title: Allopurinol as a cardiovascular drug.
abstract: Cardiovascular disease (CVD) remains the leading cause of death in the United States. There is evidence that shows a direct relationship between an elevated uric acid level and an increased risk of cardiovascular (CV) events, which has set the foundation for the investigation of uric acid-lowering drugs for the treatment of CVD. Although traditionally the cornerstone therapy for gout, allopurinol's ability to be a competitive inhibitor of the key enzyme, xanthine oxidase, needed for uric acid formation, has prompted recent clinical research evaluating allopurinol as a CV drug. Epidemiologic and biochemical studies on uric acid formation have shown that it is not only uric acid itself that leads to worsening prognosis and increased CV events, but also the free radicals and superoxides formed during xanthine oxidase activity. The combination of uric acid formation and formed free radicals could ultimately lead to coronary endothelial dysfunction and worsening of myocardial oxidative stress. Along with preventing uric acid formation, allopurinol also has the ability to behave as a free radical scavenger of the superoxide anions and free radicals released during uric acid formation.Clinical studies have shown that allopurinol improves endothelial dysfunction and subsequently improves the exercise capacity in patients diagnosed with angina pectoris. Allopurinol has also been shown to decrease oxidative stress and ameliorate the morbidity and mortality of congestive heart failure patients by possibly improving mechanoenergetic uncoupling, with the enhancement of myocardial contractility and the left ventricular ejection fraction. This review presents the pharmacologic action of allopurinol on the CV system and describes the effectiveness of allopurinol as a potential drug to treat 2 CVD morbidities: ischemic heart disease and congestive heart failure.
authors: Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors: Anita
authors: A
authors: Kelkar
authors: Allen
authors: A
authors: Kuo
authors: William H
authors: WH
authors: Frishman
mesh_terms: D000493:Allopurinol / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000201:enzymology; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D006801:Humans; D014527:Uric Acid / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D016166:Free Radical Scavengers; D014527:Uric Acid; D000493:Allopurinol; D014969:Xanthine Oxidase