With the development of social economy and the change of people's lifestyle and diet structure, the prevalence of gout and hyperuricemia in China is increasing year by year. Hyperuricemia refers to the state of hyperuricemia in blood under normal purine diet. Because hyperuricemia is the fundamental factor leading to gout, reducing uric acid level has become the focus of gout treatment. Antiuric drugs mainly include drugs that inhibit uric acid production (allopurinol, febuxostat) and drugs that promote uric acid excretion (benbromarone, probenecid, etc.). ).
Allopurinol Allopurinol belongs to drugs that inhibit uric acid production. These drugs can reduce the synthesis of uric acid by inhibiting the activity of xanthine oxidase, reduce the uric acid content in blood and urine to a level below solubility, prevent uric acid from forming crystals and depositing in joints and other tissues, and also help to redissolve uric acid crystals in gout patients' tissues.
1.
After the acute symptoms of gout disappear (usually about 2 weeks after the attack), it is not used in the acute attack of gout. Allopurinol should start from a small dose and gradually increase. The initial dose of adults is 50mg/ time, 1-2 times /d, which can be increased by 50- 100mg to 200-300mg/d every week, and the maximum dose does not exceed 600 mg/d. Serum uric acid level is detected every two weeks. Patients with renal insufficiency should be reduced, and the recommended dose is 50- 100mg/d, such as CCR.
2. Adverse reactions
Adverse reactions include rash, diarrhea, leukopenia, alopecia, liver and kidney function damage and so on. Generally, it can return to normal after stopping the drug. In addition, several cases of unexplained sudden death have been reported abroad.
Among all the adverse reactions, the most important one is rash, which can be pruritic papule, urticaria, purpura or even serious drug eruption (such as exfoliative dermatitis, severe erythema multiforme drug eruption, toxic epidermal necrosis and relaxation).
China Food and Drug Administration (CFDA) released the 57th ADR information bulletin on 20 13, reminding us of the serious drug eruption caused by allopurinol, a synthetic drug of uric acid. These include severe drug eruptions such as exfoliative dermatitis, severe erythema multiforme and toxic epidermal necrosis and relaxation. It is also pointed out that clinicians should pay attention to the dosage and special population when prescribing allopurinol tablets, avoid over-indications and prohibit the use of contraindications. Use with caution in patients with allergies and high sensitivity; Pay attention to the combination of drugs to prevent drug interaction; After taking it, if you have skin reaction or other allergic signs, you should stop taking the medicine immediately and go to the dermatology department in time.
Genetic factors of hypersensitivity: hypersensitivity syndrome often occurs in the first few months of medication, and exfoliative dermatitis is the most common. Asians (including Han people in China) have a higher risk of severe hypersensitivity when using allopurinol than whites, which is directly related to the positive rate of HLA-B*580 1 allele. The positive rate of this gene is 6%-8% in China Han population, but only 2% in whites. If conditions permit, it is suggested that Asians should carry out rapid PCR detection of HLA-B*580 1 gene before using allopurinol, and those who are positive should be prohibited.
3. Combined medication
The combination of captopril, amlodipine and hydrochlorothiazide with allopurinol will increase the risk of allergic reaction.
When allopurinol is combined with ampicillin, amoxicillin and other antibiotics, the incidence of rash increases.
Allopurinol can cause excessive accumulation of iron in tissues and hemosiderosis, so allopurinol should not be taken with iron agents (such as ferrous succinate).
Allopurinol combined with warfarin will increase the risk of bleeding. Adjust the dosage of warfarin if necessary.
Febusotan (also known as febusotan) is a new selective xanthine oxidase inhibitor, which can reduce serum uric acid concentration by inhibiting uric acid synthesis.
1.
The initial dose is 20-40mg/d, and the serum uric acid is not up to standard after 2-5 weeks, and the maximum dose is 80 mg/d. Because it is mainly cleared by the liver, it is safe for patients with renal insufficiency and kidney transplantation. Patients with mild to moderate renal insufficiency (G 1-3) do not need to adjust the dosage, and patients with severe renal insufficiency (G4-5) should use it with caution. In the early stage of taking febuxostat, the frequency of gout attacks tends to increase, because the decrease of blood uric acid concentration leads to the mobilization of urate deposited in tissues. In order to prevent gout attack in the early stage of treatment, it is suggested to take non-steroidal anti-inflammatory drugs or colchicine at the same time.
2. Adverse reactions
Common adverse reactions include abnormal liver function, such as gastrointestinal reaction, joint pain and rash. Among them, the most important thing is the increased risk of death caused by cardiovascular events.
Studies have shown that febuxostat increases the risk of cardiovascular death compared with allopurinol. On February 2, 2065438, the FDA issued a message warning that febuxostat, an anti-gout drug, may increase the risk of death of patients, and requested to limit the use of febuxostat.
The FDA reminds that before using this drug, doctors should carefully ask patients about their history of heart disease or stroke and weigh the benefits and risks of using febuxostat. If patients have chest pain, shortness of breath, rapid or irregular heartbeat, numbness or weakness on one side of the body, dizziness, difficulty in speaking, sudden and severe headache and other symptoms during taking febuxostat, they should seek medical attention immediately. Don't stop taking medicine without consulting a doctor, so as not to aggravate gout symptoms. The FDA reminds medical staff that febuxostat is only used for patients who have failed or are intolerant of allopurinol treatment, and they should be informed of their cardiovascular risks. If the above symptoms appear, they should seek medical attention immediately.
3. Combined medication
Considering the accumulation in vivo, febuxostat should be used with caution when combined with theophylline.
Considering the risk of poisoning caused by the increase of blood drug concentration, patients who are receiving azathioprine or thiopurine treatment are prohibited from using febuxostat.
According to the study on drug interaction of healthy volunteers, there is no obvious interaction between febuxostat and colchicine, naproxen, indomethacin, hydrochlorothiazide, warfarin and desipramine. Therefore, febuxostat can be used in combination with these drugs.
Benzbromarone Benzbromarone is a drug that promotes uric acid excretion, which can promote uric acid excretion and reduce blood uric acid level by inhibiting renal tubular reabsorption of uric acid.
1.
The initial dose for adults is 25-50mg/d, and the dose can be adjusted to 75mg/d or 100mg/d after 2-5 weeks according to the serum uric acid level, and taken after breakfast. These drugs can be used in patients with mild to moderate renal insufficiency or renal transplantation, and the recommended dose of EGFR is 20-60 ml/min/1.73 m 2 patients 50 mg/d; EGFR < 20ml/min/1.73m2 or uric acid kidney calculi patients are prohibited. When taking it, the urine should be alkalized, and the pH value of the urine should be adjusted to 6.2-6.9, and the urine volume of people with normal heart and kidney function should be maintained above 2000 ml. Moderate and severe renal insufficiency (patients with glomerular filtration rate less than 20ml/min and nephritis) is prohibited, and pregnant women, pregnant women and lactating women are prohibited to avoid simultaneous use with other drugs with hepatotoxicity.
2. Adverse reactions
Adverse reactions mainly include liver function damage, gastrointestinal reactions (diarrhea, stomach discomfort, nausea, etc. ), skin allergies (wheal, rash, flushing, itching, etc. Among them, liver injury is the most concerned.
CFDA issued a publication entitled "20 14 12 3 1". Be alert to the risk of liver damage caused by benzbromarone? Adverse Drug Reactions Bulletin aims to remind that such drugs may increase the risk of liver injury. Attention should be paid to the symptoms and signs of liver damage during medication, such as loss of appetite, nausea, vomiting, general fatigue, abdominal pain, diarrhea, fever, urine staining, conjunctival yellow staining and so on. , and should see a doctor in time, if necessary, check the liver function and make corresponding treatment.
3. Combined medication
It is reported in the literature that salicylate and pyrazinamide, an anti-tuberculosis drug, can reduce the uric acid excretion of this product. ? When combined with anticoagulant drugs such as nitrocoumarin acetate, phenylindanone and dicoumarin ethyl ester, the activity of anticoagulant drugs can be increased.
Probenecid is a drug to promote uric acid excretion, which can increase uric acid excretion by inhibiting the active reabsorption of uric acid by renal tubules, thus reducing the concentration of uric acid in blood.
1.
This product is suitable for patients with hyperuricemia and chronic gout. The initial dose for adults is 1.25g, 1 twice a day. After 1 .5g, the dose can be adjusted to 1 twice a day. Take enough water (about 2500ml per day) to prevent the formation of kidney calculi, and take drugs to alkalize urine if necessary. This product is not suitable for the elderly, patients with hepatic and renal insufficiency, patients with active peptic ulcer or those with a history of kidney calculi. Do not use this product when the acute attack symptoms of gouty arthritis are not controlled. If there is an acute attack during the treatment, you can continue to use the original dose and give colchicine or other non-steroidal anti-inflammatory drugs.
2. Adverse reactions
About 5% users will have gastrointestinal symptoms, such as nausea or vomiting, and occasionally lead to peptic ulcer.
To promote the formation of kidney calculi, urine ph should be 6.0-6.5. Drink plenty of water and take medicine to alkalize urine to prevent kidney calculi.
Cross-allergic reactions between this product and sulfanilamide, including rash, itchy skin and fever, are rare.
Occasionally cause rare adverse reactions such as leukopenia, bone marrow suppression and liver necrosis.
3. Combined medication
Diuretics such as drinking, chlorothiazide, uric acid, furosemide, pyrazinamide, thiazide, etc. can increase the serum uric acid concentration. When this product is combined with these drugs, the dosage should be adjusted to control hyperuricemia.
When used with aspirin or other salicylates, it can inhibit uric acid excretion of this product.
When combined with indomethacin, dapsone and naproxen, the plasma concentration of the latter increased and its toxicity increased.
When used with various penicillins and cephalosporins. The plasma concentration of the latter increases and lasts for a long time, so the toxicity of the latter increases, especially to the kidney.
When used together with oral hypoglycemic agents, the effect of the latter is enhanced.
When used with methotrexate, the plasma concentration of methotrexate may increase and its toxicity may increase.
When nitrofurantoin is used together, the anti-infection effect of nitrofurantoin in urine is reduced because it inhibits renal tubular secretion.
When combined with rifampicin, the blood concentration of rifampicin can be increased, the time can be prolonged and the toxicity can be increased due to the competition between the two drugs in the liver. It is generally not recommended to use two drugs at the same time in order to improve the blood concentration of rifampicin in clinic.
When it is used with sulfonamides, the blood concentration increases because the excretion of the latter from the kidney slows down. Long-term use of * * * should regularly detect the blood concentration of sulfonamides.