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Medication kit for treatment of Gout
Colchicine 0.5 mg x 10 boxes
Gout is a disorder of purine metabolism and it occurs when uric acid concentrates in serum. Gout can be presented in one or multiple ways:
Hyperuricemia is a concentration of uric acid in blood that exceeds mark of 416 µmol/L (7 mg%) and it plays a role of a leading symptom that factors all the other sings and symptoms. Exposure to such a diseases as gout or kidney stone disease depends on uric acid level and if this level is higher than 416 µmol/L (7 mg%) the probability of manifestation is high. Hyperuricemia can be found in 3-15,1% of adults applying to outpatient departments for ambulatory care who have passed blood chemistry tests and more frequently in hospital patients. Clinical characteristics of gout manifest when the blood plasma and extracellular water are oversaturated with uric acid and urate crystals deposit in tissues.
Uric acid is a final product of purine breakage in human body. It is contained in plasma, extracellular and joint waters in form of salts of uric acid. If the pH level is 7,4 uric acids on 98% consist of monosodium salt that can be easily removed from plasma by hemofiltration or dialysis. Concentration of uric acid saturated solution in serum at a temperature of 37% is 416 µmol/L (7 mg%). Threshold level leads to crystallization of urates. However, there are special agents in human blood plasma that assist its solvability, that’s why, generally, the crystallization does not happen even if the level is high.
Uric acid is better to be solubilized in urine than in water and the process itself depends on the pH level. Partly uric acid is located in urine in form of different salts. Purine synthesis and breakage take place in every body tissue but uric acid develops at the spots of xanthine oxidase concentration (mostly in gout and small gut). Uric acid quantity in human body is determined by its formation and excretion speeds ratio. Uric acid formation speed depends on quantity of purines in person’s food ration, on synthesis and breakage speed. Generally, about 66-75% of uric acid is removed with urine and the other part with stool.
Approximately 95% of uric acid from glomerular filter is reabsorbed in proximal tubules but one half of that quantity is released from that tubules again and only about 40% undergoes reabsorption. As a result, only about 8-12% of filtrated uric acid gets in urine. Uric acid concentration in kids’ serum depends on their age and sex, in adults’ – age, sex, height, weight, blood pressure, kidney function and alcohol consumption. Mostly children’s uric acid level is about 180-240 µmol/L (3-4 mg%). In the wake of puberty concentration of uric acid in men grows, in women the level stays low until menopause. The cause of that fact is still unknown. Upper limit of normal uric acid concentration in adults’ serum is 360 for women and 416 for men µmol/L (6-7 mg%). Uric acid concentration in serum of postmenopausal women gets higher and approaches to concentration that is common among men.
Hyperuricemia can be determined by excessive uric acid formation, lacking excretion or both. That’s why there are three types of hyperuricemia: metabolic, nephritic and combined.
Concentration of uric acid in serum is directly dependent on how much purines do your meals contain. Approximately 50% of RNA purines and 25% of DNA purines that are delivered with food, excrete with urine in form of uric acid, that’s why consumption of food rich in nucleic acid (liver, kidneys, anchovies) has a sizable effect on its concentration in serum. Avoiding of these products leads to reduction of uric acid concentration in serum on 10-15%.
Among patients with primary hyperuricemia and gout there are about 98% who suffer from uric acid excretion disorder. Gout decreases excretion on 40% independently on the level of uric acid concentration in serum. If the purines are taken with food or injected, then uric acid excretion speeds up in any patient, either with gout, or a health one. Chronic kidney disease is always accompanied by hyperuricemia, but there are no connections between uric acid concentration in serum and creatinine concentration. Patients with chronic renal insufficiency have a higher level of uric acid extraction ratio, unchanged tubular secretion, decreased reabsorption and as insufficiency worsens more and more uric acid is excreted with stool.
Decreased secretion of uric acid in proximal tubules leads to hyperuricemia even within a standard speed of uric acid formation. This explains the secondary hyperuricemia in cases of acidosis. Diabetic ketoacidosis, fast, ethanol or salicylate intoxication result in accumulation of organic acids that similarly to uric acid are excreted by the same transport system that provides secretion. Reabsorption intensification in distal segments of proximal tubules can also lead to hyperuricemia and gout. This is noticed in extracellular water volume reduction, for instance, in cases of diabetes insipidus or diuretic ingestion.
It is widely spread, when hyperuricemia turns out to be a combination of excessive uric acid formation and its low excretion level. In this case, increased production of uric acid depends on adenosine triphosphate breaking during fast or hypoglycemia. By the way, these patients have lower nucleoside monophosphates concentration. Generally, they also have excessive concentration of lactic acids what causes inhibition of uric acid tubular secretion. Both mechanisms of hyperuricemia development are noticed in case of fructose intolerance. Abusive drinking behavior also leads to combined hyperuricemia by means of:
Furthermore, some alcohol beverages contain too much purines, beer, for instance.
Plasmatic uric acid level increase – hyperuricemia – does not always demand for treatment. In that case, make sure that you know the cause of it. Treatment necessity depends on the cases of occurrence and probable consequences. The cause of hyperuricemia can be determined by daily uric acid excretion. In the absence of purines in food and normal kidneys function men’s excretion reaches about 3,6 µmol (600mg). Exceedance of this element proves intensive uric acid formation, and vice versa, its reduction demonstrates excretion disorders. While keeping a usual ration, the upper limit of normal is 4,8 µmol/day (800mg). Glomerular filtration rate decrease leads to reduction of uric acid excretion. That’s why its low daily excretion does not exclude excessive uric acid formation, but increased uric acid excretion reveals its excessive formation.
Glucocorticoids, ascorbic acid, salicylates in dosage more than 2gr/daily and some other medications intensify uric acid excretion and that should be considered in making an assessment of lab results.
Gout has different ways of manifesting but its typical development has three stages:
Urolithiasis can develop either before, or after the first stroke of gouty arthritis. Across the population of developed countries, the hyperuricemia occurrence is about 3-15,1%, gout occurrence – 1,5-3,5%. Stronger uric acid concentration in serum makes higher probability of gout onset. According to one of the studies, if the uric acid concentration in serum is more than 540 µmol/l (9mg%) the gout incidence is 4,9%, and if the concentration is 415-535 µmol/l (7-9mg%) – 0,5%. Gout’s course depends on the continuance and severity of hyperuricemia. The first gout attack often happens 20-25 years after steady hyperuricemia; men are usually subjected to attacks at age of 40-60 years, women – after the menopause.
The most evident gouty sign is acute arthritis. The first stroke onsets suddenly and is accompanied by severe pain and inflammation sings: the skin in the joints area is red, hot, swollen, the palpation brings painful feelings; fever is a rare sign to be. Previously to strokes some patients have latency period and some continuous strokes of less intensive pain. In case of treatment absence, the symptoms tend to grow within 24-48 h, then they decline and pass within 7-10 days. After the stroke, the affected joint area can be subjected to peeling skin. The first stroke damages only one joint, rarely (generally, in women) – several joints. Most commonly, those joints are joints of the legs. Even more rarely occurs extraarticular inflammation localization, such as fasciitis plantar and achillobursitis. 90% of patients suffer from first metatarsophalangeal articulation damage, 50% out of it have it damaged at the first stroke. The attack’s cause can be found in any factor that gives rise to sharp oscillations of uric acid concentration in serum.
The other underlying conditions are: stress, injuries, infections, surgeries, fast, weight loss, drinking and drug administration. 20-25% of patients (according to information from different countries), who are subjected to gout on admission for whatever reason, have an acute arthritis development. The causes of it can be some severe concomitant diseases, new treatment order, fluid and electrolyte disorders and general anesthesia. Gouty strokes can often be developed due to thiazide diuretic treatment, that causes hyperuricemia, and due to allopurinol and other hyperuricemia drugs. Some strokes occur even without any sings of hyperuricemia. It is considered, that they are mostly connected with uric acid concentration downfall in serum.
Sometimes hyperuricemia is impossible to detect despite the fact that there had been taken a lot of blood tests. Theoretically acute arthritis can be caused by any factor that leads to oversaturation of joint fluid with uric acid. Injuries and swellings enhance the volume of joint fluid with standard uric acid concentration. In the course of the treatment the water leaves the joint cavity much faster than uric acid, that’s why its concentration in joint fluid temporary rises what creates good conditions for crystallization and acute arthritis development. Some patients, who suffer from gout, experience only one stroke in a lifetime, when all the others – frequent. On the occasion, the first and the second strokes have a longer than 20-year interval. Two-thirds of patients have their second stroke within 2 years after the first one. Attack-free interval is characterized by an absence of joint pain what gives patients a feeling of full recovery. Some bad cases, especially in the absence of treatment, lead to chronic gouty arthritis. Intermissions shorten and the strokes become more continuous and damage more than one joint, however, the pain can be not that intense.
Chronic gout represents polyarthritis with constant not intensive pain and acute or subacute inflammation. Physical examination is conducted with the aim of finding tophus ¬– a deposit of uric acid crystals, in the form of monosodium urate crystals, that are surrounded by giant cells; the picture reminds of granuloma of extraneous body. They can be formed either in joints or in periarticular tissues. By destructing bone, cartilaginous and soft tissues they induce deformation and degenerative changes in joints. Rate of urates solidification and joints destruction depends on severity and continuance of hyperuricemia. Usually it takes 10 years from the first gouty stroke to tophus formation. This time is taken for gradual destruction of cartilaginous and bone tissues that can be detected by X-ray examination.
Acute gouty strokes are caused by neutrophil reaction on urate crystals that leads to activation of humoral and cellular inflammation mechanisms. Urate crystals activate classical and alternative complement pathways. Furthermore, blood-coagulation factor XII activates and stimulates bradykinin, kininogenase and plasmin formation. Neutrophil releases lysosome enzymes, oxygen free radicals, leukotriene and prostaglandin metabolites, collagenase and other proteases under the influence of urate crystals. Neutrophil phagocytosis of crystals leads to leukotriene B4 release. Leukotriene B4 and fragment of complement component C5α cause neutrophil hematosis in the initial stage of acute gouty stroke. Eventually, neutrophils are replaced by macrophages. Affected by urate crystals macrophages release prostaglandin E2, lysosome enzymes, TNF-alpha, IL-2 and IL-8 and other cytokines.
Some serum proteins have an impact on inflammation process onset by urate crystals. Absorbed IgG promotes the release of vasoactive substances from blood plates under the influence of crystals, formation of superoxide radical and release of lysosome enzymes from neutrophils. Generally, apoprotein “B” is never found in synovial fluid as far as lipoproteins can not penetrate through the hematosynovial barrier.
Renal insufficiency always comes together with hyperuricemia but gouty arthritis can be found only in 1% of patients subjected to chronic renal insufficiency. The first gouty stroke occurs after a long period of steady hyperuricemia. Furthermore, inflammation reaction intensity declines due to hypodermal urate crystals injections in chronic renal insufficiency. Gout is a quite spread complication after kidney transplantation. Gouty arthritis can be found in 7-12% of patients, who get the cyclosporine and glucocorticoid immunosuppressive therapy and more frequently in those, who are simultaneously prescribed with diuretics; it takes 18 months from the operation to the first gouty stroke.
Azathioprine and glucocorticoids treatment of gout is rarely used. Uric acid synthesis in patients, who get cyclosporine does not change, but its excretion is lower than in those, who get azathioprine. Kidneys disease in hyperuricemia can manifest in form of urolithiasis, urate nephropathy or acute hyperuricemic nephropathy. Rare urate nephropathy is characterized by uric acid crystallization in kidneys’ interstitial tissue that lead to CKD. Acute hyperuricemic nephropathy can be detected by massive uric acid crystallization in renal tubes and collector tubules that causes reversible acute renal failure.
In 40% of cases kidney stones formation are followed by arthritis. Risk of urolithiasis in gout depends on uric acid concentration in serum and urine. Kidney stones can be found in 50% of patients whose uric acid concentration level in serum is above 770 µmol/l (13 mg%) and its daily excretion is 6,5 µmol (110mg). Gout also gives rise to kidney stones formation that consist from uric acid and its salts. Approximately 13% of patients have oxalic, phosphatic or combined kidney stones. Uric acid can form a core that accumulates calcium oxalate or speeds up calcium oxalate crystallization. Moreover, kidney stones are found in cases of gouty evidence absence, also 80% of patients do not even have hyperuricemia. Sometimes hyperuricemia and uric acid concentration strengthening can be found in patients with oxalate stones in kidneys, but there are no any of gouty evidences.
Over the years, uncertainty in prevention of gouty complications made specialists prescribe hyperuricemia medicines – “Allopurinol” in cases of asymptomatic hyperuricemia. Nowadays this therapeutic approach is considered to be insupportable. Despite the risk of gouty arthritis onset simultaneously with hyperuricemia, especially with high concentration of uric acid in serum, it is unreasonable to use hypouricemic drugs as far as the most cases of high level of uric acid in serum do not come to gout. What is even more interesting, structural changes in kidneys and tophus never occur before the first disease stroke.
Asymptomatic hyperuricemia is not considered to be the cause of decreased kidneys function and it was proved that hypouricemic medicines have no effect on kidneys disease state. Although, gout is often accompanied by urolithiasis, possibility of stone formation in asymptomatic hyperuricemia is not proved. But it is highly likely that it is possible. Asymptomatic hyperuricemia screening programs were baseless. It must be added, that if hyperuricemia was defined, it should be found out whether it is possible to exclude its cause. Furthermore, comorbidities, such as hypertension, hypercholesterolemia, diabetes and fatness, should be treated. Gouty arthritis and urolithiasis can induce a severe pain, that is why it is strongly recommended to prescribe analgesics before the hyperuricemia therapy.
No matter what disease do you have, it is quite impossible to give any prescriptions without making an accurate diagnosis. The final gout diagnosis can be made only after taking of a joint or tophus tap that has showed crystals of uric acid monosodium salt in neutrophil of synovial fluid or tophus contents. There are three evidences of gouty arthritis:
However, those diagnostical criteria are not reliable enough as crystals finding in tap because of the fact, that some patients do not have hyperuricemia along with acute gouty arthritis, and colchicine is quite effective in many cases. Those diseases are quite impossible to distinguish from gouty arthritis. Moreover, sometimes acute gouty arthritis develops along with arthrempyesis, psoriatic arthritis, rheumatoid arthritis, arthropathy deformans and pseudo-gout. In cases when diagnosis is unmistakable, it is recommended to prescribe “Colchicine” or intra-articular introduction of glucocorticoids. The earlier you start treatment, the higher efficiency you will get, but if the treatment was started at the late stage of gout, immediate results will never be obtained. Intake of “Colchicine” is prescribed in dosage of 0,6 mg every hour until subsidence of clinical sings or gastrointestinal side effects occurrence. In absence of any results, the treatment is cancelled within 10 hours, and the gout diagnosis is put in question. “Colchicine” is extremely effective being ingested, but it causes some dyspeptic events – abdominal pain, diarrhea and nausea in 80% of cases.
Colchicine action in gout attack interruption is so much peculiar that in cases of doubt, trial treatment is used: its positive effect is a diagnostic criterion itself. If the diagnosis was accurately made, then it would be better to use some other drugs. Usually it is replaced by “indomethacin”, “ibuprofen”, “naproxen”, “tolmetin”, “sulindac”, “piroxicam”, “ketoprofen” and “flurbiprofen”. Intra-articular introduction of glucocorticoids is used only in cases when patient is unable to intake the drugs or he has some contraindications for colchicine. Acute gouty arthritis is also treated by single dosing of 40-50 IU corticotrophin intramuscularly.
Patients have no sense of discomfort in between the attacks of gout. Specialists do not share a common vision of the clear moment of hyperuricemia medications prescription but they have arrived at a consensus that they should be prescribed in cases of irritable joint, chronic gout, tophus development, acute gouty arthritis and urolithiasis. Some doctors consider that the first gouty stroke is a reasonable ground for treatment onset. As far as first gouty attack is cured in a quick and easy way, the others think that hyperuricemia medications should be prescribed after 1-2 repeated bouts. Steady hyperuricemia against the background of gouty arthritis leads to bony and cartilaginous tissue injuries.
In absence of any treatment, urate concretions get bigger and they also can be detected on X-ray diagrams before the hypodermic tophus development. X-ray diagrams detected tophus that was not found in physical examination in 40% of patients with intermitting gout. Bony changes development does not depend on frequency of arthritis attacks, previous treatment and uric acid concentration in serum at the examination moment. “Allopurinol” decreases concentration of uric acid in serum and that is why its administration on acute stages can prolong the stroke or cause a new one. That means, it can be prescribed only in cases of absolute absence of inflammation and only in combination with colchicine. Preventive intake of colchicine in the dose of 0,5 mg 1-3 times daily helps to stop gouty strokes in vast majority of patients. Hyperuricemia medication doses are picked up in a such way that uric acid concentration does not exceed 300 µmol/l (5 mg%). Extracellular water is saturated with uric acid if the concentration is 416 µmol/l (7 mg%), but if the concentration is higher, urates are crystalized in tissues. That’s why when uric acid concentration decreases in serum, for example, from 600 to 480 µmol/l (from 10 to 8 mg%) its gross amount in body will not get less but will rise slowly. If the concentration is less than 416 µmol/l (7 mg%), urate crystals will break down and gross amount of uric acid will get low. After a good treatment course the gouty strokes end off and tophus vanishes.
Quite recently hyperuricemia treatment lied in dietary intervention and hypouricemic medications intake. Nowadays, modern hypouricemic drugs are so much effective that dieting has no point, however it is recommended to give up alcohol beverages and change ration to reduce the risk of obesity, diabetes and hypertension contraction.
Most frequently used hyperuricemia drug is “Allopurinol” that plays a role of substrate and competitive xanthine oxidase inhibitor. The main metabolite of allopurinol is oxypurinol that also inhibits xanthine oxidase activity. Allopurinol is easily absorbed from gastrointestinal tract.
Allopurinol treatment is effective in every hyperuricemia type, especially if patient has:
Uric acid concentration in serum and its excretion decrease during the first day of allopurinol administration and its maximum effect is noticed within the first two weeks. Its average dose depends on the quantity and size of tophus and on kidneys function. 300 mg dose always has a working hypouricemic effect; absence of the effect means that patients administer it irregularly. “Allopurinol” should be taken 1 tame daily. In cases of renal insufficiency, the dose should be cut. Side effects are rare. Among them – diarrhea and other gastrointestinal disorders, rash and headache. Allopurinol prescription for patients with renal insufficiency or in complex with thiazide diuretics can lead to baldness, fever, intestinal nephritis, renal insufficiency, allergic vasculitis and even death. Fortunately, those reactions hardly ever seem to occur. When prescribing “Allopurinol”, drug interactions should be considered. Uricosuric drugs decrease uric acid concentration in serum by the means of reabsorption inhibition its distal excretion parts in proximal tubules. Those drugs are prescribed in cases of gout, if:
Uricosuric drugs are effective in 70-80% of cases. If there is no effect, then the patient is intolerant to that medication or he does not follow the prescriptions, simultaneously uses salicylates or has any kidneys disorder. Uricosuric drugs action weakening by salicylates effect depends on uric acid secretion inhibition. Sometimes at the very beginning of treatment by enhancing uric acid excretion uricosuric medications lead to kidney stones formation. Stones formation is possible to prevent by decreasing the initial dose, being dehydrated enough or urinary alkalinizing. The main side effects are allergy, rash and gastrointestinal tract dysfunction. Toxic reactions such as hepatic necrosis and nephrosis occur rarely.
Hypouricemic medications are prescribed only in cases when gout is accompanied by urate and calcium kidney stones that are caused by high uric acid concentration level in urine. Independently from stones nature, patient should be hydrated in a way when his daily diuresis exceeds 2 l. Sometimes it is necessary to undergo urinary alkalinizing by sodium bicarbonate or acetazolamide to speed up uric acid solubility. Specific therapy for treatment of kidney stones should include allopurinol for uric acid concentration decrease in urine. Moreover, allopurinol also reduces a risk of oxalic kidney stones formation in patients with gout or asymptomatic uric acid concentration level rise in serum and urine. Alternative drug against kidney or calcium stones is a potassium citrate (30-80 µmol/daily in series). Allopurinol is used in presence of kidney stones composed of 2,8-dihydroxy-adenine.
Colchicine 0.5 mg per hour (up to 16 pills daily).
After relief of gouty attacks, change the pattern to 1 pill 3 times per day within a month.
Buy 10 packs (30 pills each) of Colchicine here
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Alloril (Allopurinol) 100 or 300 mg * 3 times per day.
The dosage depends on uric acid level in serum
Make a biochemical blood test and send the results to us.
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