What Are the Different Types of Herbs for Gout?

Anti-gout drugs are a class of drugs that produce a therapeutic effect by inhibiting the synthesis of uric acid, inhibiting the reabsorption of uric acid in the renal tubules, or promoting uric acid excretion. At present, there are not many anti-gout medicines. According to the different clinical stages of gout, they can be divided into two major classes of drugs to control the symptoms of acute arthritis and anti-hyperuricemia [1].

Chinese name: Anti-gout medicine
Nature: Clinical medication

Make up: Colchicine, allopurinol, probenecid, etc.
Attend: gout

1 Anti-gout medicines 1 overview

Gout is a group of syndromes caused by increased blood uric acid and the deposition of urate crystals on joints and tissues. It includes arthritis, gout stones, urinary acidic stones, and gout nephropathy. The cause of gout is uric acid excess, the final product of purine metabolism in the body, which is higher than normal. This can be caused by the lack of urate oxidase (or urase), which prevents uric acid from being oxidized; it can also reduce uric acid excretion due to renal insufficiency, both of which can cause hyperuricemia.

2 Anti-gout drugs 2 Classification of anti-gout drugs

According to the different clinical stages of gout, anti-gout drugs can be divided into two categories of drugs to control the symptoms of acute arthritis and anti-hyperuricemia. The drugs that control the symptoms of gouty arthritis mainly include colchicine, non-steroidal anti-inflammatory drugs and glucocorticoids; the anti-hyperuricemia drugs mainly include drugs that inhibit uric acid production (such as allopurinol) and promote uric acid excretion Drugs (such as benzbromarone and probenecid).

2.1 Anti-gout drugs 2.1 drugs for controlling symptoms of acute arthritis

Colchicine

[Indications] Applicable to acute attacks of gouty arthritis, prevention of acute attacks of recurrent gouty arthritis, and familial Mediterranean fever.

[Pharmacology] (1) Pharmacodynamics: Combined with neutrophil tubulin subunits to change cell membrane functions, including inhibition of neutrophil chemotaxis, adhesion and phagocytosis; inhibition of phospholipase A2, reduction of mononuclear Cells and neutrophils release prostacyclin and leukotriene; inhibit local cells to produce IL-6 and so on, so as to control local joint pain, swelling and inflammation. Colchicine does not affect the formation, dissolution and excretion of urate, so it has no effect of lowering uric acid. (2) Pharmacokinetics: It is quickly absorbed in the gastrointestinal tract after oral administration, and the protein binding rate is low, only 10% to 34%, and the blood concentration reaches 0.5 to 2 hours after taking the drug. The peak of 2mg orally was 2.2ng / ml. This product is metabolized in the liver, excreted from the bile and kidneys, the original form and metabolites are mainly excreted from feces, and 10% to 20% are excreted by the kidneys. Patients with liver disease have increased excretion from the kidneys. Drug excretion lasted about 10 days after discontinuation. Acute gout is effective 12 to 24 hours after oral administration, and 90% of patients have no pain within 24 to 48 hours after taking the medicine.

[Adverse reactions] There is a significant correlation with the dose size, and oral administration is safer than intravenous injection. Common adverse reactions include: gastrointestinal symptoms; muscle and peripheral neuropathy; bone marrow suppression; shock; affects fertility; phlebitis and cellulitis; teratogenicity; other: hair loss, rash, liver damage And fever.

[Contraindications] Disable pregnant women and lactating women; Disable allergic to this product; Low myeloproliferation and liver and kidney dysfunction.

[Precautions] The understanding of the effects and risks of colchicine in treating gout is not consistent. Therefore, it must be used with caution when selecting this product, and try to avoid intravenous injection and long-term oral administration. Do not use both intravenous and oral routes even during the onset of gout; Reduce the dose to the elderly and those with potential damage to liver and kidney function; Colchicine can inhibit normal cell division and has teratogenic effects on the fetus. Parents who take the drug must be pregnant for several months after the drug is stopped. Peptic ulcer, inflammatory enteritis, and heart dysfunction should be used with caution. Patients must be monitored regularly for blood routine and liver and kidney function during medication.

[Drug interactions] This product can cause reversible vitamin B ₁₂ malabsorption; This product can make the central nervous system inhibitory drug synergistic and enhance the reactivity of sympathomimetic drugs; This product can reduce oral anticoagulants , The role of antihypertensive drugs, the dose needs to be adjusted when combined.

[Usage and Dosage] Oral. The common dose for adults in the acute phase is: 1mg once a day, 3 times a day, and reduce the amount as appropriate after the symptoms are relieved, or take 0.5 ~ 1 mg every 1 to 2 hours until the joint symptoms are relieved or diarrhea or vomiting occurs. The amount of treatment should not exceed 6mg within 24 hours, and this product should not be taken within 48 hours. After that, the daily dose is 0.5 ~ 1.5mg, and it is taken in divided portions for a total of 7 ~ 14 days.

2.2 Anti-gout drugs 2.2 Anti-hyperuricemia drugs

2.2.1 Drugs that inhibit uric acid production

Alloprinol

[Indications] Primary and secondary hyperuricemia, especially hyperuricemia caused by excessive uric acid production; Recurrent and chronic gout; gout stones; uric acid kidney stones and ( Or) uric acid nephropathy; hyperuricemia with renal insufficiency.

[Pharmacology] (1) Pharmacodynamics: This product is a xanthine oxidase inhibitor, which is currently the only drug that can inhibit uric acid synthesis. Allopurinol and its metabolite oxopurinol can inhibit xanthine oxidase, prevent hypoxanthine and xanthine from being metabolized to uric acid, thereby reducing the production of uric acid. Reduce the uric acid content in blood and urine to below the solubility level, prevent the formation of uric acid crystals and deposits in joints and other tissues, and also help redissolve uric acid crystals in patients with gout. Allopurinol also inhibits the synthesis of new purines in the body by acting on hypoxanthine-guanine phosphatase. (2) Pharmacokinetics: After oral administration of this product, it absorbs 80 ~ 90% in the gastrointestinal tract, and about 70% is metabolized into active oxypurinol in the liver. Allopurinol peaked at 1 to 2 hours, t _1/2 1 to 3 hours. Its metabolite, oxypurinol, peaked at 5.2 to 6.5 hours, t _1/2 14 to 28 hours. Renal impairment was significantly prolonged at t _1/2 . About 70% of the dose is excreted by the kidney with oxypurinol and 10% with allopurinol, and the rest is excreted by the intestine. Concomitant use of uric acid excretion drugs can promote the excretion of oxypurinol. However, hepatic and renal dysfunction, the discharge decreased. The blood uric acid concentration began to decrease within 24 hours, and the decrease was most obvious at 2 to 4 weeks.

[Adverse reactions] The incidence rate is 5% to 20%, about half of which need to be discontinued, and the drug can usually return to normal after discontinuation. Common adverse reactions include: rash: itchy pimples or urticaria; gastrointestinal reactions: including diarrhea, nausea, vomiting, and abdominal pain; leukopenia or thrombocytopenia or anemia; peripheral neuritis; others: Hair loss, headache, drowsiness, dizziness, fatigue, fever, lymphadenopathy, hepatotoxicity, interstitial nephritis and allergic vasculitis, etc .; Several patients have reported sudden deaths of unknown causes during the use of this product.

[Contraindications] Banned for pregnant women and lactating women; Banned for those with a history of allergies to this product.

[Precautions] This product must start with a small dose and gradually increase to an effective amount to maintain normal blood uric acid and uric acid levels. Gradually reduce the amount and maintain the minimum effective amount for a longer period of time; combined with uric acid can enhance the efficacy; this product can re-initiate and aggravate the symptoms of arthritis in the acute phase when uric acid crystals are re-dissolved, so it cannot be used for gouty joint Acute onset of inflammation; Regularly check blood uric acid and 24-hour uric acid levels before and during medication, as a basis for adjusting the dosage of the drug; Those with liver and renal impairment and the elderly should be used with caution and reduce Daily dosage; Hematology and liver and kidney function should be checked regularly during medication.

[Drug interactions] Ethanol, chlorthalidone, itanilic acid, furosemide, metoprazine, pyrazinamide or thiazide diuretics can increase the uric acid content in the serum. The use of this product with the above drugs or drinking will reduce its effectiveness in controlling gout and hyperuricemia. Pay attention to the dosage adjustment when using this product. For patients with hypertension or poor renal function, this product has been reported with renal failure and allergies when used with thiazide diuretics; When used with ampicillin, the incidence of rash increases, especially in hyperuricemia Patients with dysfunction; When used equally with anticoagulants such as dicoumarin and indanedione derivatives, the effect of the latter can be strengthened, and care should be taken to adjust the dose; when used with azathioprine or thiopurine, due to the oxidation of enzymes Obstruction is more significant, and the dosage should generally be reduced by 1/4 ~ 1/3; When used with cyclophosphamide, the bone marrow suppression can be more obvious; When used with uric acid drugs, the possibility of kidney stones can be increased.

[Usage and Dosage] Oral. Adults: 50 mg orally once a day, 1 to 2 times a day, and 50 to 100 mg per week thereafter, to 200 to 300 mg a day, divided into 2 to 3 doses. Blood and uric acid levels are measured every 2 weeks. If they have reached normal levels, they will not be increased. If they are still high, they can be increased again. However, the maximum daily amount is generally not more than 600mg. Maintenance amount: 100 ~ 200mg once, 2 ~ 3 times a day. Children: 50 mg each time under 6 years old, 100 mg each time between 6 and 10 years old, 1 to 3 times a day.

2.2.2 Drugs that promote uric acid excretion

2.2.2.1 Probenecid

[Indications] Applicable to those with frequent episodes of gouty arthritis with hyperuricemia and gout stones, but must: glomerular filtration rate> 50 ~ 60 ml / min; no history of kidney stones or kidney stones; weak acid urine; those who do not take salicylic acid drugs.

[Pharmacology] (1) Pharmacodynamics: This product can inhibit the reabsorption of urate by the proximal tubules, increase the excretion of uric acid, thereby reducing blood uric acid concentration and reducing uric acid deposition. (2) Pharmacokinetics: Quick and complete absorption after oral administration. The protein binding rate is 65 ~ 90%, which mainly binds to albumin. This product is metabolized in the liver into carboxylated metabolites and hydroxy compounds, all of which have uric acid excretion-promoting activities. The metabolites are mainly excreted by the kidneys, and about 5-10% of the administered amount is excreted in the original form within 24 to 48 hours. When renal function declines, the uric acid excretion effect of this product is obviously weakened or disappeared.

[Adverse reactions] gastrointestinal symptoms: such as nausea and vomiting. Occasionally cause gastric ulcers. It can promote the formation of kidney stones, so it is necessary to ensure the urine pH value is 6.0 ~ 6.5, drink plenty of water and take potassium citrate together to prevent the formation of kidney stones. Dyspnea, fever, skin itching, rash and other allergic reactions; Occasionally caused leukopenia, rare bone marrow suppression and liver necrosis.

[Contraindications] People with a history of allergies to sulfa drugs and allergies to this product are prohibited; Renal insufficiency, especially those with a glomerular filtration rate of less than 30ml / min; Children under 2 years old are prohibited.

[Precautions] This product has cross-allergic reactions with sulfa, including ^[1] , itching and fever of the skin, but it is rare. Elderly people, hyperuricemia with tumor, liver dysfunction, active peptic ulcer or those with a history of peptic ulcer and kidney stones should not take it. This product should not be used when the symptoms of gouty arthritis are not under control. When taking this product, you should maintain sufficient water intake (about 2500ml / day), keep the urine flowing smoothly, and prevent the formation of kidney stones. If necessary, take potassium citrate at the same time. Do not take salicylic acid preparations while taking this product. Regularly check blood and urine pH, liver and kidney function, blood uric acid and uric acid. Adjust drug dosage based on clinical manifestations and blood and uric acid levels. In principle, it is maintained for a long time with a minimum effective amount.

[Drug interactions] When this product is used, it can inhibit the excretion of penicillin, indomethacin, naproxen, and dapsone by renal tubules, increase their blood concentration and increase toxicity; this product and salicylic acid Salt and aspirin can inhibit the uric acid effect of this product. This product can affect the metabolism of rifampicin and heparin, making the latter more toxic. When patients with tophi use this product together with allopurinol, this product can accelerate the excretion of allopurinol, while allopurinol can extend the half-life of this product. Therefore, the effective dose of allopurinol needs to be appropriately increased, and the effect of this product is increased. Diuretics can increase blood uric acid concentration, and the dosage of this product should be adjusted when used with this product. The same use with methotrexate can increase methotrexate blood concentration and increase toxicity. When used together with sulfa, the sulfa is slowed down and the blood concentration is increased. When used with oral hypoglycemic agents, the effect of hypoglycemic agents is enhanced.

[Usage and Dosage] Oral. Commonly used amount for adults: To treat gout, start taking 0.25g orally once a day, twice a day for a week; afterwards, take 0.5g orally once a day, twice a day; after 1 week, it can be increased to 0.5 ~ 1.0g, twice a day, a day The maximum dose is 2.0g. Due to impaired renal function in elderly patients, the dosage should be appropriately reduced.

2.2.2.2 Benzbromarone

[Indication] This product is a powerful uric acid excretion drug, suitable for recurrent gouty arthritis with hyperuricemia and gout stones.

[Pharmacology] (1) Pharmacodynamics: Its mechanism of action is similar to probenecid, that is, it inhibits the reabsorption of uric acid by renal tubules to reduce hyperuricemia and the deposition of uric acid crystals in tissues, and can also promote the re-crystallization of uric acid. Dissolve. This product is stronger than probenecid and has a synergistic effect with probenecid. (2) Pharmacokinetics: This product is good for oral absorption. This product is taken orally at 50 ~ 100mg, which absorbs about 50%, and the rest is excreted from the feces in the original form. Due to excretion in the intestine, this medicine can also be used for patients with renal insufficiency with a serum creatinine value of 5mg / 100ml. Oral 100mg, the blood concentration reached a peak at 6 hours, but decreased slightly at 6-12 hours, and its protein binding rate was 99%. This product is metabolized in the liver and its metabolites are effective. After taking the medicine for 24 hours, the blood uric acid decreased to 66.5% before taking the medicine. After the bromine ion is removed in the liver, it is mainly excreted from the bile in free or combined form, followed by feces, and a small part is excreted in urine.

[Adverse reactions] gastrointestinal reactions: nausea, diarrhea and abdominal discomfort. cause kidney stones and renal colic. Occasionally granulocytopenia may trigger acute attacks of arthritis. None of the above adverse reactions are common. Others such as fever, rash, and liver and kidney damage are even more rare.

[Contraindications] Those who are allergic to this product. Kidney stones (glomerular filtration rate <20ml / min), pregnant women and lactating women are prohibited.

[Precautions] Drink plenty of water and alkalize urine during taking. For renal function decline, serum creatinine> 130mol / L is still effective, but daily urine volume must be maintained above 2000ml. Regularly monitor renal function and changes in blood uric acid and uric acid. Long-term medication should be used to regularly monitor liver function. This product must be applied only after the acute symptoms of gouty arthritis are controlled.

[Drug Interactions] The uric acid excretion effect of this product can be weakened by antagonisms such as salicylate and pyrazinamide. This product can enhance the effect of oral anticoagulants, so the latter dose should be adjusted when combined.

[Usage and Dosage] Oral. Usual amount for adults. Starting from a small dose, 25mg once, once a day, no adverse reactions can gradually increase to 100mg a day. After breakfast, take 3g sodium bicarbonate daily.

2.3 Anti-gout drugs 2.3 Other anti-gout drugs

Febutastat ( Febuxostat )

Febuxostat is a selective xanthine oxidase inhibitor, which can play a role in reducing blood urate concentration, and is a new drug for treating gout. Clinical studies have shown that febuxostat has good efficacy and safety in treating hyperuricemia and gout caused by it. Compared with allopurinol, febuxostat can quickly lower blood uric acid levels, especially for patients with mild to moderate renal insufficiency, without the need to adjust the dose, and there are no obvious adverse reactions.

[Indications] Long-term treatment of hyperuricemia in gout patients

[Adverse reactions] Individual patients may develop anemia, idiopathic thrombocytopenic purpura, leukocytosis / reduced neutropenia, pancytopenia, splenomegaly, and thrombocytopenia. Angina pectoris, atrial fibrillation, heart murmur, abnormal ECG, palpitation sinus bradycardia, tachycardia. Deafness, tinnitus, dizziness, and blurred vision. abdominal distension, abdominal pain, constipation, dry mouth, indigestion, flatulence, etc.

[Contraindications] This product is contraindicated in patients undergoing azathioprine and thiopurine treatment.

[Precautions] In the initial period of taking febuxostat, the frequency of gout attacks often increases. This is due to a decrease in blood uric acid concentration, resulting in urate activity deposited in the tissue. To prevent the onset of gout at the beginning of treatment, it is recommended to take non-steroidal anti-inflammatory drugs or colchicine at the same time. During the treatment of febuxostat, there is no need to discontinue febuxostat if gout occurs. Gout should be treated according to the specific circumstances of the patient.

[Drug Interactions] Febuxostat is a xanthine oxidase inhibitor. According to a drug-drug interaction study in healthy subjects, febuxostat can alter theophylline, a substrate of xanthine oxidase, in humans. Therefore, febuxostat should be used with caution in combination with theophylline. There are no studies on the interaction of febuxostat with other drugs metabolized by xanthine oxidase. Because febuxostat can inhibit the activity of xanthine oxidase, the concentration of some drugs metabolized by xanthine oxidase in plasma is increased, which leads to poisoning. Therefore febuxostat is contraindicated in patients undergoing azathioprine or thiopurine therapy. Based on drug interaction studies conducted in healthy subjects, there was no significant interaction between febuxostat and colchicine, naproxen, indomethacin, hydrochlorothiazide, warfarin, and desipramine . Therefore, febuxostat can be used in combination with these drugs.

[Usage and dosage] The recommended oral dose of febuxostat is 40 mg or 80 mg once daily. The recommended starting dose of febuxostat is 40 mg once daily. If after 2 weeks, the blood uric acid level is still not less than 6 mg / dl (about 360 mol / L), it is recommended to increase the dose to 80 mg once daily. ^[2]

3 Anti-Gout Drugs 3 Guide to Anti-Gout Drugs

3.1 In the acute onset of gout, anti-inflammatory and analgesic treatment is recommended as early as possible (usually within 24 hours ) (recommended level: 2B )

During the acute onset of gout, the targeted use of non-steroidal anti-inflammatory drugs (NSAIDs), colchicine, and glucocorticoids early (within 24 hours) can effectively anti-inflammatory and analgesic, and improve the quality of life of patients.

3.2 In the acute episode of gout, it is recommended to use NSAIDs first to relieve symptoms (recommended level: 1B )

In the acute attack of gout, first consider the relief of the patient's clinical symptoms. There is currently only indirect evidence comparing the relative efficacy and safety of different non-selective NSAIDs in the treatment of gout. Selective cyclooxygenase 2 (COX-2) inhibitors can more specifically inhibit COX-2, reduce side effects such as gastrointestinal damage, and can be used in patients with high risk factors for the digestive tract.

3.3 Patients with contraindications to NSAIDs during the acute episode of gout are advised to use low-dose colchicine alone (recommended level: 2B )

High-dose colchicine (4.8 ~ 6.0 mg / d) can effectively alleviate the clinical symptoms of patients with acute gout, but its incidence of gastrointestinal adverse reactions is high, and it is easy to cause patients to discontinue due to adverse reactions. Compared with high-dose colchicine, low-dose colchicine (1.5-1.8 mg / d) showed no significant difference in effectiveness; in terms of safety, the incidence of adverse reactions was lower. Low-dose colchicine is more effective within 48 hours.

3.4 In the acute episode of gout, short-term glucocorticoid alone has similar efficacy and safety to NSAIDs (recommended level: 2B )

For patients with acute gout, short-term glucocorticoid alone (30mg / d, 3d) can have the same effective analgesic effect as NSAIDs and good safety, especially for acute episodes of gout that are not tolerated by NSAIDs and colchicine. patient.

3.5 For patients with frequent episodes of acute gouty arthritis (> 2 times / year) and patients with chronic gouty arthritis or gout stones, uric acid lowering treatment is recommended (recommended level: 1B )

The goal of uric acid lowering treatment is to prevent the acute recurrence of gout arthritis and the formation of gout stones, and to help dissolve the gout stones. Stable control of patients' blood uric acid level below 360 mol / L (6 mg / dl) can help relieve symptoms and control the disease. Studies have shown that allopurinol, benzbromarone, allopurinol in combination with benzbromarone, febuxostat, and polyethylene glycol recombinant urase (which has not yet been approved for marketing in China) can reduce goutstones by reducing uric acid .

3.6 Gout patients are advised to use allopurinol (recommended level: 2B ) or febuxostat (recommended level: 2B ) for uric acid-lowering drugs to inhibit uric acid production; benzbroma Long (Recommended level: 2B )

For drugs that inhibit uric acid production, febuxostat has advantages over allopurinol in terms of effectiveness and safety. For drugs that promote uric acid excretion, benzbromarone and probenecid can be used in patients with chronic gout. Benzabromarone is superior to probenecid in terms of effectiveness and safety. When using allopurinol, start with a low dose. The starting dose for those with normal renal function is 0.1 g / d. The dose for renal insufficiency should be lower. Gradually increase the dose and closely monitor the presence of hypersensitivity. When using benzbromarone, it should start with a low dose, increase the amount of drinking water during the process, alkalize the urine, and avoid concurrent use with other liver damage drugs. Doctors should use the above uric acid-lowering drugs according to the specific circumstances of the patient, and be alert to possible liver, renal toxicity and other side effects during the medication.

3.7 For gout patients with chronic kidney disease, it is recommended to evaluate renal function first, and then use uric acid lowering drugs that have little effect on renal function according to the specific conditions of the patient, and closely monitor adverse reactions during the treatment (recommended level: 2C )

Chronic renal impairment can affect the half-life and excretion period of uric acid-lowering drugs, affect pharmacokinetics, and then affect the effectiveness and safety of uric acid-lowering drugs. Higher blood uric acid levels and urate deposition can affect renal function. Drugs that inhibit uric acid production (allopurinol and febuxostat) and drugs that promote uric acid excretion (benclomarone) can reduce glomerular uric acid load. When allopurinol is used in patients with renal insufficiency, the initial dose should be reduced, the dose should be gradually increased, and the occurrence of hypersensitivity should be closely monitored. No dose adjustment is required when febuxostat is used in patients with mild to moderate renal insufficiency. Uric acid excretion drugs are used with caution in patients with uric acidic kidney stones and in patients with severe renal insufficiency.

3.8 In the early stage of gout patients, colchicine is recommended to prevent the recurrence of acute gouty arthritis (recommended level: 2B )

In the early stage of uric acid lowering treatment for gout patients, the prophylactic use of colchicine for at least 3 to 6 months can reduce the acute attack of gout. Small doses of colchicine are safe and well tolerated. ^[3-4]