Primarily works at the thin descending limb of henles loop these drugs. Diureticthiazide diuretics increase urinary excretion of sodium and water by inhibiting sodium reabsorption in the early distal tubules 04. The action on the distal tubules is independent of any inhibitory effect on carbonic anhydrase or aldosterone. It shows the detailed mechanism of action of the diuretics such as the loop diuretics, the potassium sparing diuretics, and the thiazide 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. 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. Inhibit na and cl reabsorption by blocking the kna2cl symporter on the thick ascending loop and the early part of the distal tubule. Domenic sica discusses the mechanisms of action of thiazidetype diuretics, comparability to loop diuretics, and the basis for combining them with nondiuretic antihypertensive medication classes.
Osmotic diuretics have their major effect in the proximal tubule and the descending limb of henles loop. Excreted into the lumen by the anion secretory pathways of the proximal tubule. Site of action of diuretic drugs kidney international. The loop diuretics furosemide, bumetanide, and torsemide act from the lumen to inhibit the nak2cl cotransporter nkcc2, encoded by. See time course of loop and thiazide diureticinduced electrolyte complications. Check out our online video lectures and start your pharmacology course now for free.
There are basically three groups of diuretics, named according to their structure and mechanism of action. Although diuretics have been used for several decades, there is still some ambiguity and confusion regarding. Are sulfonamide derivatives ethacrynic acid is a phenoxyacetic acid derivative site of action. The following article provides an overview of the different diuretics, their renal targets, as well as the effects associated with these diuretics. Mechanism of action most diuretics produce diuresis by inhibiting the reabsorption of sodium at different segments of the renal tubular system this is accomplished by altering how the kidney handles sodium.
Diuretics, commonly called water pills, are drugs that promote diuresis, that is increased production of urine. Medline abstract for reference 2 of mechanism of action of. By decreasing sodium reabsorption, thiazide use acutely results in. The benzothiadiazines and related compounds have a moderate diuretic action spread over a longer period, whilst the potassiumsparing diuretics, triamterene, amiloride and spironolactone, have only a weak diuretic effect but a marked ability to diminish urinary potassium excretion. Crcl 50, use 25 to 50 mgd hctz crcl 20 to 50, use 50 to 100 mgd hctz crcl diuretic. It is well established that the ingestion of alcohol is followed by a substantial diuresis. Diuretic resistance is defined as a failure to achieve the therapeutically desired reduction in edema despite a full dose of diuretic. 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. The action of thiazides depends in part on renal prostaglandin production. Their mechanism depends on renal prostaglandin production. Bilal mirza 4th year download in your computer according to site of action and mechanism of action. Jun 19, 2018 the potassiumsparing diuretics cause a net increase in calcium lost in urine, but the increase is much smaller than the increase associated with other diuretic classes. Bertram katzung, basic and clinical pharmacology, mc graw hill medical, 2007.
Figure 1 schematic diagram of the nephron demonstrating the site of action of diuretics. Mechanism of action of diuretic drugs and their side effects. Additionally, nearly all diuretics increase the excretion of sodium in the kidneys, so that water is linked osmotically and also excreted. Loop diuretics are medications that help remove extra fluid volume from the blood through increased urination. Diureticsmechanism of action,diuretic types and adverse. Diuretics are used extensively in hospitals and in community medical practice for the management of cardiovascular diseases. Some of these effects can be used to treat disorders like hypercalcemia, hypocalcemia or hyperaldosteronism.
Jun 22, 2016 download basic and clinical pharmacology by katzung free. Clinical pharmacology in diuretic use american society of. Agents such as acetazolamide that act in the proximal convoluted tubule cause an enhancement of solutefree water generation ch2o, induce a phosphaturia and an increase in bicarbonate excretion, alkalinize the urine, and cause a kaliuresis. Before considering the specific action of diuretic drugs on the transport of water and electrolytes in the renal tubule, brief attention should be given to their effects on glomerular filtration since such effects may influence to a major extent the magnitude of the. Because the mechanisms for reabsorption of salt and water differ in each of the 4 major tubular segments, the diuretics acting in these segments have differing mechanisms of action. Knowledge of the pharmacologic properties and mechanisms of action of diuretic agents is a prerequisite for the successful choice and effective clinical use of these compounds. Loop diuretics are 90% bonded to proteins and are secreted into the proximal convoluted tubule through organic anion transporter 1 oat1, oat2, and abcc4. Mechanisms for blood pressure lowering and metabolic effects. Mechanism of dehydration following alcohol ingestion jama.
The molecular mechanism of action is known for diuretic agents such as acetazolamide carbonic anhydrase, theo. 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. Video animation on renal physiology and diuretics mechanism. Oct 28, 2017 thiazides are the most widely used class of diuretics. This mechanism of action accounts for a key aspect of loop and distal convoluted tubule diuretic action. 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. Reducing the amount of fluid in the blood vessels results in reduction in blood pressure. Diuretic agents increase the urine formation, by influencing any of the processes involved in urine formation. Diuretics water pills list of drugs and mechanism of action. Co2 rapidly diffuses across the cell membrane of proximal tubule cells where it is rehydrated back to h 2 co 3 by carbonic anhydrase. These agents sensitize the afferent receptors, particularly in the heart and the carotid sinus so that a given level of pressure results in a larger amount of afferent nerve traffic. The loop diuretics furosemide, bumetanide, and torsemide act from the lumen to inhibit the nak2cl.
Jun 28, 2014 22 loop diuretics furosemide, torasemide, bumetanide. As described above for the loop diuretics, the actions of thiazides can also be inhibited by nsaids under certain conditions. Oct 27, 2012 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. Nsaid reduces the effects of diuretics probenecid reduces the effects of diuretics by inhibiting its secretion into the lumen. Mechanism of action sodium is the most troubling electrolyte for patients with hypertension, as one atom of sodium binds four molecules of water. 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. Loop diuretics are relatively weak antihypertensive agents. 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. The effect of causing increased water loss is achieved by decreasing the reabsorption of sodium and chloride from the filtrate. Pharmacology and clinical use of diuretics katie herndon, pharm. Although loop diuretics have diuretic efficacy greater than that of thiazide or thiazidelike agents, effects on blood pressure are relatively brief and reflex stimulation. The causes of diuretic resistance include poor adherence to drug therapy or dietary sodium restriction, pharmacokinetic issues, and compensatory increases in sodium reabsorption in nephron sites that are not blocked by the diuretic.
Titrate single daily dose up to ceiling dose as needed thiazide diuretic. The mechanism of action of diuretics can be established by studying the molecular mechanism of action, the site of action within the nephron, and the relationship between the pharmacokinetics of the diuretic and its effect. The mechanisms of action of antihypertensive drugs chest. Diuretic resistance american journal of kidney diseases. Diuretics are tools of considerable therapeutic importance.
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. Sites and mechanisms of action of diuretics in the kidney. It is often called a highceiling diuretic because it is more effective than other diuretics. Diuretics list of drugs and mechanisms of action see online here diuretics promote the generation of a negative. Describe the mechanism of action of diuretics essay. Drugs acting on the ascending limb of the loop of henle have a powerful but short acting diuretic effect. Clinical pharmacology in diuretic use american society. Papich dvm, ms, dacvcp, in saunders handbook of veterinary drugs fourth edition, 2016. Figure 2 relationship between renal furosemide excretion rate or urinary diuretic concentration log value and excretion of sodium in normal subjects left curve and in patients with chf right curve. Mechanism of action loop diuretics act on the nephron mainly in the thick ascending links of the loop of henle. The site of action of a diuretic in turn determines the magnitude of the associated natriuresis table 10.
Diuretics are a group of drugs that induce increased production of urine. Diuretic drugs increase urine output by the kidney i. Much new information has accumulated in recent years from experi. If the kidney excretes more sodium, then water excretion will also increase 8. If the kidney excretes more sodium, then water excretion will also increase. The only class of antihypertensive agents which act on the afferent side of the sympathetic nervous system are the veratrum alkaloids fig 2. The loop diuretics, furosemide and piretanide, sharply increased fractional delivery of fluid, sodium, and potassium into the distal tubule, and, as a result, sodium reabsorption and potassium secretion were enhanced in this nephron segment. Thiazide diuretics are medications that help remove extra fluid volume from the blood through increased urination. They increase the rate of delivery of tubular fluid and electrolytes to the distal sites of hydrogen and potassium ion secretion, while plasma volume contraction increases. Diuretics or diuretic agents are the substances which enhance the urine formation and output.
Diuretics knowledge for medical students and physicians. Mechanism of action of carbonic anhydrase inhibitor diuretics. Through osmotic effects, they also oppose the action of adh in the collecting tubule. A large num ber of different diuretics are available and can be grouped either by their specific chemical similarities and structure or their site and mechanism of action. 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. Some of these effects can be used to treat disorders like hypercalcemia. One explanation is that alcohol, or one of its metabolites, could be sufficiently. Sep 27, 20 furosemide, like other loop diuretics, acts by inhibiting nkcc2, the luminal nak2cl symporter in the thick ascending limb of the loop of henle.
Diuretic dosing and adverse effects are discussed separately. Diuretics are among the most important drugs of our. 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. Such questions include issues of mechanism of action, comparability to loop diuretics in their actions, classeffect, and the basis for their additivity with nondiuretic antihypertensive. The transport char acteristics by which salt and water are reabsorbed across the various nephron segments, and the site and mecha nism by which diuretics affect these.
This tells you that the other two groups cause a loss of potassium. Site and mechanism of action of diuretics sciencedirect. The mechanisms and sites of action of the various diuretics have been studied. However, the mechanism by which these drugs chronically lower blood pressure is poorly understood. Pharmacology of diuretics authorstream presentation. Antihypertensive drugs basic concepts in pharmacology. Sodium is the most troubling electrolyte for patients with hypertension, as one atom of sodium binds four molecules of water. Download pharmacology books pdf free all medical stuff. Diuretics also called water pills are drugs that increase urine production in the kidneys, promoting the removal of salt and fluid from the body. Therefore, the more sodium is in the organism, the more water is in the patients body, and this leads to increased blood volume and consequently high blood pressure.
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. This is accomplished by altering how the kidney handles sodium. Each type works in a distinct way and in different parts of the kidney. Mechanisms for blood pressure lowering and metabolic. They are used frequently as the first line treatment for mild to moderate hypertension and are an integral part of the management of symptomatic heart failure. Thiazide and thiazidelike diuretics are among the most commonly used antihypertensives and have been available for over 50 years. General mechanism of action diuretics cause a net loss of water from the body by an action on the kidney, normally associated with a loss of sodium.
Review mechanisms and management of diuretic resistance. A second class of diuretics, sometimes termed aquaretics, instead inhibit water reabsorption by blocking vasopressin receptors along the collecting duct. Site of action of diuretic drugs diuretic drugs continue to attract the interest of renal physiologists not only for their intrinsic tubular effects but equally importantly for the insight that such studies provide into normal and abnormal mechanisms of renal function. The reason i place this book here is the lot of requests i received for this book. The ncc facilitates the absorption of sodium from the distal tubules back to the interstitium and accounts for approximately 7% of total sodium reabsorption. Certain classes of diuretic are in this category, such as the thiazides.
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