leky-latky/kyselina-mocova/snizeni-hyperurikemie
6-hydroxybenzbromarone
- Inhibice URAT1 (zpětné reabsorpce)
- Urikosurikum [10]
OAT3 (SLC22A8) stimulation / upregulation
- Promote uric acid secretion in human proximal tubules [10]
Abrupt lowering of urate levels
- Can precipitate an attack of acute gout during the intercritical period
- Patients should receive prophylactic colchicine coverage irrespective of which urate-lowering medication is used [8]
- Urate-lowering therapy
- Should not be initiated until the acute attack has completely resolved
- Since the subsequent rapid decrease in serum urate levels has been shown to exacerbate the gouty attack [9]
Alter the pH of urine
- To discourage a possible complication of uricosuric therapy [7]
- Zvyšuje rozpustnost k. močové, oddaluje vznik krystalků
- Increased urine pH facilitate uric acid excretion [17]
Sodium bicarbonate
Potassium citrate
Magnesium citrate
Shohl's Solution
- Now replaced by Bicitra [7]
Acetazolamide
- Similar effect [7]
Výběrem potravin
- Alkaline-forming properties of foods are not associated with the pH of those foods prior to their consumption [17]
- Prehistoric Homo sapiens excreted more alkaline urine
- Intake of large quantities of plant carbohydrates
- uric acid was excreted considerably more rapidly
- Current Western diet
- High-energy density foods rich in
- Saturated fatty acids
- Refined sugars
- Low on nutrients and buffers
- Increased acidity of urine
- uric acid excretion more difficult
- Role of alkalizing foods that facilitate uric acid elimination
- Human organic anion transporter 4 (hOAT4)
- Role in urate re-absorption in proximal tubules
- Dietary treatment of hyperuricemia
- Increased urine pH facilitate uric acid excretion [17]
Sulphur-containing amino acids
- Determine urine acidity
- Main components of animal proteins
- High-meat diet facilitates the production of urine with the pH lower
- Patients who prefer meat and meat products
- More prone to developing gout than vegetarians
Vegetarian alkaline foods
- More effective in uric acid elimination than a low-purine diet alone [17]
Příprava potravin
- Most unprocessed foods
- Have an alkaline pH
- Culinary treatment and food processing
- Change its alkaline pH into acidic pH
Poměr
- Adequate balance between alkaline and acidic foods
- Ratio of 3 : 1
Foods with acidic properties
- Coffee (pH = 4),
- Beer (pH = 2.5)
- Coca-Cola (pH = 2)
- Products grown with the use of pesticides or herbicides
- Aspartame, sodium glutamate, and food dyes also lower the pH of serum and urine
Alkaline properties
Různost pH
- Lemon
- Acidic pH
- Becomes alkaline once digested and metabolized
- Meat
- Alkaline taste
- Turns acidic as a result of metabolic processes
- Lowers systemic pH [17]
Dietary acid load and renal uric acid excretion and serum uric acid (SUA)
- Dietary potential renal acid load (PRAL) and SUA
- Cross-sectional analyses in 6894 participants (aged 18–79 y) of the German Health Interview and Examination Survey for Adults (DEGS1)
- Food-frequency questionnaire - intake of
- Nutritive acid load - PRAL
- uric acid equivalents - UAEs
- Multiple linear regression models, the associations of PRAL, UAEs, and relevant food groups [24]
- Participants with lower PRAL
- Had lower odds for hyperuricemia (OR: 0.60; 95% CI: 0.43, 0.83)
- Represent a potentially SUA-reducing dietary pattern
- Dietary alkalization as a possible nonpharmacologic option to influence elevated SUA concentrations [24]
Allopurinol (Zyloprim)
- Most widely used antihyperuricemic agent
- Strukturální analog purinu hypoxanthinu
- Přeměněn xanthinoxidázou (XOD) na oxypurinol (alloxanthin)
- Pevně se váže na enzym
- Zabrání tak jeho další katalytické aktivitě
- Inhibuje xanthinoxidázu - inhibitor XOD
- Blokuje tvorbu kyseliny močové
- Hromadí se hypoxanthin a xanthin
- Jsou rozpustnější [3]
- Both allopurinol and oxypurinol are competitive inhibitors of the enzyme xanthine oxidase [8]
Tak kompetitiv nebo pevná vazba ???
- Snižuje koncentraci močové kyseliny v krvi
- Tím i v jiných tekutinách (např. synoviální)
- Množství vylučovaných urátů klesá
- Stoupá vylučování o něco lépe rozpustného hypoxanthinu a xanthinu
- Konečným metabolitem není jeden produkt, ale tři
- Klesá riziko převýšení konstanty rozpustnosti [5]
Kontraindikace
- Neužívat analoga purinů jako např. azathioprin ! [3]
Indikace
- Chronic tophaceous “erosive” gouty arthritis
- Secondary hyperuricemia related to the use of cytolytics in the treatment of hematologic malignancies
- Gout complicated by renal disease or renal calculi [9]
- Inhibitors of uric acid synthesis are more toxic than uricosurics
- Especially in elderly patients
- Should be reserved for use in “overproducers” of urate
Ideal candidates for allopurinol treatment
- Uric acid overproducers
- 24-h urinary uric acid excretion
- Over 800 mg on general diet
- Over 4.76 mmol per day [9]
- Over 600 mg on a purine-restricted diet
- Patients with renal insufficiency, nephrolithiasis, or tophaceous gout
- Patients at risk for developing uric acid nephropathy
- Can be used in almost any hyperuricemic state
Dose
- Begin with 50 to 100 mg daily
- Increased in increments of 50 to 100 mg per day every two weeks
- Gradually titrating upward until the serum urate level is under 6 mg per dL (355 µmol per L) [9]
- Usual maintenance dose for adults
- 200-300 mg/d [9,8]
- 1x denně possible
- Long half-life of oxypurinol
- Adjust the dose in persons with chronic renal insufficiency
- Higher incidence of adverse effects is observed if not adjusted [8]
Adjustment to renal function
- Creatinine clearance of 100 mL per minute (1.67 mL per s) or greater
- The initial dosage can be up to 300 mg
- Maximum dosage of 600 mg
- Creatinine clearance of 60 mL per minute (1.00 mL per s)
- Maximum dosage 200 mg per day
- Creatinine clearance of 30 mL per minute (0.50 mL per s)
- Maximum dosage 100 mg per day
- Creatinine clearance of 10 mL per minute (0.16 mL per s) or less
- 100 mg every 2-3 days [9]
Efekt
- Allopurinol causes a detectable decrease in the serum urate level within the first 24 hours
- Expected maximum reduction within two weeks after initiation of therapy [9]
- Unless the serum urate level is lower than 6.4 mg per dL (380 µmol per L)
- Concentration at which urate saturates the extra-cellular fluid
- Crystals will not be absorbed
- Tophi will continue to form [9]
Side effects
- Allopurinol is well tolerated by most patients
- Potentially fatal hypersensitivity syndrome may occur
- Usually in patients with
- Underlying renal insufficency
- Concurrent thiazide use [9]
- Can be severe or fatal
- Skin rash
- May progress to a severe hypersensitivity reaction
- Fever, bone marrow suppression, hepatic toxicity, interstitial nephritis and renal failure and a systemic hypersensitivity vasculitis [9]
- Who develop a skin rash should discontinue allopurinol [8]
- Headache [9]
- Urticaria
- Interstitial nephritis [8]
- Allergic and hypersensitivity problems [12]
- Nephropathy [12]
- Liver toxicity [12]
- Enhancement of 6-mercaptopurine toxicity [12]
Desensitization protocol
Trial of oxypurinol
- Major active metabolite of allopurinol
- Only available in the United States for use on a compassionate basis [9]
Bamboo shoots
- More detailed analysis of 24-hour dietary recall revealed
- Bamboo shoots constituted an ingredient in high-energy meat dishes and fatty meals
- Consequently, their occurrence in daily food rations showed a positive correlation with increased uric acid levels
- Observed hyperuricemia was not associated with this high-fibre food itself
Benzbromarone
- Can be used in patients with chronic kidney disease
- But may cause incidental risk of hepatotoxicity [10]
- 2003 withdrawn from the market
- Because of serious hepatotoxicity [11]
- Withdrawal by the French manufacturer Sanofi-Synthélabo
- Has greatly limited its availability around the world [11]
Berberine
- Active in inhibiting the enzyme XOD [10]
Bergenin
- Inhibit activity of XOD
- Downregulate URAT1 and GLUT9 [10]
- Belongs to isocoumarin compounds
- Can protect liver
- Shrink ulcer
- Improve immune functions [10]
- Zhou and Chen used bergenin to treat hyperuricemia model mice induced by potassium oxonate [10]
Berries
Alkalizace vnitřního prostředí bikarbonátem sodným
- Prevence postižení ledvin při
- Vysokých hladinách k. močové v krvi
- Urikosurické léčbě se zvýšeným vylučováním k. močové ledvinami
Bulbs of pseudobulb cremastra seu pleiones
- Ingredient of decoctions used by Li [17], Zhang et al. [23], and others
- Contain colchicine [10]
- Užívá se v akutní fázi dny k zastavení množení se lmyfocytů - k imunosupresi
- Pro svoji toxicitu se užívá až při nedostatečném efektu nesteroidních analgetik
Celery
- Active in inhibiting the enzyme XOD [10]
Cherries
- Evidence that eating cherries is associated with a reduced risk of gout attacks [16]
- Can reduce the risk of gout
- Anthocyanin
- Catechin
- Chlorogenic acid
- Flavone glycoside
- melatonin
- Anthocyanins and hydroxycinnamate from cherries
- Inhibit oxidation of LDL-cholesterol
- Beneficial effect on liposomes similar to that of vitamin E
- Anti-inflammatory properties
- Cyclooxygenase inhibition
- Scavenging free nitric oxide (NO) radicals [17]
- Inhibit NO synthase
- Regulate the secretion of TNF alfa by activated macrophages
- Cherry consumption reduce
- Joint pain severity
- Risk of gout
- Consumption of 227 g of cherries or cherry
- Preserves for a period of 3 days to 3 months
- Normalizes serum uric acid levels
- Reduces the number of gout attacks
- Further clinical studies are necessary [17]
Deficit dihydropyrimidindehydrogenázy (DPD)
- AR dědičnost
- Porucha přeměny uracilu a thyminu na dihydrouracil a dihydrothymin
- Hromadění uracilu a thyminu v tělesných tekutinách [6]
Kompletní deficit DPD u dětí
- Epilepsií,
- Mentální retardací,
- Mikrocefalií [6]
Parciální deficit
- Bývá objeven teprve při léčbě 5-fluorouracilem (nádory)
- Není dostatečně degradován (parciální deficit DPD)
- Pro pacienta toxický
- Neutropenie
- Stomatitida
- Neurologické příznaky
- Význam snížená tvorba neurotransmiteru beta-alaninu ( produktem katabolismu pyrimidinů) [6]
Léčba
- U dětské formy není dostupná
- Při parciálním deficitu změníme chemoterapeutikum
- Možná prenatální diagnostika [6]
Dieta s nízkým obsahem purinů
- Založená hlavně na
Fruits
- Lower fructose content [9]
Obiloviny
- Breads, grains, macaroni
- No added fructose [9]
Milk products
- Cheese
- Jogurts, etc. [9]
Eggs
Vegetables
- Tomatoes
- Lettuce [9]
- ...
Dioscorea
- Saponins of Dioscorea can significantly decrease the level of SUA in hyperuricemia rats caused by adenine and ethambutol
- Mechanism may be related to
- Inhibiting XOD activity
- Increasing the excretion of uric acid
- Downregulation of high expression of URAT1
- Upregulation of OAT1 and OAT3 [10]
Total saponins
- Inhibit activity of XOD
- Downregulate URAT1
- Upregulate OAT1 and OAT3 [10]
Esculetin and esculin
- Found to improve hyperuricemia and renal dysfunction through upregulating OAT1 [10]
Estrogens
- Uricosuric effect [13]
Febuxostat
- Při kontraindikaci, intoleranci nebo nedostatečné účinnosti alopurinolu [3]
- Xanthine oxidase inhibitor
- Approved by the US Food and Drug Administration (FDA) in 2009
- The long-term treatment of hyperuricemia in patients with gout
- CONFIRMS trial, a 6-month study
- Compared febuxostat and allopurinol in 2269 subjects with gout and serum urate levels ?8.0 mg/dL
- Febuxostat 80 mg daily
- Proved superior to allopurinol in lowering uric acid levels
- In patients with normal renal function
- Febuxostat 40 mg daily
- Was equivalent to allopurinol in such patients
- In patients with mild-to-moderate renal impairment
- Febuxostat at any dose was superior to allopurinol in lowering uric acid levels [8]
- Febuxostat was as safe as allopurinol in the CONFIRMS trial
- Previous studies identified
- Cardiovascular events with febuxostat
- Large ongoing trials
- Are comparing the cardiovascular safety of febuxostat versus allopurinol [8]
Flavonoids
- Ubiquitously distributed in various foods and beverages
- Have antioxidant and XOD inhibitory activities [12]
- Consumption of flavonoids
- Shown to be associated with the protective effects of certain diets and herbs against hyperuricemia and gout [12]
Fraxetin and fraxin
- Inhibiting GLUT9 or URAT1 in kidneys of hyperuricemic mice
- Could enhance urate excretion to some extent
- Cortex fraxini coumarines
- Partly contributing to their functions of lower SUA level by regulating ABCG2 [10]
Glabrous greenbrier rhizome
- Active in inhibiting the enzyme XOD [10]
- Součástí TCM bylinných směsí k terapii dny [11]
- Astilbin as an active ingredient
- Associated with increased renal blood flow
- Anti-inflammatory and analgesic actions [11]
Green tea polyphenols - GTP (Camellia sinensis L.)
- Reduce XOD expression in liver
- Reduce URAT1 expression
- Upregulate OAT1 and OAT3 [10]
- Significantly decreased SUA levels in a dose dependent manner in potassium oxonate-induced hyperuricemic mice
- Increased OAT1 and OAT3 expressions in kidneys
- GTP might attenuate SUA level through
- Decreasing production
- Increasing excretion of uric acid [10]
- EGCG and GCG has 8 glycosylate groups that can interact with the active side of XOD enzyme
- Can be inhibited [23]
Combined oral contraceptive pills in women
- Significantly associated with lower serum uric acid [7]
Human organic anion transporter (hOAT1) - stimulation / up-regulation
- Stimulates uric acid secretion in human proximal tubules [10]
Inhibited by
- Antiuricosuric drugs [8]
- Commonly used uricosuric drugs too :-( [8]
Idnomethacin
- Inhibice URAT1 (zpětné reabsorpce)
- Urikosurikum [10]
Jasminoidin
- Jasminoidin significantly
- Lowered the SUA levels
- Increased the uric acid excretion [10]
- Compound from Chinese medicine
- Remarkably inhibited the hepatic XOD activities
- Regulated the expressions of renal urate transporters in mice [10]
Jobstears seed
- Promotion of uric acid excretion [11]
- Reduction of platelet accumulation [11]
- Improved microcirculation [11]
- Anticoagulant function [11]
- Součástí směsí TČM na ter. dny [11]
Káva
- No clear correlation between coffee consumption and serum uric acid levels
- Most guidelines suggest entirely eliminating coffee
- Reports indicating that coffee consumption inversely correlates with uric acid levels
- Third National Health and Nutrition Examination Survey
Kofein
- GreenTeaExtracts contains several substances
- Caffeine 8-30 mg per cup (240 mL) [23]
- Alkaloid
- 1,3,7-trimehylxanthine (C8H10O2N4)
- Diuretic
- Some studies suggest that caffeine consumption may trigger excessive UA formation
- In moderate consumption, caffeine may provide some benefits
- Caffeine activity inhibited because of the presence of L-theanine amino acids [23]
Strains of lactic acid bacteria isolated from Chinese sauerkraut
- Reported to efficiently degrade purine compounds
- Lactic acid bacteria may be promising candidates as an adjunctive treatment in patients with hyperuricemia [12]
Lagotis brevituba Maxim. (LBM) extracts
- Level of uric acid in hyperuricemia mice
- LBM possessed antigout effect
- Inhibit activity of XOD
- Downregulate renal URAT1 and GLUT9
- Upregulate OAT1 [10]
Lesinurad (Zurampic)
- First selective uric acid reabsorption inhibitor (SURI) approved by the FDA
- Inhibits the urate transporter - URAT1
- Responsible for the majority of the renal reabsorption of uric acid
- Inhibits organic anion transporter 4 (OAT4)
- uric acid transporter associated with diuretic-induced hyperuricemia
- Must be coadministered with a xanthine oxidase inhibitor
- Indicated for hyperuricemia associated with gout
- In patients who have not achieved target serum uric acid levels with a xanthine oxidase inhibitor alone
- Not approved for asymptomatic hyperuricemia
- Contraindicated for increased uric acid levels caused by
- Tumor lysis syndrome
- Lesch-Nyhan syndrome
- Monotherapy or higher than recommended doses
- Associated with an increased serum creatinine level
- Renal function should be assessed before initiating therapy and periodically thereafter
- More frequent monitoring is required
- Estimated creatinine clearance (CrCl) below 60 mL/min
- Do not initiate therapy
- If the CrCl is below 45 mL/min
- Discontinue
- If CrCl decreases persistently to below 45 mL/min
- Approval was based on three randomized, placebo-controlled studies
- Involving 1537 participants for up to 12 months
- Serum uric acid levels were lower in participants treated with
- Lesinurad plus allopurinol / febuxostat x placebo + xanthine oxidase inhibitor [8]
Libové maso
- Lean meat intake showed an inverse correlation with uric acid levels [17]
- Reduction in animal fat intake with a compensatory increase in consumption of plant-derived fats
- Olive oil or vegetable oils) is recommended
- Beneficial effects of mono- and polyunsaturated fatty acids on cardiovascular risk associated with hyperuricemia [17]
Lithium salts
- Improves uric acid solubility
Longan seed extract (LSE)
- Inhibit activity of XOD/ADA
- Decrease GLUT9 but increase GLUT1 [10]
Dried longan seed extract (LSE) and its active ingredients
- Inhibited XOD in a dose dependent manner [10]
- In experiment in hyperuricemic rats reduce
- Serum XOD activity
- SUA level
- LSE increased GLUT1
- But decreased GLUT9 protein level in kidney [10]
Losartan
- Antihypertensivum
- Inhibice zpětné resorbce k. močové v ledvinách [8]
Protein-rich low-fat dairy products
- Reduce uric acid levels and the risk of gout [17]
- Recommended proportion of fats in diet should not exceed 30% of the total daily energy intake [17]
Mangiferin
- Active in inhibiting the enzyme XOD [10]
Microbial fermented extracts (MFEs)
- Substantial XOD inhibition activity from:
- In mice treated with high doses of MFEs
- No treatment-related adverse effects were observed
- No organ toxicity [12]
- Effectiveness of MFEs in reducing hyperuricemia
- Suggesting that they are safe for use in the treatment and prevention of hyperuricemia [12]
Lactobacillus (MFE-21)
Acetobacter (MFE-25)
- Superior urate-lowering effects in the therapeutic model
- Significantly reduced UA [12]
MFE-120 with high uricase activity from Aspergillus oryzae
- Significantly reduced UA [12]
- Good uricase activity [12]
Modified Simiao Decoction
- Inhibit activity of XOD in liver and serum
- Upregulate OAT1 [25]
- MSD could decrease
- SUA levels
- Serum creatinine
- BUN
- Downregulated URAT1 protein expressions
- In the renal tissues of hyperuricemic mice
- In dose dependent manner [10]
Motherwort
- Active in inhibiting the enzyme XOD [10]
Oxypurinol
- Same uricostatic effects as allopurinol [10]
P. sibircum Laxm.
Alcohol extract 2.0/4.0/8.0?g/kg
- Inhibit activity of hepatic XOD
- Significantly reduced the mRNA expression level of renal GLUT9 in mice [10]
- Upregulated OAT1 mRNA expression [10]
Alcohol extract 8.0?g/kg
- Inhibit activity of XOD
- Reduce URAT1 and GLUT9
- Upregulate OAT1 [10]
Pallidifloside D
- Synergistic effects of allopurinol combined with pallidifloside D
- Associated with the
- Inhibition of serum and hepatic XOD
- Upregulation of mOAT1
- Downregulation of renal GLUT9 and URAT1 [10]
Pegloticase (Krystexxa)
- Recombinant
- Pegylated
- Uric acid–specific enzyme
- Catalyzes the oxidation of uric acid to allantoin
- Approved for use in adults with chronic gout refractory to conventional therapy
- Administered i.v. [8]
Pingwei Powder
- Směs na terapii hyperurikémie
- Swordlike atractylodes (15?g)
- Largehead atractylodes rhizome (15?g)
- Indian buead (15?g)
- Plantain seed (10?g), etc.
- Zhou 2007 36 lidí věkově kolem 53-55 let v pokusné a standardní skupině
- S SUA 518,2 -+ umol/l vstupně
- Po 21 dnech terapie střední hodnoty ve skupině na:
- Allopurinolu: SUA 56,4 umol/l +-
- Bylinné směsi: SUA 46,8 umol/l +- [11]
Pink oyster mushrooms
- Microorganisms
- Antioxidant
- XOD inhibitory activities
- Could be a potential resource for developing hypouricemic agents [12]
- Tyrosine inhibitory activity [12]
Zvýšený příjem tekutin
- Velmi vhodné doporučení všem, co mají vysoké hladiny kyseliny močové v krvi
- Prevence vzniku urátových konkrementů v ledvinách
- Další důvod, proč při přísných dietách, kdy stoupá k. močová v krvi, je vhodné pít hodně vody
Plantago asiatica L. herbs extracts (PAHEs)
- Inhibit activity of XOD
- Downregulate renal URAT1 [10]
- In hyperuricemia mice
- Results demonstrated that PAHEs could obviously improve hyperuricemia
- Downregulating hepatic ADA and XOD to reduce production of uric acid [10]
- Enhancing urate excretion [10]
- Decreasing urate reabsorption by suppressing renal URAT1 [10]
- Active ingredient aucubin
- Chen, Tan et al., Li, and Zhang et al. believe has a significant effect
- Facilitating urine production
- Promoting the excretion of urea and chloride [11]
Potassium citrate (Citra K, Polycitra K)
- Pleasant-tasting oral systemic alkalizer in a sugar-free base
- Each unit dose packet contains
- Potassium citrate monohydrate 3300 mg
- Citric acid monohydrate 1002 mg [8]
- Supplies the same amount of active ingredients as is contained in
- 15 mL (1 tablespoonful) Polycitra-K oral solution [8]
- Provides 30 mEq potassium ion
- Equivalent to 30 mEq bicarbonate [8]
- Absorbed and metabolized to potassium bicarbonate
- Acting as a systemic alkalizer [8]
- Oxidation is virtually complete
- Less than 5% of the potassium citrate is excreted in the urine unchanged [8]
- Highly concentrated administered after meals and before bedtime
- Allows one to maintain an alkaline urinary pH at all times
- Usually without necessity of 2 am dose [8]
- Alkalinizes urine without producing systemic alkalosis in recommended dosage [8]
Uric acid nephropathy prevention in the oncological setting
- Resulted in a decrease in mortality from uric acid nephropath
Probenecid (Benemid)
- Uricosuric drug
- Inhibits the tubular reabsorption of filtered and secreted urate
- Increasing urate excretion
- Ideal candidates for probenecid therapy
- Patients with a 24-hour urine uric acid excretion of less than 800 mg in 24 hours
- No history of nephrolithiasis
- Good renal function
- Creatinine clearance over 80 mL/min [8]
- Creatinine clearance must be over 60 mL per minute (1.00 mL per s) [9]
- Recurrent gout in patients who are allergic or intolerant to allopurinol
- May be combined with allopurinol in select patients with resistant hyperuricemia
- For use in patients able to maintain oral hydration [9]
- The starting dose for probenecid
- 250 mg twice a day
- Can be increased gradually
- Upward until the serum urate level is under 6 mg per dL (355 µmol per L) [9]
- To a maximum daily dose of 3 g/d
- Side effects
- Gastrointestinal irritation in approximately 2% of patients [8]
- May precipitate gouty attack or renal calculi at start of therapy [9]
- Rash [9]
- Interactions
- Therapeutic effect reversed by high-dose aspirin therapy [9]
- Inhibited by low-dose salicylates
- Accounts for a significant number of “treatment failures.”
- Patients who require low-dose aspirin therapy are not candidates for probenecid therapy [9]
- Contraindicated in patients
- With a history of urolithiasis [9]
Proteins
- Uricosuric properties
- Facilitate uric acid excretion
- Serum uric acid levels are determined by
- Quality and quantity of protein intake
Foods rich in plant proteins
- Include compounds found in leguminous plants and soya
- Rich source of purines, however, their effect on uric acid levels depends on the make-up and size of dietary portions [17]
Puerarin
- Inhibit activity of XOD [10]
- In hyperuricemic rats
- Puerarin at reasonable dosage was beneficial to improve SUA levels
- Via inhibiting activity of XOD and promoting uric acid excretion [10]
Quercetin
- At the dose of 50 and 100?mg/kg
- Could effectively upregulate OAT1
- Downregulate GLUT9 and URAT1 in the kidneys of hyperuricemic mice [10]
Radix achyranthis bidentatae
- Promotion of uric acid excretion [11]
- Součástí směsí TČM na ter. dny [11]
- Reasons Chinese medicinal herbs are able to effectively reduce the potentially adverse effects [11]
- Reduction of platelet accumulation [11]
- Improved microcirculation [11]
- Expand small arteries
- Inhibit atherosclerotic lesions
- Ameliorate renal fibrosis
- Protect the kidneys
- Anticoagulant function [11]
Radix puerariae
- Active in inhibiting the enzyme XOD [10]
Rasburicase (Elitek)
- Recombinant urate oxidase
- Derived from Saccharomyces cerevisiae -synthesized, Aspergillus flavus
- Approved for use in preventing complications of hyperuricemia during the tumor lysis syndrome
- In adults and children [8]
- Facilitates the conversion of urate to allantoin
- Allantoin is soluble and easily excreted by the kidneys
- Become the standard of care for patients at high risk of tumor lysis syndrome
- Profound and rapid lowering of plasma uric acid levels
- But is there a significant effect on patient outcomes ?
- Need for renal replacement therapy
- Mortality [8]
- Elimination half-life is 18 h [8]
- Higher doses than usual of rasburicase (600-900 mg/d)
- Administered to decrease uric acid production prior to chemotherapy
- In patients with leukemias and lymphomas [8]
- Allopurinol and hydration
- Continued for several days [8]
- If acute renal failure develops
- Early hemodialysis is indicated to reduce the total body burden of uric acid
- Facilitating recovery of renal function [8]
Recombinant uricase
Recombinant fungal uricase
- Promising drug for treating hyperuricemia in patients for short-term treatment
- Administered in high doses
- May increase of hydrogen peroxide in plasma with deleterious effects
- May induce immune responses [12]
- Clear the unmodified uricase by macrophages and hydrolyzed by proteases
- Continuous administration of low concentrations of uricase
- Could achieve a higher activity and longer half-life in vivo instead of being given once [12]
Rhizoma Dioscoreae Nipponicae
Total saponins in hyperuricemia mice models
- At different doses (600, 300, and 30?mg/kg)
- Could significantly reduce uric acid level
- Inhibiting the activities of both ADA and XOD [10]
- Upregulate OAT1 [10]
- Anti-inflammatory effect of these saponins in vitro
- Antihyperuricemia effect of saponin and nonsaponin residue
- Inhibition of hepatic XOD and ADA activities [10]
Salvia miltiorrhiza Bge.
- Reasons Chinese medicinal herbs are able to effectively reduce the potentially adverse effects [11]
- Reduction of platelet accumulation [11]
- Improved microcirculation [11]
- Expand small arteries
- Inhibit atherosclerotic lesions
- Ameliorate renal fibrosis
- Protect the kidneys
- Anticoagulant function [11]
Sea cucumber
- Cucumber saponin and polysaccharides from:
- Pearsonothuria graeffei (Pg)
- Apostichopus japonicus (Aj)
- Cucumaria frondosa (Cf)
- Isostichopus badionotus (Ib) [10]
- Could significantly lower SUA level in hyperuricemia mice induced by feeding yeast extract powder for 14 days
- All of the natural products
- Inhibit hepatic XOD and adenylate deaminase (ADA) activities [10]
- Downregulate the mRNA levels of hepatic ADA and XOD
- Downregulate mRNA of renal GLUT9 [10]
Saponin
- Inhibit activity of XOD/ADA
- Downregulate GLUT9 [10]
Saponin-EA
- Inhibit activity of XOD/ADA [10]
- Expression and activity of hepatic XOD and ADA were elevated by EA [10]
- ???
- Upregulate the mRNA levels of renal organic anion transporter 1 (OAT1)
- Decrease serum uric acid level significantly by 18.1%
- Increase the secretion of uric acid [10]
Polysaccharides
- Inhibit activity of XOD/ADA
- Downregulate XOD/ADA
- Downregulate GLUT9 [10]
Sevelamer
- In people receiving hemodialysis
- Can significantly reduce serum uric acid
- By adsorbing urate in the gut
Seven-lobed yam rhizome
- Promotion of uric acid excretion [11]
- Reduction of platelet accumulation [11]
- Improved microcirculation [11]
- Anticoagulant function [11]
- Součástí směsí TČM na ter. dny [11]
Směs Cai et al., 2014
- Cortex phellodendri chinensis (15?g)
- Swordlike atractylodes (15?g)
- Plantain seed (10?g)
- Oriental waterplantain rhizome (10?g)
- Etc. [11]
Cai S., Xu Z., Chen W. The clinical observation of clearing heat, eliminating dampness and removing the obstruction in meridians for the treatment of hyperuricacidemia. Clinical Journal of Traditional Chinese Medicine. 2014;26:907–908.
Směs Hong and Shen, 2011
- Glabrous greenbrier rhizome (15?g)
- Cortex phellodendri chinensis (10?g)
- Swordlike atractylodes (10?g)
- Jobstears seed (30?g)
- Etc.[11]
Hong Q., Shen P. Treatment of 36 cases of primary hyperuricacidemia by warming meridian, dispelling cold and removing dampness. Shanghai Journal of Traditional Chinese Medicine. 2011;45:44–46.
Směs Hu, 2006
- Glabrous greenbrier rhizome (30?g)
- Jobstears seed (15?g)
- Oriental waterplantain rhizome (15?g)
- Herba lysimachiae (20?g)
- Etc.
Hu M. The clinical efficacy of Strengthening spleen, Resolving phlegm, dredging collaterals and excreting dampness. Yunnan Journal of Traditional Chinese Medicine and Materia Medica. 2006;27:15–16.
Směs Li, 2007
- Jobstears seed (30?g)
- Glabrous greenbrier rhizome (30?g)
- Plantain deed (20?g)
- Seven-lobed yam rhizome (20?g)
- Etc
Li H. The clinical observation of decreasing serum uric acid decoction for treatment of primary hyperuricemic elderly men. Chinese Journal of Gerontology. 2007;27:1282–1284.
Směs Xiang et al., 2014
- Radix clematidis (60?g)
- Rhizoma polygonati odorati (20?g)
- Radix achyranthis bidentatae (15?g)
Xiang T., Sun B., Zhang S. Treatment of 51 cases of and heat syndrome of primary hyperuricacidemia by decreasing serum uric acid decoction. Jiangxi journal of traditionla chinese. 2014;45:37–38.
Směs Yu Q. 2012
- Glabrous greenbrier rhizome (50?g)
- Herba lysimachiae (50?g)
- Cortex phellodendri chinensis (15?g)
- Swordlike atractylodes (15?g)
- Etc. [11]
Treatment of 100 cases of hyperuricacidemia by clearing heat, detoxicating eliminating dampness and removing the obstruction in meridians. Chinese Journal of Gerontology. 2012;32:3754–3755.
Směs Zhou et al., 2010
- Glabrous greenbrier rhizome (40?g)
- Cortex phellodendri chinensis (15?g)
- Swordlike atractylodes (15?g)
- Jobstears seed (20?g)
- Etc. [11]
Zhou J., Liu C., Wei Y., Xue T. Treatment of 60 cases of primary by Gout fourteen flavour decoction. Shaanxi Journal of Traditional Chinese. 2010;31:421–422.
Směs Chen 2008
- Glabrous greenbrier rhizome (45?g)
- Seven-lobed yam rhizome (30?g)
- Carica papaya (15?g)
- Plantain seed (15?g)
- Etc. [11]
Chen L. Treatment of 38 cases of hyperuricacidemia by resolving turbidity and eliminating dampness. Yunnan Journal of Traditional Chinese Medicine and Materia Medica. 2008;2, art.10
Směs Tan et al. 2013
- Glabrous greenbrier rhizome (15?g)
- Seven-lobed yam rhizome (20?g)
- Jobstears seed (10?g)
- Herba lysimachiae (15?g)
- Etc. [11]
Tan N., Huang S., Luo X., Zhu H., Liao K. Effects of chusi huayu prescription on endothelin-1 (ET-1)and plasminogen activator inhibitor-1(PAI-1) of hperuricemia patients. Liaoning Journal of Traditional Chinese Medicine. 2013;40:1175–1177.
Směs Zhang et al., 2011
- Glabrous greenbrier rhizome (35?g)
- Seven-lobed yam rhizome (18?g)
- Pseudobulb cremastra seu pleiones (15?g)
- Radix achyranthis bidentatae (10?g)
- Etc. [11]
Zhang X., Sun W., Xu W., Wang T. Assessment on the clinical efficacy and safety of Xiezhuo Chubi recipe in treating hyperuricemla. Chinese Journal of Integrated Traditional and Western Medicine. 2011;31:1216–1219.
Smilax riparia A. D. C
- Botanical widely grown in southern and central region of China
- Roots and rhizomes of Smilax riparia in traditional Chinese medicine (TCM)
- Treat the symptoms of gout and hyperuricemia related conditions
- Including inflammation and some malignancies [10]
- Inhibit activity of XOD
- Downregulate renal URAT1 and GLUT9
- Upregulate OAT1 [10]
Soy and tofu
- Was believed to induce hyperuricemia
- Later studies indicated that soy products may have a beneficial effect on uric acid levels
- Tofu consumption
- Shown not to increase uric acid levels, even in patients with gout
- Whose serum uric acid levels exceeded 6 mg/dl [17]
- Soy protein
Sulfinpyrazone (Anturane)
- Begin with 50 mg three times daily
- Gradually titrating upward until the serum urate level is under 6 mg per dL (355 µmol per L)
- Maximum dosage: 800 mg per day
- Indication
- Recurrent gout in patients who require antiplatelet therapy
- Aspirin use may block the effects of probenecid
- Best used in patients on a regular diet who underexcrete uric acid
- Under 800 mg of urate in 24 hours
- Under 4.76 mmol per day
- Inherent antiplatelet activity [9]
Syntetická analoga purinů a pyrimidinů
Onkologická medikace k potlačení proliferace
- 5-Fluorouracil
- 6-thioguanin
- 6-merkaptopurin
- 5-nebo 6-azauridin
- Azacytidin [5]
Imunosupresiva
- Azathioprin
- Metabolizován na 6-merkaptopurin
- Tlumí proliferaci imunokompetentních buněk
- Pro potlačení rejekce transplantovaných orgánů [5]
Snižování k. močové
- Purinový analog 4-hydroxypyrazolopyrimidin (allopurinol)
- Brzdí nejen de novo syntézu purinů (
potencionální NÚ...)
- Ale též aktivitu xanthinoxidázy
- Tím přeměnu xanthinu na močovou kyselinu
- Proto při léčení hyperurikemie [5]
Tisorurinol
- Same uricostatic effects as allopurinol [10]
Topiroxostat
- Same uricostatic effects as allopurinol [10]
Turmeric
- Active in inhibiting the enzyme XOD [10]
Urate anion exchanger 1 (URAT1/SLC22A12) inhibition
- Renal proximal tubules
- Play important roles in uric acid reabsorption [10]
- Identified in the brush-border membrane of the kidneys
- Inhibice vede k poklesu k. močové v krvi
Inhibited by
- Angiotensin II receptor blocker, losartan [8]
- Some herbal substances
Uricase
- Uricase has been found in
- Mammals
- Plants
- Microorganisms such as bacteria, yeast, and filamentous fungi
- Uricase is an important medical enzyme
- Advantages for gout treatment compared with AP [12]
- Uricase activity of fermented food microorganisms
- Lactobacillus microbial fermented extract (MFE)-21
- Acetobacter MFE-25
- Expressed a high XOD inhibitory effect [12]
- Aspergillus MFE-120
- Expressed high uricase activity [12]
Urikosurika
- Zvyšují vylučování kys. močové ledvinami
- Nejsou registrována v České republice
- Při nefrolithiáze či nefropatii lze podávat pouze urikostatika [3]
- Zvyšují riziko uratove nefropatie
- By reducing the reabsorption of uric acid once the kidneys [7]
Probenecid
Benzbromaron
Vitamin C
- Vitamin C in dosages of 500mg/day has mild urate lowering effect [20]
- May help lower uric acid levels
- Talk to your doctor about whether a 500-milligram vitamin C supplement fits into your diet and medication plan [16]
Weight loss
- Being overweight increases the risk of developing gout, and losing weight lowers the risk of gout.
- Reducing the number of calories and losing weight — even without a purine-restricted diet
- Lower uric acid levels
- Reduce the number of gout attacks
- Lessens the overall stress on joints [16]
Xanthines
- Naturally in foods
- Structurally similar to allopurinol [17]
Zinc and magnesium
- Important nutrients with anti-inflammatory properties
- Chinese studies
- Have linked low dietary levels to hyperuricemia in men
- A study by Xie et al in 2697 men and 2471 women indicated that
- Dietary zinc intake was inversely associated with hyperuricemia in middle-aged and older males
- But not in females
- Wang et al reported that in 5168 subjects
- Dietary magnesium intake was inversely associated with hyperuricemia
- Independent of some major confounding factors
- But only in males [8]
