The causes of urinary stones are very complex and many factors influence them. The current research shows that some drugs play a direct or indirect role in the formation of urinary stones during renal excretion, and it is important to understand the clinical application and mechanism of action of these drugs for the basic research and prevention of urolithiasis.
(A) Sulfonamides
It is generally believed that p-aminobenzoic acid (PABA) is the “growth substance” of bacteria, and sulfonamides play an antibacterial role by competing with PABA to prevent the synthesis of folic acid by sensitive bacteria. Sulfonamides inhibit many gram-positive bacteria and some gram-negative bacteria. It is suitable for infectious diseases such as urinary tract infections caused by Escherichia coli and Aspergillus and epidemic cerebrospinal l meningitis.
2, adverse reactions: ① metabolic reactions: generally within 7 to 10 days after the drug, can be manifested as drug rash, severe exudative erythema multiforme, exfoliative dermatitis and maculopapular epidermolysis bullosa atrophica dermatitis; also manifested as photosensitive dermatitis, drug fever, joint and muscle pain, fever and other serum sickness-like reactions. (ii) Hematologic reactions: granulocytopenia, thrombocytopenia, occasionally aplastic anemia, hemolytic anemia and hemoglobinuria may occur. Hyperbilirubinemia and neonatal jaundice: Since sulfa drugs compete with bilirubin for protein binding sites, free bilirubin may increase and neonatal liver function may be imperfect, so hyperbilirubinemia and neonatal jaundice may occur more easily, and occasionally nuclear jaundice may occur. ④Liver damage: jaundice and liver function decline may occur, and acute hepatic necrosis may occur in severe cases ⑤Renal damage: crystalluria, hematuria and tubular urine may occur. ⑥Other: nausea, vomiting, loss of appetite, diarrhea, headache, weakness, etc. may occur.
2. Effects on the formation of urinary stones
Sulfonamides are mainly excreted by the kidneys, and the amount of drug reabsorbed in the renal tubules is much less than that of water reabsorption, so the drug concentration in the renal tubules and collecting ducts increases and can be tens of times of the blood concentration. Sulfonamides have low solubility in acidic urine and are easily crystallized and precipitated, even forming stones. The crystals are often formed in the renal tubules, and can fuse into stones in the collecting ducts and renal pelvis. The stones can enter the ureter and cause renal colic and other symptoms, and in serious cases, acute tubular necrosis, interstitial nephritis, acute glomerulonephritis and acute renal failure can occur due to damage to renal tissues and blood vessels.
3, the clinical manifestations of drug damage and diagnosis
Sulfathiazole most often causes crystalluria and is not used clinically, followed by sulfadiazine (SD), sulfamethazine (SM), and sulfadimethazine (SM2), while sulfisozole (SIZ) and sulfamethazine (SMZ) are soluble substances and are not easily caused by crystalluria. However, it has been reported that the combination of SMZ and methomyl pyrimidine (TMP) can cause crystalluria and even acute renal failure resulting in death, which is thought to be caused by the precipitation of SMZ crystals rather than TMP.
Clinical manifestations of lumbago, lumbago, dysuria, hematuria, proteinuria with oliguria, anuria and uremia.
Diagnosis is based on: ① history of sulfa drug application; ② clinical manifestations due to crystalluria; ③ corresponding other sulfa drug adverse reactions; ④ sulfa crystals visible on microscopic examination of urine sediment.
4. Prevention and treatment of drug damage
Sulfanilamide crystallization is related to the concentration of sulfanilamide in blood, acidic urine, dehydration status and the solubility of the drug itself, so during the treatment with sulfanilamide, attention should be paid to take necessary measures to avoid crystallization.
The dose should not be increased arbitrarily, the number of doses should be increased or the course of treatment should be prolonged. Sulfanilamide combination can be used because the respective doses in the combination are smaller, or easy to use solvents such as sulfanilamide isofzole and sulfamethoxazole.
2. Reduce the precipitation of crystals. Drink more water and use the same amount of sodium bicarbonate to alkalize the urine and increase the solubility.
3.Urinal examination every 2-3 days to check the urine routine to test the sulfonamide crystals.
4.After the crystallization of sulfonamide, if the drug is stopped and more water is drunk in time, the crystallization can disappear sooner. In a few patients, severe obstruction may occur, which requires further examination and surgery or conservative treatment.
(B) Acetazolamide
1.Clinical application
1.Pharmacological mechanism The drug inhibits renal tubular carbonic anhydrase to reduce H+ secretion, H+-Na+ exchange and Na+ reabsorption, resulting in increased Na+, H20 and bicarbonate excretion, thus producing diuretic effect. The drug was originally used for diuresis, but nowadays it is mostly used for the treatment of glaucoma.
2, adverse reactions: ① drowsiness, hand and foot numbness, headache, dizziness, movement disorders, etc.; ② long-term application may cause metabolic acidosis and hypokalemia; ③ granulocytopenia and platelet deficiency may occur; ④ allergic skin reactions may occur; ⑤ may cause renal complications, such as renal colic, urinary crystals, nephrotic syndrome, etc.
2. Effects on the formation of urinary stones
Acetazolamide is mainly excreted from the body in its original form by the renal tubules. Wit drug can cause a significant reduction in the excretion of urinary calcium stabilized citrate, prompting the deposition of calcium phosphate in the renal tubules and renal pelvis, causing tissue calcification and stone formation.
3, the clinical manifestations of drug damage
It is necessary to alkalinize the urine during the application of this drug, but it has been reported that 16g of oral sodium bicarbonate daily still cannot correct the acidosis of the renal tubules and increase the excretion of citrate caused by this drug, the urinary acidity continues to increase, calcified renal insufficiency continues to worsen, accompanied by the formation of ureteral stones. Patients with hypercalciuria are more likely to have ureteral stones with this drug.
Clinical manifestations of back pain, often with episodes of back colic, hematuria, in severe cases, urinary scarcity, urinary closure, renal insufficiency.
Diagnosis is based on: ① history of acetazolamide drug application; ② clinical manifestations of concomitant stones; ③ corresponding adverse reactions to other acetazolamide drugs; ④ evidence of crystalluria and urolithiasis by auxiliary examinations, such as urinary routine and imaging.
4. Prevention and treatment of drug damage
Drink more boiled water during drug administration, and add potassium salt, magnesium salt and oral sodium bicarbonate to alkalize the urine. Calcium intake should be restricted for those with high calcium urine. The 24-hour urinary calcium level can be measured. Regular review of urine routine and X-ray examination, etc.
(iii) Indinavir
1.Clinical application
1.Pharmacological mechanism Indinavir has anti-HIV-1 and HIV-2 protease effect, with a selectivity of {10 times for HIV-1. It binds reversibly to the active site of protease and exerts a competitive inhibitory effect, thus preventing the replication of viral precursor polyproteins and interfering with the maturation of new viral particles, delaying the spread of HIV between cells. Thus, protease inhibition prevents the occurrence of new foci of infection. It is often used clinically in combination with viral nucleoside analogues to treat patients with advanced or progressive immunodeficiency in HIV-1 infection.
Common adverse effects are fatigue, headache, gastrointestinal discomfort, drowsiness, skin reactions, taste abnormalities, dizziness, insomnia, allergy, dry mouth, dysuria, analgia, nephrolithiasis, {bilirubinemia, thrombocytopenia, and hyperglycemia.
2. Effects on the formation of urinary stones
Indinavir is rapidly absorbed after oral administration, with 65% oral drug utilization, and can be excreted in the urine 1 – 2 hours after administration. The drug is easy to produce precipitation in the urine, leading to the formation of kidney stones.
3.Clinical manifestations of drug damage
Indinavir was first marketed in the United States in 1996 and in the United Kingdom in December of the same year. It is generally well tolerated in the treatment of AIDS, but the incidence of side effects causing kidney stones was found to be higher {. It is often used in combination with other drugs in the treatment of AIDS, so attention should also be paid to the occurrence of adverse reactions to other anti-AIDS drugs. The clinical manifestations are similar to those of the previous drugs.
4. Prevention and treatment of drug damage
There is no specific prevention method for the adverse reactions of indinavir kidney stones, the main measure is to drink more water during the drug. Treatment for kidney stones to make the appropriate treatment.