Chlorthalidone, diuretic drugs

Thiazide diuretics (benzothiadia-zines) include hydrochlorothiazide, benzthiazide, trichlormethiazide, and cyclothiazide. A long-acting analogue is chlorthalidone. These drugs affect the intermediate segment of the distal tubules, where they inhibit a Na+/Ch cotransport, Thus, reabsorption of NaQ and water is inhibited. Renal excretion of Ca decreases, that of Mg + increases. Indications are hypertension, cardiac failure, and mobilization of edema. 

Tyrosine hydroxylase 1 Thiazide diuretics, a group of drugs with moderate diuretic activity, includes hydrochlorothiazide, chlorthalidone, and xipamide. They decrease active reabsorption of sodium and accompanying chloride by binding to the chloride site of the electroneutral Na+/CF cotransport system in the distal convoluted tubule and inhibiting its action. 

Diuretics - Generally initiate therapy with a thiazide or other oral diuretic. Thiazide-type diuretics are drugs of choice hydrochlorothiazide or chlorthalidone are generally preferred. Reserve loop diuretics for selected patients. This therapy alone may control many cases of mild hypertension. Consider treating diuretic-induced hypokalemia (less than 3.5 mEq/L) with potassium supplementation or by adding a potassium-sparing diuretic to therapy. 

Thiazide diuretics consist of two distinct groups those containing a benzothiadiazine ring, such as hydrochlorothiazide and chlorothiazide, referred to as thiazide diuretics, and those that lack this heterocyclic structure but contain an unsubstituted sulfonamide group. The latter are called thiazidelike diuretics they include metolazone, xipamide, and indapamide. The major thiazide and thiazidelike drugs available in the United States are bendrofiumethiazide, benzthiazide, chlorothiazide, hydrochlorothiazide, hydroflumethiazide, methyclothiazide, polythiazide, and trichlormethiazide and chlorthalidone, indapamide, metolazone, and quinethazone, respectively. 

AMP is related to certain mental diseases and may be involved in the action of tranquilizers and antidepressant drugs (60). Whether the ability of diuretic agents such as ethacrynic acid and chlorthalidone to inhibit the enzyme in kidney (68) is related to their diuretic action is also not known. It has been suggested that inhibition of diesterase by diazoxide (59) may explain the hyperglycemic activity of this agent. Several materials are known to activate the enzyme. Imidazole produces strong activation of the enzyme from mammalian tissues (36, 38, 42) but not from E. coli (41). It has been reported (61) that insulin activates the beef heart enzyme in vitro, but it is not known if this has relevance... 

There are uLso other commonly used dmgs that arc sulfonamides or sulfanilaniidcs. Among thc.se are the oral hypoglycemic drug lolbulumidc. the diuretic furo.scmide. and the diuretic chlorthalidone. 

The model substance used in this work is chlorthalidone (CT), which has (in racemic form) some use as a diuretic and anti-hypertensive drug. CT is stereolabile (i.e., it can be racemised rather easily) [5]. Chemicals were purchased from Merck (Darmstadt, Germany), with the exception of CT (Sigma Aldrich, Steinheim, Germany). 

Thiazides are absorbed in varying degrees from the gastrointestinal tract. Bendroflumethiazide is 100% absorbed, benzthiazide 25%, chlorothiazide 10-21%, chlorthalidone 65%, hydrochlorothiazide 65-75%, hydroflumethiazide 50%, indapamide 93%, and metolazone 40-65% absorption data are unavailable for the other drugs in this class. Plasma levels do not correlate with diuretic effects. The onset of diuretic action occurs at 2 h with the exception of metolazone whose onset is 1 h, indapamide 1-2 h, and... 

An interesting sulfonamide diuretic that has little resemblance structurally to the thiazides is chlorthalidone, a benzophenone derivative. On a dose basis, it has an activity comparable to hydrochlorothiazide but is a much stronger carbonic anhydrase inhibitor than the thiazides, approximately 40 times sulfanilamide. Physical data indicate this compound to have the isoindoline structure rather than the benzophenone structure, I. The outstanding feature of this drug is its long duration of action, up to 72 hours (22, 32, 66). 

Chlorthalidone in a dose of 50 to 100 mg daily is indicated in edema, and a dose of 25 mg/day is used in hypertension. The thiazide diuretics, also called sulfonamide or benzothi-adiazide diuretics, vary in their actions. For instance, the potency of hydrochlorothiazide (Hydro-Diuril and Esidrix) is ten times greater than that of chlorothiazide (Diuril), but the two drugs have equal efficacy. The duration of action of hydrochlorothiazide, which is 6 to 12 hours, is equal to that of chlorothiazide. On the other hand, chlorthalidone has a duration of action lasting 48 hours. Some thiazide... 

Campfns-Falco, R Herraez-Herndndez, R. Sevillano-Cabeza, A. Solid-phase extraction techniques for assay of diuretics in human urine samples. J.Liq.Chromatogr., 1991, 14, 3575-3590 [SPE hydrox-yethyltheophylline (IS) extracted acetazolamide, amiloride, bendroflumethiazide, bumetanide, chlorthalidone, ciclothiazide, ethacrynic acid, furosemide, hydrochlorothiazide, probenecid, spironolactone] Shah, V.R Walker, M.A. Prasad, V.K. Application of flow programming in the analysis of drugs and their metabolites in biological fluids. J.Liq.Chromatogr., 1983, 6, 1949-1954 [urine plasma also chlorothiazide, hydrochlorothiazide]... 

Several chiral drugs were first obtained in enantiomerically pure form using this technique, such as the diuretics chlorthalidone [127] and benzothiadiazines [128], the benzo-diazepinone oxazepam [129], the muscle relaxant chlormezanone [130], hypnotic and anticonvulsant methaqualone [131], the anti-inflammatory drug oxindanac [132], and the antiaromatase fadrozole [133]. 

Singer JM, O Hare MJ, Rehm CR and Zarembo JE, Chlorthalidone, APDS, 14, 1-34 (1985) Fleurren ALJ, van Ginneken CAM and van Rossum JM, Differential potentiometric method for determining dissociation constants of very sli tly water soluble drugs applied to die sulfonamide diuretic chlorthalidone, /. Pharm. Sci., 68(8), 1056-1058 (1979). NB The sulfonamide function present in chlordialidone, is considered to be responsible for the acid dissociation. The ionization constant of chlorthalidone was determined based on spectrophotometric measurements of the concentration [chlor] at various pH values ... 

Many of the benzothiazide-type diuretic agents are chiral. As a class, the chiral diuretics include chlorthalidone, indapamide, metolazone, bendro-flumethiazide, trichlormethiazide, methyclothiazide, and polythiazide. The diuretics have been largely overlooked from the perspective of stereoselectivity in pharmacodynamics and pharmacokinetics. Stereospecific pharma-cokinetic/dynamic data for these drugs are scarce. 

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