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Respiratory, endocrine, cardiac, and renal topics
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
The benzothiadiazide derivatives are sulfonamides. They are weak diuretics that inhibit the reabsorption of NaCl at the diluting site in the early distal tubule. The main thiazides include chlorothiazide and hydrochlorothiazide. Thiazide-like agents, such as chlorthalidone and metolazone, belong to this group.
Sodium Intake and Hypertension
Published in Austin E. Doyle, Frederick A. O. Mendelsohn, Trefor O. Morgan, Pharmacological and Therapeutic Aspects of Hypertension, 2020
T. O. Morgan, F. A. O. Mendelsohn, A. E. Doyle
Benzothiadiazine diuretics and the closely related drugs, chlorthalidone and metolazone, act on this tubule segment.140 This segment is a functional segment distal to the ascending limb of the loop of Henle. If transport in the ascending limb of the loop of Henle is completely blocked by a drug, the concentrating ability is abolished, but the urine may still be diluted due to transport in this segment. Inhibition of transport in this segment does not affect the concentrating aspect of the countercurrent system. These drugs act at this site. In the cortical diluting segment, 5 to 8% of the sodium chloride filtered may be reabsorbed. Sodium reabsorption may not be completely inhibited, with the result that the natriuresis and subsequent sodium depletion is correspondingly limited. Furthermore, the increased delivery of sodium chloride and water to the collecting tubule and duct resulting from inhibition of the diluting segments leads to modification of collecting duct function, which modifies urinary composition. Also, the reduced plasma volume and altered flow at the macula densa may produce alterations in function in the more proximal parts of the nephron, and alterations in tubuloglomerular feedback may explain the acute reduction in renal filtration which has been observed with i.v. administration.141 In addition to their effect on the diluting segment, these diuretics may also inhibit carbonic anhydrase. This effect varies among the different thiazides. These diuretics differ only slightly in their pharmacological effects, but differences in their durations of action can produce important clinical differences in response.
Preoperative treatment of benign insulinoma: diazoxide or somatostatin analogues?
Published in Acta Chirurgica Belgica, 2022
Quentin Gilliaux, Claude Bertrand, François Hanon, Julian E. Donckier
Insulinoma is a rare neuroendocrine tumour of the pancreas with an incidence of four cases per one million persons per year [1,2]. Its resection is the only curative treatment. However, medical therapy may be needed to prevent severe preoperative hypoglycaemia, when surgery is contraindicated, delayed or refused and in case of unresectable metastatic disease. Diazoxide, a non-diuretic benzothiadiazine derivative diminishing insulin secretion from beta-cells by opening ATP-dependent potassium channels has been used for controlling hypoglycaemia [3,4]. Somatostatin analogues (octreotide or lanreotide) can also suppress insulin secretion by activating somatostatin receptors (SSTR), in particular SSTR2 [4,5]. They have been regarded as second line in benign insulinoma or as first line in malignant insulinoma because of their antiproliferative effects and a higher expression of SSTR2 in malignant tumours [4,5]. To our knowledge, the effects of these two medications have never been compared in a same patient with insulinoma.
Contemporary medicinal-chemistry strategies for discovery of blood coagulation factor Xa inhibitors
Published in Expert Opinion on Drug Discovery, 2019
Xia Hao, Xiaofang Zuo, Dongwei Kang, Jian Zhang, Yuning Song, Xinyong Liu, Peng Zhan
Compound YM-60828 (142) was a previously reported, potent, selective and orally active FXa inhibitor. Its L-shape conformation in the active site of FXa was considered to be a key factor for its FXa inhibitory potency, and therefore a series of conformationally restricted cyclic platforms bearing a similar preferred conformation was investigated. This study resulted in the discovery of a novel class of benzothiadiazine-4-one derivatives as FXa inhibitors (143–145). Compound 145 (YM-169920) was identified as the most potent anticoagulant agent in this class (Figure 12) [80].
Evaluation of WO2017098421: GSK’s benzothiazine compounds as CD73 inhibitor filings
Published in Expert Opinion on Therapeutic Patents, 2018
Ya-Ping Gong, Ren-Zhong Wan, Zhao-Peng Liu
The invention in this patent application relates to the substituted benzothiadiazine derivatives represented generally by formula (2) as CD73 inhibitors. These benzothiadiazines have the potential for the treatment of cancer and autoimmune diseases [48].