What are the mechanism of action and clinical applications of Acetohydroxamic acid?
Background and overview[1][2]
Acetohydroxamic acid (Acetohydroxamic Acid, AHA), a kind of hydroxamic acid, is an isomer of acetohydroxamic acid. It was developed abroad in the 1970s. Drugs for urinary stones and urinary tract infections. Because Acetohydroxamic acid has the -CONHOH functional group, in medicine, it can chelate with the nickel atom of urease to inactivate urease, thereby preventing the decomposition of urea, restoring the normal pH of urine, and improving the magnesium ammonium phosphate and carbonate-containing properties. The apatite supersaturated physiological environment prevents the formation of stones and inhibits their growth. And because AHA is weakly acidic, it can gradually dissolve, shrink or even disappear stones, and AHA has certain antibacterial activity. Therefore, Acetohydroxamic acid has been used clinically to treat refractory urinary tract infections caused by urease-secreting bacteria. , infectious urinary tract stones, stones caused by long-term retention of urinary catheters and other diseases.
In agriculture, Acetohydroxamic acid can also be used as a competitive inhibitor of urease, slowing down urea or reducing the rate of protein decomposition into ammonia, thereby improving protein utilization.
In the metallurgical industry, as a good organic ligand, it can be used in the extraction and analysis of metal mineral components. The special structure of Acetohydroxamic acid makes it widely used in various industries.
In animal husbandry, AHA is a good competitive inhibitor of urease. It is generally used as a feed additive for ruminants and is a good rumen microbial urease inhibitor. . As a rumen microbial urease inhibitor, AHA has strong specificity and can slow down the decomposition rate of urea and increase the synthesis of microbial protein, thereby improving the production level of ruminants, saving protein feed and improving protein utilization.
AHA is easily soluble in water, ethanol, methanol or ether, and is widely used in various industries such as medicine, animal husbandry, agriculture, environmental protection, and metallurgy. In medicine, Acetohydroxamic acid is commonly used to treat refractory urinary tract infections caused by urease-secreting bacteria, infectious urinary stones, stones caused by long-term retention of urinary catheters and other diseases.
Medical properties and applications[1]
Urinary tract stones are caused by the decomposition of urea under the action of urease, causing the content of urinary ammonia, bicarbonate and carbonate to increase, and the urine pH to increase. Magnesium phosphate and calcium phosphate are supersaturated to form stones. This product has a chemical structure similar to that of urea, and can competitively form a chelate with the nickel atom in urease, inhibiting the activity of urease, thus preventing the decomposition of urea, reducing the formation of urinary ammonia and lowering the urine pH. This product also participates in the metabolism of bacterial nucleotides, can block the biosynthesis of DNA, and also has certain antibacterial and stone-dissolving effects. Rapidly absorbed after oral administration. t1/2 is dose related. The peak value is reached 15 to 60 minutes after oral administration, and t1/25 to 10 hours. After intravenous injection of 50 mg/kg of this product, 54% of the drug is excreted in the urine as the original drug and 17% is biotransformed into acetamide. Clinically used to prevent and treat infectious urolithiasis and urinary tract infections. After use, the urine becomes clear, the urine volume increases, the urination is smooth, the urine ammonia and urine pH value of most patients decrease, and the symptoms of inflammatory stimulation are reduced or disappeared. For those with indwelling urinary catheters or cystostomy, the inflammatory manifestations such as wounds and urethral secretions disappear, and the tubes are clean and free of blockage.
Oral administration: 0.25g, 3 times/d.
Other applications[1]
CN201910552018.5 reported that Acetohydroxamic acid has no significant effect on the tension of isolated thoracic aortic rings in rats in the basal state, but Acetohydroxamic acid can relax NE in a concentration-dependent manner. The pre-shrunk endothelial intact thoracic aortic ring also has a relaxing effect on the endothelial-removed thoracic aortic ring, but the relaxing effect is significantly less than that of the endothelial intact group. The vasodilatory effect of Acetohydroxamic acid is also related to NO released by endothelial cells, and also related to Kir. , KCa2+, internal calcium release and external calcium influx are related. The diastolic blood pressure and systolic blood pressure of the Acetohydroxamic acid group both tended to decrease. It is speculated that it may be due to the relaxation of the rat blood vessels and the reduction of peripheral vascular resistance, thereby causing the reduction of blood pressure. From the vascular reactivity experiment, it was found that the thoracic aorta of rats in each group was in The diastolic rate of Ach under PE pre-contraction was greater than 80%, and the vascular endothelium was not damaged; and through HE staining of tissue sections of the heart and thoracic aorta, it was found that there was no significant change in the vascular tissue of the administration group, and the cardiac histological examination was better than that of the control group. In comparison, there is no significant change. Acetohydroxamic acid can lower blood pressure without significant effects on blood vessels and heart tissue.
Adverse reactions[2]
A few patients may have mild headache, gastrointestinal discomfort, nausea and skin itching, etc., which will generally disappear on their own without stopping the medication.
Notes[2]
A few people may have mild headache, gastrointestinal discomfort, nausea, and skin itching, which will disappear on their own and generally do not require discontinuation of medication.
Main reference materials
[1] [Invented in China] CN201910552018.5 Application of Acetohydroxamic acid in promoting vasodilation
[2] New Practical Drug Manual
