Allopurinol is also called allopurinol.

(1) Features: This product and its metabolite oxypurinol can inhibit the activity of xanthine oxidase, hindering the biochemical process of converting hypoxanthine into uric acid and reducing the production of uric acid.

Oral absorption is 80-90%, and most of the absorbed drugs are metabolized in the liver into the active substance oxypurinol. This product is excreted by the kidneys. About 10% is the original drug and 70% is the metabolite. The t1/2 of allopurinol is 2 to 8 hours, and that of oxypurine is 18 to 30 hours, which can be significantly prolonged in cases of renal insufficiency.

(2) Application: used for chronic gout. It is ineffective for acute attacks and can aggravate or prolong the acute inflammation period. Colchicine or anti-inflammatory analgesics should be used simultaneously for acute inflammation. It can also be used for urate deposition in the body caused by the application of anti-cancer drugs.

① Treatment of gout: Adult dosage: start with 50 mg each time, 3 times a day, gradually increase to 100 mg each time, 3 times a day, or 300 mg once a day.

② Treatment of kidney stones: 100 mg each time, 1 to 2 times a day or 300 mg once a day. Reduce dosage in patients with renal insufficiency. The creatinine clearance rate is 10 to 20 ml/min, 200 mg per day; the clearance rate is 3 to 10 ml/min, 100 mg per day; if it is less than 3 ml/min, use 100 mg at an interval of more than 24 hours.

For children, it is limited to hyperuricemia caused by anti-tumor therapy. For children under 6 years old, take 50 mg each time, 3 times a day; for 6 to 10 years old, take 100 mg each time, 3 times a day, or once a day, 300 mg each time, and adjust the dosage according to the condition and reaction after taking the medicine for 2 days.

③Notes:

a) Adverse reactions are common, including rash (often maculopapular rash), itching, urticaria, purpura, erythema multiforme, etc., once If this occurs, the medication should be discontinued immediately. There are also nausea, vomiting, diarrhea, abdominal pain, peripheral neuritis, agranulocytosis, anemia, thrombocytopenia, and systemic allergic vasculitis, which can cause serious damage and the drug should be discontinued immediately.

b) Pregnant women, lactating women, and those with renal insufficiency should use with caution.

c) Drink plenty of water when taking the medicine, and properly alkalize the urine to reduce the occurrence of uric acid stones. When you start taking the medicine, you may have an acute attack of gout, and you can add colchicine or anti-inflammatory analgesics

④Interactions

a) This product can inhibit purine, The normal metabolism of azathioprine enhances its effect, so the dosage of the latter two drugs can be reduced by 1/4 to 1/3 to ensure safety.

b) This product can enhance the effect of oral anticoagulants, so care should be taken to reduce its dosage.

c) Can enhance the bone marrow suppression effect of cyclophosphamide.

d) Combined use with urine acidifying drugs may increase the possibility of kidney stone formation. Renal failure and allergies have been reported when combined with thiazide diuretics.

The preparation is in the form of tablets, each tablet is 0.1g.

Allopurinol is the only xanthine oxidase inhibitor currently available for the treatment of hyperuricemia. Its principle for treating gout is: xanthine oxidase is the enzyme necessary for the conversion of hypoxanthine into uric acid. Allopurinol is a hypoxanthine analogue that is metabolized primarily to oxypurinol. Oxypurinol is also a xanthine oxidase inhibitor. By inhibiting the enzyme, it loses its activity and has no effect. Therefore, xanthine cannot be oxidized into uric acid, and the production of uric acid is reduced, thus reducing blood uric acid. Hyperuricemia is eliminated. It can be seen that the principle of allopurinol in treating gout is to inhibit the production of uric acid.

Whether it is primary or secondary gout, allopurinol can be used to treat it, which means that all gout patients can take it. However, because allopurinol causes certain damage to the liver, gout patients with liver disease are generally not advised to use this drug. Since allopurinol and oxypurinol are excreted in the urine, patients with kidney disease, especially those with reduced renal function, should use them with caution or not use them.

In addition, allopurinol can cause a toxic reaction of bone marrow suppression in individual patients, leading to leukopenia. Therefore, gout patients with leukopenia should not use this drug.

However, allopurinol only has the effect of reducing blood uric acid, and is ineffective in treating symptoms such as redness, swelling, heat, and pain in joints during an acute attack of gout. Therefore, colchicine and nonsteroidal drugs can be used to treat acute attacks of gouty arthritis.

Regarding the question of whether allopurinol has a preventive effect on gout, experts believe that because allopurinol can inhibit the production of uric acid, taking this drug in an appropriate amount for a long time can keep blood uric acid at normal levels. Within the range, it can effectively prevent the acute attack of gouty arthritis.

Allopurinol has a strong inhibitory effect on xanthine oxidase, thereby blocking the metabolic conversion of hypoxanthine to xanthine and xanthine to uric acid, and gradually oxidizes into xanthine that is easily soluble in water in the human body. Purine and excreted in urine. It can also be converted into the corresponding nucleotide in the presence of 5-phosphate ribose-1-pyrophosphate, consuming 5-phosphate ribose-1-pyrophosphate to reduce the synthesis of hypoxanthine nucleotides, thus quickly reducing blood uric acid levels. , and can reduce the concentration of uric acid in urine to promote the dissolution of tophi, and prevent the formation of tophi and kidney stones.

So, after the blood uric acid drops to normal, can allopurinol be stopped? Experts believe that when blood uric acid drops to normal, allopurinol should be continued to be taken in small amounts to keep blood uric acid in a stable state for a long time. If blood uric acid fluctuates while taking the maintenance dose, the dose can be adjusted at any time. If the drug is stopped immediately after the blood uric acid drops to normal, the blood uric acid may rise again, which is detrimental to the complete control of the disease.

Allopurinol is available as oral tablets, 100 mg each. Experts believe that the dosage and method of use are: 100 mg each time, 2 to 3 times a day, and the maximum daily dose does not exceed 600 mg. You should start with a small dose and gradually increase to the full dose. When the blood uric acid drops to normal, then gradually reduce the dosage. You can take 100 mg or 50 mg daily to keep the blood uric acid normal, which is the lowest effective maintenance dose. Then take this maintenance dose for a long time.

Common side effects of allopurinol are:

(1) Gastrointestinal reactions: such as nausea, vomiting, loss of appetite, etc.

(2) Skin allergic reactions: such as skin itching, rash, etc.

(3) Bone marrow suppression reaction: there may be leukocyte and thrombocytopenia, etc.

(4) Hepatocellular damage: Abnormal liver function may occur, mainly elevated transaminases, and a few may have jaundice.

(5) Allergic syndrome: It is an immunological reaction to the drug, which may clinically include fever, increased acid granulocytosis, worsening of renal function, liver cell damage and various rashes. These include erythema multiforme, toxic epidermal necrolysis, erythematous maculopapular rash, and exfoliative skin lesions. This reaction is serious but rare clinically and should be paid attention to.

The occurrence of these side effects is related to the dosage. The higher the dose, the greater the chance of side effects. In addition, there are individual differences. In order to prevent the occurrence of these side effects, patients should carefully observe and experience any abnormal sensations during the medication process, such as fatigue, liver discomfort, skin itching, etc., and should undergo white blood cell, platelet, and liver function tests in a timely manner. Even if there are no above-mentioned abnormal feelings, blood routine and liver function should be checked regularly while taking the medicine. Once abnormalities are found, appropriate treatment can be given or discontinuation of medication can be considered.

Since allopurine may also cause liver damage, other drugs that may damage the liver should be avoided when taken together with allopurinol. Examples include the antituberculosis drugs rifampicin, isoniazid, pyrazinamide, para-aminosalicylic acid, and some sleeping pills and sedatives. In addition, some drugs that inhibit uric acid excretion, such as aspirin, hydrochlorothiazide, furosemide, diuretic acid, Telden, trimethoprim, etc., should not be used together with allopurinol to avoid weakening the efficacy.

3. Probenecid is also known as carboxybenzamide.

It is one of the three major uricosuric drugs in clinical practice (the other two are benzotrione and benzbromarone)

(1) Features: This product can inhibit the resorption of urate in the proximal renal tubule. Absorption, increases urate excretion, reduces plasma uric acid concentration, thereby reducing uric acid deposition; can inhibit the renal tubular secretion of some weak acid drugs and prolong the action time of drugs in the body; can be used to enhance penicillins and cephalosporins role.

It is rapidly absorbed after oral administration, with a protein binding rate of 65 to 90. Adults take 1g orally, reaching the peak value (30mg/ml) in 2 to 4 hours; taking 2g orally, reaching the blood peak (150~200mg/ml) in 4h. The effective concentration of uric acid is 100~200mg/ml, and the maximum effective time is 30min. Inhibition of penicillin The excretion requirement is 40 to 60 mg/ml, and the maximum effective time is 2 hours. After intrahepatic metabolism, it is mainly excreted through the kidneys, and 5 to 10% of the drug is excreted in its original form.

(2) Application

① Treatment of chronic gout: For adults, take 250 mg each time, twice a day. After taking the medicine for 1 week, increase to 500 mg each time, twice a day. In order to prevent uric acid from crystallizing, you need to drink a lot of water (2500 to 3000ml per day) and alkalize the urine (sodium bicarbonate, 3 to 7.5g per day; or potassium citrate, 7.5g per day).

② To inhibit the excretion of penicillin or cephalosporin: 500 mg each time for adults, 4 times a day. Elderly patients need to reduce the dosage appropriately due to decreased renal function. From 2 to 14 years old, start taking 25mg/kg (or 0.7g/m2) per day, and later increase to 40mg/kg (or 1.2g/m2) per day, divided into 4 doses. For those weighing more than 50kg, the adult dose should be used.

(3) Precautions

① Adverse reactions include headache, dizziness, liver damage, vomiting, nausea, loss of appetite, gum pain, kidney damage, uric acid stones, renal colic, Aplastic anemia, leukopenia, anemia, dermatitis, alopecia, skin flushing, allergies, drug fever, urticaria, itching, etc.

② This product is generally not used until the acute attack of gout has subsided. Within 3 to 6 months after starting to use this product, the frequency of acute gout attacks can often increase, so a small amount of colchicine should be added. If an acute attack occurs during treatment, colchicine or anti-inflammatory analgesics can be added.

③For patients with chronic renal insufficiency, especially those with glomerular filtration rate <30ml/min, the efficacy of this product is often poor, and the dosage of this product can be increased, but once The daily dosage should not exceed 2g.

(4) Interaction

① This product can inhibit the excretion of the following drugs: penicillins, cephalosporins, indomethacin, naproxen, dapsone, and Trimethrexate, oral hypoglycemic drugs, sulfonamides, PAS pantothenic acid, etc., increase the concentration of these drugs and enhance their effects. This product reduces the urinary excretion of nitrofurantoin and makes it less effective.

② Competes with rifampicin for liver uptake and increases rifampicin blood concentration, which may cause toxic reactions.

③ Aspirin and other salicylic acid drugs can reduce the uric acid excretion effect of this product. Diuretics such as thiazides, furans, diuretics, and amothiales, pyrazinamide, and drinking alcohol can reduce the excretion of uric acid in the body and affect the therapeutic effect.

④This product can pass through the placenta and affect fetal development.

⑤ May cause cross-reaction with sulfa drugs.

(5) The preparation is in the form of tablets, each tablet is 0.25g.

It is generally believed that the common dose of probenecid starts at 250mg, twice a day, and gradually increases to 500mg, 3 times a day after 2 weeks. The maximum daily dose does not exceed 2000mg. When the blood uric acid drops to After normalization, the dose can be reduced to the maintenance amount and continued taking. The main side effects of probenecid are:

①Gastrointestinal reactions such as nausea, stomach discomfort, loss of appetite, etc. In severe cases, vomiting and diarrhea may occur.

②Skin allergic reactions, including itchy skin, rash, urticaria, etc. A very small number of patients may develop severe dermatitis.

③ Side effects of blood system, such as leukopenia, thrombocytopenia and hemolytic anemia.

④A few patients may develop drug fever.

⑤Urine glucose may show a false positive reaction during medication.

⑥A very small number of patients can cause renal colic and acute attacks of gouty arthritis while taking the medicine.

Therefore, gout patients with the following conditions should not take probenecid: those with a history of allergies to sulfa drugs; those with obvious abnormal liver function and liver disease; those with renal impairment; those with leukopenia and those with Severe anemia; severe gastric and duodenal ulcers, severe gastritis, etc.