RU2549493C1 - Method for lithokinetic therapy in ureteral calculi - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method involves prescribing a drug therapy comprising administering Tamsulosin, selective alpha-1-adrenoreceptor blocking agent in tablets, orally in a dose of 40 mg with a meal once a day; it is combined with M-cholinomimetic neostigmine methylsulphate injected subcutaneously in 0.05% solution 1 ml that makes a daily dose of 0.5 mg once a day, 6 hours after administering Tamsulosin, selective alpha-1-adrenoreceptor blocking agent. The lithokinetic therapy following the presented schedule is conducted for 1 to 7 days in the period of which calculi are removed from the ureter.

EFFECT: method enables providing more effective calculi removal from the ureter, reducing the length of treatment, reducing the need for surgical manipulations and the number of complications.

2 ex, 1 tbl

Description

The invention relates to medicine, in particular urology, and can be used in the treatment of urolithiasis, in particular for the expulsion of ureter stones, including fragments of kidney stone, migrated to the ureter after remote lithotripsy to destroy them.

Migration of stones into the ureter in case of urolithiasis (ICD), including multiple stone fragments that occur after performing distant shock wave lithotripsy to destroy kidney stones, leads to obstruction of the ureter. This can lead to the development of further complications, damage to the kidney parenchyma, disruption and loss of its function (Bely L.E. Renal colic: a Guide for doctors. - M .: Medical Information Agency LLC, 2009. - S.9-29) .

There are analogues of the proposed method of lithokinetic therapy for ureteral stones for their expulsion when using herbal medicines containing essential oils and terpenes (Guide to Clinical Urology: edited by A.Ya. Pytelya. - M .: Publishing House "Medicine", 1969 . - p. 447). However, to achieve the effect using these methods, long periods of treatment reaching 30-40 days are required. This is a significant drawback, as it is accompanied by prolonged disability, impaired renal function and a high risk of complications.

There are analogues of the method proposed in the invention, when antispasmodic agents of myotropic action are used to expel stones from the ureter. For example, papaverine hydrochloride and drotaverine hydrochloride, under the influence of which there is a relaxation of the smooth muscles of internal organs (Mashkovsky MD Medicines. In two volumes. T.1. - Kharkov: Publishing house "Torsing", 1998. - S.430-431 ) In this case, analogues have significant drawbacks, namely, for dilatation of the ureter, high doses of the drug are required, and the antispasmodic effect occurs not only in the ureter at the level of localization of the stone and below it, but also in the upper parts of the ureter, which reduces the effectiveness of treatment. Another disadvantage of using these drugs is a decrease in smooth muscle tone not only of the ureter, but also of other organs, which leads to the development of side effects.

There is information about the use of M-anticholinergics, in particular atropine sulfate, platyphyllin and hyoscine butyl bromide, to facilitate stone discharge from the ureter (Tiktinsky OL, Aleksandrov VP Urolithiasis. - St. Petersburg: Piter Publishing House, 2000. - С .195-196 .; Gurbuz M.C., Polat N., Canat L, et al. Efficacy of three different alpha 1-adrenergic blockers and hyoscine N-butylbromide for distal ureteral stones. Int Braz J Urol. 2011 Mar-Apr; 37 (2): 195-200). However, the use of these drugs also has significant disadvantages, namely, it leads to a decrease in the tone of smooth muscles not only in the ureters, but also in other organs, which is the reason for the development of side effects. There is no information on the effect of drugs with an effect opposite to that of M-anticholinergics, namely M-cholinomimetics, on stones located in the ureter, including the likelihood of expulsion.

The common disadvantages of the analogues are the low effectiveness of the treatment, since they make it possible to expel stones up to 5 mm in size from the ureter, in addition, the duration of treatment in most cases exceeds 10 days. At this time, obstruction of the ureter persists, which in turn increases the risk of complications and damage to the kidney parenchyma. The effectiveness of analogues is even less if they are used to expel stones from the ureter that exceed 5 mm in size, since in most cases it is not possible to expel the stone from the ureter. In the absence of the effect of drug therapy, various surgical procedures are required to remove the stone from the ureter.

The closest analogue prototype is a method of expelling ureteral stones by prescribing drugs belonging to the group of selective alpha-1-blockers, for example tamsulosin, doxazosin and terazosin (Clinical recommendations of the European Association of Urology: Urolithiasis. - M .: ABV-press, 2010. - S. 57-58). The effect of therapy is achieved by relaxing smooth muscles in the pelvic ureter due to the suppression of alpha-1-adrenergic receptors, which are localized in the lower parts of the ureters.

However, the disadvantages of the prototype are:

- the prototype method does not lead to normalization or increased peristalsis of the upper urinary tract, which limits the effectiveness of therapy;

- the prototype method is not effective enough in cases where the size of the ureter stone exceeds 5 mm;

- the prototype method allows to achieve the expulsion of stones, usually with a treatment period of more than ten days, which increases the risk of complications and damage to the kidney parenchyma;

- when using the prototype method, it is often required to perform surgical procedures aimed at removing the stone due to treatment inefficiency;

- treatment of patients by the prototype method requires a long hospitalization and disability.

The objective of the invention: to offer a method of lithokinetic therapy for ureteral stones, devoid of the above disadvantages, the use of which allows you to expel stones from the ureter, the sizes of which are from 5 to 9 mm, reduces treatment time and temporary disability, reduces the need for surgical procedures to remove the stone and reduces number of complications.

The technical result consists in reducing the treatment time required to expel the stone from the ureter, increasing the efficiency of expelling stones from the ureter from 5 to 9 mm in size, reducing the possibility of complications, reducing damage to the renal parenchyma, and reducing the need for surgical removal of ureter stones.

The technical result is achieved by using the pharmacological effect of selective alpha-1-adrenergic blocking agent tamsulosin in combination with the pharmacological action of M-cholinomimetic neostigmine methyl sulfate. A patient who, on the basis of clinical and instrumental diagnostic methods, revealed a ureter stone up to 9 mm in size, lithokinetic therapy is used according to the following scheme. The first prescribed alpha-1-blocker is tamsulosin at a dose of 40 mg, which is given in the form of tablets orally, with meals, once a day. 6 hours after taking the tamsulosin tablet, the patient is injected subcutaneously with 1 ml of a 0.05% solution of M-cholinomimetic neostigmine methyl sulfate, which is a daily dose of 0.5 mg, once a day. Lithokinetic therapy according to the proposed scheme is carried out for 1 to 7 days. If during this period the stone is expelled from the ureter, lithokinetic therapy is stopped. If within 7 days lithokinetic therapy is ineffective, they switch to another treatment method.

Under the influence of selective alpha-1-adrenergic blocking agent tamsulosin, there is a decrease in the tone of the smooth muscles of the lower parts of the ureter, including those located in the area where the stone is located and below it. In this case, there is an expansion of the lumen of the ureter, which facilitates the passage of stone along it. The described effects are most pronounced after reaching the maximum concentration of tamsulosin in the plasma, which is achieved six hours after its oral administration. After reaching the maximum concentration of tamsulosin in plasma, M-cholinomimetic neostigmine methyl sulfate is injected subcutaneously, under the influence of which the tone and peristalsis of the upper ureter, including those located above the site of localization of the stone, increase. An increase in the tone and peristalsis of the upper ureter under the influence of M-cholinomimetic neostigmine methyl sulfate against the background of the action of alpha-1-adrenergic blocking agent tamsulosin occurs due to the fact that there is no effect of alpha-1-adrenergic blocking agent tamsulosin on the upper parts of the ureter. The increased peristalsis of the upper parts of the ureter while reducing the tone of the muscle layer of the ureter and expanding its lumen below the stone contributes to the effective expulsion of the stone from the ureter. The advantages of the proposed method:

- the proposed method allows to achieve the expulsion of stones faster than when treated by the prototype method, which reduces damage to the kidney parenchyma and reduces the risk of complications;

- the proposed method allows you to drive larger stones than the prototype method, including stones whose sizes are from 5 to 9 mm;

- when using the proposed method reduces the need for surgical procedures aimed at removing the stone from the ureter than during treatment by the prototype method;

- treatment of patients with the proposed method leads to a reduction in hospitalization and disability.

By lithokinetic therapy according to the proposed method, we treated 26 patients with ureteral stones, while in the period up to 7 days the stones were expelled from the ureter in 20 patients, and surgical removal of the stone was required only in 6 cases. For comparison, the control group included 22 patients who were prescribed treatment by the prototype method, while only 7 patients exiled the stone within 7 days, and surgical removal of the stone was required in 15 cases. The main results of treating patients with the proposed method in comparison with the treatment by the prototype method are presented in table 1. When analyzing the table, it was found that the treatment according to the proposed method, in comparison with the treatment by the prototype method, allowed to expel larger stones in a shorter time, as well as achieve exile stones in more cases and reduce the need for their surgical removal.

Example 1

Patient A., 46 years old, was admitted to the hospital with acute pain in the lumbar region on the left. The pains bother for ten hours, periodically intensify. The pain syndrome was stopped by the introduction of a non-narcotic analgesic. According to the ultrasound examination of the kidneys, an expansion of the pyelocaliceal system of the right kidney was revealed. According to the survey urography, the projection of the pelvic part of the right ureter determines the shadow of a stone measuring 7 mm. When performing excretory urography, it was found that the excretion of contrast is not synchronous, reduced on the right, the pyelocaliceal system and ureter are expanded along the entire length above the stone. Diagnosed with ICD: obturating stone of the lower third of the right ureter 7 mm. The patient was prescribed lithokinetic therapy according to the proposed method, which included oral administration of tamsulosin alpha-1-adrenergic blocking tablets in a dose of 40 mg at 9:00 and subcutaneous injections of 1 ml of a 0.05% solution of M-cholinomimetic neostigmine methyl sulfate, six hours after the administration of tamsulosin, at 15:00. On the fifth day from the start of lithokinetic therapy during urination, a stone of 7 mm in size stood out. When performing a second ultrasound, the disappearance of the expansion of the pyelocaliceal system of the right kidney was established. The patient was discharged with recovery. During treatment, recurrence of bouts of renal colic and other complications were not observed.

Example 2

The patient, B., 57 years old, was admitted to the hospital with a diagnosis of ICD: left kidney pelvis stone. According to the ultrasound of the kidneys, a hyperechoic signal up to 15 mm in size with an acoustic shadow was revealed in the pelvis on the left, the expansion of all groups of calyxes was up to 8 mm. According to survey urography, the projection of the pelvis of the left kidney determines the shadow of a round-shaped stone with a size of 15 mm; when performing excretory urography, it was found that the contrast excretion is synchronous, the calyx-pelvis system on the left is expanded due to the presence of a stone in the pelvis. Remote shock wave lithotripsy was performed, resulting in stone fragmentation. On the next day after the remote shock-wave lithotripsy session, control review urography was performed, according to which multiple fragments of stone with sizes from 2 to 6 mm according to the type of "stone path" with a length of 5 cm were determined in the projection of the pelvic left ureter. The patient was prescribed lithokinetic therapy according to the proposed method, including oral administration of tablets of alpha-1-adrenergic blocking agent tamsulosin at a dose of 40 mg at 9:00 and subcutaneous injection of 1 ml of a 0.05% solution of M-cholinomimetic neostigmine methyls ulfata, six hours after taking tamsulosin, at 15:00. On the second day after the start of lithokinetic therapy during urination, fragments of stone began to stand out. On the fifth day after the start of therapy, the control review urography was repeated, according to which no shadow of stones in the projection of the ureter was revealed. When performing ultrasound, the cupping of the expansion of the pyelocaliceal system of the left kidney was established. During treatment, the development of attacks of renal colic and other complications were not observed. The patient was discharged with recovery.

Table 1 Comparison of the effectiveness of the treatment of patients with stones of the ureter according to the prototype and the proposed method Prototype The proposed method The number of patients treated 22 26 The number of patients who have exiled a stone 7 (31%) 20 (77%) Number of patients requiring surgical stone removal 15 (68%) 6 (23%) The average duration of treatment before the expulsion of stones (min.-max.), Days 8 (4-12) 6 (2-7) The average size of the exiled stones (min.-max.), Mm 5 (3-6) 7 (3-9) The number and proportion of patients in whom the size of the released stones exceeded 5 mm 1 in 7 (14%) 12 out of 20 (60%)

Claims (1)

A method of lithokinetic therapy for ureteral stones, including the appointment of a selective alpha-1-adrenergic blocker of tamsulosin in a dose of 40 mg, which is given in the form of tablets, orally, during meals, once a day, characterized in that six hours after taking alpha-1 of tamsulosin β-blocker by injection, subcutaneously injected M-cholinomimetic neostigmine methyl sulfate in the form of 1 ml of a 0.05% solution, at a dose of 0.5 mg, once a day, the course of drug administration is continued from 1 to 7 days.