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 macula densa. 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 different classes of diuretics have different mechanisms of action but the. Utilization of classical clearance methodology for the determination of diuretic mechanism and site of action is based on four kinds of observations. Thus they prevent reabsorption of water and also, by more complex mechanisms, of sodium principally in the proximal convoluted tubule and. Mechanisms for blood pressure lowering and metabolic. The protein bound nature of the loop diuretic molecules causes it to be secreted via several transporter molecules along luminal wall of the proximal convoluted tubules to be able to exert its function.
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. Mechanism of action sodium is the most troubling electrolyte for patients with hypertension, as one atom of sodium binds four molecules of water. Most diuretics act from the luminal side of the membrane. The initial decrease in bp results from diuretic induced reduction in plasma volume and cardiac output with a slight increase in peripheral resistance is followed by a decrease in vascular resistance. This segment of the nephron is responsible for resorbing roughly 25% of the tubular salt and distal segments have limited reserve to compensatorily increase sodium resorption. Classification mechanism of action pharmacokinetics uses and indications adverse effects diuretic braking classification of diuretics mechanism of action. Mechanisms for blood pressure lowering and metabolic effects of thiazide and thiazidelike diuretics. Diuretic resistance is defined as a failure to achieve the therapeutically desired reduction in edema despite a full dose of diuretic. Learn vocabulary, terms, and more with flashcards, games, and other study tools.
For some drugs, the mechanisms of action have not been fully identified. As a result, there is increased excretion of sodium and water and an associated loss of potassium. Thiazide diuretics, which are the most commonly used diuretic, inhibit the sodiumchloride transporter in the distal tubule. Find interesting nursing courses notes, nursing diagnoses, practice with our free nclex questions, and get different nursing care plans for different medical conditions.
Clinical pharmacology in diuretic use american society. Diuretics free download as powerpoint presentation. This mechanism of action ac counts for a key aspect of loop and distal convoluted tubule diuretic action. This video discusses about the mechanisms of action of diuretics as antihypertensives agents. Because this transporter normally only reabsorbs about 5% of filtered sodium, these diuretics are less efficacious than loop diuretics in producing diuresis and natriuresis. Thiazide diuretics uses, list, thiazide mechanism of. Clinically useful agents that block sodium reabsorption effectively in the proximal tubule are lacking. A second way to group drugs is by their dominant mechanism of action.
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. By blocking the reabsorption of these prominent solutes, diuretics create osmotic pressure within the nephron that prevents the passive reabsorption of. Mechanism of action of carbonic anhydrase inhibitor diuretics. Several of the other mechanisms of action of different diuretic classes are summarized in table 1 16. These drugs can also be shown to have effects on acidifi cation in the. Site of action of diuretic drugs kidney international. Some diuretics are used at lower doses to reduce raised blood pressure. They can increase potassium excretion in hyperkalemic states loop diuretics, thiazides, increase calcium excretion. 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 mechanism by which almost all diuretics manage to eliminate excess sodium is a bit complex, but it is enough to say that they lower the reabsorption of sodium in the kidneys. The current treatment of essential hypertension is based on the following concepts.
In pharmacology, the term mechanism of action moa refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. Diuretics and their mechanisms of action brainkart. One way is by grouping drugs based on their therapeutic use or class such as antiarrhythmic or diuretic drugs. Osmotic diuretics an overview sciencedirect topics. Based on the call for research and issues raised in this article, future research is needed help to better elucidate the mechanisms of thiazides desired and undesired effects. You have free access to this content prescriber volume 22, issue 5, version of record online. 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. The diuretics are generally divided into four major classes, which are distinguished by the site at which they impair sodium reabsorption.
A common clinical complaint is tinnitus, but there are also notable threshold shifts for sound sensation across all frequencies. If the kidney excretes more sodium, then water excretion will also increase. Combination diuretic therapy to overcome resistance to ld. Excreted into the lumen by the anion secretory pathways of the proximal tubule. Video animation on renal physiology and diuretics mechanism. 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.
Diuretic drugs increase urine output by the kidney i. As described above for the loop diuretics, the actions of thiazides can also be inhibited by nsaids under certain conditions. They serve to rid the body of excess fluid that accumulates in the tissues owing to various disease states. Oral furosemide produces diuresis within 3060 minutes of administration, with the maximum diuretic effect in 12 hours. Mechanism of action of potasium sparing diuretics source. Indeed, essential hypertension appears to be a multifactorial disorder. Diuretics can be used in various situations associated with dyselectrolytemia.
Moreover, this knowledge is a prerequisite for the frequent use of diuretics as tools in studies of renal physiology. This paper provides a a survey of the basic tubule transport mechanisms of sodium and potassium ions along the nephron, b a comparison of the overall renal effects of two diuretic agents torasemide and furosemide, as assessed by renal clearance techniques, c an analysis of the tubule sites of action of torasemide evaluated by freeflow micropuncture and microperfusion techniques, and. Thiazide diuretics are indicated only in the treatment of edema due to pathologic causes or as a short course of treatment in patients with severe hypervolemia. 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. 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. Pharmacology diuretics list of drugs and mechanisms of action see online here diuretics promote the generation of a negative. It is likely that the mechanism whereby ecf volume losses lead to decreases in.
Most diuretics produce diuresis by inhibiting the reabsorption of sodium at different segments of the renal tubular system. Loop diuretics, or highceiling diuretics, such as furosemide, are the most potent and rapidly produce an intense dosedependent diuresis of relatively short duration. Sites and mechanisms of action of diuretics in the kidney. Inhibit na and cl reabsorption by blocking the kna2cl symporter on the thick ascending loop and the early part of the distal tubule. 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. Diuretic thiazide diuretics increase urinary excretion of sodium and water by inhibiting sodium reabsorption in the early distal tubules 04.
Nonopen access articles that fall outside this five year window are available only to institutional subscribers and current aspet members, or through the article purchase feature at the bottom of the page. Mechanism of action and therapy seminars in nephrology. Combination of loop diuretics with thiazidetype diuretics. Pharmacology and clinical use of diuretics katie herndon, pharm. Diuretics increase urinary excretion of water and electrolytes and are used to relieve oedema associated with heart failure, nephrotic syndrome or hepatic cirrhosis. In examining the effects of diuretics on mg and k metabolism, the following factors should be taken into account.
What does the blocking of the reabsorption of sodium and chloride create and cause. Contact inhibition increased cell adhesiveness increased cellular matrix motility none of the above the most common cause of the additions disease is. Additionally, nearly all diuretics increase the excretion of sodium in the kidneys, so that water is linked osmotically and also excreted. Despite the dramatic results in bp lowering, the exact mechanism of action of the thiazide diuretics has not been definitely established. Osmotic diuretics are mainly used to treat cerebral oedema, and also to lower raised intraocular pressure. As mentioned, loop diuretics act at the level of the ascending henle and inhibit the na2clk symporter. The action of thiazides depends in part on renal prostaglandin production. Furosemide lasix, ethacrynic acid edecrin, and possibly organomercurial agents are effective in the ascending limb of henles loop. Inhibition of the enzyme leads to an increase in the intracellular concentration of sodium and thus by stimulation of sodiumcalcium exchange an increase in the intracellular concentration of calcium. Pharmacology of diuretics authorstream presentation.
A mechanism of action usually includes mention of the specific molecular targets to which the drug binds, such as an enzyme or receptor. Diuretic resistance american journal of kidney diseases. 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. Fifty years of thiazide diuretic therapy for hypertension. Urine output in such patients can be reduced with a low sodium diet, nsaids and thiazide diuretics. Review mechanisms and management of diuretic resistance. Two major questions about the mechanism of action of the carbonic anhydrase inhibitors have recently been partially answered. Lasix, torasemide, bumetanide, xipamide, piretanide, ethacrynic acid. 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. Mechanisms of action of tb drugs under development.
There are different ways to group or classify drugs. Lung and blood institute emphasizes the need for a better understanding of the mechanisms of action of thiazide and thiazidelike diuretics. Starting with the physiology of the kidney, it progresses to explain how diuretics actually work, via symports on the inside of the renal tubules. Loop diuretics such as furosemide, ethacrynic acid, and bumetadine i. Osmotic diuretics are small molecular weight substances that are filtered by the glomerulus but not reabsorbed by the renal tubule, and thus increase the osmolarity of the tubular fluid. Thiazide diuretics do not prevent development of toxemia of pregnancy, and there is no satisfactory evidence that they are useful in the treatment of toxemia. Gain access to their site of action via organic acid secretory pathway in pt. Pharmrev articles become freely available 12 months after publication, and remain freely available for 5 years. Thiazide or thiazidetype diuretics are most frequently used to lower bp, but loop and potassiumsparing diuretics are used in some situations. Diuretics act primarily by blocking reabsorption of sodium at four major sites in the nephron. The nephron, depicting sites of diuretic action on sodium reabsorption.
Renal and extrarenal sites of action of diuretics springerlink. However, of late, mainly because of the increased incidence of new onset diabetes mellitus and availability of better drugs with lower. A diuretic is a substance that increases the rate of urine volume output, as the name implies. Gfr is related to a reduction in glomerular capillary plasma flow. They act by diminishing sodium reabsorption at different sites in the nephron. Tuberculosis drugs target various aspects of mycobacterium tuberculosis biology, including inhibition of cell wall synthesis, protein synthesis, or nucleic acid synthesis. In peritoneal dialysis or hemodialysis, more solutes are lost decreasing the osmolarity and water from vascular compartment moves into intracellular spaces.
Bilal mirza 4th year download in your computer according to site of action and mechanism of action. Diuretics were always the first line drugs in hypertension. We report here that 3hmetolazone, a diuretic with a thiazidelike mechanism of action, labels a site in rat kidney membranes that has characteristics of the thiazidesensitive ion transporter. Knowledge of the pharmacologic properties and mechanisms of action of diuretic agents is a prerequisite for the successful choice and effective clinical use of. Diuretics promote the removal from the body of excess water, salts, poisons, and accumulated metabolic products, such as urea. Potassiumsparing diuretics an overview sciencedirect. Mechanisms for blood pressure lowering and metabolic effects. Bertram katzung, basic and clinical pharmacology, mc graw hill medical, 2007. What is the basic mechanism of action that most diuretics share. Most diuretics also increase urinary excretion of solutes, especially sodium and chloride.
This article discusses the mechanisms of action, pharmacological effects and clinical indications of the various diuretic classes used in everyday clinical practice. Natriuretic diuretics are among the most commonly used drugs. Co2 rapidly diffuses across the cell membrane of proximal tubule cells where it is rehydrated back to h 2 co 3 by carbonic anhydrase. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way. Digoxin inhibits sodiumpotassium atpase, an enzyme that regulates the quantity of sodium and potassium inside cells. Mechanism of action and clinical application springerlink. The mechanisms of action of antihypertensive drugs. Although all diuretics act primarily by impairing sodium reabsorption in the renal tubules, they differ in their mechanism and site of action and.
Fulltext pdf hypertension, diuretic use, and risk of hearing loss. Diuretics acetazolamide, furosemide are sometimes used to prevent or reduce the accumulation of fluid in the ventricles. Classification of this group by the action mechanism and caused effects is provided. This is accomplished by altering how the kidney handles sodium. Mechanism of action in hypertension full details of the sites and mechanisms of action of diuretics on the kidney and their unwanted effects are considered in chapter 14.
In the nephron, amiloride acts on the distal convoluted tubule. Site and mechanism of action of diuretics the american journal of. Mannitol is used with diuretics to regain the balance. Diuretic dosing and adverse effects are discussed separately. Loop diuretics are highly protein bound and therefore have a low volume of distribution. Pharmacokinetics and pharmacodynamics features, indications and principles of diuretics usage in clinics are considered. The effects of carbonic anhydrase inhibitors as diuretics are due to the preceding events. Diuretic, any drug that increases the flow of urine. For the rapid elimination of edema suitable diuretic medication group saluretikov, namely, loop diuretics, and osmolar diuretics. Their mechanism depends on renal prostaglandin production.
The ability to induce negative fluid balance has made diuretics useful in the treatment of a variety of conditions, particularly edematous states and hypertension. Therefore, the more sodium is in the organism, the more water is in the patients body, and this leads to increased. Implications for drug effectiveness and adverse effects. Review mechanisms and management of diuretic resistance in congestive heart failure. Clinical pharmacology of diuretics in the international system of atc anatomictherapeuticchemical is presented. The theory that all thiazides do not have a similar efficacy or mechanism of action would help explain the conflicting findings in many studies investigating their blood pressurelowering and metabolic effects, and has been addressed previously by others. 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 in the collecting tubules. 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. 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. Diuretics, kidney, pharmacokinetics, mechanism of action.
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