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This discrepancy could be due Post Date: Wed, 15 Oct 2008 0:40:20 +0000 The immediate effect of the drug is a prompt fall in UogM to a U/P ratio of essentially unity, and an increase in the ratios CK+/GFR and CNa+/GFR. Note that the latter ratio returns toward control levels before the urinary concentrating ability is restored, as indicated by U0SM. This discrepancy could be due either to the fact that, with a decrease in GFR, less sodium chloride is available for reabsorption by the ascending limb, or that there is a time lag involving the replenishment of solute to the medullary interstitium. Autor of the post: Undefined The excretion of magnesium Post Date: Wed, 15 Oct 2008 0:22:20 +0000 hydrase; however, as judged by their effect on bicarbonate excretion, such an action, if any, must be extremely weak (Stein et al, 1968; 0stergaard et al, 1972).The increase in potassium excretion results from its distal secretion and is approximatelyproportional to the increased rate of flow in this segment (Duarte et al, 1971). The excretion of magnesium and calcium is increased by about the same percentage as that of sodium. Autor of the post: Undefined Since these drugs are organic Post Date: Wed, 15 Oct 2008 0:05:40 +0000 The phosphaturic response is variable; for unexplained reasons, the natriuresis induced by furosemide may be accompanied by a decrease in the excretion of phosphate (Goldberg, 1973). The high-ceiling diuretics may cause hyperuricemia in man. Since these drugs are organic acids that are secreted in the proximal tubule, it is presumed that they act competitively to inhibit urate secretion at this site. Autor of the post: Undefined (See Hook et al, 1966 Post Date: Tue, 14 Oct 2008 23:50:44 +0000 Depending on the experimental conditions, in-cluding the dose and speed of administration of the diuretic, either an increase or a decrease in renal blood flow, as well as its redistribution within the kidney, may occur. There is generally an increase in blood flow in the cortex, accompanied by a decrease in the outer medulla. (See Hook et al, 1966; Birtch et al, 1967; Dluhy et al, 1970; Kilcoyne et al, 1973; Stowe et al, 1973. Autor of the post: Undefined Although renal vasodilatation may modify Post Date: Tue, 14 Oct 2008 23:37:08 +0000 ) These findings have raised the possibility that changes in intrarenal blood flow might influence electrolyte transport. Conversely, there is good evidence that acute diuresis increases tubular volume and intraluminal pressure; the latter might be transmitted and influence blood flow. Although renal vasodilatation may modify the response to these diuretics, this is a minor effect compared to their direct action on renal tubular transport. Autor of the post: Undefined This compli-cates the analysis Post Date: Tue, 14 Oct 2008 23:26:29 +0000 With proper clinical usage, renal blood flow is not compromised. These agents, like the thia-zide diuretics, also stimulate the release of renin from the kidney (see Ganong, 1972). This compli-cates the analysis of a possible direct vasodilator effect. Autor of the post: Undefined In isolated systems Post Date: Tue, 14 Oct 2008 23:11:10 +0000 Furosemide, along with the thiazides and mercurials, greatly augments the urinary excretion of 5-hydroxytryptamine and depletes it from intrarenal stores (Kassab et al, 1973).Extrarenal Sites of Action. In isolated systems and with high doses, these agents act upon electrolyte transport in a variety of tissues. Autor of the post: Undefined These actions have no known Post Date: Tue, 14 Oct 2008 22:54:27 +0000 However, with usual doses the high-ceiling diuretics have no significant pharmacological effects other than on renal function. For example, there may be a slight decrease in bile flow (Erlinger et al, 1970) or changes in the ionic fluxes of isolated erythrocytes (Dunn, 1973). These actions have no known clinical implications. Autor of the post: Undefined Biochemical Mechanism of Action Post Date: Tue, 14 Oct 2008 22:35:51 +0000 An exception is the action on the inner ear, consisting in a depression of the cochlear microphonic and neural potentials, and a transient increase in the sodium and potassium concentrations in the endolymph (Brusilow and Gordcs, 1973). This may result from a direct toxic action on the hair cells (Prazma et al, 1972).Biochemical Mechanism of Action. Autor of the post: Undefined For example, the drug irreversiblycombines Post Date: Tue, 14 Oct 2008 22:17:31 +0000 Ethacrynic acid was developed as an agent that would combine with thiol groups. There is ample evidence for this type of reaction. For example, the drug irreversiblycombines with two thiol groups of glyceraldehyde 3-phosphate dehydrogenase, thus inactivating the enzyme (Birkitt, 1973). 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