Тиазидтер: Химиялық қосылыстар класы және диуретиктер қолданысы

Class of chemical compounds

Thiazide ('/θ//aɪ//ə//z//aɪ//d/) refers to both a class of sulfur containing organic molecules and a class of diuretics based on the chemical structure of benzothiadiazine. The thiazide drug class was discovered and developed at Merck and Co. in the 1950s. The first approved drug of this class, chlorothiazide, was marketed under the trade name Diuril beginning in 1958. Thiazide organic molecules are bi cyclic structures that contain adjacent sulfur and nitrogen atoms on one ring. Confusion sometimes occurs because thiazide like diuretics such as indapamide are referred to as thiazides despite not having the thiazide chemical structure. When used this way, "thiazide" refers to a drug which acts at the thiazide receptor. The thiazide receptor is a sodium chloride transporter that pulls NaCl from the lumen in the distal convoluted tubule. Thiazide diuretics inhibit this receptor, causing the body to release NaCl and water into the lumen, thereby increasing the amount of urine produced each day.

Thiazide diuretics are primarily used to treat the hypertension (high blood pressure) and edema (swelling) caused by water overload as well as certain conditions related to unbalanced calcium metabolism.

Thiazides are useful in treating kidney stones and bladder stones that result from hypercalciuria (high urine calcium levels). Thiazides increase the uptake of calcium in the distal tubules, to moderately reduce urinary calcium. Thiazides combined with potassium citrate, increased water intake and decreased dietary oxalate and sodium can slow or even reverse the formation of calcium containing kidney stones. High dose therapy with the thiazide like diuretic indapamide can be used to treat idiopathic hypercalcinuria (high urine calcium with unknown cause).

Thiazides may be used to treat the symptoms of Dent's disease, an X linked genetic condition that results in electrolyte imbalance with repeated episodes of kidney stones. A case study of two brothers with the condition, two years of treatment with hydrochlorothiazide reduced the incidence of kidney stones and improved kidney function. The thiazide like diuretic chlortalidone reduced urine calcium oxalate in seven of the eight males with inactivated CLCN5 gene that participated in the study. Inactivation of the CLCN5 gene causes Dent's disease Type 1. The rare nature of Dent's disease makes it difficult to coordinate large controlled studies, so most evidence for thiazide use is with too few patients to make broad recommendations possible. Higher levels of retained calcium are associated with increased bone mineral density and fewer fractures in individuals with osteoporosis.

Bromine intoxication can be treated by giving intravenous saline with either thiazides or Loop diuretics.

Thiazide diuretics control hypertension in part by inhibiting reabsorption of sodium (Na+) and chloride (Cl−) ions from the distal convoluted tubules in the kidneys by blocking the thiazide sensitive Na+ Cl− symporter. The term "thiazide" is also often used for drugs with a similar action that do not have the thiazide chemical structure, such as chlorthalidone, metolazone and indapamide. These agents are more properly termed thiazide like diuretics. Thiazide diuretics also increase calcium reabsorption at the distal tubule. By lowering the sodium concentration in the tubule epithelial cells, thiazides indirectly increase the activity of the basolateral Na+/Ca2+ antiporter to maintain intracellular Na+ level, facilitating Ca2+ to leave the epithelial cells into the renal interstitium. Thus, intracellular Ca2+ concentration is decreased, which allows more Ca2+ from the lumen of the tubules to enter epithelial cells via apical Ca2+ selective channels (TRPV5). In other words, less Ca2+ in the cell increases the driving force for reabsorption from the lumen. Thiazides are also thought to increase the reabsorption of Ca2+ by a mechanism involving the reabsorption of sodium and calcium in the proximal tubule in response to sodium depletion. Some of this response is due to augmentation of the action of parathyroid hormone.

Thiazides pass into breast milk and can decrease the flow of breast milk. Thiazides have been associated with significant side effects in some nursing infants and should be administered to nursing mothers with caution.

The thiazide diuretics were developed by scientists Karl H. Beyer, James M. Sprague, John E. Baer, and Frederick C. Novello of Merck and Co. in the 1950s, and led to the marketing of the first drug of this class, chlorothiazide, under the trade name Diuril in 1958. The research leading to the discovery of chlorothiazide, leading to "the saving of untold thousands of lives and the alleviation of the suffering of millions of victims of hypertension" was recognized by a special Public Health Award from the Lasker Foundation in 1975.