a new dihydroflavonol, (2R,3S)‐(−)‐4′‐O‐methyldihydroquercetin (1), together with seven known compounds has been isolated. Their structures were elucidated on the basis of spectroscopic data. Compounds 1–4 and 6–8 displayed significant xanthine oxidase inhibitory activity in a concentration‐dependent manner, and compounds 1, 6 and 8 showed more potent inhibitory activity, with IC50 values ranging from 0.23 to 1.91 µ m, than that of a positive control allopurinol (IC50 2.50 µ m). Copyright © 2012 John Wiley & Sons, Ltd. (Source: Phytotherapy Research)

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Febuxostat Edges Allopurinol in Women With GoutFebuxostat Edges Allopurinol in Women With Gout

Medscape Medical News Headlines — Wed, 04 Jan 2012 02:54:01 +0100

A post-hoc analysis looking at urate-lowering therapies in women with gout shows that febuxostat 80 mg daily was more effective than lower doses of the same drug, or allopurinol. Reuters Health Information (Source: Medscape Medical News Headlines)

Adenine phosphoribosyltransferase deficiency in children

Pediatric Nephrology — Mon, 02 Jan 2012 16:47:56 +0100

Abstract Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder characterized by 2,8-dihydroxyadenine (2,8-DHA) crystalluria that can cause nephrolithiasis and chronic kidney disease. The aim of our study was to assess the clinical presentation, diagnosis, and outcome of APRT deficiency in a large pediatric cohort. All pediatric cases of APRT deficiency confirmed at the same French reference laboratories between 1978 and 2010 were retrospectively reviewed. Twenty-one patients from 18 families were identified. The median age at diagnosis was 3 years. Diagnosis was made after one or more episodes of nephrolithiasis (17 patients), after urinary tract infection (1 patient), and by family screening (3 patients). The diagnosis was based o...

Acquired perforating dermatosis successfully treated with photodynamic therapy

Photodermatology, Photoimmunology and Photomedicine — Sun, 01 Jan 2012 07:44:05 +0100

SummaryAcquired perforating dermatosis is a rare perforating skin disorder characterized by intensely pruritic papules or nodules with central adherent plugs mainly observed on the lower extremities and transepidermal elimination of collagen bundles. Treatment of acquired perforating dermatosis is a matter of debate and conventional treatment options including topical and systemic retinoids, topical corticosteroids and keratolytics, ultraviolet B phototherapy, psoralen plus ultraviolet A (PUVA), allopurinol and cryosurgery show mixed results. Herein, we describe a 60‐year‐old woman with a diagnosis of acquired perforating dermatosis secondary to diabetes mellitus in whom we achieved excellent results with photodynamic treatment. As far as we are aware, this is the first case report of ...

Rilonacept (IL‐1 Trap) in the prevention of acute gout flares during initiation of urate‐lowering therapy: results of a Phase 2 clinical trial

Arthritis and Rheumatism — Sun, 01 Jan 2012 05:00:00 +0100

Conclusion:Rilonacept significantly reduced gout flares during initiation of ULT and demonstrated a favorable safety profile. (NCT00610363 [ClinicalTrials.gov Identifier] (Source: Arthritis and Rheumatism)

Febuxostat edges allopurinol for urate-lowering in women with gout

Modern Medicine — Fri, 30 Dec 2011 05:00:00 +0100

NEW YORK (Reuters Health) - A post-hoc analysis looking at urate-lowering therapies in women with gout shows that febuxostat 80 mg daily was more effective than lower doses of the same drug, or allopurinol. (Source: Modern Medicine)

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Horizon scanning: Phase III clinical development program of lesinurad for gout

NeLM - News — Tue, 20 Dec 2011 05:00:00 +0100

Source: BioSpace Area: News According to a BioSpace report, the first of four planned phase III clinical trials of lesinurad for the chronic treatment of gout has been initiated. The program is anticipated to involve approximately 2,000 gout patients at sites around the world. The remaining Phase III studies in the program are expected to begin shortly. Lesinurad is an oral, once-daily inhibitor of the URAT1 transporter in the kidney that regulates uric acid excretion from the body. Lesinurad has been evaluated in phase I and II clinical trials as a single agent and in combination with allopurinol and febuxostat. (Source: NeLM - News)

[Familial juvenile hyperuricemic nephropathy.]

Nephrologie and Therapeutique — Tue, 20 Dec 2011 05:00:00 +0100

Authors: Hummel A Abstract Familial juvenile hyperuricemic nephropathy is a rare autosomal dominant disease. It is characterized by abnormal handling of urate responsible for hyperuricaemia often complicated of gouty arthritis. Renal failure is due to tubulointerstitial nephritis. Ultrasonography sometimes finds renal cysts of variable size and number. Renal histology, although not specific, shows interstitial fibrosis, atrophic tubules, sometimes enlarged and with irregular membrane thickening. Renal failure progresses to end stage between 30 and 60 years of age. Allopurinol treatment is recommended at the early stages of the disease, its efficacy on slowing down the progression of the disease is however not proven. There is genetic heterogeneity in familial juvenile hyperuricemic...

Allopurinol intake does not modify the slow component of V(.)O(2) kinetics and oxidative stress induced by severe intensity exercise.

Physiological Research — Tue, 20 Dec 2011 05:00:00 +0100

Authors: Olek RA, Safranow K, Jakubowska K, Olszewska M, Chlubek D, Laskowski R Abstract The aim of this study was to test the hypothesis that allopurinol ingestion modifies the slow component of V(.)O(2) kinetics and changes plasma oxidative stress markers during severe intensity exercise. Six recreationally active male subjects were randomly assigned to receive a single dose of allopurinol (300 mg) or a placebo in a double-blind, placebo-controlled crossover design, with at least 7 days washout period between the two conditions. Two hours following allopurinol or placebo intake, subjects completed a 6-min bout of cycle exercise with the power output corresponding to 75 % V(.)O(2)max. Blood samples were taken prior to commencing the exercise and then 5 minutes upon completion. All...

Febuxostat Better Than Allopurinol for Women With Gout Febuxostat Better Than Allopurinol for Women With Gout

Medscape Today Headlines — Fri, 16 Dec 2011 22:21:20 +0100

Data from 3 clinical trials show that febuxostat is more effective than allopurinol for treating gout in women, even those with mild or moderate renal failure. Medscape Medical News (Source: Medscape Today Headlines)

Sorafenib-Induced Liver Failure: A Case Report and Review of the Literature

Clinical and Developmental Immunology — Mon, 12 Dec 2011 23:53:11 +0100

In patients with hepatocellular carcinoma characterized by vascular invasion and/or extrahepatic disease, Sorafenib is considered treatment of choice. Although mild liver test abnormalities were reported in less than 1% of the patients in the two large randomized, controlled phase III trials, four cases of severe acute Sorafenib-induced hepatitis have been described. One of these four cases died from liver failure. In this paper, a patient with HCC with lung metastases developed high fever and a severe hepatitis that rapidly evolved into liver coma and death, two weeks after the initiation of Sorafenib. Biochemical parameters pointed to a hepatocellular type of injury. Clinical and biochemical presentations were compatible with a drug-induced hypersensitivity syndrome such as it has mainly...

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Two Brothers with Skewed Thiopurine Metabolism in Ulcerative Colitis Treated Successfully with Allopurinol and Mercaptopurine Dose Reduction

Digestive Diseases and Sciences — Tue, 06 Dec 2011 16:59:20 +0100

Abstract Thiopurine therapy effectively maintains remission in inflammatory bowel disease. However, many patients are unable to achieve optimum benefits from azathioprine or 6-mercaptopurine because of undesirable metabolism related to high thiopurine methyltransferase (TPMT) activity characterized by hepatic transaminitis secondary to increased 6-methylmercaptopurine (6-MMP) production and reduced levels of therapeutic 6-thioguanine nucleotide (6-TGN). Allopurinol can optimize this skewed metabolism. We discuss two brothers who were both diagnosed with ulcerative colitis (UC). Their disease remained active despite oral and topical mesalamines. Steroids followed by 6-mercaptopurine (MP) were unsuccessfully introduced for both patients and both were found to have high 6-MMP...

HLA alleles and drug hypersensitivity reactions

International Journal of Immunogenetics — Thu, 01 Dec 2011 05:00:00 +0100

SummaryThe human leucocyte antigen (HLA) system is well known for its association with certain diseases such as ankylosing spondylitis, celiac disease and many others. More recently, severe and even fatal drug hypersensitivity reactions linked to particular HLA alleles have been discovered. The significance of these discoveries has led the European Medicines Agency (EMA) and its member state agencies to recommend HLA gene testing before initiation of drug treatment. To date, the following drugs have been identified as causing significant drug hypersensitivity reactions in patients who have the following HLA alleles: abacavir and HLA‐B*57:01, carbamazepine and HLA‐B*15:02/A*31:01 and finally allopurinol and HLA‐B*58:01. This review will outline and discuss these three drugs and their ...

The last defence? Surgical aspects of gouty arthritis of hand and wrist.

Hong Kong Med J — Thu, 01 Dec 2011 05:00:00 +0100

CONCLUSION. While medical treatment remains the mainstay of treatment for gouty arthritis of the hand and wrist, 5% of patients may not respond. In this group, surgery is often performed in advanced stages, but yields less-than-satisfactory outcomes. Gouty arthritis is difficult to treat when it starts to cause stiffness and deformities. Although more studies are needed to evaluate the outcomes, the authors suggest that one possible solution is pre-emptive surgery. PMID: 22147319 [PubMed - in process] (Source: Hong Kong Med J)

Allopurinol pharmacogenetics: assessment of potential clinical usefulness

Future Medicine: Pharmacogenomics — Fri, 25 Nov 2011 17:37:05 +0100

Pharmacogenomics , December 2011, Vol. 12, No. 12, Pages 1741-1749. (Source: Future Medicine: Pharmacogenomics)

Use of Uric Acid-Lowering Agents Limits Experimental Cyclosporine Nephropathy.

Nephron Experimental Nephrology — Fri, 25 Nov 2011 05:00:00 +0100

Conclusions: An increase in uric acid exacerbates CsA nephropathy in the rat. Concomitant treatment with allopurinol or benzbromarone reduced the severity of renal disease. The similar protection observed with both drugs suggests that the effect is associated more with lowering uric acid levels than the antioxidant effect of allopurinol. PMID: 22126908 [PubMed - as supplied by publisher] (Source: Nephron Experimental Nephrology)

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Allopurinol/amoxicillin/clavulanic acid: Toxic epidermal necrolysis treated with ciclosporin: 3 case reports

Reactions — Tue, 22 Nov 2011 06:51:47 +0100

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Risk factors for acute kidney injury by non-steroidal anti-inflammatory drugs in patients with hyperuricaemia

Rheumatology — Tue, 22 Nov 2011 05:00:00 +0100

Conclusion. Low GFR and low serum albumin are risk factors for AKI in hyperuricaemic patients treated with NSAIDs. Our results suggest that NSAIDs should be used with caution in patients with low serum albumin. (Source: Rheumatology)

Oxypurinol, allopurinol and allopurinol‐1‐riboside in plasma following an acute overdose of allopurinol in a patient with advanced chronic kidney disease

British Journal of Clinical Pharmacology — Sat, 19 Nov 2011 06:35:33 +0100

(Source: British Journal of Clinical Pharmacology)

Xanthine Oxidoreductase Is Involved in Macrophage Foam Cell Formation and Atherosclerosis Development.

Arteriosclerosis, Thrombosis and Vascular Biology — Thu, 17 Nov 2011 05:00:00 +0100

CONCLUSIONS: These results strongly suggest XOR activity and/or its expression level to contribute to macrophage foam cell formation. Thus, XOR inhibitors may be useful for preventing atherosclerosis. PMID: 22095983 [PubMed - as supplied by publisher] (Source: Arteriosclerosis, Thrombosis and Vascular Biology)

Combination Therapy Gives Patients With IBD Another OptionCombination Therapy Gives Patients With IBD Another Option

Medscape Today Headlines — Fri, 04 Nov 2011 15:21:26 +0100

After 5 years, 73% of patients with inflammatory bowel disease (IBD) were doing well on combination therapy with allopurinol plus low-dose thiopurines. Medscape Medical News (Source: Medscape Today Headlines)

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ACG: Allopurinol Helps in IBD (CME/CE)

MedPage Today State Required CME — Wed, 02 Nov 2011 14:00:00 +0100

WASHINGTON (MedPage Today) -- Adding allopurinol to thiopurine therapy can help increase response rates in patients with refractory inflammatory bowel disease, a researcher said here. (Source: MedPage Today State Required CME)

Women with gout: The efficacy and safety of urate‐lowering with febuxostat and allopurinol

Arthritis Care and Research — Wed, 02 Nov 2011 04:00:00 +0100

Conclusions:These data suggest that febuxostat 80 mg may be more efficacious than commonly prescribed doses of allopurinol in female gout subjects with high rates of comorbidities. © 2011 by the American College of Rheumatology (Source: Arthritis Care and Research)

Latex of Euphorbia Antiquorum Induces Apoptosis in Human Cervical Cancer Cells via c-Jun N-terminal Kinase Activation and Reactive Oxygen Species Production.

Nutrition and Cancer — Tue, 01 Nov 2011 04:00:00 +0100

Authors: Hsieh WT, Lin HY, Chen JH, Kuo YH, Fan MJ, Wu RS, Wu KC, Wood WG, Chung JG Abstract Latex of Euphorbia antiquorum (EA) has inhibitory effects on several different cancer cell lines. However, the molecular mechanism of EA inhibitory effects on human cervical cancer HeLa cell growth has not been explored. EA induced apoptosis, which was characterized by morphological change, DNA fragmentation, increased sub-G1 population, and alterations in levels of apoptosis-associated proteins. Treatment with EA increased cell death and expression levels of caspase-8, -9, and -3. EA suppressed expression of Bcl-2, increased Bax, and reduced cleavage of Bid and the translocation of tBid to the mitochondria and the release of cytochrome c from mitochondria. EA caused a loss of mitochondrial...

HLA-B58 can help the clinical decision on starting allopurinol in patients with chronic renal insufficiency

Nephrology Dialysis Transplantation — Fri, 28 Oct 2011 04:00:00 +0100

Conclusions. In this study, the incidence of allopurinol-induced SCARs was considerably high in CRI patients with HLA-B58. This finding indicates that the presence of HLA-B58 may increase the risk of allopurinol-induced SCARs. Screening tests for HLA-B58 in CRI patients will be clinically helpful in preventing severe allopurinol hypersensitivity reactions. (Source: Nephrology Dialysis Transplantation)

Allopurinol: Multiple congenital disorders following in utero exposure: case report

Reactions — Wed, 26 Oct 2011 13:05:17 +0100

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Cutaneous adverse drug reactions to allopurinol: 10 year observational survey of the dermatology department – cagliari university (Italy)

Journal of the European Academy of Dermatology and Venereology — Mon, 24 Oct 2011 04:00:00 +0100

Conclusion Considering the populations size of Southern Sardinia, is plausible that 1.5/100 000 Sardinian will be affected by allopurinol related ADR per year. Advanced age, and inappropriate allopurinol prescription were the main conditions affecting morbidity and mortality. (Source: Journal of the European Academy of Dermatology and Venereology)

Different Characteristics of Reactive Oxygen Species Production by HaCaT Cells in Response to Allergens and Irritants

Experimental Dermatology — Sat, 22 Oct 2011 04:56:15 +0100

In this study, we investigated the 1) ROS production, 2) potential sites of ROS production, 3) expression of cell surface molecules, 4) secretion of cytokines, 5) and ROS‐dependent protein carbonylation in chemical‐treated HaCaT cells. Treatment of HaCaT cells with 2,4‐dinitrochlorobenzene (DNCB) and benzalkonium chloride (BKC) increased ROS levels in a time and dose‐dependent manner, as determined with dichlorodihydrofluorescein diacetate (CM‐H2DCFDA), without reducing cell viability. Potential sources of ROS production were evaluated with pre‐treatment of diphenylene iodonium (DPI), an inhibitor of NADPH oxidase; rotenone, an inhibitor of the mitochondrial electron transport chain complex; or allopurinol, a xanthine oxidase inhibitor. DNCB‐induced ROS was related to both ...

Different characteristics of reactive oxygen species production by human keratinocyte cell line cells in response to allergens and irritants

Experimental Dermatology — Fri, 21 Oct 2011 04:00:00 +0100

In this study, we investigated the (i) ROS production; (ii) potential sites of ROS production; (iii) expression of cell surface molecules; (iv) secretion of cytokines; and (v) ROS‐dependent protein carbonylation in chemical‐treated human keratinocyte cell line (HaCaT) cells. Treatment of HaCaT cells with 2,4‐dinitrochlorobenzene (DNCB) and benzalkonium chloride (BKC) increased ROS levels in a time‐ and dose‐dependent manner, as determined with dichlorodihydrofluorescein diacetate (CM‐H2DCFDA), without reducing cell viability. Potential sources of ROS production were evaluated with pretreatment of diphenylene iodonium (DPI), an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase; rotenone, an inhibitor of the mitochondrial electron transport chain complex or...

Lysis syndrome during therapy of visceral leishmaniasis

Infection — Tue, 18 Oct 2011 05:44:04 +0100

Conclusion A lysis syndrome may complicate the treatment of visceral leishmaniasis. Awareness of this complication can lead to the initiation of prophylactic treatment as well as to early recognition and management of this syndrome in susceptible patients. Content Type Journal ArticleCategory Clinical and Epidemiological StudyPages 1-3DOI 10.1007/s15010-011-0202-9Authors E. N. Liberopoulos, Department of Internal Medicine, University of Ioannina Medical School, 451 10 Ioannina, GreeceA. A. Kei, Department of Internal Medicine, University of Ioannina Medical School, 451 10 Ioannina, GreeceM. S. Elisaf, Department of Internal Medicine, University of Ioannina Medical School, 451 10 Ioannina, Greece Journal InfectionOnline ISSN 1439-0973Print ISSN 0300-8126 (Sourc...

Six-year Retrospective Review of Drug Reaction with Eosinophilia and Systemic Symptoms.

Acta Dermato-Venereologica — Mon, 17 Oct 2011 04:00:00 +0100

Authors: Wongkitisophon P, Chanprapaph K, Rattanakaemakorn P, Vachiramon V Abstract Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, severe adverse drug reaction. The aim of this study was to characterize the aetiology, clinical features, laboratory findings, and management of patients with DRESS, diagnosed from January 2005 to April 2010 in a tertiary centre in Thailand. Twenty-seven patients were included in the study with a mean age of 52 years. Phenytoin, allopurinol, and nevirapine were the most commonly implicated medications. Mean duration of drug administration before the onset of symptoms was 34 days. The latent period was longer for allopurinol (103 days) and shorter for nevirapine (10 days). Skin rash was seen in all patients, while fever and lymp...

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Beware the low urine ph ‐ the major cause of the increased prevalence of nephrolithiasis in the patient with type 2 diabetes

Diabetes, Obesity and Metabolism — Sat, 15 Oct 2011 07:40:27 +0100

There is an increased prevalence of nephrolithiasis and an increase in the incidence of renal colic in patients with diabetes, obesity, hypertension and insulin resistance due to an increased frequency of uric acid crystallization. Uric acid crystallization occurs in the milieu of an acid urine and is not due to hyperuricosuria since with insulin resistance, urinary uric acid levels are generally decreased due to increased renal tubular reabsorption. However, in the presence of insulin resistance, there is decreased renal tubular generation of ammonia and increased sodium absorption leading to acidification of the urine and uric acid crystalization. The presence of a low urine pH should alert the clinician to the increased risk of nephrolithiasis particularly in the obese, diabetic or hype...

Beware the low urine pH—the major cause of the increased prevalence of nephrolithiasis in the patient with type 2 diabetes

Diabetes, Obesity and Metabolism — Wed, 12 Oct 2011 04:00:00 +0100

There is an increased prevalence of nephrolithiasis and an increase in the incidence of renal colic in patients with diabetes, obesity, hypertension and insulin resistance because of an increased frequency of uric acid crystallization. Uric acid crystallization occurs in the milieu of an acid urine and is not due to hyperuricosuria as with insulin resistance, urinary uric acid levels are generally decreased because of increased renal tubular reabsorption. However, in the presence of insulin resistance, there is decreased renal tubular generation of ammonia and increased sodium absorption leading to acidification of the urine and uric acid crystalization. The presence of a low urine pH should alert the clinician to the increased risk of nephrolithiasis particularly in the obese, diabetic or...

Optimizing 6-mercaptopurine and azathioprine therapy in the management of inflammatory bowel disease.

World Journal of Gastroenterology : WJG — Fri, 07 Oct 2011 04:00:00 +0100

In this report, we will review different approaches to administer the thiopurine medications, including the administration of 6-mercaptopurine in those unsuccessfully treated with azathioprine; co-administration of thiopurine with allopurinol; co-administration of thiopurine with anti-tumor necrosis factor α; 6-TGN administration; desensitization trials; and split dosing of 6-MP. PMID: 22072847 [PubMed - in process] (Source: World Journal of Gastroenterology : WJG)

Systematic review of clinical effectiveness of allopurinol in treating gout, compared to febuxostat, AMONG patients with confirmed diagnosis of gout

International Journal of Surgery — Thu, 06 Oct 2011 22:52:31 +0100

Introduction: Gout is a disorder of urate metabolism characterised by hyperuricaemia/crystal deposition. Successful treatment depends on maintenance of plasma urate levels. Allopurinol is a direct inhibitor of xanthine oxidase (XO), Febuxostat acts through non-competitive blockage of the active site of XO. (Source: International Journal of Surgery)

Allopurinol: Drug hypersensitivity syndrome and acute generalised exanthematous pustulosis: case report

Reactions — Mon, 03 Oct 2011 06:00:13 +0100

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Allopurinol: Pure red cell aplasia: case report

Reactions — Mon, 03 Oct 2011 06:00:13 +0100

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Contraindications to Pharmacologic Therapies for Gout

The American Journal of Medicine — Sat, 01 Oct 2011 04:00:00 +0100

Keenan et al highlight the potential hazards of prescribing in patients with multiple comorbidities, using the example of gout. As nephrologists, we have to consider these issues in many consultations, but we rarely encounter significant limitations when prescribing treatment for gout in our patients with chronic kidney disease (CKD). In contrast to the suggested contraindications, prescription information from the US National Library of Medicine does not list CKD as an absolute contraindication for either allopurinol and/or colchicine; rather, these drugs can be prescribed to patients with CKD, with appropriate dose reduction and additional monitoring of renal function. This misinterpretation of cautionary advice as contraindication may explain the surprising finding that, despite nonster...

The Reply

The American Journal of Medicine — Sat, 01 Oct 2011 04:00:00 +0100

The concerns of Lewis and Herrington, regarding caution being misconstrued as contraindication, are reasonable. However, our translation of caution into moderate contraindication was warranted because such a designation conveys that although the particular treatment is not absolutely contraindicated, its use deserves careful consideration; and it allowed us to operationalize a more inclusive range of drug risks and toxicities. Most primary care physicians do not currently dose-adjust colchicine or allopurinol for renal function, and tend to prescribe set doses regardless of comorbidity or current medication use. In the case of allopurinol, 300 mg has been documented as the “average dose” of allopurinol prescribed by many physicians, regardless of renal function. On the other hand, the ...

Virtual and In vitro bioassay screening of phytochemical inhibitors from flavonoids and isoflavones against Xanthine oxidase and Cyclooxygenase‐2 for gout treatment

Chemical Biology and Drug Design — Sat, 01 Oct 2011 04:00:00 +0100

In this study, we report the screening of 9 compounds of flavonoids from the ZINC and PubChem databases (containing 2,092 flavonoids) using the iGEMDOCK software tool against the XO and COX‐2 3D protein structures. Each compound was also evaluated by an in vitro bioassay testing the inhibition of XO and COX‐2. Myricetin and luteolin were found to be the potential dual inhibitors of XO and COX‐2 as demonstrated by IC50: 62.7 and 3.29μg/mL (XO) / 70.8 and 16.38μg/mL (COX‐2), respectively. In addition, structure activity relationships and other important factors of the flavonoids binding to the active site of XO and COX‐2 were discussed, which is expected for further rational drug design. (Source: Chemical Biology and Drug Design)

ALLOPURINOL (Allopurinol) Tablet [REMEDYREPACK INC. ]

DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST) — Fri, 30 Sep 2011 05:00:00 +0100

Updated Date: Sep 30, 2011 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

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Novel mutations in xanthine dehydrogenase/oxidase cause severe hypouricemia: Biochemical and molecular genetic analysis in two Czech families with xanthinuria type I.

International Journal of Clinical Chemistry — Thu, 22 Sep 2011 04:00:00 +0100

CONCLUSIONS: We found two nonconsanguineous compound heterozygotes with xanthinuria type I caused by three nonsense changes. The methods used did not confirm consanguinity in the probands, thus there might be an unconfirmed biological relationship or mutational hotspot. PMID: 21963464 [PubMed - as supplied by publisher] (Source: International Journal of Clinical Chemistry)

Treatment of acquired reactive perforating collagenosis with allopurinol incidentally improves scleredema diabeticorum

Journal of the American Academy of Dermatology — Sun, 18 Sep 2011 01:35:55 +0100

We report a case of acquired reactive perforating collagenosis treated with allopurinol treatment. Surprisingly, the concomitant SD improved simultaneously. This case implied the therapeutic effect of allopurinol in SD. (Source: Journal of the American Academy of Dermatology)

Letter: DRESS syndrome associated with raltegravir.

Dermatol Online J — Thu, 15 Sep 2011 21:44:02 +0100

Authors: Zhang KS, Modi GM, Hsu S Abstract Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome or drug-induced hypersensitivity is a potentially life-threatening drug hypersensitivity syndrome most commonly associated with anticonvulsants, allopurinol, long-acting sulfonamides, dapsone, and minocycline. In the setting of HIV infection, the antiretroviral medicines abacavir, nevirapine, and efavirenz have all shown well-documented associations with DRESS syndrome. There has only been one case (in a poster presentation) of this syndrome in a patient who was taking raltegravir. PMID: 21906494 [PubMed - in process] (Source: Dermatol Online J)

Patch testing in fixed drug eruptions–a 20‐year review

Contact Dermatitis — Thu, 15 Sep 2011 18:16:08 +0100

Conclusions. Patch testing was shown to be a simple and safe method to confirm drug imputabililty in fixed drug eruption, mainly when NSAID or multiple drugs are suspected. Persistent lack of reactivity to drug classes such as antibiotics and allopurinol represent an important limitation. (Source: Contact Dermatitis)

Factors associated with acute gout attacks in normouricaemic gout patients receiving allopurinol: a retrospective study.

Scandinavian Journal of Rheumatology — Thu, 15 Sep 2011 04:00:00 +0100

Conclusion: The presence of tophi and multiple joint involvement were associated with acute attacks in normouricaemic gout patients receiving allopurinol. PMID: 21916803 [PubMed - as supplied by publisher] (Source: Scandinavian Journal of Rheumatology)

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A whole-genome association study of major determinants for allopurinol-related Stevens–Johnson syndrome and toxic epidermal necrolysis in Japanese patients

The Pharmacogenomics Journal — Tue, 13 Sep 2011 04:00:00 +0100

A whole-genome association study of major determinants for allopurinol-related Stevens–Johnson syndrome and toxic epidermal necrolysis in Japanese patients The Pharmacogenomics Journal advance online publication, September 13, 2011. doi:10.1038/tpj.2011.41 Authors: M Tohkin, N Kaniwa, Y Saito, E Sugiyama, K Kurose, J Nishikawa, R Hasegawa, M Aihara, K Matsunaga, M Abe, H Furuya, Y Takahashi, H Ikeda, M Muramatsu, M Ueta, C Sotozono, S Kinoshita & Z Ikezawa (Source: The Pharmacogenomics Journal)

Quercetin regulates organic ion transporter and uromodulin expression and improves renal function in hyperuricemic mice

European Journal of Nutrition — Fri, 09 Sep 2011 16:47:17 +0100

Conclusions These results suggest that quercetin has the uricosuric and nephroprotective actions mediated by regulating the expression levels of renal organic ion transporters and UMOD. Content Type Journal ArticleCategory Original ContributionPages 1-14DOI 10.1007/s00394-011-0243-yAuthors Qing-Hua Hu, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093 People’s Republic of ChinaXian Zhang, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093 People’s Republic of ChinaXing Wang, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093 People’s Republic of ChinaRui-Qing Jiao, State ...

Association of HLA-B*5801 Allele and Allopurinol-Induced Stevens Johnson Syndrome and Toxic Epidermal Necrolysis: A Systematic Review and Meta-analysis

BMC Medical Genetics - Latest articles — Fri, 09 Sep 2011 04:00:00 +0100

This study aims to systematically review and meta-analyze the association between HLA-B*5801 allele and allopurinol-induced SJS/TEN. Methods: A comprehensive search was performed in databases including MEDLINE, Pre-MEDLINE, Cochrane Library, EMBASE, International Pharmaceutical Abstracts (IPA), CINAHL, PsychInfo, the WHO International, Clinical Trial Registry, and ClinicalTrial.gov from their inceptions to June 2011. Only studies investigating association between HLA-B*5801 with allopurinol-induced SJS/TEN were included. All studies were extracted by two independent authors. The primary analysis was the carrier frequency of HLA-B*5801 comparison between allopurinol-induced SJS/TEN cases and each comparative group. The pooled odds ratios were calculated using a random effect model. Results:...

ALLOPURINOL (Allopurinol) Tablet [REMEDYREPACK INC. ]

DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST) — Fri, 02 Sep 2011 05:00:00 +0100

Updated Date: Sep 2, 2011 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

The Epidemiology of Uric Acid and Fructose

Seminars in Nephrology — Thu, 01 Sep 2011 04:00:00 +0100

Summary: During the past few decades, the mean serum uric acid levels and the prevalence of hyperuricemia in the general population appear to have increased. Correspondingly, the prevalence and incidence of gout have doubled. Potential reasons behind these trends include the increasing prevalence of obesity and metabolic syndrome, Western lifestyle factors, increased prevalence of medical conditions (eg, renal conditions, hypertension, and cardiovascular disorders), and use of medications that increase uric acid levels (eg, diuretics and low-dose aspirin). The substantial increase in sugar-sweetened soft drinks and associated fructose consumption also has coincided with the secular trend of hyperuricemia and gout. Recently, several large-scale epidemiologic studies have clarified a number ...

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Chronic phase of Chagas disease: why should it be treated? A comprehensive review.

Memorias do Instituto Oswaldo Cruz — Thu, 01 Sep 2011 04:00:00 +0100

Authors: Coura JR, Borges-Pereira J Abstract The pathogenesis and evolutive pattern of Chagas disease suggests that the chronic phase should be more widely treated in order to (i) eliminate Trypanosoma cruzi and prevent new inflammatory foci and the extension of tissue lesions, (ii) promote tissue regeneration to prevent fibrosis, (iii) reverse existing fibrosis, (iv) prevent cardiomyopathy, megaoesophagus and megacolon and (v) reduce or eliminate cardiac block and arrhythmia. All cases of the indeterminate chronic form of Chagas disease without contraindications due to other concomitant diseases or pregnancy should be treated and not only cases involving children or recently infected cases. Patients with chronic Chagas cardiomyopathy grade II of the New York Heart Association clas...

Therapeutic Use of High-Dose Allopurinol in Angina PectorisTherapeutic Use of High-Dose Allopurinol in Angina Pectoris

Medscape Today Headlines — Tue, 30 Aug 2011 11:04:57 +0100

High-dose allopurinol has recently been shown to prolong the time to chest pain and to ST-segment depression during exercise in patients with chronic stable angina. Can it do more? Journal of the American College of Cardiology (Source: Medscape Today Headlines)

Novel insights into interactions between mitochondria and xanthine oxidase in acute cardiac volume overload.

Free Radical Biology and Medicine — Tue, 30 Aug 2011 04:00:00 +0100

Authors: Gladden JD, Zelickson BR, Wei CC, Ulasova E, Zheng J, Ahmed MI, Chen Y, Bamman M, Ballinger S, Darley-Usmar V, Dell'italia LJ Abstract Xanthine oxidoreductase (XOR) is increased in the left ventricle (LV) of humans with volume overload (VO), and mitochondrial inhibition of the respiratory chain occurs in animal models of VO. Because mitochondria are both a source and a target of reactive oxygen and nitrogen species, we hypothesized that activation of XOR and mitochondrial dysfunction are interdependent. To test this we used the aortocaval fistula (ACF) rat model of VO and a simulation of the stretch response in isolated adult cardiomyocytes with and without the inhibitor of XOR, allopurinol, or the mitochondrially targeted antioxidant MitoQ. Xanthine oxidase (XO) activity ...

Impact of elevated uric acid on ventricular remodeling in infarcted rats with experimental hyperuricemia

AJP: Heart and Circulatory Physiology — Mon, 29 Aug 2011 23:00:00 +0100

Hyperuricemia is associated with cardiovascular disease, but it is usually considered a marker rather than a risk factor. Previous studies using uric acid-lowering drugs in normouricemic animals are not suitable to answer the effect of hyperuricemia on ventricular remodeling after myocardial infarction. The purpose of this study was to determine whether hyperuricemia adversely affects ventricular remodeling in infarcted rats with elevated uric acid. Male Wistar rats aged 8 wk were randomly assigned into either vehicle, oxonic acid, oxonic acid + allopurinol, oxonic acid + benzbromarone, oxonic acid + ABT-627, or oxonic acid + tempol for 4 wk starting 24 h after ligation. Postinfarction was associated with increased oxidant production, as measured by myocardial superoxide, isoprostane, xant...

Improving the use of allopurinol in chronic gout: monitoring oxypurinol levels to guide therapy.

Clinical Pharmacology and Therapeutics — Sat, 27 Aug 2011 06:58:28 +0100

Authors: Keith MP, Gilliland WR Abstract Urate-lowering therapy (ULT), adjusted to achieve and maintain a serum uric acid (SUA) of <6 mg/dl, remains the standard of care for the chronic management of gout. New urate-lowering medications are important options; however, these agents should be reserved for patients who do not tolerate or cannot achieve SUA <6 mg/dl on allopurinol. The result of oxypurinol monitoring to guide allopurinol therapy suggests that allopurinol should still be considered first-line ULT for gout. PMID: 21862966 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics)

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Phenotype and Outcome in Hereditary Tubulointerstitial Nephritis Secondary to UMOD Mutations.

Clinical Journal of the American Society of Nephrology : CJASN — Wed, 24 Aug 2011 23:00:00 +0100

Conclusions Hyperuricemia disproportionate to renal function represents the hallmark of renal disease caused by UMOD mutation. Renal survival is highly variable in patients with UMOD mutation. Our data also add novel insights into the interpretation of uricemia and UAEF in patients with chronic kidney diseases. PMID: 21868615 [PubMed - as supplied by publisher] (Source: Clinical Journal of the American Society of Nephrology : CJASN)

Kyrle’s disease successfully treated with allopurinol

International Journal of Dermatology — Sat, 20 Aug 2011 15:40:43 +0100

(Source: International Journal of Dermatology)

Allopurinol vascular effects support potential role in CAD therapy

MedWire News - Cardiology — Thu, 18 Aug 2011 00:00:00 +0100

Researchers have shown that allopurinol reduces vascular oxidative stress and improves endothelial dysfunction in patients with coronary artery disease receiving current optimal medical therapy. (Source: MedWire News - Cardiology)

Amelioration of diabetes‐induced cavernosal fibrosis by antioxidant and anti‐transforming growth factor‐β1 therapies in inducible nitric oxide synthase‐deficient mice

BJU International — Wed, 17 Aug 2011 23:00:00 +0100

CONCLUSION• Both allopurinol and decorin appear as promising approaches either as a single or a combined pharmacological modality for protecting the diabetic corpora from undergoing apoptosis and fibrosis although their functional effects still need to be defined. (Source: BJU International)

Efficacy and Tolerability of Pegloticase for the Treatment of Chronic Gout in Patients Refractory to Conventional Treatment: Two Randomized Controlled Trials [Original Contribution]

JAMA — Mon, 15 Aug 2011 23:00:00 +0100

Conclusion Among patients with chronic gout, elevated serum uric acid level, and allopurinol intolerance or refractoriness, the use of pegloticase 8 mg either every 2 weeks or every 4 weeks for 6 months resulted in lower uric acid levels compared with placebo. Trial Registration clinicaltrials.gov Identifier: NCT00325195 (Source: JAMA)

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Management of Gout in the Older Adult.

The American Journal of Geriatric Pharmacotherapy — Sun, 14 Aug 2011 23:00:00 +0100

CONCLUSION: Management of gout in the older adult involves careful selection of treatment based on potential benefits and consequences of therapy, considered in tandem with individual patient-specific characteristics. ClinicalTrials.gov identifiers NCT00549549, NCT01101035, NCT00241839, NCT01157936, NCT00997542, NCT00288158, and NCT00987415. PMID: 21849262 [PubMed - as supplied by publisher] (Source: The American Journal of Geriatric Pharmacotherapy)

Allopurinol/prednisolone: Drug eruption and disseminated strongyloidiasis with CMV infection in an elderly patient: case report

Reactions — Wed, 10 Aug 2011 17:36:32 +0100

(Source: Reactions)

Allopurinol: A New Anti-Ischemic Role for an Old Drug⁎

Journal of the American College of Cardiology — Wed, 10 Aug 2011 16:23:47 +0100

Pharmacologic treatment of stable ischemic heart disease has, until recently, been limited to the traditional agents that primarily improve the myocardial oxygen (O2) supply/demand balance by reducing myocardial O2 demand (). Beta-adrenergic blockers, nitrates, and calcium channel blockers have been the mainstays of such therapeutic strategies and they have enabled patients with a flow-limiting fixed luminal obstruction to increase their exercise capacity by reducing heart rate, blood pressure, and/or myocardial contractility. Because such therapy typically does not enhance myocardial blood flow, the maximum tolerated rate pressure product (heart rate × systolic blood pressure)—the routine marker of myocardial O2 demand—does not change during active therapy; the patient can simply exe...

Mechanistic Insights Into the Therapeutic Use of High-Dose Allopurinol in Angina Pectoris

Journal of the American College of Cardiology — Wed, 10 Aug 2011 16:23:46 +0100

Conclusions: Our study demonstrates that, in optimally treated CAD patients, high-dose allopurinol profoundly reduces vascular tissue OS and improves 3 different measures of vascular/endothelial dysfunction. The former effect on OS might underpin the anti-ischemic effect of allopurinol in CAD. Both effects (on OS and endothelial dysfunction) increase the likelihood that high-dose allopurinol might reduce future cardiovascular mortality in CAD, over and above existing optimum therapy. (Exploring the therapeutic potential of xanthine oxidase inhibitor allopurinol in angina; ISRCTN15253766) (Source: Journal of the American College of Cardiology)

The aged-related increase in xanthine oxidase expression and activity in several tissues from mice is not shown in long-lived animals.

Biogerontology — Mon, 08 Aug 2011 23:00:00 +0100

Authors: Vida C, Rodríguez-Terés S, Heras V, Corpas I, De la Fuente M, González E Xanthine oxidase (XO) is an important source of oxidant production and plays an essential role in several oxidative stress-related diseases. Aging is associated with a progressive deregulation of homeostasis as a result of a chronic oxidative stress situation. In the present work the age-related changes in XO expression and activity, as well as the activities of superoxide dismutase and catalase have been investigated in liver, kidney and thymus from four different age groups of mice, including long-lived animals. Furthermore, we have evaluated the contribution of the XO to the oxidative stress-associated with aging, in comparison to another enzymatic key source of oxidant generation, the NADPH oxidase...

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Potential teratogenic effects of allopurinol: A case report

American Journal of Medical Genetics Part A — Tue, 02 Aug 2011 23:00:00 +0100

We report on a case of a multiple congenital anomalies in a newborn infant whose mother was on allopurinol treatment through the pregnancy. The pattern of congenital anomalies that was noted in our patient was similar to the pattern described in a number of published reports following mycophenolate mofetil [CellCept®] treatment during pregnancy. The anomalies present in our patient include: diaphragmatic hernia, unilateral microtia and absence of external auditory canal, micrognathia, microphthalmia, optic nerve hypoplasia, hypoplasia of the corpus callosum, unilateral renal agenesis, pulmonary agenesis, and cleft lip and palate. Since both allopurinol and mycophenolate mofetil act by disrupting purine biosynthesis and given the similarities in anomalies seen after prenatal exposure, we s...

Association of Serum Uric Acid With Graft Survival After Kidney Transplantation: A Time‐Varying Analysis

American Journal of Transplantation — Tue, 02 Aug 2011 23:00:00 +0100

We examined the predictive value of UA during the first year posttransplant as a time‐varying factor for graft survival after adjustment for time‐dependent and independent confounding factors. Four hundred and eighty‐eight renal allograft recipients transplanted from January 2004 to June 2006 and followed for 41.1 ± 17.7 months were included. Data on UA, estimated glomerular filtration rate (eGFR), tacrolimus level, mycophenolate mofetil (MMF) and prednisone doses, use of allopurinol, angiotensin‐converting enzyme‐inhibitor/angiotensin‐receptor‐blocker (ACEi/ARB) and diuretics at 1, 3, 6, 9 and 12 months were collected. Primary endpoint of the study was graft loss, defined as graft failure and death. Cox proportional hazard models and generalized estimating equations were us...

Lesinurad Cuts Uric Acid in Refractory Gout: Ninety percent of patients who remained on treatment for 28 weeks met the study's target level.

Rheumatology News — Sun, 31 Jul 2011 23:00:00 +0100

Major Finding: After 4 weeks of treatment with a combination of 200-600 mg/day lesinurad plus allopurinol and colchicine, 71%-87% of patients had serum uric acid levels lower than 6 mg/dL, compared with 28% of patients who were treated with allopurinol, colchicine, and placebo. (Source: Rheumatology News)

Improved management of acute gout during hospitalization following introduction of a protocol

APLAR Journal of Rheumatology — Wed, 27 Jul 2011 23:00:00 +0100

Conclusion: Following introduction of a hospital‐wide protocol for acute gout management, there have been significant improvements in the management of acute gout by non‐rheumatologist clinicians. (Source: APLAR Journal of Rheumatology)

Thiazide and Loop Diuretics

The Journal of Clinical Hypertension — Tue, 26 Jul 2011 23:00:00 +0100

Key Points and Practical Recommendations• Although chlorthalidone and hydrochlorothiazide are structurally similar, they are very different pharmacokinetically, with chlorthalidone having both an extremely long half‐life (approximately 40 to 60 hours) and a large volume of distribution, with gradual elimination from the plasma compartment by tubular secretion.• Furosemide usage, the most widely used diuretic in the loop diuretic class, can be complicated by extremely erratic absorption, with a bioavailability range of 12% to 112%.• Chlorthalidone, at a dose of 25 mg, is comparatively more potent than 50 mg of hydrochlorothiazide, particularly as related to overnight blood pressure reduction.• In ALLHAT, there was no difference among chlorthalidone, amlodipine, lisin...

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Initiating allopurinol therapy: do we need to know the patient's HLA status?

Internal Medicine Journal — Sun, 24 Jul 2011 23:00:00 +0100

Conclusions: Cases of AH manifesting as SJS/TENS in Australians are more likely to be in those of Asian heritage. The place of routine testing for HLA‐B*5801 prior to commencing allopurinol therapy requires further investigation. However, Han Chinese origin patients commencing allopurinol might be informed of the test and may elect to have it performed as there are alternative hypouricaemic medicines such as probenecid thereby reducing the risk of a catastrophic reaction to allopurinol. (Source: Internal Medicine Journal)

Allopurinol: Agranulocytosis in an elderly patient: case report

Reactions — Sun, 24 Jul 2011 19:59:43 +0100

(Source: Reactions)

A Randomized Study of Allopurinol on Endothelial Function and Estimated Glomular Filtration Rate in Asymptomatic Hyperuricemic Subjects with Normal Renal Function.

Clinical Journal of the American Society of Nephrology : CJASN — Thu, 21 Jul 2011 23:00:00 +0100

Conclusions Treatment of hyperuricemia with allopurinol improves endothelial dysfunction and eGFR in subjects with asymptomatic hyperuricemia. PMID: 21784838 [PubMed - as supplied by publisher] (Source: Clinical Journal of the American Society of Nephrology : CJASN)

Potential Pharmacologic Treatments for Cystinuria and for Calcium Stones Associated with Hyperuricosuria.

Clinical Journal of the American Society of Nephrology : CJASN — Wed, 13 Jul 2011 23:00:00 +0100

Authors: Goldfarb DS Two new potential pharmacologic therapies for recurrent stone disease are described. The role of hyperuricosuria in promoting calcium stones is controversial with only some but not all epidemiologic studies demonstrating associations between increasing urinary uric acid excretion and calcium stone disease. The relationship is supported by the ability of uric acid to "salt out" (or reduce the solubility of) calcium oxalate in vitro. A randomized, controlled trial of allopurinol in patients with hyperuricosuria and normocalciuria was also effective in preventing recurrent stones. Febuxostat, a nonpurine inhibitor of xanthine oxidase (also known as xanthine dehydrogenase or xanthine oxidoreductase) may have advantages over allopurinol and is being tested in a similar ...

Reactive oxygen species (ROS) from NADPH and xanthine oxidase modulate the cutaneous local heating response in healthy humans

Journal of Applied Physiology — Sun, 10 Jul 2011 23:00:00 +0100

Local cutaneous heating produces vasodilation that is largely nitric oxide (NO) dependent. We showed that angiotensin II (ANG II) attenuates this by an ANG II receptor, type 1 (AT1R)-dependent mechanism that is reversible with the antioxidant ascorbate, indicating oxidative stress. Reactive oxygen species (ROS) produced by ANG II employ NADPH and xanthine oxidase pathways. To determine whether these mechanisms pertain to skin, we measured cutaneous local heating with 10 µM ANG II, using apocynin to inhibit NADPH oxidase and allopurinol to inhibit xanthine oxidase. We also inhibited superoxide with tempol, and H2O2 with ebselen. We heated the skin of the calf in 8 healthy volunteers (24.5–29.9 yr old) to 42°C and measured local blood flow to assess the percentage of maximum ...

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Results of and further prevention of hypoxic fetal brain damage by inhibition of xanthine oxidase enzyme with allopurinol

Journal of Perinatal Medicine — Thu, 07 Jul 2011 20:53:09 +0100

Journal of Perinatal Medicine 39 (4): 441-444 Abstract Several experimental models on adult and newborn animals showed that in cerebral hypoxic-ischemic conditions similar to clinical states the main source of the excessive production of free oxygen radicals is the highly activated xanthine oxidase (XO) enzyme reaction. Long before this data were available, it became known that the main role of allopurinol (AP) is the inhibition of XO. On the basis of these results, many therapeutic trials with AP were performed both in experimental and clinical studies of ischemia and reperfusion. However, it has been shown that only preventive administration of AP has favorable effects. The explanation for the poor results of AP treatment in human fetal brain damage (FBD) cases is that the drug was appli...

Allopurinol/thiopurines: Infectious complications: 5 case reports

Reactions — Sun, 03 Jul 2011 18:34:01 +0100

(Source: Reactions)

Safety and Efficacy of Febuxostat Treatment in Subjects with Gout and Severe Allopurinol Adverse Reactions.

J Rheumatol — Thu, 30 Jun 2011 23:00:00 +0100

CONCLUSION: In 12 of our 13 gout patients with previously documented severe allopurinol AE, FEB treatment was safe. However, the development of a hypersensitivity type cutaneous vasculitis (likely but not definitively FEB-related) early in treatment mandates caution, careful dose escalation, and close monitoring when FEB urate-lowering therapy of allopurinol-intolerant patients is considered. PMID: 21724706 [PubMed - as supplied by publisher] (Source: J Rheumatol)

As First-Line Gout Tx, Allopurinol Is Effective, Economical

Rheumatology News — Thu, 30 Jun 2011 23:00:00 +0100

SAN DIEGO – Allopurinol should remain the first-line agent for gout prophylaxis, despite competition from a newer drug, febuxostat, according to Dr. John Pendleton. Allopurinol is very effective, can be safely titrated for those with renal impairment, and is the most cost-effective option, he said at the meeting. (Source: Rheumatology News)

Management of asymptomatic hyperuricaemia in patients with chronic kidney disease by Japanese nephrologists: A questionnaire survey

Nephrology — Tue, 28 Jun 2011 15:48:55 +0100

Conclusion: Most Japanese nephrologists treat AHU in pre‐dialysis CKD with an aim to prevent CKD progression or CVE mainly by allopurinol. (Source: Nephrology)

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Profile and Pattern of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in a General Hospital in Singapore: Treatment Outcomes.

Acta Dermato-Venereologica — Mon, 27 Jun 2011 23:00:00 +0100

In conclusion, anti-convulsants, especially carbamazepine, were the most frequently implicated drugs, followed by antibiotics and NSAIDS. High-dose corticosteroids were effective in SJS, whereas intra-venous immunoglobulin were useful in TEN and SJS/TEN overlap syndrome. Key words: Stevens-Johnson syndrome; toxic epidermal necrolysis; Singapore. PMID: 21710108 [PubMed - as supplied by publisher] (Source: Acta Dermato-Venereologica)

Minimally important differences of the gout impact scale in a randomized controlled trial

Rheumatology — Wed, 15 Jun 2011 23:00:00 +0100

Conclusion. The MID estimates for GIS scales are between 5 and 8 points (0–100 scale). This information can aid in interpreting the GIS results in future gout RCTs. Trial Registration. Clinicaltrials.gov, www.clinicaltrials.gov, NCT00610363. (Source: Rheumatology)

Rilonacept Inhibits Gout Flares in Patients on Allopurinol

Medscape Today Headlines — Mon, 06 Jun 2011 17:38:19 +0100

Phase 3 data support the concept of IL-1 inhibition in preventing gout flares in patients receiving uric-acid-lowering therapy. Medscape Medical News (Source: Medscape Today Headlines)

Allopurinol: Hypersensitivity syndrome, Stevens-Johnson syndrome and toxic epidermal necrolysis: 25 case reports

Reactions — Sun, 05 Jun 2011 19:54:23 +0100

(Source: Reactions)

Allopurinol/bevacizumab interaction: Toxic epidermal necrolysis: case report

Reactions — Sun, 05 Jun 2011 19:54:23 +0100

(Source: Reactions)

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Urate Inhibitor Shows Promise in Gout

Medscape Today Headlines — Fri, 03 Jun 2011 19:48:23 +0100

Lesinurad in combination with allopurinol achieves rapid reductions in urate levels in patients with uncontrolled gout. Medscape Medical News (Source: Medscape Today Headlines)

Stevens–Johnson syndrome after lenalidomide therapy for multiple myeloma: a case report and a review of treatment options

Hematological Oncology — Tue, 31 May 2011 23:00:00 +0100

AbstractStevens‐ Johnson syndrome (SJS) is a severe and life‐threatening condition. Although allopurinol, an antihyperuricemia drug, is the drug most commonly associated with SJS, more than 100 different causative drugs have been reported. Among hematologic drugs recently introduced into the market, drugs such as rituximab, imatinib, and bortezomib are reported. Here, we describe a patient with SJS while receiving lenalidomide in combination with prednisolone for treatment‐naïve multiple myeloma. Although SJS has been reported rarely as an adverse reaction to Lenalidomide, this drug should be considered in the etiology of SJS, and the increased number of prescriptions of Lenalidomide for the therapy of multiple myeloma has to stress the awareness of its potentially serious side‐ef...

Tumour lysis syndrome in children: experience of last decade

Hematological Oncology — Tue, 31 May 2011 23:00:00 +0100

AbstractThe strategy against tumour lysis syndrome (TLS) had been hyperhydration, urine alkalinization, and allopurinol. Recently, rasburicase was added to the armament against this life‐threatening condition. In Korea, rasburicase is used as a rescue therapy for cases with allopurinol‐resistant hyperuricemia, because of the restriction by the National Health Insurance. We reviewed our experiences to re‐assess the risk factors of TLS and the efficacy of rasburicase. Medical records were retrospectively reviewed for 396 children who were diagnosed as positive with acute leukemia and non‐Hodgkin lymphoma between the years 2000 and 2009. The risk factors for TLS were analyzed statistically, and those before and after the availability of rasburicase were compared. Sixty eight patients ...

Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol treatment: results of a double-blind, randomised study

Annals of the Rheumatic Diseases — Thu, 26 May 2011 23:00:00 +0100

Conclusions Single canakinumab doses ≥50 mg or four 4-weekly doses provided superior prophylaxis against flares compared with daily colchicine 0.5 mg. (Source: Annals of the Rheumatic Diseases)

Impact of Elevated Uric Acid on Ventricular Remodeling in infarcted Rats with Experimental Hyperuricemia.

American Journal of Physiology. Heart and Circulatory Physiology — Thu, 26 May 2011 23:00:00 +0100

Authors: Chen CC, Hsu YJ, Lee TM Hyperuricemia is associated with cardiovascular disease, but it is usually considered a marker rather than a risk factor. Previous studies using uric acid-lowering drugs in normouricemic animals are not suitable to answer the effect of hyperuricemia on ventricular remodeling after myocardial infarction. The purpose of this study was to determine whether hyperuricemia adversely affects ventricular remodeling in infarcted rats with elevated uric acid. Male Wistar rats aged 8 weeks were randomly assigned into either vehicle, oxonic acid, oxonic acid + allopurinol, oxonic acid + benzbromarone, oxonic acid + ABT-627, or oxonic acid + tempol for 4 weeks starting 24 hours after ligation. Post-infarction was associated with increased oxidant production, as meas...

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EULAR: Novel Drug Effective for Refractory Gout (CME/CE)

MedPage Today Rheumatology — Thu, 26 May 2011 20:43:11 +0100

LONDON (MedPage Today) -- Patients with refractory gout had rapid and sustained lowering of serum urate after a month of treatment with the investigational agent lesinurad along with allopurinol, a researcher said here. (Source: MedPage Today Rheumatology)

Additional Results From A Phase 2b Study Of Lesinurad In Combination With Allopurinol

Health News from Medical News Today — Thu, 26 May 2011 15:00:00 +0100

Ardea Biosciences, Inc. (Nasdaq: RDEA) announced today that additional positive clinical and preclinical results from its development program of lesinurad, the Company's lead product candidate for the treatment of hyperuricemia and gout, were presented at the Annual European Congress of Rheumatology hosted by the European League Against Rheumatism (EULAR) in London, UK... (Source: Health News from Medical News Today)

Febuxostat vs Allopurinol: And the Winner Is...

Medscape Today Headlines — Tue, 24 May 2011 18:00:00 +0100

Dr. Kevin Deane discusses CONFIRMS trial data comparing the efficacy and safety of febuxostat in the treatment of hyperuricemia in gout with that of allopurinol. Medscape Rheumatology (Source: Medscape Today Headlines)

Major histocompatibility complex class I-related chain A/B (MICA/B) expression in tumor tissue and serum of pancreatic cancer: Role of uric acid accumulation in gemcitabine-induced MICA/B expression

BMC Cancer — Sun, 22 May 2011 23:00:00 +0100

Conclusions: The levels of MICA/B expression in serum and tissue of pancreatic cancer are elevated. DNA damage-induced MICA/B expression is mediated through increased uric acid production. (Source: BMC Cancer)

Gout treatment and comorbidities: a retrospective cohort study in a large US managed care population.

BMC Musculoskeletal Disorders — Thu, 19 May 2011 23:00:00 +0100

Conclusions: Comorbidities affected gout treatment patterns and the occurrence and frequency of acute attacks. Cardiometabolic comorbidities, common in this patients' population, were associated with an increased risk of flares. (Source: BMC Musculoskeletal Disorders)

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Tophaceous Gout and Renal Insufficiency: A New Solution for an Old Therapeutic Dilemma

Clinical and Developmental Immunology — Sat, 14 May 2011 14:00:32 +0100

The prevalence of gout is increasing with increased life expectancy. Approximately half of the patients with gout have some degree of renal impairment. If both conditions persistently coexist, and in severe tophaceous gout, in particular, treatment has been difficult. We here report on the case of an 87-year-old woman, who had been suffering from recurrent gouty arthritis over 4 years. Monthly polyarthritis attacks were accompanied by subcutaneous tophi. Serum uric acid levels were constantly above 600 μmol/L (10 mg/dL). Allopurinol was no option because of intolerance, while benzbromarone was ineffective because of renal impairment. Therefore, the novel xanthin oxidase inhibitor febuxostat was started, achieving rapid control of serum urate levels (<360 ...

Adenuric film-coated tablets (febuxostat) - Revised SPC

NeLM - SPC Changes — Thu, 12 May 2011 23:00:00 +0100

Source: eMC (electronic Medicines Compendium) Area: Other Library Updates > SPC Changes Section 4.8 of the SPC for Adenuric has been updated to include the following: There have been post marketing reports of rare serious rashes, generalised skin rashesand severe hypersensitivity reactions. In most cases, these reactions occured during the first month of therapy with febuxostat. Some of these patients, but not all, reported previous hypersensitivity to allopurinol. Please see below for link to SPC and full prescribing information. (Source: NeLM - SPC Changes)

Allopurinol/azathioprine interaction: Pure red cell aplasia: case report

Reactions — Wed, 11 May 2011 17:13:45 +0100

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Effects of Genistein, Apigenin, Quercetin, Rutin and Astilbin on serum uric acid levels and xanthine oxidase activities in normal and hyperuricemic mice.

Food and Chemical Toxicology — Mon, 09 May 2011 23:00:00 +0100

Authors: Huang J, Wang S, Zhu M, Chen J, Zhu X Flavonoids are widely found in plants and many of them possess biological and pharmacological activities. In the present study, we assessed the effects of the flavonoids Genistein, Apigenin, Quercetin, Rutin and Astilbin on xanthine oxidase (XO) activities in vitro, and in serum and the liver. The effects of the flavonoids on serum uric acid levels were also measured in vivo. In vitro studies indicated that the flavonoids tested did not significantly affect XO activity. However, significant increases and decreases in XO activities were observed in vivo. Moreover, serum XO activity was correlated with serum uric acid levels, while no correlation was observed for liver XO activity. The present study showed that serum uric acid levels in mice...

ALLOPURINOL (Allopurinol) Tablet [REMEDYREPACK INC. ]

DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST) — Mon, 09 May 2011 05:00:00 +0100

Updated Date: May 9, 2011 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

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Gastric Ulcerogenic and Healing Impairment Actions of Alendronate, A Nitrogen-Containing Bisphosphonate - Prophylactic Effects of Rebamipide.

Current Pharmaceutical Design — Thu, 05 May 2011 23:00:00 +0100

Authors: Takeuchi K, Kato S, Amagase K Alendronate, a nitrogen containing bisphosphonate (BP), when given p.o., decreased the transmucosal potential difference by direct irritating action, resulting in non-hemorrhagic lesions in both the corpus and antrum of fasted rats. After refeeding for 3 days the lesions in the corpus healed, while those in the antrum developed into large ulcers with increased vascular permeability; the damaged mucosa was covered with a white cap, mainly composed of fibrin-like substances and exfoliated cells. These ulcers were accompanied by an increase in MPO activity and lipid peroxidation as well as a decrease in SOD activity and GSH content in the mucosa. Neither omeprazole nor indomethacin had any effect, while allopurinol and SOD reduced the severity of the...

Effects of allopurinol and preconditioning on apoptosis due to ischemia-reperfusion on a double jejunum-segment canine model.

Acta Cirurgica Brasileira — Thu, 05 May 2011 22:01:03 +0100

Authors: Brath E, Miko I, Nemeth N, Kovacs J, Peto K, Furka I To investigate the duration of apoptosis caused by ischemia-reperfusion in the intestine in a new double jejunum-segment model, and to analyze the protective effects of allopurinol or ischemic preconditioning (IPC). PMID: 21537520 [PubMed - in process] (Source: Acta Cirurgica Brasileira)

Allopurinol: DRESS syndrome in an elderly patient: case report

Reactions — Sun, 24 Apr 2011 16:50:04 +0100

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A new method for the quantification of superoxide dismutase mimics with an allopurinol-xanthine oxidase-lucigenin enhanced system.

Journal of Biological Inorganic Chemistry : JBIC — Fri, 22 Apr 2011 23:00:00 +0100

Authors: Stoica BA, Bordeianu G, Stanescu R, Serban DN, Nechifor M Allopurinol is a prodrug converted to oxypurinol by xanthine oxidase, a process followed by an efficient enzyme inhibition. Using a lucigenin-enhanced chemiluminescence method, we found that, under alkaline conditions, superoxide radicals are produced in large amounts in the first step of the interaction between the enzyme and the inhibitor. A comparison between lucigenin and cytochrome c as final detectors revealed that only the chemiluminescence technique is able to detect the superoxide anions from allopurinol oxidation. The allopurinol-xanthine oxidase-lucigenin system can be used for the quantification of various free-radical scavengers, in particular superoxide dismutase mimics. Three manganese compounds from diff...

Rapid screening for the detection of HLA‐B57 and HLA‐B58 in prevention of drug hypersensitivity

Tissue Antigens — Mon, 18 Apr 2011 23:00:00 +0100

HLA‐B57 and HLA‐B58 are major histocompatibility class (MHC)‐I allotypes that are potentially predictive of important clinical immune phenotypes. HLA‐B*5701 is strongly associated with hypersensitivity to the HIV drug abacavir, liver toxicity from the antibiotic flucloxacillin and is a marker for slow progression of HIV AIDS. HLA‐B*5801 is associated with hypersensitivity to allopurinol used to treat hyperuricaemia and recurrent gout. Here we describe a monoclonal antibody (mAb) specific for HLA‐B57 and HLA‐B58 that provides an inexpensive and sensitive screen for these MHC‐I allotypes. The usefulness of HLA‐B57 screening for prediction of abacavir hypersensitivity was shown in three independent laboratories, including confirmation of the mAb sensitivity and specificity i...

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Frequency and risk factors of gout flares in a large population-based cohort of incident gout

Rheumatology — Thu, 14 Apr 2011 23:00:00 +0100

Conclusions. Gout flares are relatively common among patients with gout. Some of the underlying cardiometabolic comorbid conditions are themselves independent risk factors for flares, which further contribute to the complexity of treatment of gout flares. (Source: Rheumatology)

Febuxostat inhibition of endothelial-bound XO: Implications for targeting vascular ROS production.

Free Radical Biology and Medicine — Thu, 14 Apr 2011 23:00:00 +0100

Authors: Malik UZ, Hundley NJ, Romero G, Radi R, Freeman BA, Tarpey MM, Kelley EE Xanthine oxidase (XO) is a critical source of reactive oxygen species (ROS) that contribute to vascular inflammation. Binding of XO to vascular endothelial cell glycosaminoglycans (GAGs) results in significant resistance to inhibition by traditional pyrazolopyrimidine-based inhibitors such as allopurinol. Therefore, we compared the extent of XO inhibition (free and GAG-bound) by allopurinol to that by febuxostat, a newly approved nonpurine XO-specific inhibitor. In solution, febuxostat was 1000-fold more potent than allopurinol at inhibiting XO-dependent uric acid formation (IC(50)=1.8nM vs 2.9μM). Association of XO with heparin-Sepharose 6B (HS6B-XO) had minimal effect on the inhibition of uric acid for...

Infectivity to Phlebotomus perniciosus of dogs naturally parasitized with Leishmania infantum after different treatments

Parasites and Vectors — Tue, 12 Apr 2011 23:00:00 +0100

Conclusion: The three treatment regimens tested significantly reduced the infectivity of dogs towards sand flies, thus diminishing the epidemiological risks of treated dogs both for human beings and other healthy dogs. Despite its low cure rate, the use of allopurinol after a course of leishmanicide treatment is proposed to keep dogs non-infectious during the disease transmission season (4-6 months in southern Europe). (Source: Parasites and Vectors)

Is it the inflammation or the free radicals that cause ischemia/reperfusion lung injury?

Translational Research — Tue, 12 Apr 2011 23:00:00 +0100

Ischemia-reperfusion (I/R)-related pulmonary injury is a clinical problem responsible for some cases of acute allograft failure after lung transplantation and is important after spontaneous and surgical resolution of pulmonary emboli, for lung reexpansion after pneumothorax, and during the return of spontaneous circulation after cardiac arrest. Much mechanistic data link reactive oxygen species (ROS) such as H2O2, O2-, and peroxynitrites to the pathophysiology of I/R injury in lung, heart, intestine, liver, and kidney allografts; other data show that interruption of ROS generation or scavenging attenuates injury in these organs. For this reason, most allografts are preserved with a cold solution containing, among other things, antioxidants such as allopurinol and glutathione. Although a ro...

Inhibition of Xanthine Oxidase by Thiosemicarbazones, Hydrazones and Dithiocarbazates Derived from Hydroxy-Substituted Benzaldehydes.

ChemMedChem — Thu, 07 Apr 2011 23:00:00 +0100

Authors: Leigh M, Raines DJ, Castillo CE, Duhme-Klair AK Nonpurine xanthine oxidoreductase (XOR) inhibitors represent important alternatives to the purine analogue allopurinol, which is still the most widely used drug in the treatment of conditions associated with elevated uric acid levels in the blood. By condensing mono-, di- and trihydroxybenzaldehydes with aromatic thiosemicarbazides, aryl hydrazides and dithiocarbazates, three series of structurally related Schiff bases were synthesised, characterised and tested for XOR inhibitory activity. Hydroxy substitution in the para-position of the benzaldehyde component was found to confer high inhibitory activities. Acyl hydrazones were generally less potent than thiocarbonyl-containing Schiff bases. Within the thiosemicarbazone series, c...

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Allopurinol/antibacterials: Toxic epidermal necrolysis, Stevens-Johnson syndrome and bullous erythema multiforme: 4 case reports

Reactions — Mon, 04 Apr 2011 16:58:12 +0100

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A study of HLA class I and class II 4‐digit allele level in Stevens–Johnson syndrome and toxic epidermal necrolysis

International Journal of Immunogenetics — Thu, 31 Mar 2011 23:00:00 +0100

SummaryStevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are represented by rare but life‐threatening cutaneous adverse reactions to different drugs. Previous studies have found that in a Han Chinese population from Taiwan and other Asian Countries, a strong genetic association between HLA‐class I alleles (B*15:02, B*58:01) and SJS and TEN was induced by carbamazepine and allopurinol, respectively. To identify genetic markers that covered the MHC region, we carried out a case–control association enrolling 20 Caucasian patients with SJS/TEN. Our patient series included 10 cases related to paracetamol, 7 to allopurinol and 3 to different drugs (plaquenil, itraconazol, nabumetone). Healthy controls were represented by 115 Caucasian bone marrow or stem cell donors. Th...

Hypouricemic Effects of Anthocyanin Extracts of Purple Sweet Potato on Potassium Oxonate‐induced Hyperuricemia in Mice

Phytotherapy Research — Thu, 24 Mar 2011 00:00:00 +0100

Gout is a clinical syndrome in which tissue damage is induced by a chronic metabolic disorder associated with increased concentrations of uric acid in the blood. The study investigated the hypouricemic effects of anthocyanin extracts from purple sweet potato (APSP), and allopurinol, on serum uric acid levels in hyperuricemic mice. It was found that administration of a single oral dose of 100 mg/kg APSP to such animals reduced the serum uric acid concentration to 4.10 ± 0.04 mg/dL, compared with a concentration of 10.25 ± 0.63 mg/dL in the hyperuricemic control group. Copyright © 2011 John Wiley & Sons, Ltd. (Source: Phytotherapy Research)

An unusual cause of elevated liver function tests in an elderly female

Journal of Clinical Virology — Wed, 23 Mar 2011 00:00:00 +0100

An 84-years-old female patient was admitted to a hospital from a nursing home in Hamburg (Germany) for the optimization of her insulin regimen for diabetes mellitus type 2. She further suffered from coronary heart disease, heart insufficiency NYHA III, cardiac arrhythmia, malignant melanoma, chronic obstructive lung disease, dementia and hypothyreosis. Her daily medication comprised a fixed insulin scheme, simvastatin, aspirin, clopidogrel, molsidomine, digitoxin, metoprolol, enalapril, furosemide, hydrochlorothiazide, spironolactone, pantoprazole, allopurinol, levothyroxine, oxazepam, acetylcysteine, as well as inhaled formoterol. She had signs of diabetic polyneuropathia and was obese (body mass index 31). (Source: Journal of Clinical Virology)

Management of Common Oncologic Emergencies

Indian Journal of Pediatrics — Fri, 11 Mar 2011 18:09:25 +0100

Abstract The common oncologic emergencies include Superior Vena Cava Syndrome (SVCS) and Superior Mediastinal Syndrome (SMS), Tumor Lysis Syndrome (TLS), Hyperleukocytosis and Febrile Neutropenia. SVCS denotes compression, obstruction or thrombosis of SVC and SMS denotes SVCS and tracheal compression. The diagnosis should be established early with minimum invasive techniques. Steroids should be administered immediately. Sedatives are contraindicated. TLS describes the metabolic derangements in various combinations that include hyperuricemia, hyperphosphatemia, hyperkalemia hypocalcemia and uremia which arise from death of and release of contents from tumor cells. Early recognition of patients at risk and initiation of preventive therapy for TLS is essential. Treatment is d...

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A case series of allopurinol-induced toxic epidermal necrolysis

Indian Journal of Dermatology — Thu, 10 Mar 2011 00:00:00 +0100

We report four cases of toxic epidermal necrolysis from allopurinol, three of which resulted in death. Our aim is to highlight that allopurinol in all these cases was not indicated and prescribed for asymptomatic hyperuricemia. The incidence and potentially severe and lethal consequences of allopurinol hypersensitivity syndrome and toxic epidermal necrolysis could be kept to a minimum by strictly adhering to the established indications of allopurinol treatment. (Source: Indian Journal of Dermatology)

Allopurinol, uric acid, and oxidative stress in cardiorenal disease

International Urology and Nephrology — Wed, 09 Mar 2011 16:51:20 +0100

Abstract In humans, the hepatic end product of purine metabolism is uric acid. Serum uric acid levels physiologically and gradually rise during human lifetime. Hyperuricemia also arises from excess dietary purine or ethanol intake, decreased renal excretion of uric acid, tumor lysis in lymphoma, leukemia or solid tumors, and sometimes pharmacotherapy. The definition of hyperuricemia is currently arbitrary. Hyperuricemia is associated with chronic kidney disease, arterial hypertension, coronary artery and heart disease, cerebrovascular disease and diabetes mellitus. Xanthine oxidase, a hepatic enzyme, catalyzes the production of uric acid, nitric oxide, and reactive oxygen species, which potentially damage deoxyribonucleic acid, ribonucleic acid and proteins, inactivate enz...

Case report of extensive metabolism by aldehyde oxidase in humans: Pharmacokinetics and metabolite profile of FK3453 in rats, dogs, and humans.

Xenobiotica — Wed, 09 Mar 2011 00:00:00 +0100

We describe the preclinical and clinical pharmacokinetic profiles of FK3453 [6-(2-amino-4-phenylpyrimidin-5-yl)-2-isopropylpyridazin-3(2H)-one] and the mechanism responsible for poor oral exposure of FK3453 in humans. FK3453 showed favourable profiles in preclinical pharmacokinetic studies, including satisfactory absolute bioavailability and total body clearance in animals (30.5%-41.4%, 54.7%-68.2%, and 71.3%-93.4% and 10.8-17.6, 1.9-17.1, and 5.0 mL/min/kg in male rats, female rats, and dogs, respectively), and good metabolic stability in liver microsomes (42.3, 14.5, and 1.1 mL/min/kg in male rats, dogs, and humans, respectively). However, despite these promising preclinical findings, plasma concentrations of FK3453 in humans were extremely low, with the oxidative metabolite of the a...

Horizon scanning: Rilonacept (Arcalyst®) meets primary and secondary endpoints in second phase III trial of prevention of gout flares in patients initiating allopurinol

NeLM - News — Fri, 04 Mar 2011 00:00:00 +0100

Source: BioSpace Area: News Interleukin-1 (IL-1) is key driver of inflammation in a variety of diseases. In gout, uric acid crystals stimulate the production of IL-1, which causes an inflammatory response in the joints and surrounding tissues. Rilonacept, also known as IL-1 Trap (Arcalyst®) inhibits IL-1. In a second phase III trial examining its use for the prevention of gout flares in patients initiating allopurinol, rilonacept met the primary and secondary endpoints. The primary endpoint was the number of gout flares per patient over the 16-week treatment period. Patients who received rilonacept at a weekly, self-administered, subcutaneous dose of either 160mg (n=84) or 80 mg (n=82) had a 72% (p<0.0001) relative reduction in mean number of gout flares compared to the pla...

Contemporary epidemiology of gout in the UK general population

Arthritis Research and Therapy — Thu, 03 Mar 2011 00:00:00 +0100

Conclusions: The contemporary incidence of gout in UK remains substantial. In this general population cohort, associations with previously purported risk factors were evident including psoriasis, heart failure, hypertriglyceridemia, and cyclosporine therapy. Use of gout-specific treatment has remained relatively constant in recent years except for an increase of colchicine. (Source: Arthritis Research and Therapy)

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The DRESS Syndrome: The Great Clinical Mimicker

Pharmacotherapy: Official Journal of the American College of Clinical Pharmacy — Tue, 01 Mar 2011 00:00:00 +0100

We describe a 44-year-old woman who was brought to the emergency department with new-onset hemorrhagic stroke. She was admitted to the intensive care unit where she received supportive care that included clonidine and hydralazine for blood pressure control and phenytoin for seizure prophylaxis. On hospital day 21, the patient developed signs and symptoms of severe sepsis. Despite receipt of broad-spectrum antibiotics (vancomycin and piperacillin-tazobactam) and supportive care, the patient's clinical condition worsened with progressive jaundice, severe oliguria, and labile blood pressures. All cultures revealed no growth, and her chest radiograph remained clear. Several days after the onset of her fever, the patient developed several hematologic abnormalities including thrombocytopenia, wi...

Febuxostat for treatment of chronic gout.

American Journal of Health-System Pharmacy : AJHP — Tue, 01 Mar 2011 00:00:00 +0100

Conclusion Febuxostat is efficacious as a second-line therapy in lowering serum uric acid levels in patients with gout. Febuxostat may be an alternative for patients with gout who are unable to take allopurinol due to hypersensitivity, intolerance, or lack of efficacy. PMID: 21330679 [PubMed - in process] (Source: American Journal of Health-System Pharmacy : AJHP)

Allopurinol: DRESS syndrome and fatal liver failure in an elderly patient: case report

Reactions — Sun, 27 Feb 2011 18:11:29 +0100

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Phenytoin- and cranial radiotherapy-induced toxic epidermal necrolysis treated with combination therapy: systemic steroid and intravenous immunoglobulin

Medical Oncology — Thu, 24 Feb 2011 07:58:13 +0100

Abstract Toxic epidermal necrolysis (TEN) is a rare dermatological disease that causes serious morbidity and mortality. It may be caused by antibiotics, anticonvulsants, nonsteroidal anti-inflammatory agents, allopurinol, infections, autoimmune diseases, and radiotherapy. A 49-year-old man was admitted to our hospital because of skin changes. Prophylactic phenytoin was administered, and cranial radiotherapy was planned for brain metastases. During these treatments, erythematous lesions and blisters were observed on his scalp, face, neck, the front and back of his body, and his arms. Detachment of the skin, especially on the back, was also observed. TEN was diagnosed, and phenytoin was discontinued. Methylprednisolone 80 mg/day IV and intravenous immunoglobulin 1 ...

Allopurinol hypersensitivity syndrome with acute generalized exanthematous pustulosis manifestations.

Cutaneous and Ocular Toxicology — Thu, 24 Feb 2011 00:00:00 +0100

We report a case of AHS with the cutaneous manifestation of acute generalised exanthematous pustulosis(AGEP). A 47 year old gentleman, with no previous skin disease, presented with a generalized mildly pruritic erythematous rash on the trunk and all 4 limbs, with patches of superficial non-follicular pustules. Our patient fulfilled both criteria for AGEP and AHS. PMID: 21345152 [PubMed - as supplied by publisher] (Source: Cutaneous and Ocular Toxicology)

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Pharmacogenetics of cutaneous adverse drug reactions

The Journal of Dermatology — Wed, 23 Feb 2011 16:28:11 +0100

This article reviews the progress in pharmacogenomics, associated mainly with carbamazepine and allopurinol in different ethnic populations. Pharmacogenetic screening based on associations between adverse reactions and specific HLA alleles helps to avoid serious conditions associated with drug hypersensitivity. (Source: The Journal of Dermatology)

Hyperuricemia as a Mediator of the Proinflammatory Endocrine Imbalance in the Adipose Tissue in a Murine Model of the Metabolic Syndrome.

Diabetes — Wed, 23 Feb 2011 00:00:00 +0100

CONCLUSIONS Hyperuricemia might be partially responsible for the proinflammatory endocrine imbalance in the adipose tissue, which is an underlying mechanism of the low-grade inflammation and insulin resistance in subjects with the metabolic syndrome. PMID: 21346177 [PubMed - as supplied by publisher] (Source: Diabetes)

Meta-analysis of prophylactic allopurinol use in post-endoscopic retrograde cholangiopancreatography pancreatitis

NeLM - Disease Focused Reviews — Fri, 18 Feb 2011 00:00:00 +0100

Source: DARE Area: Evidence > Disease Focused Reviews CRD Summary: This review reported that allopurinol treatment showed no significant benefit for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis. This review was generally well-conducted and the authors' conclusion is likely to be reliable. CRD Commentary: This review's inclusion criteria were clear. Several relevant databases were searched. Efforts were made to find published but not unpublished studies, thereby introducing the potential for publication bias. Publication bias was investigated but little evidence was found. The authors did not state whether language restrictions were applied in the search, which made it difficult to assess the risk of language bias. Steps were taken to minimise bias ...

Allopurinol: Gingivostomatitis: case report

Reactions — Thu, 17 Feb 2011 16:50:41 +0100

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Management of asymptomatic hyperuricemia in patients with chronic kidney disease by Japanese nephrologists: A questionnaire survey

Nephrology — Tue, 08 Feb 2011 00:00:00 +0100

Conclusions: Most Japanese nephrologists treat AHU in predialysis CKD with an aim to prevent CKD progression or CVE mainly by allopurinol. (Source: Nephrology)

Allopurinol/amoxicillin/carbamazepine: DRESS syndrome and drug hypersensitivity: 2 case reports

Reactions — Sun, 06 Feb 2011 16:33:07 +0100

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Pharmacokinetic and Pharmacodynamic Interaction Between Allopurinol and Probenecid in Patients with Gout.

J Rheumatol — Tue, 01 Feb 2011 00:00:00 +0100

CONCLUSION: Coadministration of allopurinol with probenecid had a significantly greater hypouricemic effect than allopurinol alone despite an associated reduction of plasma oxypurinol concentrations. Australian Clinical Trials Registry ACTRN012606000276550. PMID: 21285173 [PubMed - as supplied by publisher] (Source: J Rheumatol)

Differential Effect of NADPH Oxidase and Xanthine Oxidase Inhibition on Sympathetic Reinnervation in Post-infarcted Rat Hearts.

Free Radical Biology and Medicine — Tue, 01 Feb 2011 00:00:00 +0100

Authors: Lee TM, Chen CC, Hsu YJ Superoxide has been shown to play a major role in ventricular remodeling and arrhythmias after myocardial infarction. However, the source of increased myocardial superoxide production and the role of superoxide on sympathetic innervation remain to be further characterized. Male Wistar rats after ligating coronary artery were randomized to either vehicle, allopurinol, or apocynin for 4 weeks. To determine the role of peroxynitrite in sympathetic reinnervation, we also used 3-morpholinosydnonimine (a peroxynitrite generator). Post-infarction was associated with increased oxidative stress, as measured by myocardial superoxide, nitrotyrosine, xanthine oxidase activity, NADPH oxidase activity and dihydroethidine fluorescent staining. Measurement of myocardia...

In vitro antiperoxidative, free radical scavenging and xanthine oxidase inhibitory potentials of ethyl acetate fraction of Saraca ashoka flowers.

Natural Product Research — Tue, 01 Feb 2011 00:00:00 +0100

This study investigated the antiperoxidative, free radical scavenging and xanthine oxidase (XO) inhibitory potential of the ethyl acetate fraction of S. ashoka flowers (SAF) and compared it with standard compounds like gallic acid, ascorbic acid, butylated hydroxyl toluene and allopurinol. The ethyl acetate fraction of SAF exhibited free radical scavenging activity against the 1,1-diphenyl-2-picrylhydrazyl radical and superoxide radical, along with hydroxyl radical scavenging activity. Lipid peroxidation inhibitory potential of SAF was studied using a linoleic acid emulsion system, which shows significant antioxidant potential. SAF also demonstrated significant XO (key enzyme linked to inflammation) inhibitory activity, which revealed its therapeutic potential as an antioxidant and XO inhi...

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Exploratory study on biomarkers associated with severe cutaneous adverse reactions.

Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan — Tue, 01 Feb 2011 00:00:00 +0100

Authors: Kaniwa N Most of adverse drug reactions (ADRs) occur as an extension of pharmacological effects. They occur dependently on their blood concentrations and can be potentially reduced by controlling their dose. On the other hand, ADRs categorized as Type B usually occur irrelevantly to their pharmacological effects at different organs from their target, and are often life-threatening and unpredictable. The incidences of Type B ADRs are very low. Severe cutaneous adverse reactions including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are delayed allergic reactions in which T-cells are involved and categorized as Type B ADRs. Recent progress of pharmacogenomic studies has revealed that particular types of human leukocyte antigen (HLA) class I antigens have s...

Allopurinol/lamotrigine/traditional Chinese medicine: DRESS syndrome: 6 case reports

Reactions — Mon, 31 Jan 2011 15:44:00 +0100

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Using allopurinol above the dose based on creatinine clearance is effective and safe in patients with chronic gout, including those with renal impairment

Arthritis and Rheumatism — Fri, 28 Jan 2011 20:20:30 +0100

ConclusionIncreasing the dose of allopurinol above the proposed creatinine clearance–based dose led to a significant reduction in the serum urate concentration. Approximately 89% of patients achieved a serum urate concentration of <0.36 mmoles/liter. In this cohort, toxicity was not increased in patients receiving higher doses of allopurinol, including those with renal impairment. (Source: Arthritis and Rheumatism)

Allopurinol/methylprednisolone: Stevens-Johnson syndrome/toxic epidermal necrolysis and pneumonia: case report

Reactions — Mon, 24 Jan 2011 17:42:36 +0100

(Source: Reactions)