First, refractory gout should be paid attention to
With the improvement of people's living standards, the prevalence of gout is increasing year by year, reaching 1.26% ~ 1.59% and 0.3% ~ 0.36% respectively for men and women in China, while refractory gout accounts for about 1% of the total number of gout patients. For example, among the 665,438+10,000 gout patients in the United States, about 5 cases are refractory. The serum uric acid level of patients with refractory gout is difficult to reach the standard, and the curative effect of routine analgesics for recurrent arthritis is poor, often accompanied by tophus formation, joint deformity, renal insufficiency, hypertension, diabetes, coronary heart disease, etc., which brings great pain to patients and affects their quality of life and longevity.
Second, the suggestion of "continuous standard" treatment.
"Continuously reaching the standard" has two meanings: persistence and reaching the standard. "Persistence" refers to the persistence of uric acid reduction, and the course of treatment takes years, decades or even a lifetime. The longer the course of disease, the more gout stones in the body and the longer the duration of uric acid reduction. "reaching the standard" means "reaching the control standard of blood uric acid" For common gout, the ideal target value of serum uric acid is < 6mg/dl(360umol/L), but for refractory patients, it should be controlled below 4mg/dl, which can bring the following benefits to patients:
(1) The frequency of acute attack of arthritis decreased. Becke et al. showed that after 756 gout patients with serum uric acid >: 8mg/dl were treated with febuxostat 120mg/d 1 year, the proportion of patients with acute gout who needed treatment decreased from 23% to 6%.
(2) tophi dissolves quickly. There is a linear negative correlation between serum uric acid level and the dissolution rate of uric acid stones, which is helpful for the rapid dissolution of gout stones after reaching the treatment standard. Serum uric acid levels were 6. 1 ~ 7 mg/dl, 5. 1 ~ 6.0 mg/dl, 4. 1~5.0 mg/dl, respectively.
(3) It is helpful to slow down the progress of renal insufficiency. If high-dose allopurinol is used to treat gout patients with chronic renal insufficiency, the proportion of patients whose renal function deteriorates and needs long-term dialysis will decrease from 46. 1% (control group) to 65.438+06%.
(4) Improve the prognosis of patients with heart failure. A retrospective study of 25,090 patients with gout showed that taking allopurinol for more than 30 days could significantly reduce the readmission rate and all-cause mortality of patients with gout heart failure (adjusted RR values were 0.69 and 0.74, respectively).
Third, the strategy of "continuously reaching the standard" of uric acid
For patients with refractory gout, non-drug treatment should be emphasized first and throughout the treatment, such as strictly controlling high purine diet, soft drinks and fructose, prohibiting drinking beer and white wine, drinking more water (the amount of drinking water should be more than 2000ml within 24 hours) and alkalizing urine (keeping the pH value of urine at 6.2~6.8). In addition, there are many places that need to be emphasized in drug treatment.
1. With regard to the dosage of existing drugs, most clinicians use allopurinol, a synthetic drug that inhibits uric acid. The conventional dosage is 300mg/d, mainly to avoid the occurrence of fatal allergic syndrome. However, most studies show that long-term low and medium doses of allopurinol can not reduce the occurrence of fatal allergic syndrome, and the effect of reducing uric acid is not good. However, from low doses such as 50~ 100 mg/day,
At high dose, the curative effect increased obviously, but the adverse reactions did not increase. Similarly, on the basis of strict monitoring of adverse reactions, other drugs for reducing uric acid, such as benbromarone, can gradually increase the dose from a small dose, and finally exceed the conventional dose to make the blood uric acid reach the standard.
2, advocate the use of "kill two birds with one stone" drugs. Many drugs can lower blood pressure, blood lipid and/or blood sugar, and also lower blood uric acid, which has the effect of "killing two birds with one stone" or even "killing three birds with one stone". Losartan and fenofibrate can reduce blood pressure and triglyceride respectively, and at the same time, they can reduce serum uric acid by 15% ~ 30% by promoting uric acid excretion. They also have the advantages of increasing the pH value of urine without increasing the crystallization and anti-inflammation of urinary tract and without inducing acute gout attack, and are suitable for gout patients with hypertension and hypertriglyceridemia respectively.
Atorvastatin can reduce serum uric acid by 6.4% ~ 8.2% by inhibiting the synthesis of uric acid, which is suitable for gout patients with hypercholesterolemia. Etfenprox and Arholofenate can not only reduce blood sugar and triglyceride, but also promote uric acid excretion in a dose-dependent manner, thus reducing serum uric acid 15% ~ 29%, which is suitable for gout patients with diabetes and hyperlipidemia.
3. It should also be said that for patients with single drug ineffective or poor curative effect, combined medication can improve the effect of reducing uric acid. Combined medication is mainly a combination of drugs that promote uric acid excretion and drugs that inhibit uric acid synthesis. For example, a stable dose of allopurinol (200~600mg/d) is combined with benbromarone (100 mg/d), probenecid (0.5g/d) or RDEA594(200~600mg/d) respectively, and the second generation promotes uric acid.