Mechanisms of action, pharmacological effects and clinical indications of diuretic compounds. They act by diminishing sodium reabsorption at different sites in the nephron. Mechanism of action of potasium sparing diuretics source. Indeed, essential hypertension appears to be a multifactorial disorder. Loop diuretics are very potent and fast acting, and they are commonly used intravenously to lower the blood pressure quickly when it reaches extreme. Diuretic agents increase the urine formation, by influencing any of the processes involved in urine formation. Bicarbonate absorption by the proximal tubule is dependent on the activity of carbonic anhydrase ca which converts bicarbonate hco 3 to co 2 and h 2 o.
The diuretics that have a primary effect on the medullary segment furosemide, bumetanide, ethacrynic acid inhibit the concentrating mechanisms, whereas the. Despite the bewildering number of diuretics available to the physician, these drugs can be divided into 4 main groups, characterised by their site of action on sodium reabsorption in the kidney diuretics. The term low ceiling diuretic is used to indicate a diuretic has a rapidly flattening dose effect curve in contrast to high ceiling, where the relationship is close to linear. Mechanism of action and therapy seminars in nephrology. A second class of diuretics, sometimes termed aquaretics, instead inhibit water reabsorption by blocking vasopressin receptors along the collecting duct. Review mechanisms and management of diuretic resistance. Diuretics work on the kidneys to eliminate water and. Furosemide decreases the sodium, chloride, and potassium reabsorption from the tubule. They are often used to treat hypertension, or high blood pressure. Chlorothiazide, by virtue of its activity as an inhibitor of carbonic anhydrase, induces natriuresis and. It is likely that the mechanism whereby ecf volume losses lead to decreases in. The nephron, depicting sites of diuretic action on sodium reabsorption. Bilal mirza 4th year download in your computer according to site of action and mechanism of action.
Furosemide lasix, ethacrynic acid edecrin, and possibly organomercurial agents are effective in the ascending limb of henles loop. Although loop diuretics have diuretic efficacy greater than that of thiazide or thiazidelike agents, effects on blood pressure are relatively brief and reflex stimulation. Sodium is the most troubling electrolyte for patients with hypertension, as one atom of sodium binds four molecules of water. Their mechanism depends on renal prostaglandin production. Natriuretic diuretics are among the most commonly used drugs. In examining the effects of diuretics on mg and k metabolism, the following factors should be taken into account.
Starting with the physiology of the kidney, it progresses to explain how diuretics actually work, via symports on the inside of the renal tubules. As described above for the loop diuretics, the actions of thiazides can also be inhibited by nsaids under certain conditions. Diuretic dosing and adverse effects are discussed separately. This mechanism of action ac counts for a key aspect of loop and distal convoluted tubule diuretic action. Learn vocabulary, terms, and more with flashcards, games, and other study tools.
Based on the call for research and issues raised in this article, future research is needed help to better elucidate the mechanisms of thiazides. Combination diuretic therapy to overcome resistance to ld. Combination of loop diuretics with thiazidetype diuretics. The action of thiazides depends in part on renal prostaglandin production. The second group of drugs works by increasing water and sodium excretion, thereby reducing intravascular volume, or by causing vasodilatation through nonras pathways, for example, diuretics and calcium channel blockers ccbs. Pharmacokinetics and pharmacodynamics features, indications and principles of diuretics usage in clinics are considered. Diuretics, also known as water pills, belong to a class of medications that remove excess salt and water from the body. Mechanism of action loop diuretics act on the nephron mainly in the thick ascending links of the loop of henle. Diuretics act primarily by blocking reabsorption of sodium at four major sites in the nephron. Several of the other mechanisms of action of different diuretic classes are summarized in table 1 16. Mannitol is a polyalcohol which is filtered by the glomerulus and not reabsorbed by the nephron. Mechanism of action and clinical application springerlink. It is often called a highceiling diuretic because it is more effective than other diuretics. They act by diminishing sodium reabsorption at different sites in the nephron, thereby increasing urinary sodium and water losses.
Potassiumsparing diuretics pharmacology the essential. Reducing the amount of fluid in the blood vessels results in reduction in blood pressure. Clinical pharmacology of diuretics in the international system of atc anatomictherapeuticchemical is presented. Site of action of diuretic drugs kidney international. The ability to induce negative fluid balance has made diuretics useful in the treatment of a variety of conditions, particularly edematous states and hypertension. Co2 rapidly diffuses across the cell membrane of proximal tubule cells where it is rehydrated back to h 2 co 3 by carbonic anhydrase. Sites and mechanisms of action of diuretics in the kidney. It is a long 8 minute 47 second animation showing the molecular mechanism of the working of the nephron and the drugs which act on the various different regions of the nephron. This article discusses the mechanisms of action, pharmacological effects and clinical indications of the various diuretic classes used in everyday clinical practice.
Additionally, nearly all diuretics increase the excretion of sodium in the kidneys, so that water is linked osmotically and also excreted. Pharmacology and clinical use of diuretics katie herndon, pharm. For more detailed explanation, particularly related to ion and fluid movement across the renal. Clinically useful agents that block sodium reabsorption effectively in the proximal tubule are lacking. Site and mechanism of action of diuretics the american journal of. Diuretics useful in the treatment of hypertension may be divided into four major groups according to their primary site of action within the renal tubule, starting in the proximal portion and moving to the collecting duct. The carbonic anhydrase inhibitor acetazolamide has been extensively studied using a variety of techniques. We report here that 3h metolazone, a diuretic with a thiazidelike mechanism of action, labels a site in rat kidney membranes that has characteristics of the thiazidesensitive ion transporter. However, when amiloride is used alongside another diuretic, it enhances total diuresis and counteracts potassium loss to a greater extent than it otherwise would on its own. Mechanism of action of carbonic anhydrase inhibitor diuretics. Firstly into two groups based on the principle action, which is either naturesis loss of sodium or aquaresis loss of water directly. Bertram katzung, basic and clinical pharmacology, mc graw hill medical, 2007. Diuretic drugs are typically classified first according to their predominant site of action along the nephron and second by the mechanism by which they inhibit transport. A recent call for research by the nih national heart, lung and blood institute emphasizes the need for a better understanding of the mechanisms of action of thiazide and thiazidelike diuretics.
Each type works in a distinct way and in different parts of the kidney. Antihypertensive drugs bja education oxford academic. Fulltext pdf hypertension, diuretic use, and risk of hearing loss. Mechanisms for blood pressure lowering and metabolic. Clinical pharmacology in diuretic use american society. The loop diuretics furosemide, bumetanide, and torsemide act from the lumen to inhibit the nak2cl cotransporter nkcc2, encoded by slc12a1 along the thick ascending limb and. Mutation of a key phenylalanine f372 alters diuretic binding reconstruction adapted from somasekharan et al. While these drugs have multiple mechanisms of action, their predominant effect is to cause vasodilatation. Review mechanisms and management of diuretic resistance in congestive heart failure.
Loop diuretics act on a different part of the renal tubules and have a slightly different mechanism of action than thiazide diuretics, but the result is the same elimination of excess water. Classification of this group by the action mechanism and caused effects is provided. Diuretics are a group of drugs that induce increased production of urine. Mechanism of action loop diuretics are 90% bonded to proteins and are secreted into the proximal convoluted tubule through organic anion transporter 1 oat1, oat2, and abcc4. These substances increase the excretion of water, sodium, and chloride through urine. The following discussion and accompanying illustration provide a simple overview of how the kidney handles water and electrolytes. Diuretics pdf diuretics pharmacology pdf diuretics classification pdf. Diuretics knowledge for medical students and physicians. It shows the detailed mechanism of action of the diuretics such as the loop diuretics, the potassium sparing diuretics, and the thiazide diuretics. The pocket for ion translocation and diuretic binding is shown by the arrow. Urine output in such patients can be reduced with a low sodium diet, nsaids and thiazide diuretics.
Depending on the class, diuretics act on different renal structures and lead to varying changes in the volume and composition of urine as well as electrolyte balance. Certain classes of diuretic are in this category, such as the thiazides. The mechanisms of action of antihypertensive drugs. The intravenous administration of chlorothiazide, acetazoleamide and chlormerodrin to dogs in various combinations and in doses capable individually of producing maximal renal responses, has led to the following conclusions concerning the mechanism of action of chlorothiazide.
In the nephron, amiloride acts on the distal convoluted tubule. Some of these effects can be used to treat disorders like hypercalcemia, hypocalcemia or hyperaldosteronism. Diuretics also called water pills are drugs that increase urine production in the kidneys, promoting the removal of salt and fluid from the body. The different classes of diuretics have different mechanisms of action but the overall aim of diuretic therapy is to increase the amount of water excreted in the urine.
Thiazide diuretics appear to exert their effect by a combination effects, one of which is by producing a mild hypovolemia, which causes an increase in proximal sodium and water reabsorption, and decreased water delivery to the adhsensitive sites. Pharmacology diuretics list of drugs and mechanisms of action see online here diuretics promote the generation of a negative. Utilization of classical clearance methodology for the determination of diuretic mechanism and site of action is based on four kinds of observations. Despite the bewildering number of diuretics available to the physician, these drugs can be divided into 4 main groups, characterised by their site of action on sodium reabsorption in the kidney. It therefore increases the tubular fluid osmolality, which decreases water reabsorption. Nsaid reduces the effects of diuretics probenecid reduces the effects of diuretics by inhibiting its secretion into the lumen. The current treatment of essential hypertension is based on the following concepts. Diuretics, commonly called water pills, are drugs that promote diuresis, that is increased production of urine. Gfr is related to a reduction in glomerular capillary plasma flow. Therefore, the more sodium is in the organism, the more water is in the patients body, and this leads to increased.
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