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{{CMG}}
{{CMG}}
== Overview ==
== Overview ==
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Another possibility is use of [[acetazolamide]], one of the first diuretics discovered. This drug inhibits the action of carbonic anhydrase on the proximal convoluted tubules within the kidneys, which effectively inhibits reabsorption of [[bicarbonate]], thus alkalinizing the urine. After two to three days of usage, the diuretic effects of this drug decline because of increased downstream reabsorption of ions and water by the renal tubules; however, the alkalinization of urine persists, and this basic urine attracts weak acids such as '''uric acid''' and cystine into the urine, thus increasing their urinary excretion.<sup>35</sup>
Another possibility is use of [[acetazolamide]], one of the first diuretics discovered. This drug inhibits the action of carbonic anhydrase on the proximal convoluted tubules within the kidneys, which effectively inhibits reabsorption of [[bicarbonate]], thus alkalinizing the urine. After two to three days of usage, the diuretic effects of this drug decline because of increased downstream reabsorption of ions and water by the renal tubules; however, the alkalinization of urine persists, and this basic urine attracts weak acids such as '''uric acid''' and cystine into the urine, thus increasing their urinary excretion.<sup>35</sup>
== Preventive Medical Therapy ==
===Medications===
* [[Allopurinol]] and [[azathioprine]] (Imuran) used together present a risk of a potentially fatal [[drug interaction]], a severe risk of allopurinol use which is of importance to transplant patients being treated with azathioprine for [[immunosuppression]].[http://www.medsafe.govt.nz/Profs/PUarticles/azathioprine.htm]
* [[Febuxostat]] ((2-[3-cyano-4-isobutoxyphenyl]-4-methylthiazole-5-carboxylic acid) - a non-purine inhibitor of xanthine oxidase seems to be an alternative that is superior to allopurinol; it is currently in [[Clinical trials#Phase III| Phase III trials]].<ref>{{cite journal | author = Becker M, Schumacher H, Wortmann R, MacDonald P, Eustace D, Palo W, Streit J, Joseph-Ridge N | title = Febuxostat compared with allopurinol in patients with hyperuricemia and gout | journal = N Engl J Med | volume = 353 | issue = 23 | pages = 2450–61 | year = 2005 | id = PMID 16339094}}</ref>
* [[Probenecid]], a uricosuric drug that promotes the excretion of uric acid in urine, is also commonly prescribed - often in conjunction with [[colchicine]]. The drug [[fenofibrate]] (which is used in treating [[hyperlipidemia]]) also exerts a beneficial uricosuric effect.<ref>{{cite journal | author = Bardin T | title = Fenofibrate and losartan | journal = Ann Rheum Dis | volume = 62 | issue = 6 | pages = 497–8 | year = 2003 | id = PMID 12759281 | url=http://ard.bmjjournals.com/cgi/content/full/62/6/497}}</ref>
* As arterial hypertension quite often coexists with gout, treating it with [[losartan]], an [[angiotensin II receptor antagonist]], might have an additional beneficial effect on uric acid plasma levels. This way losartan can offset the negative side-effect of [[thiazide]]s (a group of [[diuretic]]s used for [[arterial hypertension|high blood pressure]]) on uric acid metabolism in patients with gout.
* It is suspected that in many cases gout may be secondary to untreated [[sleep apnea]], when oxygen-starved cells break down and release purines as a by-product. Treatment for apnea can be effective in lessening incidence of acute gout attacks.<ref>{{cite journal | author = Abrams B | title = Gout is an indicator of sleep apnea | journal = Sleep | volume = 28 | issue = 2 | pages = 275 | year = 2005 | id = PMID 16171252}}</ref>
* A study in 2004 suggests that animal flesh sources of purine, such as beef and seafood, greatly increase the risk of developing gout. However, high-purine vegetable sources did not. Dairy products such as milk and cheese significantly reduced the chances of gout. The study followed over 40000 men over a period of 12 years, in which 1300 cases of gout were reported.<ref name="Choi et al 2004">{{cite journal | author = Choi H, Atkinson K, Karlson E, Willett W, Curhan G | title = Purine-rich foods, dairy and protein intake, and the risk of gout in men | journal = N Engl J Med | volume = 350 | issue = 11 | pages = 1093–103 | year = 2004 | id = PMID 15014182 | url=http://www.nutritionaustralia.org/News_in_Nutrition/Journal_Articles/purine%20rich%20foods.pdf | format=PDF}}</ref>
* PEG-uricase, a polyethylene glycol ("PEG") conjugate of recombinant porcine uricase (urate oxidase), which breaks down the uric acid deposits is being studied in [[clinical trial#Phase III|Phase III clinical trials]] for the treatment of severe, treatment-refractory gout in the United States in 2006.[http://www.savientpharma.com/pipeline/puricase.asp Pipeline]
*[[Sodium bicarbonate]] (baking soda) is an old remedy,<ref>The British Pharmaceutical Codex. Published by direction of the Council of the Pharmaceutical Society of Great Britain, 1911. [http://www.henriettesherbal.com/eclectic/bpc1911/sodium.html Sodium]</ref> thought to work by raising blood pH (lowering blood acidity). However, the added sodium may be inappropriate for some people.
*Research from the University of British Columbia suggests long-term coffee consumption is associated with a lower risk of gout.<ref>{{cite journal | author = Hyon K. Choi, Walter Willett, Gary Curhan | title =
Coffee consumption and risk of incident gout in men: A prospective study | journal = Arthritis & Rheumatism | volume = 56 | issue = 6 | pages = 2049–2055 | year = 2007 | id = PMID 17530645}}</ref> <ref>{{cite journal | author = Choi HK, Curhan G. | title =
Coffee, tea, and caffeine consumption and serum uric acid level: The third national health and nutrition examination survey | journal = Arthritis & Rheumatism | volume = 57 | issue = 5 | pages = 816–821 | year = 2007 | id = PMID 17530681 }}</ref>
===Diet===
''See Saag and Choi, 2006, an open-access review article, for detailed references and further information.''<ref>{{cite journal |author=Saag KG, Choi H |title=Epidemiology, risk factors, and lifestyle modifications for gout |journal=Arthritis Res. Ther. |volume=8 Suppl 1 |issue= |pages=S2 |year=2006 |pmid=16820041 |doi=10.1186/ar1907 |url=http://arthritis-research.com/content/8/S1/S2 }}</ref>
The serum level of uric acid is the primary risk factor for gout. The serum level is the result of both intake (diet) and output (excretion).
====Reduce intake of purines====
The solubility threshold for uric acid is approximately 6.7 mg/dl; above this threshold crystals may form. Healthy subjects in the Normative Aging Study who had serum levels of uric acid over 9.0 mg/dl suffered a 22% incidence of gout over six years, compared to less than one percent for those with 7.0-8.9 mg/dl. The average uric acid level in men is 5.0 mg/dl, and substitution of a purine-free formula diet reduces this to 3.0 mg/dl. A purine-restricted diet lowers the level nearly as much (1-2 mg/dl).
A diet low in purines reduces the serum level of uric acid. Notable sources of dietary purines include:
*beer (high in [[guanosine]]
'''Protein''' is a crude proxy for purines; a more precise proxy is '''muscle'''. Apart from the notable dietary purines above, the main source of dietary purines is [[DNA]] and [[RNA]], via their bases [[adenine]] and [[guanine]]. All sources of dietary protein supply some purines, but some sources provide far more purines than others. Meat (particularly dark meat) and seafood are high in purine because [[muscle]] cells are packed with [[mitochondrion|mitochondria]], which have their own DNA and RNA. In a large prospective study, high consumption of meat and seafood were found associated with an elevated risk of gout onset (41% and 50%, respectively). High consumption of dairy products, high in protein but very low in DNA and RNA, was associated with a 44% ''decrease'' in the incidence of gout. Consumption of the more purine-rich vegetables or a high protein diet per se had no significant correlation.
Consumption of '''beer''' is associated with a 49% increase in relative risk per daily 12-oz serving. By contrast, consumption of spirits was associated with only a 15% increase in relative risk, and no association at all was found with consumption of wine.
Some '''medical drugs''' are purine-based. Notable among these are the purine-analog [[antimetabolite]] drugs, sometimes used as [[chemotherapy]] agents.
====Increase output of uric acid====
Ingestion of 500 mg of [[Vitamin C]] per day has been shown to bring about a 0.5 mg/dl decrease in serum uric acid through increased excretion. Some Gout sufferers have recently found that taking up to 1,000 mg of Vitamin C, combined with a small dosage (approx. 10-15 mg./day) of [[Lithium]] have had very beneficial effects on their uric acid levels.
Vitamin C, taken in high doses, can help decrease blood uric acid levels, but should not be taken without a doctor's supervision. Note that there is a small subset of people with gout who will actually get worse with high levels of vitamin C. Also, a single high dose can free up too much uric acid and cause kidney stones. (University of Maryland Medical Center for Integrative Medicine).
====Other approaches====
Additional dietary recommendations can be made which reduce gout indirectly, by reducing gout risk factors such as [[obesity]], [[hypertension]], [[cardiovascular disease]], [[diabetes]], and [[metabolic syndrome]].
'''The following suggestions do not meet with universal approval among medical practitioners.'''
Low [[purine]] diet:
* To lower uric acid:
** cherries were reported to reduce uric acid in a small study.<ref>{{cite journal |author=Jacob RA, Spinozzi GM, Simon VA, ''et al'' |title=Consumption of cherries lowers plasma urate in healthy women |journal=J. Nutr. |volume=133 |issue=6 |pages=1826-9 |year=2003 |pmid=12771324 |doi=}}</ref><ref>{{cite journal |author=BLAU LW |title=Cherry diet control for gout and arthritis |journal=Tex. Rep. Biol. Med. |volume=8 |issue=3 |pages=309-11 |year=1950 |pmid=14776685 |doi=}}</ref>
** [[celery]] extracts (celery or celery seed either in capsule form or as a tea) is believed by many to reduce uric acid levels (although these are also [[diuretic]]s). Celery extracts have been reported to act synergistically with anti-inflammatory drugs.<ref>{{cite journal |author=Whitehouse MW, Butters DE |title=Combination anti-inflammatory therapy: synergism in rats of NSAIDs/corticosteroids with some herbal/animal products |journal=Inflammopharmacology |volume=11 |issue=4 |pages=453-64 |year=2003 |pmid=15035799 |doi=10.1163/156856003322699636}}</ref>
** Cheese has been recommended as a low-purine food,<ref>{{cite journal |author=Harris MD, Siegel LB, Alloway JA |title=Gout and hyperuricemia |journal=American family physician |volume=59 |issue=4 |pages=925-34 |year=1999 |pmid=10068714 |doi= |url=http://newcms.aafp.org/afp/990215ap/925.html}}</ref> and dairy products have been found to reduce the risk of gout.
*Food to avoid:
**foods high in [[purine]]s
*** limit food high in protein such as meat, fish, poultry, or [[tofu]] to 8 ounces (226 grams) a day. Avoid entirely during a flare up. Tofu has been proposed as a safe source of protein for gout patients due to its small and transient effect on plasma urate levels.<ref>{{cite journal |author=Yamakita J, Yamamoto T, Moriwaki Y, Takahashi S, Tsutsumi Z, Higashino K |title=Effect of Tofu (bean curd) ingestion and on uric acid metabolism in healthy and gouty subjects |journal=Adv. Exp. Med. Biol. |volume=431 |issue= |pages=839-42 |year=1998 |pmid=9598181 |doi=}}</ref>
***sweetbreads, [[kidney]]s, [[liver]], [[brain]]s, or other offal meats.<ref>{{cite journal |author=Robinson CH |title=The low purine diet |journal=Am. J. Clin. Nutr. |volume=2 |issue=4 |pages=276-7 |year=1954 |pmid=13188851 |doi= |url=http://www.ajcn.org/cgi/reprint/2/4/276}}</ref><ref>{{cite journal |author=Chou P, Soong LN, Lin HY |title=Community-based epidemiological study on hyperuricemia in Pu-Li, Taiwan |journal=J. Formos. Med. Assoc. |volume=92 |issue=7 |pages=597-602 |year=1993 |pmid=7904493 |doi=}}</ref>
***[[seafood]] <ref>{{cite journal |author=Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G |title=Purine-rich foods, dairy and protein intake, and the risk of gout in men |journal=N. Engl. J. Med. |volume=350 |issue=11 |pages=1093-103 |year=2004 |pmid=15014182 |doi=10.1056/NEJMoa035700}}</ref>
***[[alcohol]].<ref>{{cite journal |author=Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G |title=Alcohol intake and risk of incident gout in men: a prospective study |journal=Lancet |volume=363 |issue=9417 |pages=1277-81 |year=2004 |pmid=15094272 |doi=10.1016/S0140-6736(04)16000-5}}</ref> Some claim that this applies especially to beer, on the basis that brewer's yeasts are very rich in purine. Since most modern commercial beer contains only trace amounts of yeast, this claim requires further substantiation. Formerly, port wine was sweetened with litharge, causing [[lead poisoning]], of which gout is a complication. Ironically, red wines, particularly those produced by traditional methods,<ref>{{cite journal |author=Corder R, Mullen W, Khan NQ, ''et al'' |title=Oenology: red wine procyanidins and vascular health |journal=Nature |volume=444 |issue=7119 |pages=566 |year=2006 |pmid=17136085 |doi=10.1038/444566a}}</ref> contain procyanidins released from grape seeds during wine making, which have been reported to lower serum uric acid levels by an indirect mechanism.<ref>{{cite journal |author=Wang Y, Zhu JX, Kong LD, Yang C, Cheng CH, Zhang X |title=Administration of procyanidins from grape seeds reduces serum uric acid levels and decreases hepatic xanthine dehydrogenase/oxidase activities in oxonate-treated mice |journal=Basic Clin. Pharmacol. Toxicol. |volume=94 |issue=5 |pages=232-7 |year=2004 |pmid=15125693 |doi=10.1111/j.1742-7843.2004.pto940506.x}}</ref> However, withdrawal of urate-lowering therapy is associated with recurrence of acute gouty arthritis.<ref>{{cite journal |author=Perez-Ruiz F, Atxotegi J, Hernando I, Calabozo M, Nolla JM |title=Using serum urate levels to determine the period free of gouty symptoms after withdrawal of long-term urate-lowering therapy: a prospective study |journal=Arthritis Rheum. |volume=55 |issue=5 |pages=786-90 |year=2006 |pmid=17013833 |doi=10.1002/art.22232}}</ref>
** Drink plenty of liquids, especially [[water]], to dilute and assist excretion of urates;
** Avoid [[diuretic]] foods or medicines like [[aspirin]](aspirin should be avoided from those suffering from gout, unless specified by a trained physician), [[vitamin C]], [[tea]] and alcohol. The role of diuretics in triggering gout has been disputed.<ref>{{cite journal |author=Janssens HJ, van de Lisdonk EH, Janssen M, van den Hoogen HJ, Verbeek AL |title=Gout, not induced by diuretics? A case-control study from primary care |journal=Ann. Rheum. Dis. |volume=65 |issue=8 |pages=1080-3 |year=2006 |pmid=16291814 |doi=10.1136/ard.2005.040360}}</ref>
* Moderate intake of purine-rich vegetables is not associated with increased gout.<!--
Colchicine was previously the drug of choice in acute attacks of gout, as it impairs the motility of granulocytes and can prevent the inflammatory phenomena that initiate an attack. Colchicine should be taken within the first 12 hours of the attack and usually relieves the pain within 48 hours, although side effects (gastrointestinal upset such as diarrhea and nausea) can complicate its use. NSAIDs are the preferred form of analgesia for patients with gout.
Before medical help is available, some over-the-counter medications can provide temporary relief from pain and swelling. NSAIDs such as ibuprofen can reduce the pain and inflammation slightly, although aspirin should not be used as it can worsen the condition. Preparation Hhemorrhoidalointment can be applied to the swollen skin to reduce the swelling temporarily. Professional medical care is needed for long-term management of gout.
Ice may be applied for 20–30 minutes several times a day, and a randomized controlled trial found that patients who used ice packs had better relief of pain without side effects.[2] Keeping the affected area elevated above the level of the heart also may help.
Due to swelling around affected joints for prolonged periods, shedding of skin may occur. This is particularly evident when small toes are affected and may promote fungal infection in the web region if dampness occurs, and treatment is similar to that for common athlete's foot.
Some sufferers of Gout report an aggravation of the condition in the knees and toes associated with long periods of immobility, such as when sitting at a computer desk for long hours. This can be particularly unfortunate if the sufferer is searching for work as the aggravation can interefere with mobility. Sufferers who notice early swelling or early pain may appear to be able to arrest the aggravation when medical treatment is applied before the condition gets worse. Where this is the case, a medically prescribed anti-inflammatory oral treatment taken with food and bed rest may provide relief within 6-8 hours.
Another possibility is use of acetazolamide, one of the first diuretics discovered. This drug inhibits the action of carbonic anhydrase on the proximal convoluted tubules within the kidneys, which effectively inhibits reabsorption of bicarbonate, thus alkalinizing the urine. After two to three days of usage, the diuretic effects of this drug decline because of increased downstream reabsorption of ions and water by the renal tubules; however, the alkalinization of urine persists, and this basic urine attracts weak acids such as uric acid and cystine into the urine, thus increasing their urinary excretion.35
References
↑Man CY, Cheung IT, Cameron PA, Rainer TH (2007). "Comparison of oral prednisolone/paracetamol and oral indomethacin/paracetamol combination therapy in the treatment of acute goutlike arthritis: a double-blind, randomized, controlled trial". Annals of emergency medicine. 49 (5): 670–7. doi:10.1016/j.annemergmed.2006.11.014. PMID17276548.CS1 maint: Multiple names: authors list (link)
↑Schlesinger N, Detry MA, Holland BK; et al. (2002). "Local ice therapy during bouts of acute gouty arthritis". J. Rheumatol. 29 (2): 331–4. PMID11838852.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)