70-414: PZA may refer to: Pyrazinamide , a medication used to treat tuberculosis PZA Loara , a Polish armored radar-directed self-propelled anti-aircraft gun system PZA, the station code for Pazhavanthangal railway station , Chennai, Tamil Nadu, India Topics referred to by the same term [REDACTED] This disambiguation page lists articles associated with
140-520: A combination of abdominal obesity , hypertension , insulin resistance , and abnormal lipid levels , occurs in nearly 75% of cases. Other conditions commonly complicated by gout include lead poisoning , kidney failure , hemolytic anemia , psoriasis , solid organ transplants , and myeloproliferative disorders such as polycythemia . A body mass index greater than or equal to 35 increases male risk of gout threefold. Chronic lead exposure and lead-contaminated alcohol are risk factors for gout due to
210-466: A diagnosis of early gout. They may show signs of chronic gout such as bone erosion. A definitive diagnosis of gout is based upon the identification of monosodium urate crystals in synovial fluid or a tophus . All synovial fluid samples obtained from undiagnosed inflamed joints by arthrocentesis should be examined for these crystals. Under polarized light microscopy, they have a needle-like morphology and strong negative birefringence . This test
280-503: A diet high in low-fat dairy products may be preventive. Gout affects about 1–2% of adults in the developed world at some point in their lives. It has become more common in recent decades. This is believed to be due to increasing risk factors in the population, such as metabolic syndrome , longer life expectancy, and changes in diet. Older males are most commonly affected. Gout was historically known as "the disease of kings" or "rich man's disease". It has been recognized at least since
350-507: A diet with moderate purine-rich vegetables (e.g., beans , peas , lentils , and spinach ) is not associated with gout. Neither is total dietary protein . Alcohol consumption is strongly associated with increased risk, with wine presenting somewhat less of a risk than beer or spirits . Eating skim milk powder enriched with glycomacropeptide (GMP) and G600 milk fat extract may reduce pain but may result in diarrhea and nausea. Physical fitness, healthy weight, low-fat dairy products, and to
420-461: A direct association between these rpsA mutations and pyrazinamide resistance has not been established. The pyrazinamide-resistant M. tuberculosis strain DHMH444, which harbors a mutation in the carboxy terminal coding region of rpsA , is fully susceptible to pyrazinoic acid and pyrazinamide resistance of this strain was previously associated with decreased pyrazinamidase activity. Further, this strain
490-505: A joint, can be mistaken for basal cell carcinoma or other neoplasms . Risk of gout attacks can be lowered by complete abstinence from drinking alcoholic beverages , reducing the intake of fructose (e.g. high fructose corn syrup ), sucrose, and purine -rich foods of animal origin, such as organ meats and seafood . Eating dairy products , vitamin C -rich foods, coffee , and cherries may help prevent gout attacks, as does losing weight. Gout may be secondary to sleep apnea via
560-401: A lesser extent, coffee and taking vitamin C, appear to decrease the risk of gout; however, taking vitamin C supplements does not appear to have a significant effect in people who already have established gout. Peanuts, brown bread, and fruit also appear protective. This is believed to be partly due to their effect in reducing insulin resistance . Other than dietary and lifestyle choices,
630-409: A little fever... The night is passed in torture, sleeplessness, turning the part affected and perpetual change of posture; the tossing about of body being as incessant as the pain of the tortured joint and being worse as the fit comes on. In the 18th century, Thomas Marryat distinguished different manifestations of gout: The Gout is a chronical disease most commonly affecting the feet. If it attacks
700-527: A particularly high risk. Calcium channel blockers and losartan are associated with a lower risk of gout compared to other medications for hypertension . Gout may be diagnosed and treated without further investigations in someone with hyperuricemia and the classic acute arthritis of the base of the great toe (known as podagra). Synovial fluid analysis should be done if the diagnosis is in doubt. Plain X-rays are usually normal and are not useful for confirming
770-593: A person has had two attacks of gout, unless destructive joint changes, tophi, or urate nephropathy exist. It is not until this point that medications are cost-effective. They are not usually started until one to two weeks after an acute flare has resolved, due to theoretical concerns of worsening the attack. They are often used in combination with either an NSAID or colchicine for the first three to six months. While it has been recommended that urate-lowering measures should be increased until serum uric acid levels are below 300–360 μmol/L (5.0–6.0 mg/dL), there
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#1732884248867840-465: A premature old age—of such dissolute habits none being more common than the premature and excessive indulgence in venery and the like exhausting passions. The victim goes to bed and sleeps in good health. About two o'clock in the morning he is awakened by a severe pain in the great toe; more rarely in the heel, ankle, or instep. The pain is like that of a dislocation and yet parts feel as if cold water were poured over them. Then follows chills and shivers and
910-672: A second attack within one year. Those with gout are at increased risk of hypertension , diabetes mellitus , metabolic syndrome , and kidney and cardiovascular disease and thus are at increased risk of death. It is unclear whether medications that lower urate affect cardiovascular disease risks. This may be partly due to its association with insulin resistance and obesity, but some of the increased risk appears to be independent. Without treatment, episodes of acute gout may develop into chronic gout with destruction of joint surfaces, joint deformity, and painless tophi . These tophi occur in 30% of those who are untreated for five years, often in
980-457: A strong association with the consumption of alcohol, sugar-sweetened beverages, meat, and seafood. Among foods richest in purines yielding high amounts of uric acid are dried anchovies , shrimp, organ meat , dried mushrooms , seaweed , and beer yeast . Chicken and potatoes also appear related. Other triggers include physical trauma and surgery. Studies in the early 2000s found that other dietary factors are not relevant. Specifically,
1050-654: A woman, or women except those in whom the menses have become suppressed... some have obtained lifelong security by refraining from wine , mead and venery . Benjamin Welles, an English physician, authored the first medical book on gout, A Treatise of the Gout, or Joint Evil , in 1669. In 1683, Thomas Sydenham , an English physician, described its occurrence in the early hours of the morning and its predilection for older males: Gouty patients are, generally, either old men or men who have so worn themselves out in youth as to have brought on
1120-418: Is joint pains (arthralgia), but this is not usually so severe that patients need to stop taking it. Pyrazinamide can precipitate gout flares by decreasing renal excretion of uric acid. The most dangerous side effect of pyrazinamide is hepatotoxicity , which is dose-related. The old dose for pyrazinamide was 40–70 mg/kg daily and the incidence of drug-induced hepatitis has fallen significantly since
1190-429: Is septic arthritis . This should be considered in those with signs of infection or those who do not improve with treatment. To help with diagnosis, a synovial fluid Gram stain and culture may be performed. Other conditions that can look similar include CPPD (pseudogout), rheumatoid arthritis , psoriatic arthritis , palindromic rheumatism , and reactive arthritis . Gouty tophi, in particular when not located in
1260-449: Is a medication used to treat tuberculosis . For active tuberculosis, it is often used with rifampicin , isoniazid , and either streptomycin or ethambutol . It is not generally recommended for the treatment of latent tuberculosis. It is taken by mouth . Common side effects include nausea, loss of appetite, muscle and joint pains, and rash. More serious side effects include gout , liver toxicity , and sensitivity to sunlight. It
1330-478: Is also available as part of fixed-dose combinations with other TB drugs such as isoniazid and rifampicin ( Rifater is an example). Pyrazinamide was first discovered and patented in 1936, but not used against tuberculosis until 1952. Its discovery as an antitubercular agent was remarkable since it has no activity against tuberculosis in vitro , due to not being active at a neutral pH, so would ordinarily not be expected to work in vivo . However, nicotinamide
1400-499: Is an alternative for those unable to tolerate NSAIDs. At high doses, side effects (primarily gastrointestinal upset) limit its usage. At lower doses, which are still effective, it is well tolerated. Colchicine may interact with other commonly prescribed drugs, such as atorvastatin and erythromycin , among others. Glucocorticoids have been found to be as effective as NSAIDs and may be used if contraindications exist for NSAIDs. They also lead to improvement when injected into
1470-468: Is available as a generic medication. Pyrazinamide is only used in combination with other drugs such as isoniazid and rifampicin in the treatment of Mycobacterium tuberculosis and as directly observed therapy (DOT). It is never used on its own. It has no other indicated medical uses . In particular, it is not used to treat other mycobacteria ; Mycobacterium bovis and Mycobacterium leprae are innately resistant to pyrazinamide. Pyrazinamide
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#17328842488671540-456: Is becoming more common. Some 5.8 million people were affected in 2013. Rates of gout approximately doubled between 1990 and 2010. This rise is believed to be due to increasing life expectancy, changes in diet and an increase in diseases associated with gout, such as metabolic syndrome and high blood pressure . Factors that influence rates of gout include age, race, and the season of the year. In men over 30 and women over 50, rates are 2%. In
1610-464: Is common. Other animals with uricase include fish, amphibians and most non-primate mammals. The Tyrannosaurus rex specimen known as " Sue " is believed to have had gout. A number of new medications are under study for treating gout, including anakinra , canakinumab , and rilonacept . Canakinumab may result in better outcomes than a low dose of a glucocorticoid, but costs five thousand times more. A recombinant uricase enzyme ( rasburicase )
1680-515: Is defined as a plasma urate level greater than 420 μmol/L (7.0 mg/dL) in males and 360 μmol/L (6.0 mg/dL) in females. Other blood tests commonly performed are white blood cell count , electrolytes , kidney function and erythrocyte sedimentation rate (ESR). However, both the white blood cells and ESR may be elevated due to gout in the absence of infection. A white blood cell count as high as 40.0×10 /l (40,000/mm ) has been documented. The most important differential diagnosis in gout
1750-423: Is difficult to perform and requires a trained observer. The fluid must be examined relatively soon after aspiration, as temperature and pH affect solubility. Hyperuricemia is a classic feature of gout, but nearly half of the time gout occurs without hyperuricemia and most people with raised uric acid levels never develop gout. Thus, the diagnostic utility of measuring uric acid levels is limited. Hyperuricemia
1820-493: Is little evidence to support this practice over simply putting people on a standard dose of allopurinol. If these medications are in chronic use at the time of an attack, it is recommended that they be continued. Levels that cannot be brought below 6.0 mg/dL while attacks continue indicates refractory gout. While historically it is not recommended to start allopurinol during an acute attack of gout, this practice appears acceptable. Allopurinol blocks uric acid production, and
1890-594: Is more likely to do so as levels increase. Other triggers believed to be important in acute episodes of arthritis include cool temperatures, rapid changes in uric acid levels, acidosis , articular hydration and extracellular matrix proteins. The increased precipitation at low temperatures partly explains why the joints in the feet are most commonly affected. Rapid changes in uric acid may occur due to factors including trauma, surgery, chemotherapy and diuretics. The starting or increasing of urate-lowering medications can lead to an acute attack of gout with febuxostat of
1960-509: Is not recommended in those with significant liver disease or porphyria . It is unclear if use during pregnancy is safe but it is likely okay during breastfeeding . Pyrazinamide is in the antimycobacterial class of medications. How it works is not entirely clear. Pyrazinamide was first made in 1936, but did not come into wide use until 1972. It is on the World Health Organization's List of Essential Medicines . Pyrazinamide
2030-467: Is only recommended in those who cannot tolerate allopurinol. There are concerns about more deaths with febuxostat compared to allopurinol. Febuxostat may also increase the rate of gout flares during early treatment. However, there is tentative evidence that febuxostat may bring down urate levels more than allopurinol. Probenecid appears to be less effective than allopurinol and is a second line agent. Probenecid may be used if undersecretion of uric acid
2100-480: Is present (24-hour urine uric acid less than 800 mg). It is, however, not recommended if a person has a history of kidney stones . Probenecid can be used in a combined therapy with allopurinol is more effective than allopurinol monotherapy. Pegloticase is an option for the 3% of people who are intolerant to other medications. It is a third line agent. Pegloticase is given as an intravenous infusion every two weeks, and reduces uric acid levels. Pegloticase
2170-551: Is required by the bacterium to synthesize fatty acids although this has been discounted. The accumulation of pyrazinoic acid was also suggested to disrupt membrane potential and interfere with energy production, necessary for survival of M. tuberculosis at an acidic site of infection. However, since an acidic environment is not essential for pyrazinamide susceptibility and pyrazinamide treatment does not lead to intrabacterial acidification nor rapid disruption of membrane potential, this model has also been discounted. Pyrazinoic acid
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2240-469: Is safe. In the US, pyrazinamide is not used in pregnancy, citing insufficient evidence of safety. Pyrazinamide is removed by haemodialysis , so doses should always be given at the end of a dialysis session. Pyrazinamide is a prodrug that stops the growth of M. tuberculosis . Pyrazinamide diffuses into the granuloma of M. tuberculosis , where the tuberculosis enzyme pyrazinamidase converts pyrazinamide to
2310-450: Is the cause in less than 10%. About 10% of people with hyperuricemia develop gout at some point in their lifetimes. The risk, however, varies depending on the degree of hyperuricemia. When levels are between 415 and 530 μmol/L (7 and 8.9 mg/dL), the risk is 0.5% per year, while in those with a level greater than 535 μmol/L (9 mg/dL), the risk is 4.5% per year. Dietary causes account for about 12% of gout, and include
2380-509: Is the most commonly used agent. Long term therapy is safe and well-tolerated and can be used in people with renal impairment or urate stones, although hypersensitivity occurs in a small number of individuals. The HLA-B*58:01 allele of the human leukocyte antigen B ( HLA-B ) is strongly associated with severe cutaneous adverse reactions during treatment with allopurinol and is most common among Asian subpopulations, notably those of Korean , Han-Chinese , or Thai descent. Febuxostat
2450-402: Is used in the first 2 months of treatment to reduce the duration of treatment required. Regimens not containing pyrazinamide must be taken for 9 months or more. Pyrazinamide is a potent antiuricosuric drug and consequently has an off-label use in the diagnosis of causes of hypouricemia and hyperuricosuria . It acts on URAT1 . The most common (roughly 1%) side effect of pyrazinamide
2520-419: Is useful decreasing tophi but has a high rate of side effects and many people develop resistance to it. Using lesinurad 400 mg plus febuxostat is more beneficial for tophi resolution than lesinural 200 mL with febuxostat, with similar side effects. Lesinural plus allopurinol is not effective for tophi resolution. Potential side effects include kidney stones, anemia and joint pain. In 2016, it
2590-465: Is well absorbed orally. It crosses inflamed meninges and is an essential part of the treatment of tuberculous meningitis . It is metabolised by the liver and the metabolic products are excreted by the kidneys. Pyrazinamide is routinely used in pregnancy in the UK and the rest of the world; the World Health Organization (WHO) recommends its use in pregnancy; and extensive clinical experience shows that it
2660-514: The United States , gout is twice as likely in males of African descent than those of European descent. Rates are high among Polynesians , but the disease is rare in aboriginal Australians , despite a higher mean uric acid serum concentration in the latter group. It has become common in China , Polynesia , and urban Sub-Saharan Africa . Some studies found that attacks of gout occur more frequently in
2730-546: The helix of the ear, over the olecranon processes, or on the Achilles tendons . With aggressive treatment, they may dissolve. Kidney stones also frequently complicate gout, affecting between 10 and 40% of people, and occur due to low urine pH promoting the precipitation of uric acid. Other forms of chronic kidney dysfunction may occur. Gout affects around 1–2% of people in the Western world at some point in their lifetimes and
2800-461: The kidneys , resulting in kidney stone formation and subsequent acute uric acid nephropathy . The crystallization of uric acid , often related to relatively high levels in the blood, is the underlying cause of gout. This can occur because of diet, genetic predisposition, or underexcretion of urate , the salts of uric acid. Underexcretion of uric acid by the kidney is the primary cause of hyperuricemia in about 90% of cases, while overproduction
2870-414: The action of its target, but indirectly triggers its destruction. Mutations in the pncA gene of M. tuberculosis , which encodes a pyrazinamidase and converts pyrazinamide to its active form pyrazinoic acid, are responsible for the majority of pyrazinamide resistance in M. tuberculosis strains. A few pyrazinamide-resistant strains with mutations in the rpsA gene have also been identified. However,
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2940-431: The active form pyrazinoic acid . Under acidic conditions of pH 5 to 6, the pyrazinoic acid that slowly leaks out converts to the protonated conjugate acid, which is thought to diffuse easily back into the bacilli and accumulate. The net effect is that more pyrazinoic acid accumulates inside the bacillus at acid pH than at neutral pH. Pyrazinoic acid was thought to inhibit the enzyme fatty acid synthase (FAS) I, which
3010-401: The application of ice for 20 to 30 minutes several times a day to decrease pain. Options for acute treatment include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine , and glucocorticoids . While glucocorticoids and NSAIDs work equally well, glucocorticoids may be safer. Options for prevention include allopurinol , febuxostat , and probenecid . Lowering uric acid levels can cure
3080-486: The blood ( hyperuricemia ). This occurs from a combination of diet, other health problems, and genetic factors. At high levels, uric acid crystallizes and the crystals deposit in joints, tendons , and surrounding tissues, resulting in an attack of gout. Gout occurs more commonly in those who regularly drink beer or sugar-sweetened beverages; eat foods that are high in purines such as liver, shellfish, or anchovies; or are overweight. Diagnosis of gout may be confirmed by
3150-408: The deposition of needle-like crystals of uric acid known as monosodium urate crystals . Pain typically comes on rapidly, reaching maximal intensity in less than 12 hours. The joint at the base of the big toe is affected ( Podagra ) in about half of cases. It may also result in tophi , kidney stones , or kidney damage . Gout is due to persistently elevated levels of uric acid (urate) in
3220-622: The disease of kings" or as "rich man's disease". The Ebers papyrus and the Edwin Smith papyrus , ( c. 1550 BC ) each mention arthritis of the first metacarpophalangeal joint as a distinct type of arthritis. These ancient manuscripts cite (now missing) Egyptian texts about gout that are claimed to have been written 1,000 years earlier and ascribed to Imhotep . Greek physician Hippocrates around 400 BC commented on it in his Aphorisms , noting its absence in eunuchs and premenopausal women. Aulus Cornelius Celsus (30 AD) described
3290-618: The disease. Treatment of associated health problems is also important. Lifestyle interventions have been poorly studied. It is unclear whether dietary supplements have an effect in people with gout. NSAIDs are the usual first-line treatment for gout. No specific agent is significantly more or less effective than any other. Improvement may be seen within four hours and treatment is recommended for one to two weeks. They are not recommended for those with certain other health problems, such as gastrointestinal bleeding , kidney failure , or heart failure . While indometacin has historically been
3360-462: The form of monosodium urate, precipitating and forming deposits (tophi) in joints, on tendons, and in the surrounding tissues. Microscopic tophi may be walled off by a ring of proteins, which blocks interaction of the crystals with cells and therefore avoids inflammation. Naked crystals may break out of walled-off tophi due to minor physical damage to the joint, medical or surgical stress, or rapid changes in uric acid levels. When they break through
3430-432: The former more so when used in combination with hydrochlorothiazide. Hyperuricemia may be induced by excessive use of Vitamin D supplements. Levels of serum uric acid have been positively associated with 25(OH) D. The incidence of hyperuricemia increased 9.4% for every 10 nmol/L increase in 25(OH) D (P < 0.001). Gout is a disorder of purine metabolism , and occurs when its final metabolite, uric acid , crystallizes in
3500-465: The harmful effect of lead on kidney function. Diuretics have been associated with attacks of gout, but a low dose of hydrochlorothiazide does not seem to increase risk. Other medications that increase the risk include niacin , aspirin (acetylsalicylic acid), ACE inhibitors , angiotensin receptor blockers , beta blockers , ritonavir , and pyrazinamide . The immunosuppressive drugs ciclosporin and tacrolimus are also associated with gout,
3570-654: The joint . A joint infection must be excluded, however, as glucocorticoids worsen this condition. There were no short-term adverse effects reported. Interleukin-1 inhibitors, such as canakinumab , showed moderate effectiveness for pain relief and reduction of joint swelling, but have increased risk of adverse events , such as back pain, headache, and increased blood pressure. They, however, may work less well than usual doses of NSAIDS. The high cost of this class of drugs may also discourage their use for treating gout. Without treatment, an acute attack of gout usually resolves in five to seven days; however, 60% of people have
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#17328842488673640-549: The knees, it is called Gonagra ; if the hands, Chiragra ; if the elbow, Onagra; if the shoulder, Omagra ; if the back or loins, Lumbago . Dutch scientist Antonie van Leeuwenhoek first described the microscopic appearance of urate crystals in 1679. In 1848, English physician Alfred Baring Garrod identified excess uric acid in the blood as the cause of gout. Gout is rare in most other animals due to their ability to produce uricase , which breaks down uric acid. Humans and other great apes do not have this ability; thus, gout
3710-403: The linkage with alcohol, later onset in women and associated kidney problems: Again thick urine, the sediment from which is white, indicates that pain and disease are to be apprehended in the region of joints or viscera... Joint troubles in the hands and feet are very frequent and persistent, such as occur in cases of podagra and cheiragra. These seldom attack eunuchs or boys before coition with
3780-425: The medical literature, although best practice discourages the abbreviating of drug names to prevent mistakes. Pyrazinamide is a generic drug , and is available in a wide variety of presentations. Pyrazinamide tablets form the bulkiest part of the standard tuberculosis treatment regimen. Pyrazinamide tablets are so large, some people find them impossible to swallow: pyrazinamide syrup is an option. Pyrazinamide
3850-424: The most commonly used NSAID, an alternative, such as ibuprofen , may be preferred due to its better side effect profile in the absence of superior effectiveness. For those at risk of gastric side effects from NSAIDs, an additional proton pump inhibitor may be given. There is some evidence that COX-2 inhibitors may work as well as nonselective NSAIDs for acute gout attack with fewer side effects. Colchicine
3920-498: The night and peaks within 24 hours of onset. This is mainly due to lower body temperature. Other symptoms may rarely occur along with the joint pain, including fatigue and high fever. Long-standing elevated uric acid levels ( hyperuricemia ) may result in other symptoms, including hard, painless deposits of uric acid crystals called tophi . Extensive tophi may lead to chronic arthritis due to bone erosion. Elevated levels of uric acid may also lead to crystals precipitating in
3990-479: The presence of crystals in the joint fluid or in a deposit outside the joint . Blood uric acid levels may be normal during an attack. Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids , or colchicine improves symptoms. Once the acute attack subsides, levels of uric acid can be lowered via lifestyle changes and in those with frequent attacks, allopurinol or probenecid provides long-term prevention. Taking vitamin C and having
4060-654: The recommended dose has been reduced to 12–30 mg/kg daily. In the standard four-drug regimen (isoniazid, rifampicin, pyrazinamide, ethambutol ), pyrazinamide is the most common cause of drug-induced hepatitis. It is not possible to clinically distinguish pyrazinamide-induced hepatitis from hepatitis caused by isoniazid or rifampicin; test dosing is required (this is discussed in detail in tuberculosis treatment ) Other side effects include nausea and vomiting , anorexia , sideroblastic anemia , skin rash , urticaria , pruritus , dysuria , interstitial nephritis , malaise , rarely porphyria , and fever . Pyrazinamide
4130-1039: The recurrence of gout attacks is also linked to the weather. High ambient temperature and low relative humidity may increase the risk of a gout attack. Gout is partly genetic, contributing to about 60% of variability in uric acid level. The SLC2A9 , SLC22A12 , and ABCG2 genes have been found to be commonly associated with gout and variations in them can approximately double the risk. Loss-of-function mutations in SLC2A9 and SLC22A12 causes low blood uric acid levels by reducing urate absorption and unopposed urate secretion. The rare genetic disorders familial juvenile hyperuricemic nephropathy , medullary cystic kidney disease , phosphoribosylpyrophosphate synthetase superactivity and hypoxanthine-guanine phosphoribosyltransferase deficiency as seen in Lesch–Nyhan syndrome , are complicated by gout. Gout frequently occurs in combination with other medical problems . Metabolic syndrome ,
4200-436: The release of purines from oxygen-starved cells. Treatment of apnea can lessen the occurrence of attacks. As of 2020, allopurinol is generally the recommended preventative treatment if medications are used. A number of other medications may occasionally be considered to prevent further episodes of gout, including probenecid , febuxostat , benzbromarone , and colchicine . Long term medications are not recommended until
4270-833: The spring. This has been attributed to seasonal changes in diet, alcohol consumption, physical activity, and temperature. Taiwan, Hong Kong and Singapore have relatively higher prevalence of gout. A study based on the National Health Insurance Research Database (NHIRD) estimated that 4.92% of Taiwanese residents have gout in 2004. A survey hold by the Hong Kong government found that 5.1% of Hong Kong resident between 45–59 years and 6.1% of those older than 60 years have gout. A study hold in Singapore found that 2,117 in 52,322 people between 45–74 years have gout, roughly equals to 4.1%. The English term "gout" first occurs in
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#17328842488674340-423: The time of the ancient Egyptians. Gout can present in several ways, although the most common is a recurrent attack of acute inflammatory arthritis (a red, tender, hot, swollen joint). The metatarsophalangeal joint at the base of the big toe is affected most often, accounting for half of cases. Other joints, such as the heels, knees, wrists, and fingers, may also be affected. Joint pain usually begins during
4410-451: The title PZA . If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=PZA&oldid=1109671727 " Category : Disambiguation pages Hidden categories: Short description is different from Wikidata All article disambiguation pages All disambiguation pages Pyrazinamide Pyrazinamide
4480-705: The tophi, they trigger a local immune -mediated inflammatory reaction in macrophages , which is initiated by the NLRP3 inflammasome protein complex . Activation of the NLRP3 inflammasome recruits the enzyme caspase 1 , which converts pro-interleukin 1β into active interleukin 1β , one of the key proteins in the inflammatory cascade. An evolutionary loss of urate oxidase (uricase), which breaks down uric acid, in humans and higher primates has made this condition common. The triggers for precipitation of uric acid are not well understood. While it may crystallize at normal levels, it
4550-449: The tuberculosis strain, or 3) looking for mutations in the pncA gene of tuberculosis. Concerns exist that the most widely used method for phenotypic resistance testing may overestimate the number of resistant strains. Global resistance of tuberculosis to pyrazinamide has been estimated to be in 16% of all cases, and 60% of people with multidrug-resistant tuberculosis . The abbreviations PZA and Z are standard, and used commonly in
4620-526: The work of Randolphus of Bocking, around 1200 AD. It derives from the Latin word gutta , meaning "a drop" (of liquid). According to the Oxford English Dictionary , this originates from humorism and "the notion of the 'dropping' of a morbid material from the blood in and around the joints ". Gout has been known since antiquity. Historically, wits have referred to it as "the king of diseases and
4690-445: Was found to be susceptible to pyrazinamide in a mouse model of tuberculosis. Thus, current data indicate that rpsA mutations are not likely to be associated with pyrazinamide resistance. Currently, three main methods of testing are used for pyrazinamide resistance: 1) phenotypic tests where a tuberculosis strain is grown in the presence of increasing concentrations of pyrazinamide, 2) measuring levels of pyrazinamidase enzyme produced by
4760-420: Was known to have activity against tuberculosis and pyrazinamide was thought to have a similar effect. Experiments in mice at Lederle and Merck confirmed its ability to kill tuberculosis and it was rapidly used in humans. Gout Gout ( / ɡ aʊ t / GOWT ) is a form of inflammatory arthritis characterized by recurrent attacks of pain in a red, tender, hot, and swollen joint , caused by
4830-479: Was proposed to bind to the ribosomal protein S1 (RpsA) and inhibit trans-translation , but more detailed experiments have shown that it does not have this activity. The current hypothesis is that pyrazinoic acid blocks synthesis of coenzyme A . Pyrazinoic acid binds weakly to aspartate decarboxylase ( PanD ), triggering its degradation. This is an unusual mechanism of action in that pyrazinamide does not directly block
4900-640: Was withdrawn from the European market. Lesinurad reduces blood uric acid levels by preventing uric acid absorption in the kidneys. It was approved in the United States for use together with allopurinol, among those who were unable to reach their uric acid level targets. Side effects include kidney problems and kidney stones . The initial aim of treatment is to settle the symptoms of an acute attack. Repeated attacks can be prevented by medications that reduce serum uric acid levels. Tentative evidence supports
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