Currently lowering uric acid, mainly drug-based, diet as a supplement. Drugs mainly include inhibit uric acid production drugs (allopurinol, febuxostat) and promote uric acid excretion drugs (benzbromarone, probenecid). The man's uric acid 610, with 3 months down to 420, probably attributed to the efficacy of the drug!

With the social and economic development, people's lifestyles and dietary structure changes, China's gout and hyperuricemia (HUA) prevalence is increasing year by year. Hyperuricemia refers to a state of high uric acid in the blood that occurs under a normal purine diet. Since hyperuricemia is the underlying factor leading to gout, lowering uric acid levels has become the focus of gout treatment. Uric acid-lowering drugs mainly include inhibitors of uric acid production (allopurinol, febuxostat) and promote uric acid excretion (benzbromarone, probenecid, etc.).

Allopurinol

Allopurinol belongs to the inhibitors of uric acid production, this kind of drugs through the inhibition of xanthine oxidase activity to reduce the synthesis of uric acid, so that the blood and urine uric acid content is reduced to the level below the level of solubility, to prevent the formation of uric acid crystals deposited in the joints and other tissues, but also to help the gout patients to tissue uric acid crystals re-dissolved.

1. Use

The use of Allopurinol is initiated after the disappearance of the acute symptoms of gout (usually about 2 weeks after the attack), and it is not used in acute attacks of gout. Allopurinol needs to be started in small doses and gradually increased. Adults, the initial dose of 50mg / times, 1-2 times / d, can be increased by 50-100mg per week, to 200-300mg / d, divided into 2-3 oral, the maximum amount does not exceed 600mg / d, every 2 weeks should be tested for blood uric acid levels. Patients with renal insufficiency should reduce the dose, the recommended dose of 50-100mg/d, such as patients with Ccr<15ml/min prohibit the use of this drug.

2. Adverse reactions

Adverse reactions include rash, diarrhea, leukopenia, alopecia, hepatic and renal impairment, etc., which generally return to normal after stopping the drug. Several cases of sudden death of unspecified cause have also been reported abroad in patients taking this product.

Among all the adverse reactions, the most important is the rash, which can be pruritic papules, urticaria, purpura, and even severe drug rash (such as exfoliative dermatitis, severe erythema multiforme drug rash, toxic epidermal necrolysis laxity).

The 57th Adverse Drug Reaction Information Bulletin (ADRIB), released by the State Food and Drug Administration (CFDA) in 2013, suggests that we should be vigilant against adverse reactions such as severe drug rash caused by allopurinol, a drug that inhibits uric acid synthesis. These include severe drug rashes such as exfoliative dermatitis, severe erythema multiforme drug rash, and toxic epidermal necrolysis and laxity. And pointed out that clinicians in the prescription of allopurinol tablets, need to pay attention to the dosage, special populations, to avoid the use of ultra-indications, prohibited contraindications to the use of drugs; allergic patients, hypersensitivity patients with caution; attention to the combined use of drugs, to prevent the occurrence of drug interactions; after taking, if there is any skin reaction or other signs of hypersensitivity reactions should be immediately discontinued, and promptly go to dermatology consultation and treatment.

Genetic factors of hypersensitivity: hypersensitivity syndrome often occurs within a few months of the initial use of the drug, the most common is exfoliative dermatitis. Asian populations, including Han Chinese, have a higher risk of severe hypersensitivity reactions with allopurinol than whites, and such reactions are directly related to the prevalence of positivity for the leukocyte antigen HLA-B*5801 allele. The rate of positivity for this gene is 6%-8% in Chinese Han Chinese, compared with only 2% in whites. If conditions permit, it is recommended that Asian populations undergo rapid PCR testing for the HLA-B*5801 gene before using allopurinol, and positive individuals are contraindicated.

3. Drug combinations

The combination of the Prilosec antihypertensive drug captopril, the diphenhydramine antihypertensive drug amlodipine, and the thiazide diuretic hydrochlorothiazide with allopurinol increases the risk of hypersensitivity reactions.

The incidence of rash is increased when allopurinol is combined with antibiotics such as ampicillin and amoxicillin.

Allopurinol can cause excessive accumulation of iron in the tissues, causing ferrous hemoflavin deposits, so allopurinol should not be taken with iron (such as ferrous succinate).

Allopurinol increases the risk of bleeding when combined with warfarin. Adjust the dose of warfarin if necessary.

Febuxostat (also known as febuxostat)

Febuxostat belongs to the group of drugs that inhibit uric acid production, and is a new selective xanthine oxidase inhibitor that reduces serum uric acid concentration by inhibiting uric acid synthesis.

1. Use

The initial dose is 20-40 mg/d, and for those who do not meet the blood uric acid standard after 2-5 weeks, the dose is gradually increased to a maximum of 80 mg/d. Because it is mainly cleared through the liver, it has a high degree of safety in patients with renal insufficiency and renal transplantation, and mild-to-moderate renal insufficiency (stage G1-3) No dose adjustment is required in patients, and caution should be exercised in patients with severe renal insufficiency (stages G4-5). An increase in the frequency of gouty attacks often occurs during the initial period of febuxostat administration, due to the mobilization of urate deposited in the tissues as a result of a decrease in blood uric acid concentration. To prevent gouty attacks in the initial phase of treatment, concomitant administration of nonsteroidal anti-inflammatory drugs or colchicine is recommended.

2. Adverse reactions

Common adverse reactions are abnormalities of hepatic function, adverse reactions such as gastrointestinal reactions, arthralgia, and rash. Of these, the one that has attracted the most attention is that it may lead to an increased risk of death from cardiovascular events.

Some studies have concluded that febuxostat increases the risk of death from cardiovascular events in patients compared to allopurinol.On February 21, 2019, the FDA released information warning that the anti-gout drug febuxostat may increase the risk of death in patients and requesting that the use of febuxostat be restricted.

The FDA cautioned that doctors should carefully ask patients about their history of heart disease or stroke before using this drug and weigh the benefits and risks of using febuxostat. If a patient develops chest pain, shortness of breath, rapid or irregular heartbeat, numbness or weakness on one side of the body, dizziness, difficulty speaking, or sudden severe headache while taking febuxostat, he or she should seek medical attention immediately. Do not stop taking the drug without consulting your doctor to avoid worsening gout symptoms.The FDA reminds healthcare professionals that febuxostat is only used in patients who have failed or are intolerant to allopurinol therapy, and patients should be advised to be aware of their cardiovascular risk and to seek immediate medical attention for any of the above symptoms.

3. Drug combinations

Febuxostat should be used with caution in combination with theophylline due to accumulation factors.

Considering the risk of toxicity due to elevated blood levels, febuxostat is contraindicated in patients being treated with azathioprine or mercaptopurine.

Based on drug interaction studies in healthy subjects, febuxostat has no significant interactions when combined with colchicine, naproxen, indomethacin, hydrochlorothiazide, warfarin, and disopyramide. Therefore, Febuxostat can be used in combination with these drugs.

Benbromarone

Benbromarone belongs to the class of drugs that promote uric acid excretion, by inhibiting the reabsorption of uric acid in the renal tubules and thus promoting uric acid excretion and lowering blood uric acid levels.

1. Use

Adults starting dose of 25-50mg/d, after 2-5 weeks according to the blood uric acid level, the dose can be adjusted to 75mg/d or 100mg/d, taken after breakfast. These drugs can be used for mild to moderate renal dysfunction or renal transplant patients, eGFR 20-60ml/min/1.73m^2 patients recommended dose of 50mg/d; eGFR<20ml/min/1.73m^2 or uric acid nephrolithiasis patients are prohibited. The urine must be alkalized and the urine pH adjusted to 6.2-6.9 at the time of administration, and the urine volume of 2000 ml or more must be maintained in patients with normal cardiac and renal function. Moderate to severe renal impairment (glomerular filtration rate of less than 20 ml/min and nephritis) is prohibited, pregnant women or women with the possibility of pregnancy and breastfeeding women are prohibited, and avoid concomitant use with other drugs with hepatotoxicity.

2. Adverse reactions

Adverse reactions mainly include hepatic impairment, gastrointestinal reactions (diarrhea, stomach upset, nausea, etc.), skin allergies (wheals, maculopapular rash, flushing, itching, etc.). Of these, the one that has caused the most concern is liver damage.

The CFDA released a report on December 31, 2014, titled ? Alert to the Risk of Liver Damage from Benzbromarone? an Adverse Drug Reaction Bulletin designed to alert that such drugs may increase the risk of liver damage. During the use of the drug, one should watch out for signs and symptoms of liver damage, such as loss of appetite, nausea, vomiting, generalized feeling of tiredness, abdominal pain, diarrhea, fever, urine thick dye, yellowish coloration of the conjunctiva of the eyeballs, etc., and should consult the doctor in time, and if necessary, check the liver function and treat accordingly.

3. Combined use of drugs

There are literature data reporting that salicylates, anti-tuberculosis drug pyrazinamide will reduce the effect of uric acid excretion of this product.? Increased anticoagulant activity may occur in combination with anticoagulants such as acenocoumarol, phenindione, and bicoumarol ethyl ester.

Propofol

Propofol belongs to the promotion of uric acid excretion drugs, through the inhibition of active reabsorption of urate in the renal tubules, increase the excretion of urate, thereby reducing the concentration of urate in the blood.

1. Use

This product is suitable for hyperuricemia patients with chronic gout, the starting dose for adults is 0.25g once, twice a day, and the dose can be adjusted to 0.5g once, twice a day after 1 week. Adequate water intake (about 2500ml per day) should be taken during the period of administration to prevent the formation of kidney stones, and drugs for alkalizing urine should be taken at the same time if necessary. This product should not be used in the elderly, hepatic and renal insufficiency, active peptic ulcer or history and kidney stones. This product is not used when the symptoms of acute attacks of gouty arthritis have not been controlled. If there is an acute attack during treatment with this product, the original dosage can be continued and colchicine or other non-steroidal anti-inflammatory drugs can be given at the same time.

2. Adverse reactions

Gastrointestinal symptoms, such as nausea or vomiting, are seen in about 5% of those who take it, and may occasionally cause peptic ulcers.

It can promote the formation of kidney stones, you should ensure that the urine ph value of 6.0-6.5. drink a lot of water and take the same medication to alkalize the urine, in order to prevent kidney stones.

Cross-allergic reactions to sulfonamide, including rash, itching and fever, are rare.

Occasionally causes rare adverse reactions such as leukopenia, bone marrow suppression and hepatic necrosis.

3. Combined use of drugs

Alcohol consumption, chlorthalidone, diuretic acid, furosemide, pyrazinamide, and thiazides and other diuretics can increase the serum uric acid concentration, the product and these drugs need to pay attention to the dosage adjustment, in order to control hyperuricemia.

When used with aspirin or other salicylates, it can inhibit the uric acid-excreting effect of this product.

When used with indomethacin, ampicillin, naproxen, etc., the blood concentration of the latter increases and toxicity increases.

When used with various types of penicillin, cephalosporin. The blood concentration of the latter increases and is maintained for a longer period of time, thus increasing the toxicity, especially to the kidneys.

When used with oral hypoglycemic drugs, the latter effect is enhanced.

When used with methotrexate, the latter may increase blood levels and increase toxicity.

When used with furotoxin, the anti-infective efficacy of furotoxin in the urine is reduced due to inhibition of renal tubular secretion.

When used with rifampicin, the blood concentration of rifampicin can be increased and prolonged, increasing toxicity due to competition between the two drugs for hepatic uptake. Clinically, it is generally not recommended to increase the blood concentration of rifampicin and the use of two drugs.

When used in conjunction with sulfonamides, the latter's excretion by the kidneys is slowed, and the blood concentration is increased. Long-term **** use should be regularly tested for sulfonamide blood levels.