Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0451641 (urolithiasis)
 3,973 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We compared the potency of a selective ureteral relaxant KUL-7211 (beta(2)/beta(3)-adrenoceptor agonist; (-)-2-[4-(2-{[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino}ethyl)phenyloxy]acetic acid) with those of various spasmolytics on contractions in isolated canine ureteral preparations. Drug effects were evaluated on the tonic contraction induced by KCl (80 mM) and on spontaneous, 1x10(-5) M phenylephrine-, and 1x10(-6) M PGF(2alpha)-induced rhythmic contractions in isolated canine ureteral preparations using a functional experimental technique. The potencies (pD(2) value) of the following drugs were compared: KUL-7211, tamsulosin (an alpha(1A/1D)-adrenoceptor antagonist), prazosin (an alpha(1)-adrenoceptor antagonist), verapamil (a Ca(2+)-channel blocker), butylscopolamine (a nonselective muscarinic antagonist), and papaverine (a phosphodiesterase inhibitor). The rank order of relaxing potencies against KCl-induced tonic contraction was KUL-7211 (6.60)>tamsulosin(5.90)>verapamil(5.70)>papaverine(4.88)>prazosin (4.54). The rank order of potencies for reductions in spontaneous rhythmic contractions was KUL-7211 (6.80)>verapamil(6.12)>papaverine(5.05). Conversely, high concentrations of the two alpha-adrenoceptor antagonists (tamsulosin and prazosin) and of butylscopolamine enhanced the spontaneous contractions, although at low concentrations (up to 1x10(-6) M) they had no significant effects. For suppression of spasmogen-induced rhythmic contractions, the rank order of potencies was, against phenylephrine-induced contractions: KUL-7211 (6.95)>tamsulosin(6.26)>prazosin(5.68)>verapamil(5.64)>papaverine (5.03), and against PGF(2alpha)-induced contractions: KUL-7211 (7.05)>verapamil(6.70)>papaverine (5.27). Our results suggest that in dogs, the beta(2)/beta(3)-adrenoceptor agonist KUL-7211 is the most efficacious ureteral relaxant among the spasmolytics tested against various contractions. Possibly, KUL-7211 might be useful for promoting stone passage and relieving ureteral colic in urolithiasis patients.
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PMID:The potency of KUL-7211, a selective ureteral relaxant, in isolated canine ureter: comparison with various spasmolytics. 1613 79

Urolithiasis is a disease characterized by the presence of stones in the kidney or urinary tract. It is often detected accidentally during an ultrasound or an abdominal x-ray performed for other reasons. However, the first symptom of kidney stone disease can be severe pain called renal colic. Pain caused by a colic attack is characterized by sudden onset. In half of the cases it is associated with nausea or vomiting and can lead to hypotension and fainting. The exact location and radiation of the pain depends on the location of the stone in the urinary tract. The first most commonly performed study is abdominal ultrasound with estimation of the deposit size and evaluation of urinary tract obstruction. Alternative or complementary studies are: an abdominal x-ray where radiopaque deposits can be shown, or unenhanced helical computed tomography of the abdomen. The severity of pain depends on the individual pain threshold and on the change in hydrostatic pressure in the part of the urinary system above the obstruction. Prolonged deposition of the stone in one place causes the activation of autoregulatory mechanisms to lower the pressure of the upper urinary tract, which limits the pain. The basic treatment for renal colic is analgetic therapy. The most commonly used drugs are NSAIDs and opiates. Another important component of renal colic treatment are medications that facilitate urinary stone passage by reducing oedema or limiting urethral contractions, such as: calcium channel blockers, alpha blockers, phosphodiesterase inhibitors. Intensive hydration is not currently recommended. Patients who are unlikely to spontaneously excrete the stone are eligible for minimally invasive treatment. The risk of urolithiasis recurring is high, reaching up to 40% in 5 years and up to 50% in 10 years. However, it can be reduced by proper prevention. The paper describes the pathophysiology of pain in renal colic, the treatment methods, and the case of a boy with recurrent renal colic.
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PMID:Pathophysiology and symptoms of renal colic in children - a case report. 3028 23

Medical expulsive therapy (MET) is used especially in distal ureteral stones to reduce colics and decrease the number of endourological surgical interventions. A broad spectrum of agents can be used for the relaxation and the dilatation of the ureter, reducing the intraureteric pressure. Alfa-blockers, calcium channel blockers, phosphodiesterase (PDE) inhibitors, and spasmolytics have been shown as effective in clinical trials on urolithiasis. It is a fact that the urothelium itself, the interstitial cells and the ureteric smooth muscle, have B-beta-2 and beta-3 adrenoreceptors. Stimulation of these receptors results in relaxation of the ureter. A recent beta-3 agonist, mirabegron, is commonly used for overactive bladder nowadays. The mechanism of action is adrenergic agonism that affects with the storage phase of the bladder, without interfering the voiding phase, which is regulated by parasympathetic pathways, commonly muscarinic. Agonism of the beta-3 receptors in the ureter has been shown to decrease the intraluminal pressure. By this mechanism, mirabegron can be thought as an alternative MET agent. Acting through different pathways, and having low adverse effect profile, can be thought as the most striking advantages of mirabegron as a MET. In vitro and in vivo trials should be conducted to support this hypothesis.
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PMID:Mirabegron: A Novel and Promising Medical Expulsive Treatment for Ureteral Stones? 3063 May 75