Basic knowledge about febuxostat.📃📃📃

Febuxostat is a xanthine oxidase inhibitor. It inhibits the production of uric acid. While allopurinol can only inhibit the reduced form of xanthine oxidase, febuxostat can inhibit both the reduced and oxidized forms of xanthine oxidase. Therefore, febuxostat's ability to lower uric acid is faster and stronger. 80% of blood uric acid is synthesized in the body, and only 20% is absorbed from food. Patients with gout need to control their blood uric acid within the target range (<360 μmol/mL) throughout their lives to reduce the frequency of gout attacks, prevent tophi formation, prevent bone destruction, and reduce the risk of death. Therefore, they may need to take long-term uric acid-lowering medications.

What are the indications for Febuxostat?

Allopurinol, febuxostat, and benzbromarone are recommended for patients with gout. However, febuxostat is not recommended for use in asymptomatic hyperuricemia. In patients with asymptomatic hyperuricemia in stages 3 and 4 chronic kidney disease, the dose of allopurinol needs to be adjusted and severe hypersensitivity reactions may occur. Therefore, febuxostat may be a better treatment. Febuxostat is indicated for the long-term treatment of hyperuricemia in patients with gout. However, it is not recommended for use in patients with asymptomatic hyperuricemia. Febuxostat has little effect on renal function. No dose adjustment is required in patients with renal insufficiency.

When should uric acid-lowering drugs be used?

Some guidelines recommend that patients with gout can start uric acid-lowering drug treatment after the acute gout attack is completely relieved for 2 to 4 weeks. This is because urate-lowering medications can worsen the symptoms of gouty arthritis. However, if gout attacks are frequent, uric acid-lowering medication can be started at the time of the gout attack. Therefore, they should not be used until the symptoms of acute inflammation of gouty arthritis have resolved. In addition, allopurinol is generally recommended as the first-choice uric acid-lowering drug, but HLA-B*5801 genotype monitoring should be performed before use. Allopurinol is contraindicated in patients with positive HLA-B*5801 genotype.

What is the dosage of Febuxostat?

Common tablet doses of febuxostat are 20mg, 40 mg and 80 mg. The recommended starting dose of febuxostat is 20 mg daily. Patients whose serum uric acid levels do not reach the target value after 2 to 4 weeks of treatment can be increased to 40 mg per day, with a maximum dose of 80 mg per day. Febuxostat tablets can usually be taken in split doses without affecting the effectiveness of the medicine. Its uric acid-lowering effect is not affected by food. 

What are the adverse effects of Febuxostat?

Common adverse reactions generally refer to adverse reactions that occur in at least 1% of patients and are at least 0.5% higher than those in the placebo group. Abnormal liver function, arthralgia, nausea, and rash are common adverse reactions of febuxostat. Abnormal liver function is the most common adverse reaction causing patients to discontinue febuxostat treatment. Therefore, patients should undergo a liver function test before doctors prescribe febuxostat. In addition, if patients experience fatigue, loss of appetite, right upper quadrant discomfort, soy sauce-colored urine or jaundice during the medication period, they should seek medical treatment in time.

Side effect	Placebo group	Allopurinol	Febuxostat
			40 mg/day	80 mg/day
Abnormal liver function	0.7%	4.2%	6.6%	4.6%
Arthralgia	0%	0.7%	1.1%	0.7%
Nausea	0.7%	0.8%	1.1%	1.3%
Rash	0.7%	1.6%	0.5%	1.6%

Febuxostat is more likely to increase the risk of cardiovascular death in patients with gout than allopurinol. Therefore, febuxostat should be used with caution in elderly patients with gout and cardiovascular and cerebrovascular diseases. Allopurinol is the first-line treatment for gout patients with severe cardiovascular disease (such as myocardial infarction, history of stroke, unstable angina). During the medication period, patients should seek medical attention immediately if they develop symptoms such as chest pain, shortness of breath, fast or irregular heartbeat, numbness or weakness on one side of the body, dizziness, difficulty speaking, or sudden severe headache.

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What is the difference between allopurinol, benzbromarone and febuxostat?💫💫💫

Hyperuricemia is a very common metabolic disease today. It not only causes kidney stones, chronic kidney disease and gout in patients, but may also cause diabetes and cardiovascular and cerebrovascular diseases. Allopurinol, benzbromarone and febuxostat are the most commonly used urate-lowering drugs in clinical practice. What is the difference between the three of them?

How to choose uric acid-lowering drugs for treatment?

Febuxostat is approved only for the long-term treatment of hyperuricemia in patients with gout. In addition, due to the potential cardiovascular risks of febuxostat, it is not recommended for the treatment of patients with asymptomatic hyperuricemia. 

The first-line urate-lowering drugs for patients with asymptomatic hyperuricemia are allopurinol or benzbromarone. Patients start with the lowest dose and slowly increase to the highest available dose. If the patient's blood uric acid level does not reach the target range, allopurinol and benzbromarone can be used in combination.

First-line urate-lowering drugs for patients with diagnosed gout are allopurinol, benzbromarone and febuxostat. Patients start with the lowest dose and slowly increase to the highest available dose. If the patient's serum uric acid level fails to reach the target range, allopurinol or febuxostat is used in combination with benzbromarone. In order to reduce the frequency of gout attacks, prevent tophi formation, prevent bone destruction, and reduce the risk of death in gout patients, they need to control their blood uric acid levels to <360 μmol/ml throughout their lives. Therefore, they may need to take urate-lowering medications for life. 

What is the difference in the uric acid-lowering abilities of allopurinol, benzbromarone and febuxostat?

Increased blood uric acid levels are mainly due to increased uric acid synthesis or decreased uric acid excretion in the body. 

1. Allopurinol: It is a hypoxanthine analogue. Its active metabolites are xanthine analogs. Allopurinol inhibits the reduced form of xanthine oxidase and reduces uric acid synthesis.
2. Benzbromarone: It inhibits urate transporter-1 on the renal tubules and reduces uric acid reabsorption. The excretion of uric acid will increase and the patient's blood uric acid level will decrease.
3. Febuxostat: It is a non-purine analogue. It inhibits both the oxidized and reduced forms of xanthine oxidase. Therefore, its ability to inhibit uric acid synthesis will be stronger than that of allopurinol.

Uric acid-lowering intensity: febuxostat > allopurinol ≈ benzbromarone.

What are the advantages and risks of allopurinol?

Some studies have pointed out that allopurinol can improve vascular endothelial function and exercise tolerance in patients with angina pectoris. It can also reduce the morbidity and mortality of heart failure. Both systolic and diastolic blood pressure are lowered by allopurinol. Allopurinol may also increase creatinine clearance and decrease serum creatinine in patients with chronic kidney disease.

However, allopurinol can cause hypersensitivity syndromes such as fatal exfoliative dermatitis. HLA-B*5801 gene positivity is a risk factor for hypersensitivity reactions to allopurinol. Therefore, it is recommended that patients undergo HLA-B*5801 gene testing before using allopurinol. Allopurinol may cause renal damage, so the dose needs to be adjusted based on the patient's renal function.

What are the advantages and risks of febuxostat?

Febuxostat has the strongest uric acid-lowering ability among the three. Moreover, it is mainly cleared by the liver and has little impact on kidney function. Therefore, there is no need to adjust its dose for patients with CrCl ≥ 30ml/min.

However, febuxostat is associated with a greater risk of death from cardiovascular events than allopurinol. Therefore, allopurinol is a first-line treatment for gout patients with severe cardiovascular disease (such as myocardial infarction, history of stroke, or unstable angina).

What are the advantages and risks of benzbromarone?

Benzbromarone is a uricosuric drug. It is generally used as an alternative treatment to xanthine oxidase inhibitors. It is contraindicated in patients with CrCl <30 ml/min or in patients with kidney stones.

What are the drug interactions with uric acid-lowering drugs?

Allopurinol and febuxostat are xanthine oxidase inhibitors. Significant drug interactions may occur when they are combined with drugs that are metabolized by xanthine oxidase (such as aminophylline, azathioprine, mercaptopurine and theophylline). 

Allopurinol: It combined with amoxicillin may increase the incidence of rash. The combination of allopurinol and captopril may result in fatal Stevens-Johnson syndrome, especially in patients with chronic renal failure. Allergy and renal failure may occur when thiazide diuretics are used with it. Aluminum hydroxide may decrease the absorption of allopurinol. It will cause iron-containing hemoglobin deposition when combined with iron, so the two cannot be taken at the same time. It will also increase the bleeding risk of anticoagulant drugs, and it is recommended to monitor the patient's prothrombin time when used together.

Benzbromarone: Diuretics can increase uric acid and reduce the effectiveness of benzbromarone. It is also not suitable for use in combination with anticoagulant drugs.

What are the indications and dosages of uric acid-lowering drugs?

Allopurinol: It is indicated for primary and secondary gout, hyperuricemia secondary to malignancy, hyperuricemia after organ transplantation, and calcium oxalate stone disease. Its initial dose is 50 to 100 mg daily, taken in 1 to 3 divided doses. Its maximum dose is 600mg daily. To prevent the formation of xanthine stones, patients should drink plenty of water while taking medication. Patients need to alkalinize their urine if necessary.

Febuxostat: It is indicated for the long-term treatment of hyperuricemia in patients with gout. Its initial dose is 20 to 40 mg once daily. Its maximum dose is 80mg daily. To prevent the formation of xanthine stones, patients should drink plenty of water while taking medication. Patients need to alkalinize their urine if necessary.

Benzbromarone: It is indicated for primary and secondary hyperuricemia, gout caused by various causes, and gouty arthritis. Its initial dose is 25 to 50 mg once daily. Its maximum dose is 100mg daily. To prevent the formation of uric acid crystals, patients should drink no less than 1.5 to 2L of water per day while taking medication. Patients need to alkalinize their urine if necessary.

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What are the common problems of gout?🔍🔍🔍

Gout is a very common metabolic disease clinically. Here are some practical facts and frequently asked questions about gout.

1. What is the difference between hyperuricemia and gout?

Hyperuricemia refers to the blood uric acid levels of both men and women are higher than 420 μmol/L twice on different days. In patients with hyperuricemia, urate crystallizes and deposits in the body. It can cause patients to develop gouty arthritis, uric acid nephropathy, and kidney stones called gout. Some researchers now refer to gouty arthritis as gout. In addition, some patients with hyperuricemia have no obvious symptoms such as arthritis for life, which is called asymptomatic hyperuricemia. Subclinical gout can be diagnosed in patients with asymptomatic hyperuricemia if sodium urate crystal deposition and/or gouty bone erosions are found on examination.

2. Are Gout and Hyperuricemia Inherited to Offspring?

The probability of blood uric acid level being inherited is approximately 27 to 41% and the probability of gout being inherited is about 30%. About 20% of gout patients have a family history of it. Environmental factors such as alcohol consumption, overeating and weather are closely related to the occurrence of gout. Environmental factors such as alcohol consumption, overeating and weather are closely related to the occurrence of gout. Acute gouty arthritis has the characteristics of rapid onset. Within hours, patients experience redness, swelling, heat, pain, and dysfunction in affected joints. Midnight or early morning is the more common time of onset. In addition, due to the poor blood supply, low skin temperature, low interstitial fluid pH and high pressure of the foot, the first metatarsophalangeal joint is the first joint of most gout.

3. What is the relationship between high blood pressure and hyperuricemia/gout?

It is generally believed that for every 60 μmol/L increase in blood uric acid in a patient, his relative risk of hypertension will increase by 1.4 times. Blood vessels and kidneys can be damaged by high blood pressure. It will reduce uric acid excretion and increase blood uric acid level. Angiotensin converting enzyme inhibitors (eg, captopril), angiotensin-receptor blockers (eg, irbesartan, except losartan.), β-blockers (eg, metoprolol), and thiazide diuretics (eg, hydrochlorothiazide and indapamide) significantly increase the risk of gout attacks. Patients with hypertension complicated with hyperuricemia or gout should preferably choose antihypertensive drugs that do not affect blood uric acid levels, such as amlodipine and losartan. Atorvastatin is the first choice for patients with hyperuricemia or gout combined with hypercholesterolemia, which can promote the excretion of uric acid by the kidneys. Fenofibrate is the first choice for patients with hyperuricemia or gout with hypertriglyceridemia, which can inhibit uric acid reabsorption.

4. Are people with hyperuricemia or gout more likely to develop diabetes?

For every 60 μmol/L increase in the blood uric acid level of a patient, the risk of new-onset diabetes increased by 17%. Uric acid-lowering treatment can reduce the incidence of diabetes in people with hyperuricemia. Their incidence of cardiovascular and renal complications will also be reduced. In addition, insulin can lead to elevated blood uric acid levels in patients. Therefore, hypoglycemic drugs such as α-glucosidase inhibitors, metformin, SGLT-2 inhibitors and thiazolidinediones will increase insulin levels in patients. Patients with gout who use hypoglycemic drugs should try to avoid using the above drugs.

5. Do patients with asymptomatic hyperuricemia need uric acid-lowering therapy?

Non-drug treatments such as diet adjustment and weight control will be the first choice for patients with asymptomatic hyperuricemia. Treatment guidelines in China and Japan suggest that patients with asymptomatic hyperuricemia should be treated with uric acid-lowering drugs when the blood uric acid level is ≥540 μmol/L. Treatment guidelines in Europe and the United States recommend that patients with asymptomatic hyperuricemia need to start uric acid-lowering drug therapy only when they have chronic kidney disease and cardiovascular risk factors. Among the urate-lowering drugs, allopurinol can cause fatal allergic reactions in patients, benzbromarone can seriously damage the liver function of patients and febuxostat can increase the risk of cardiovascular events in patients.

6. What value should the blood uric acid target value be reduced to in patients with gout?

Studies have pointed out that when the patient's blood uric acid is controlled at <360 μmol/L for a long time, it can dissolve the urate crystals in the patient's body, and reduce the number and volume of crystals. It also prevents the formation of new urate crystals in the body. It is recommended to control the blood uric acid level of all gout patients to <360 μmol/L, and the blood uric acid level of severe gout patients to be controlled to <300 μmol/L. However, it is not recommended to control the patient's blood uric acid level at <180 μmol/L for a long time.

7. Which uric acid-lowering drugs can be used in patients with gout?

Allopurinol, benzbromarone, and febuxostat are the first-line drugs for uric acid-lowering therapy in patients with gout. Allopurinol and febuxostat inhibit uric acid synthesis in patients. Benzbromarone stimulates the excretion of uric acid. Allopurinol and benzbromarone are the first-line uric acid-lowering drugs for patients with asymptomatic hyperuricemia. If the patient's blood uric acid still does not reach the target value after using a sufficient amount and a full course of monotherapy, two uric acid-lowering drugs with different mechanisms of action can be considered in combination.

8. What uric acid-lowering drugs should be used in patients with gout and chronic kidney disease?

For gout patients with chronic kidney disease, uric acid-lowering therapy can inhibit the progression of their chronic kidney disease. Uric acid synthesis inhibitors such as allopurinol and febuxostat will be given priority to gout patients with chronic kidney disease stage 3 or above (glomerular filtration rate <60ml/min).Since the fatality rate of hypersensitivity reaction to allopurinol is as high as 30% and is obviously related to the HLA-B*5801 gene, patients should be tested for their HLA-B*5801 gene before using it. Therefore, febuxostat is especially suitable for gout patients with chronic renal insufficiency.

9. Do patients with gout who taking benzbromarone need to also take sodium bicarbonate?

Although oral administration of sodium bicarbonate has a certain effect on reducing uric acid in patients with gout, the effect on reducing uric acid is limited. In addition, long-term use of sodium bicarbonate can cause water and sodium retention in patients, which can cause and aggravate high blood pressure and induce heart failure. Therefore, patients only need to take sodium bicarbonate if the pH of the morning urine is <6.0.

10. What is the correct way to use colchicine?

Compared with taking large doses of colchicum, the effect of small doses of gout is similar and the side effects will be significantly reduced. When the patient has an acute gout attack, the first dose of colchicine is 1 mg, and then an additional 0.5 mg is given every hour. Until 12 hours later, take 0.5mg once or twice a day. When patients start uric acid-lowering drug therapy, fluctuating blood uric acid levels can easily induce acute gout attacks. Therefore, patients can take colchicine for at least 3 to 6 months to prevent acute gout attacks. The dosage is 0.5 to 1 mg per day.

11. Why are obese people more prone to gout attacks?

Gout is a metabolic disease and many patients with gout will be accompanied by obesity. The daily caloric intake of obese patients will be greater than the daily consumption. Purine synthesis in the body will increase with the increase in calorie intake, and the production of uric acid will also increase. In addition, obesity, especially abdominal obesity, can cause insulin resistance in patients. Insulin resistance can increase blood uric acid levels in the body. Therefore, many gout treatment guidelines recommend that patients with gout control their weight. 

12. Why are patients prone to gout attacks after drinking alcohol?

Some studies have pointed out that liquor and beer can increase the risk of gout attacks in patients, but there is little evidence that red wine increases the risk of gout attacks. Some studies have pointed out that hard alcohol and beer can increase the risk of gout attacks in patients, but there is little evidence that red wine increases the risk of gout attacks. Metabolism of alcohol increases consumption of ATP. Serum lactic acid will increase due to alcohol, thereby reducing uric acid excretion. The purines in alcohol lead to increased uric acid production. These are the reasons why alcohol consumption can increase blood uric acid levels.

13. What vegetables and fruits should patients with gout eat?

Patients with gout should not eat foods with too much sugar. Therefore, fruits with too much sugar such as apples, oranges and grapefruit should not be eaten too much. Plant foods with high purine content such as mushrooms, seaweed and kelp should not be eaten too much. Patients with gout can eat watermelon, coconut, grapes, strawberries, plums and peaches in moderation. Lemons, cherries and olives have certain benefits for patients with gout. It is recommended to eat low-purine foods such as most melons, tubers, root and leafy vegetables.

14. What kind of meat should patients with gout eat?

White meat such as chicken and duck has lower purine content than red meat such as beef and pork. The purine content of animal offal is generally higher than that of meat. Patients with gout should not consume more than 100g of meat per day. Cured or smoked meats are high in purines and sodium, which interfere with the metabolism of uric acid. Patients with gout are not suitable for eating these foods.

15. How much and how should patients with gout drinking water?

Patients with gout but without contraindications such as kidney disease or heart failure are recommended to drink 2 to 3L of water per day. Patients should try to maintain a daily urine output of about 2 L and a urine pH of 6.3 to 6.8. In addition, lemon water can help lower uric acid. It can add 1 to 2 fresh lemon slices to 2 to 3L of water.

16. How can patients with gout exercise?

Vigorous exercise can increase sweating in patients with gout. It reduces blood volume, renal blood flow, and uric acid excretion. It can even induce gout attacks. Low-intensity aerobic exercise such as jogging can reduce gout attacks in patients. Low-intensity aerobic exercise such as jogging can reduce gout attacks in patients. It is recommended that patients perform low-intensity aerobic exercise 4 to 5 times a week, 0.5 to 1 hour each time. In addition, since low temperature can easily induce acute gout attacks in patients, patients should avoid taking cold baths after exercise.

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These habits before bed can help lower uric acid.👍👍👍

As more and more people suffer from hyperuricemia, more and more people
are concerned about how to reduce uric acid in the body. The increase in uric acid in humans is mainly due to insufficient uric acid excretion and excessive uric acid production. The human body generally has about 1200mg of uric acid, and the human body produces about 700mg of uric acid every day. Under normal circumstances, About 500mg of uric acid is excreted through the kidneys, and the remaining 200mg of uric acid is excreted through the intestines. The body's daily excretion of uric acid and the production of uric acid should maintain a balance. Clinically, normal values for uric acid are 149 to 416 μmol/L in men and 89 to 357 μmol/L in women. When the blood uric acid concentration is higher than the normal value, it can be diagnosed as hyperuricemia clinically. Excessive uric acid in patients with hyperuricemia can form urate crystals. The crystals deposit in the patient's joint synovium, bursa, cartilage, and other tissues, causing a recurring inflammatory disease called gout. Gout attacks can cause gouty nephropathy, gouty acute arthritis, chronic arthritis, tophi and joint deformities.

Why does uric acid in the body increase?

Elevated uric acid is caused by an imbalance between the excretion and production of uric acid. However, only about 10% of patients with elevated uric acid are caused by excessive uric acid production, and most (more than 90%) patients are caused by decreased uric acid excretion.

Causes of decreased uric acid excretion:

• Innate factors: Inherited genes cause a patient's decreased uric acid clearance and decreased excretion.
• Acquired factors: Obesity, hypertension, metabolic diseases (eg, hypothyroidism, hyperthyroidism, lactic acidosis, diabetic ketosis), drugs (eg, aspirin, thiazide diuretics, cyclosporine).

Causes of increased uric acid production:

• Innate factors: Genetically related enzyme deficiencies lead to metabolic abnormalities.
• Acquired factors: Blood disorders (eg, myelodysplasia), strenuous exercise, diet (eg, excessive alcohol consumption, foods and beverages high in fructose, frequent consumption of foods high in purines), taking cytotoxic drugs (eg, chemotherapy drugs).

These habits before bed can help lower uric acid.

Try not to eat late night supper:

It is well known that diet plays an important role in the prevention and treatment of hyperuricemia. In daily life, many foods contain purines, especially animal offal, seafood, mushrooms and soybeans. These purines absorbed from food are called exogenous purines. It makes up about 20% of purines in the body. The human liver metabolizes purines into uric acid, so excessive intake of high-purine foods will increase blood uric acid. Eating late night supper is not only bad for your health. It has a more severe effect on patients with hyperuricemia, especially late night supper that are high in purines. Therefore, it is recommended that patients with hyperuricemia try not to eat late night supper. Even if you have a late night supper, eat foods that are low in purines and light.

Drink some water before bed:

In addition to taking uric acid-lowering drugs to reduce blood uric acid, drinking more water can also effectively reduce uric acid. Clinicians recommend that patients with hyperuricemia should drink plenty of water. Drinking plenty of water is a simple, inexpensive, and side-effect-free way to lower uric acid. Clinicians recommend that you should drink more than 1500ml of water per day. If the patient has urinary uric acid stones, the daily drinking water should be more than 2 liters. This promotes the excretion of more uric acid in the urine. In addition, since most gout attacks occur at night, drinking some water before going to bed can prevent the increase of blood uric acid during long sleep. During sleep, with the loss of blood water, blood uric acid will be concentrated, which will increase the concentration of uric acid. Therefore, hyperuricemia patients and gout patients are especially advised to drink some water before going to bed. In addition to drinking plain water, soda water can also help patients reduce uric acid. Because it alkalizes the urine, this increases the solubility of urate in the urine and promotes the excretion of more uric acid from the body.

Finally, although strenuous exercise may lead to increased uric acid production, moderate exercise can still be beneficial in patients with hyperuricemia (Appropriate stretching exercises can be done before going to bed.). Clinically, it is recommended that patients with hyperuricemia actively engage in aerobic exercise, and at the same time cooperate with muscle resistance training. For patients with gouty arthritis, activities should be reduced during an acute attack, but with the relief of symptoms, reasonable exercise can be performed under the guidance of experts. This is more helpful for the long-term management of uric acid.

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Some common misconceptions of gout that many people have.🙀🙀🙀

Some people eat too much meat, seafood or drink a lot of alcohol at a
dinner party, and their toes or joints will suddenly experience redness, swelling and pain. Most of this is a gout attack. Many people think that only the elderly develop gout. In fact, gout not only occurs in the elderly, but young people are also at risk of gout. Here are some common misconceptions about gout.

The difference between gout and hyperuricemia.

In fact, gout and hyperuricemia are two different concepts.

Hyperuricemia is defined as serum uric acid levels greater than 420 μmol/L measured twice on different days in men or women. Hyperuricemia can be divided into three types according to the patient's serum uric acid level and uric acid in urine: too much uric acid production, poor uric acid excretion, and mixed type. About 90% of patients with primary hyperuricemia are caused by poor uric acid excretion.

Gout is due to the deposition of urate crystals, which causes uric acid nephropathy, uric acid nephrolithiasis and gouty arthritis in patients with hyperuricemia. Gout is more commonly referred to as gouty arthritis. When a patient is diagnosed with hyperuricemia, he should be actively treated with medication or lifestyle intervention. This avoids developing gout.

Do only the elderly get gout?

With the improvement of living conditions in today's society, the incidence of hyperuricemia and gout is getting higher and higher, and the patients are also getting younger. Although the incidence of hyperuricemia and gout increases with age, younger people are also at risk. Males have a higher incidence than females.

Serum uric acid levels rise during a gout attack?

Serum uric acid is temporarily reduced because of acute gout attack caused by the deposition of serum uric acid in the joints. At the same time, the acute phase of gout will increase the excretion of uric acid through the kidneys. Therefore, serum uric acid levels do not necessarily increase during a gout attack. 

Does only gout require treatment and hyperuricemia does not require treatment?

In fact, chronically high levels of serum uric acid can cause or worsen damage to many organs. Hyperuricemia is also an independent risk factor for many diseases such as hypertension, diabetes and chronic kidney disease. Therefore, hyperuricemia also requires treatment. The basis for the treatment of hyperuricemia is lifestyle intervention. It is a recommended lifestyle intervention for 3 to 6 months, with the addition of medication if there is no improvement. Additionally, if the patient has a serum uric acid level >540 μmol/L or has risk factors for cardiovascular disease, drug therapy is recommended.

Can diet alone control serum uric acid?

In the human body, serum uric acid is converted from purines. In general, 80% of serum uric acid is converted from purines in the body, while only 20% is converted from purines in the diet. Therefore, even severely restricting purine intake from the diet can only reduce the conversion of purines to uric acid by about 20%. Serum uric acid is not well controlled by diet alone.

Diet control means not eating meat and eating more fruits and vegetables?

Dietary control includes a low-purine diet, drinking more water, and limiting alcohol.

• Low-purine diet: Patients should limit total daily calorie intake and eat a balanced diet. Limit consumption of high-purine foods such as seafood, meat, and organ meats. Eat more foods such as eggs, fresh vegetables, and low-fat or skim milk. Beans and soy products should be consumed in moderation. Some studies have pointed out that some high-purine vegetables such as spinach and mushrooms have no significant correlation with hyperuricemia and gout attacks. In addition, patients should maintain good eating habits and avoid overeating.
• Drinking more water: Drinking plenty of water can reduce the symptoms and duration of gout attacks. Patients with normal heart and kidney function are advised to drink plenty of water. Daily urine output should be maintained at 2000 to 3000ml. Avoid sugar-sweetened beverages or high-fructose fruit juices such as apple juice and orange juice. It is recommended to consume fresh fruits such as strawberries, peaches, and cherries that are low in fructose. In addition, proper alkalization of urine (pH of 6.2 to 6.9) can facilitate the dissolution and excretion of urate crystals.
• Limiting alcohol: It is recommended to drink ≤2 alcohol units/day for men and ≤1 alcohol unit/day for women. (1 alcohol unit is about 14g pure alcohol. It is equivalent to 145ml of red wine at 12°, 497ml of beer at 3.5°, and 43ml of distilled wine at 40°)

Is more exercise better?

Regular exercise can reduce gout attacks, but more often or harder is not necessarily better. In addition, activities should be reduced during acute gout attacks. It is recommended to do at least 150 minutes of moderate-intensity aerobic exercise per week (about 30 minutes per day, 5 days a week). Moderate-intensity means heart rate during exercise = (220 - age) × 50% to (220 - age) × 70%. Strenuous exercise may trigger acute gout attacks. Lifestyle interventions also include smoking cessation and weight control.

Are the treatments all the same? Can the medication be stopped once the pain is relieved?

Treatment regimens require individualized dose titration and long-term management.

Gout treatment is divided into two types: acute treatment and uric acid-lowering treatment. 

1. Colchicine, NSAIDs, and glucocorticoids are used in the acute phase. Continuous use of low-dose colchicine or NSAIDs for 6 months is effective in preventing acute gout attacks. If the patient is intolerant, has contraindications or has no effect, it can be switched to continuous use of low-dose glucocorticoids for 6 months.
2. Uric acid-lowering therapy is a long-term treatment process that gradually reduces serum uric acid to the target range. Allopurinol and febuxostat inhibit the production of uric acid. Probenecid and benzbromarone promote uric acid excretion. They are commonly used uric acid-lowering drugs. Uric acid-lowering drugs should be selected according to the type of hyperuricemia of the patient.

Is uric acid down to normal enough?

Serum uric acid should be reduced to <360 μmol/L in patients with hyperuricemia. For gout patients, it is recommended to reduce serum uric acid to <300 μmol/L. This prevents gout from recurring.

Patients with hyperuricemia and gout should maintain a healthy lifestyle and choose appropriate drug therapy. Regularly check uric acid and adjust the serum uric acid level to the target value as soon as possible.

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Briefly talk about the impact of hyperuricemia.(Part. 2)😎😎😎

Hyperuricemia (Part. 2)✌

1. Life management of patients with hyperuricemia.

Health education:

Patients should avoid high-purine diets, and avoid inducements such as fatigue, cold, and stress. Patients should also regularly monitor blood pressure, blood sugar and other risk factors. At the same time, the blood uric acid level should be monitored regularly and checked regularly to improve the treatment effect.

Patients try to avoid using drugs that raise uric acid. Such as low-dose aspirin, immunosuppressive agents (cyclosporine), anti-tuberculosis drugs, most chemotherapy drugs, etc. Many people have to use anti-tuberculosis drugs, chemotherapy drugs and other treatments because of certain diseases such as tuberculosis and cancer. After weighing the pros and cons, it is generally believed that the harm of patients with hyperuricemia is not enough to make them give up those treatments.

Patients should quit smoking and carry out weight management. Target BMI <20 kg/m^2, male waist circumference <90 cm, female waist circumference <80 cm. The patient should have proper aerobic exercise.

Diet:

Patients should eat more fresh vegetables, a low-sugar and low-fat diet, and limit the intake of red meat, fish, and foods containing fructose and sucrose. Patients should also avoid the intake of animal offal, crustaceans, thick soups and broths. The daily purine content of the patient's diet is controlled below 200 mg.

The patient should consume 300 mL of skimmed or low-fat dairy products, 1 egg, and maintain a water intake of more than 2L per day. Patients can drink water, tea or unsweetened coffee.

Patients should strictly control drinking alcohol, especially beer and hard alcohol. The total amount of alcohol consumed daily should not exceed 28 grams for men (650 mL of beer, 280 mL of wine, or 50 mL of liquor), and 14 grams for women.

2. Drug treatment of hyperuricemia.

National guidelines have different recommendations on whether patients with asymptomatic hyperuricemia need medication.

Drugs that inhibit the synthesis of uric acid: 

They reduce the synthesis of uric acid by inhibiting the activity of xanthine oxidase.

1. Allopurinol: It is recommended that the initial dose of 50 mg for adults is 1-2 times a day, and thereafter it is increased by 50-100 mg each time. The general dose is 200-300 mg/d, divided into two to three doses. The maximum daily dose is 600 mg. Patients with renal insufficiency must reduce the dose. When eGFR is less than 10 mL/min or for dialysis patients, it is contraindicated. Use the lowest effective dose to maintain blood uric acid below the target level.
2. Febuxostat: The recommended initial dose is 20-40 mg, once a day, with an increase of 20 mg each time, and the maximum daily dose is generally 80 mg. After the blood uric acid level reaches the target, maintain the lowest effective dose. It should be noted that the FDA black box warns that febuxostat may increase the risk of cardiovascular death in patients. Febuxostat should be considered only when the patient does not respond to or cannot tolerate allopurinol treatment, and the specialist must fully assess the patient's condition and the risk of cardiovascular events before taking the drug.

Uric acid excretion drugs: 

They promote uric acid excretion by inhibiting renal tubular uric acid-anion transporter 1 (URAT1) and inhibiting renal tubular uric acid reabsorption.

1. Probenecid: Urinary stones and renal insufficiency are relatively contraindicated. For patients with renal insufficiency with eGFR> 30 mL/min, the recommended starting dose for adults is 25 mg/d, and the maximum dose is 75-100 mg/d. Drink more water during the administration to increase urine output.

Allopurinol, probenecid and febuxostat are all first-line drugs for lowering uric acid treatment. Patients with asymptomatic hyperuricemia can choose the first two categories, and patients with gout can choose the above. For patients with chronic kidney disease, the above all three types of drugs can be used, but febuxostat is the first choice when renal function is severely impaired.

Alkalized urine:

Urine pH <6 is an important factor in the formation of uric acid kidney stones. For patients with hyperuricemia and gout, the optimal morning urine pH is recommended to be 6.2 to 6.9. When the urine pH is <6, alkaline drugs, such as sodium bicarbonate, citric acid preparations, etc., can be used to alkalize urine according to the drug's indications, contraindications, and the individual characteristics of the patient.

Treatment of acute episodes:

When hyperuricemia develops into an acute attack of gout, it is recommended to use anti-inflammatory analgesia as soon as possible to improve the pain. Patients can use small doses of colchicine or adequate, short-term non-steroidal anti-inflammatory drugs, or systemic glucocorticoids. For patients with more serious conditions (such as acute gout involving multiple joints, large joints, or combined systemic symptoms), systemic glucocorticoid therapy is recommended. When the patient has severe pain, polyarthritis, or cumulative seizures of ≥ 2 large joints, a combination of two or more analgesic drugs can be used. During an acute attack, there is no need to adjust the dose of uric acid-lowering drugs that have been used.

Choice of drugs when there are comorbidities:

The principle of medication for each disease should be considered for comprehensive treatment. Try to choose drugs that lower uric acid and avoid drugs that raise uric acid.

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Briefly talk about the impact of hyperuricemia.(Part. 1)😎😎😎

Uric acid is a catabolite of purine nucleotides in the human body. It is a weakorganic acid. 80% of purine nucleotides are produced by human cell metabolism and 20% are obtained from food. The main cause of the increase in uric acid is excessive uric acid production and decreased uric acid excretion. 90% of hyperuricemia is related to decreased renal uric acid excretion.

1. Uric acid metabolism.

Synthesis:

The catabolism of purine nucleotides in the body is mainly carried out in the liver, small intestine and kidney. The abnormality of various key enzymes in the metabolic process will lead to an increase in uric acid synthesis, which accounts for about 10%.

Excretion:

Uric acid is mainly excreted through the kidneys and intestines. Normally, the amount of uric acid excreted into the intestinal cavity through the liver every day is about 1/4 to 1/3 of that produced, and then it is decomposed by bacteria in the intestinal cavity and then excreted from the body. The remaining 3/4 to 2/3 are excreted in urine by the kidneys. The abnormality of uric acid transporter located in the glomerulus and renal tubules and intestinal tract can affect the excretion of uric acid.

2. Causes of hyperuricemia.

Hyperuricemia is a metabolic syndrome caused by a disorder of purine metabolism. At a body temperature of 37 ℃, the saturated solubility of monosodium urate (MSU) in serum is 404.5 umol/L (6.8 mg/dL). It is usually defined as hyperuricemia when the serum uric acid level is> 420 umol/L (about 7 mg/dL). According to the cause, hyperuricemia is mainly divided into two categories: primary and secondary.

Primary hyperuricemia is mainly caused by abnormal enzyme activity during purine metabolism.

Secondary urinary hyperuricemia is characterized by defects in enzyme structure, excessive purine intake, alcohol consumption, enhanced nucleic acid metabolism (such as leukemia, anemic hemolysis, and malignant tumors) and accelerated purine decomposition (such as type I glycogen accumulation disease, hypoglycemia, hunger or exercise). The main causes of secondary hyperuricemia are: blood system disease, kidney disease, drug-induced, and excessive production of organic acids.

3. The effect of hyperuricemia on the body.

When uric acid or urate exceeds the normal solubility limit in body fluids, it will form crystals and deposit in any soft tissues except nerve tissues, which will cause different pathological changes.

Gout:

Hyperuricemia is the main risk factor for gout. Uric acid crystals deposit on joints and cause gout attacks. It causes bone and joint damage. Studies have shown that about 5% to 12% of hyperuricemia eventually develops into gout.

Hypertension:

Hyperuricemia can activate the renin-angiotensin system. It reduces the synthesis of nitric oxide in vascular endothelial cells and stimulates the proliferation of vascular smooth muscle. This can lead to increased blood pressure through various mechanisms such as vascular remodeling. In addition, long-term hypertension also affects uric acid metabolism through glomerular arteriosclerosis and other pathways, thereby aggravating hyperuricemia.

Abnormal blood lipid metabolism:

There is a mutual influence between uric acid metabolism and fat metabolism. Hyperuricemia and blood lipids can cause a decrease in lipoproteinase activity. At the same time, hyperlipidemia will also increase the rise of uric acid. In addition, hyperuricemia and hyperlipidemia are risk factors for arteriosclerosis and hypertension.

Diabetes:

Hyperuricemia can directly damage the function of pancreatic β-cells, thereby affecting insulin secretion and leading to diabetes. It can also aggravate metabolic disorders and insulin resistance in diabetic patients. It promotes the occurrence of macrovascular and microvascular complications in diabetic patients. At the same time, diabetic nephropathy and insulin resistance can also lead to aggravation of hyperuricemia.

Arteriosclerosis:

Uric acid crystals stimulate the blood vessel wall and induce an inflammatory response that damages vascular endothelial cells. In addition, hyperuricemia can also promote the formation of atherosclerosis together with hypertension, hyperlipidemia and hyperglycemia.

Heart failure:

Most cardiovascular diseases eventually lead to heart failure. Hyperuricemia is a risk factor for heart failure. This is closely related to its occurrence, development and prognosis.

Kidney damage:

Uric acid crystals are deposited in the kidneys. It causes uric acid nephropathy, increases the incidence of kidney stones and the risk of kidney failure.

Androgenetic alopecia:

Studies have shown that there is a significant correlation between hyperuricemia and androgenic alopecia, especially in patients with early-onset androgenic alopecia (< 30 years).

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Drink enough water when taking these drugs.💧💧💧

In general, almost all medicines are taken with water. However, the amount of drinking water is various when taking different medicines. There are some medicines require drinking a lot of water. Most of medicines taken by the human body are eliminated by the kidneys. Drinking plenty of water when taking medicines can reduce the burden on the kidneys, excrete toxins and enhance metabolism of medicines. The following types of drugs should be noted to drink a lot of water when taking:

1. Antipyretic and analgesic

When you have a cold and you are taking antipyretic and analgesics, you should drink more water. Your urine output should not be less than 1.5 liters per day. You should pay more attention when you have a high fever or in summer. First of all, since these drugs can irritate the stomach at high concentrations, this irritation can be reduced by drinking more water. In addition, drinking water during a cold helps the body to urinate a lot to metabolize toxins in the body. Finally, antipyretic drugs have the effect of reducing fever and sweating occurs during the process of reducing fever. When sweat evaporates, it can take away a large amount of body temperature and water, thereby returning body temperature to normal. It is necessary to properly supplement water. If you drink too little water, it is not conducive to sweating and reducing fever. It will also cause collapse because the body's water is not replenished in time.

2. Antibacterial drugs

Aminoglycoside antibiotics: such as amikacin, gentamicin, etc. Aminoglycoside antibiotics are highly toxic to the kidneys. The higher the concentration, the greater damage to the renal tubules. Therefore, it is advisable to drink more water to dilute and accelerate the excretion of the drug.

Sulfonamide antibacterial drugs: Sulfonamide drugs and their metabolites are mainly excreted through the kidneys. Sometimes they precipitate out from the urine and form crystals, causing low back pain, proteinuria and hematuria. In severe cases, the crystals can block the urinary tract and obstruct urine excretion. Drinking a lot of water can increase urine output and reduce the concentration of drugs in the urine. It can also combine with some drugs that can alkalize urine at the same time, such as sodium bicarbonate, to avoid precipitation of crystals and damage the kidneys.

Quinolone antibacterial drugs: such as levofloxacin, ciprofloxacin, etc., are mainly excreted through the kidneys. Crystal urine may occur when large doses of fluoroquinolones are used or the urine pH is above 7. In order to avoid the occurrence of crystal urine, you should drink more water and maintain a 24-hour urine output above 1200ml.

3. Antiviral drugs

Antiviral drugs such as acyclovir and famciclovir can cause crystalline renal failure. Therefore, it is advisable to drink more water during the medication period, especially the elderly. Due to the decline of physiological renal function, the dosage should be reduced. Combined use with zidovudine can cause nephrotoxicity. It manifests as fatigue, deep lethargy. It also competitively inhibit the secretion of organic acids with probenecid, which can slow down the excretion of this class of drugs. It will accumulate the amount of drugs in the body.

4. Anti-gout drugs

When you are taking anti-gout drugs such as benzbromarone, allopurinol, etc., you should drink more water and ensure that the drinking amount is not less than 2 liters. It can reduce the irritation to the digestive tract. At the same time, enough water can alkalize the urine to prevent the formation of stones in the urinary tract during the excretion of uric acid.

5. Bisphosphate

Bisphosphonates such as alendronate sodium, clodronate disodium, etc. In the treatment of hypercalcemia, bisphosphonates can cause electrolyte disturbance and water loss. Therefore, you should pay attention to supplement body fluids and make the daily urine output reaching more than 2000ml. Bisphosphonates are also very irritating to the gastrointestinal tract. Drinking plenty of water when taking it can help reduce the irritation of bisphosphonates to the gastrointestinal tract. In addition, it is not advisable to lie down immediately after taking the medicine and keep the upper body upright for at least 30 minutes (Ibandronate should keep the upper body upright for 60 minutes).

👉In addition to drinking plenty of water when taking these drugs, you should also drink enough water at ordinary times.

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Gout: why does uric acid still raising although control the diet strictly?😵😵😵

Changes in uric acid can be affected by many factors. Although patients with gout have to control their diet, the effect of controlling uric acid is also uncertain. Some patients even usually do not eat seafood and animal offal, and legumes are rarely high, but uric acid is still increasing. Faced with this situation, should the patient take uric acid-lowering drugs?

1. Although patients have controlled their diet, why are the uric acid still increasing?

Hyperuricemia can be divided into 3 types: high uric acid production, poor uric acid excretion and mixed type. Researches found that 90% of primary hyperuricemia belong to the type of poor uric acid excretion. 80% of blood uric acid comes from the body's synthesis and 20% comes from diet. Therefore, the effect of reducing uric acid only by controlling diet is very limited. However, since high sodium salt can affect the excretion of uric acid, patients with gout should control their salt intake.

2. Why do hyperuricemia and gout cause kidney damage?

In patients with hyperuricemia, if urate crystals are deposited in the joints, it will cause gouty arthritis. If urate crystals are deposited in the kidneys, it will cause kidney stones, interstitial nephritis, acute and chronic renal failure. Kidney damage is the second most common comorbidity of hyperuricemia and gout.

3. Blood uric acid is not too high, why do gout attacks?

20% of patients with gout have a family history. There are three major factors that induce gout attacks: 

The blood uric acid level is too high

• According to statistics, the blood uric acid level at the first attack of gout was 527μmol/L for men and 516μmol/L for women. Therefore, when the blood uric acid level is greater than or equal to 540 μmol/L, uric acid-lowering treatment should be started. The blood uric acid should be controlled to be less than 420 μmol/L.

The blood uric acid level fluctuates too much

• A sudden increase in blood uric acid levels can cause gout attacks. In male patients, the most important factor inducing gout attacks is drinking (25.5%), followed by high-purine diet (22.9%). A sudden drop in blood uric acid levels can also cause gout attacks. For the first 3 to 6 months of taking uric acid lowering drugs, colchicine (0.5 to 1 mg/day) should be taken orally to prevent gout attacks.

A sudden cold of limbs

• At a body temperature of 37°C, the saturated solubility of blood urate is 404.5 μmol/L. The lower the temperature, the lower the solubility of urate. When the blood supply of the foot is poor, the temperature of skin and the pH of the tissue fluid are low and under a great pressure. Most of the joints of first time gout are the first metatarsophalangeal joints.

4. Why must patients with gout avoid from alcohol and lose weight?

Alcohol metabolism requires the participation of adenosine triphosphate. The consumption of adenosine triphosphate can directly increase the production of uric acid. Alcohol also leads to an increase in serum lactic acid levels which can reduce uric acid excretion. Therefore, patients with gout must abstain from alcohol. Obesity can lead to insulin resistance which increases kidney reabsorption of uric acid and increases blood uric acid levels. Therefore, obese hyperuricemia and gout patients must lose weight.

Patients with gout should not eat fruits with high fructose content such as oranges, apples, grapefruits, longans, lychees,  persimmons and pomegranates. Patients with gout should not eat more plant foods with high purine content such as shiitake seaweed, mushrooms, asparagus, straw mushrooms, kelp and grain germs.

Lemons, cherries and olives are relatively beneficial to patients with gout.

5. Which uric acid lowering drug is better for patients with gout?

At present, the commonly used clinically for lowering uric acid are febuxostat, allopurinol and benzbromarone. Uric acid-lowering drugs can be selected according to the following 3 points:

1. Uric acid-lowering effect: febuxostat > allopurinol ≈ benzbromarone.
2. Potential cardiovascular event risk: febuxostat > allopurinol.
3. Fatal exfoliative dermatitis: allopurinol (prohibited for those with positive HLA-B*5801 gene).
4. Hepatotoxicity: benzbromarone> allopurinol ≈ febuxostat.

180μmol/L ≤ blood uric acid ＜ 300μmol/L can promote the dissolution of tophi. The control target of blood uric acid in patients with gout is < 360μmol/L. For patients with hyperuricemia without comorbidities, the control target is < 420μmol/L.

6. Should the patient use uric acid lowering drugs?

For all gout patients, it is recommended to start uric acid-lowering drug treatment when blood uric acid is ≥480μmol/L.

Patients with chronic kidney disease, hypertension, diabetes, dyslipidemia, stroke, ischemic heart disease, heart failure and gout whose age of onset is less than 40 years old. It is recommended to start uric acid-lowering drug treatment when blood uric acid is ≥ 420μmol/L.

The glomerular filtration rate of this patient is less than 60ml/min. The uric acid production inhibitor febuxostat or allopurinol can be preferred.

👉When combined medicines, they should be used that do not affect or reduce the level of uric acid.

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