L37 MOA Diuretics 2011 - Mammalian Physiology BIOAP 4580...

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-1/11- Mammalian Physiology BIOAP 4580 Prof. Beyenbach Spring 2011 COPYRIGHT THE MECHANISM OF ACTION OF DIURETICS A. The needs for diuretic therapy. Increasing the flow of urine, i.e. decreasing the extracellular fluid volume (ECF) and the effective circulatory volume (ECV), is useful in the treatment of general edema or the wash-out of ingested poisons. Most often, diuretics are given today to treat high blood pressure. The rationale is found in the reduction of volume and hence pressure in the vascular space. Diuretics are also used to prevent pulmonary bleeding in race horses and to lower body weight in order to reach a certain weight class. A very feeble looking Mohammed Ali lost his boxing match to Frazier in 1971. It later became known that Ali had been given a loop diuretic prior to the fight, for reasons that are not clear. After all, not every human being is a race horse. Apparently, Ali had taken too much of the diuretic. The volume loss had compromised his cardiovascular fitness. Several factors should be considered when examining the effects of a diuretic: 1) The specific nephron segment where the diuretic is active, preventing the tubular reabsorption of solute and water, 2) The response of downstream nephron segments to the action of the diuretic. Reabsorptive transport in downstream segments often increases in view of the increased delivery rate to apical surfaces of epithelial cell, 3) The extracellular fluid volume (ECF) and effective circulation volume (ECV). By reducing ECF and ECV, diuretics reduce glomerular filtration and increase active tubular reabsorption (the normal physiological response to volume loss) producing an anti- diuretic effect. Under normal conditions of health, diuresis is produced in the absence of the antidiuretic hormone ADH. The diuresis is a water diuresis in that large volumes of dilute urine (~60 mOsm/kgH 2 O) are voided. In contrast, the diuresis produced by diuretics increase not only the excretion of water but also of salts and other solutes. Accordingly, diuretics are also „soluretic‟, i.e. natriuretic, chloruretic, etc. And herein rests the danger of long-term diuretic therapy: the loss of solute, in particular K + and other solutes that normally are present in the plasma at low concentrations. Diuretics are most effective in actively transporting epithelia, i.e. in leaky epithelia such as the renal proximal tubule, and in the rather active thick ascending limb of the Loop of Henle. The effect of diuretics in tight epithelia is relatively small in view of the small transport rates here. Thus, diuretics effective in the renal proximal tubule and tALH are considered potent, and those affecting the distal convoluted tubule and collecting duct are considered mild. One speaks of potent and mild diuretics. B. Osmotic diuretics.
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L37 MOA Diuretics 2011 - Mammalian Physiology BIOAP 4580...

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