Diuretics chemical structure

Therapeutic Function Diuretic Chemical Name 6-phenyl-2,4,7-pteridinetriamine Common Name Ademine pterophene Structural Formula ... 

Dietary salt restriction was one of the first successful therapeutic maneuvers for the reduction of blood pressure. During the past two decades, a variety of pharmacologic agents have been developed which promote diuresis by interfering with the tubular reabsorption of sodium. Although diuretic agents differ significantly in chemical structure and in their mechanism of action on the renal tubule, they all have in common the ability to decrease blood pressure. 

Fig. 8.4 Chemical structures of commonly used diuretic drugs.

Although they differ chemically, all diuretics exert their beneficial effects by acting directly on the kidneys to increase water and sodium excretion.13 Diuretic drugs can be subclassified according to their chemical structure or the manner in which they affect kidney function. The primary subclassifications of diuretics are listed here. 

Schafer JA, Troutman SL, Andreoli TE (1974) Volume reabsorption, transepithelial potential differences, and ionic permeability properties in mammalian superficial proximal straight tubules. J Gen Physiol 64 582-607 Schlatter E, Greger R, Weidtke C (1983) Effect of high ceiling diuretics on active salt transport in the cortical thick ascending limb of Henle s loop of rabbit kidney. Correlation of chemical structure and inhibitory potency. Pfltigers Arch 396 210-217... 

Figure 1, Chemical structures of the commonly utilized diuretic agents grouped according to drug class.

In spile of ethacrynie aeid s unique chemical structure and avid reactivity toward various nucleophiles, it has many pharmacological features in common with the sulfamoyl-containing loop diuretics. After oral administration, onset of action is about 30 minutes, and duration of action is 6 to 8 hours. After parenteral administration, onset of action and... 

The non-mercurial diuretics may be classified on the basis of their chemical structures together with their physical characteristics as follows ... 

A final example of the capability of MLC to characterize bioactive substances is the report of Medina Hernandez et al. [31 ], related to the action of diuretics in the nephron. A wide variety of compounds with different chemical structures have been described to act as diuretics. These compounds enhance renal excretion of water and electrolytes through interference of the mechanisms of ionic transport all along the nephron, which is constituted of a glomerule and a long tubule where a filtration process takes place (Fig. 9.13). Each individual segment in the nephron... 

The chromatographic retention of diuretics decreased as the concentration of SDS in mobile phase increased, which made retention times closer to each other. Among the micellar mobile phases, 0.03 M SDS gave the best correlations between retention factors and site of action. It is interesting to note that the correlations hold in spite of the largely diverse chemical structures of diuretics. The order of retention attained with other mobile phases in conventional RPLC systems was checked to be completely different from that of MLC, and a correlation with regard to physiological properties could not be drawn. 

A procedure for the determination of diuretics of different therapeutical character high (bumetanide, ethacrynic acid, furosemide), intermediate (bendroflumethiazide, chlorthalidone, hydrochlorothiazide, xipamide) and low (acetazolamide, amiloride, spironolactone, triamterene) efficacy diuretics, and the uricosuric agent probenecid, in urine samples, illustrates a method development implying the control of pH, surfactant and modifier [23]. The greatest analytical problems in the detection of these compounds are basically their wide variety of chemical structures, functional groups and protonation constants. This implies the use of several experimental conditions for their analysis with conventional aqueous-organic mobile phases and laborious liquid-liquid or solid-liquid extraction prior to chromatographic separation. In contrast, the same micellar eluent can produce a satisfactory separation after direct injection. 

Therapeutic Function Cholecystokinetic, Diuretic, Pharmaceutic aid Chemical Name D-Glucitol Common Name d-Glucitol Sorbit Sorbitol Structural Formula ... 

Therapeutic Function Diuretic, Anti hypertensive Chemical Name 4-Chloro-5-sulfamoyl-2, 6 -salicyloxylidide Common Name -Structural Formula ... 

The major bases found in nucleic acids are adenine and guanine (purines) and uracil, cytosine, and thymine (pyrimidines). Thymine is found primarily in DNA, uracil in RNA, and the others in both DNA and RNA. Their structures, along with their chemical parent compounds, purine and pyrimidine, are shown in Figure 10.1, which also indicates other biologically important purines that are not components of nucleic acids. Hypoxanthine, orotic acid, and xanthine are biosynthetic and/or degradation intermediates of purine and pyrimidine bases, whereas xanthine derivatives—caffeine, theophylline, and theobromine—are alkaloids from plant sources. Caffeine is a component of coffee beans and tea, and its effects on metabolism are mentioned in Chapter 16. Theophylline is found in tea and is used therapeutically in asthma, because it is a smooth muscle relaxant. Theobromine is found in chocolate. It is a diuretic, heart stimulant, and vasodilator. 

The present classes of diuretic drugs have contributed much useful information to the chemist and to the biologist. From the mercurial diuretics, on the biological side, some facts have been learned about their site of action, if not the exact mechanism of action, and they have been helpful in the study of the site of the transport of various ions by the kidney. The importance of sulfhydryl enzyme systems has been demonstrated, although the specific enzyme has not been identified. On the chemical side, the chemist has learned about the structural requirements for useful activity, the nature of the carbon-mercury attachment, and the organic structures most useful as carrying moieties for mercury. 

Another example of how new chemical entities can be derived from compounds with unrelated biological effects is that of the development of the potassium channel agonist diazoxide (Fig. 2.29). This compound was developed as a result of the observation that the thiazide diuretics, such as chlorothiazide, not only had a diuretic component, because of inhibition of sodium absorption in the distal convoluted tubule, but also a direct effect on the renal vasculature. Structural modification to enhance this direct effect led to the development of diazoxide and related potassium channel agonists for the treatment of hypertension (see Chapter 29). 

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