Pdf actual place of diuretics in hypertension treatment. Most diuretics produce diuresis by inhibiting the reabsorption of sodium at different segments of the renal tubular system. Diuretic drugs are used almost universally in patients with congestive heart failure, most frequently the potent loop diuretics. Potassiumsparing diuretics are diuretic drugs that do not promote the secretion of potassium into the urine they are used as adjunctive therapy, together with other drugs, in the treatment of hypertension and management of congestive heart failure. Thiazide diuretics also have a wellcharacterized site and mechanism of action for inhibition of sodium reabsorption, but their effect on magnesium reabsorption is less clear. For some drugs, the mechanisms of action have not been fully identified. A diuretic is any substance that promotes diuresis, the increased production of urine. To study ut inhibition in rats, we screened about 10,000 drugs, natural products and urea analogs for inhibition of rat uta1. Inhibitors of kidney urea transporter ut proteins have potential use as saltsparing diuretics urearetics with a different mechanism of action than diuretics that target salt transporters. 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.
Antihypertensive drugs bja education oxford academic. Download figure open in new tab download powerpoint. Nsaid reduces the effects of diuretics probenecid reduces the effects of diuretics by inhibiting its secretion into the lumen. We have examined surrogates for magnesium wasting in heart transplant patients on combinations of calcineurin inhibitors and diuretics. Therefore, thiazide diuretics coupled with loop diuretics are most logical because they affect. Co2 rapidly diffuses across the cell membrane of proximal tubule cells where it is rehydrated back to h 2 co 3 by carbonic anhydrase. Interaction of cyclosporine and fk506 with diuretics in.
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. 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. Bilal mirza 4th year download in your computer according to site of action and mechanism of action. Digoxin inhibits sodiumpotassium atpase, an enzyme that regulates the quantity of sodium and potassium inside cells. Indeed, essential hypertension appears to be a multifactorial disorder. Thiazides and thiazidelike diuretics have remained a cornerstone in the management of hypertension for more than half a century since their introduction in 1958. Studies on the mechanism of action of chlorothiazide in cardiac and renal disease. In peritoneal dialysis or hemodialysis, more solutes are lost decreasing the osmolarity and water from vascular compartment moves into intracellular spaces. Based on the site and mechanism of diuretic action. Increase the osmolarity of the glomerular filtrate. Diuretic agents major site of action mechanism of action clinical use. An account is given of the adverse effects of diuretics and how they come about.
Oral furosemide produces diuresis within 3060 minutes of administration, with the maximum diuretic effect in 12 hours. Interactions between antihypertensive drugs and other medications. The term potassiumsparing refers to an effect rather than a mechanism or location. Mechanism of action of beta blockers pdf download 3d39b66ab9 amer ms. Diuretics agent increasing urine volume, natriuretics increasing renal sodium excretion aquareticsincreasing excretion of solute free water.
Diuretics in the treatment of patients who present nature. H the effect of chlorothiazide on renal excretion of electrolytes and free water. An important property of thiazide diuretics is their action on the luminal membrane, which means they must be present in the tubular fluid to have any effect on the nacl cotransporter. 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. While these drugs have multiple mechanisms of action, their predominant effect is to cause vasodilatation. The ability to induce negative fluid balance has made diuretics useful in the treatment of a variety of conditions, particularly edematous states and hypertension. In addition to the ion transport inhibitors, other types of diuretics include osmotic diuretics, aldosterone antagonists, and carbonic anhydrase inhibitors. Clinically useful agents that block sodium reabsorption effectively in the proximal tubule are lacking. The antihypertensive actions of some diuretics thiazides and loop diuretics in. This causes an increase in renal free water excretion aquaresis, an.
Pdf ototoxic effects and mechanisms of loop diuretics. The loop diuretics furosemide, bumetanide, and torsemide act from the. Earleyeffect of furosemide on free water excretion in edematous patients with hyponatremia. Renal and extrarenal sites of action of diuretics springerlink. Diuretics impair the reabsorption of sodium at various sites in the nephron. Mechanisms of action of tb drugs under development. 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. Tuberculosis drugs target various aspects of mycobacterium tuberculosis biology, including inhibition of cell wall synthesis, protein synthesis, or nucleic acid synthesis.
Sites and mechanisms of action of diuretics in the kidney. Pdf diuretics represent a large and heterogeneous class of drugs, differing from each other by structure, site and mechanism of action. This mechanism of action accounts for a key aspect of loop and distal. Choose from 500 different sets of diuretics flashcards on quizlet. Utilization of classical clearance methodology for the determination of diuretic mechanism and site of action is based on four. Pharmacology and clinical use of diuretics katie herndon, pharm.
Clinical pharmacology in diuretic use american society. The current treatment of essential hypertension is based on the following concepts. Mechanisms and management of diuretic resistance in. 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.
Salem and kirchner, albumin as an adjunct to diuretics for the treatment of edema. Diuretics act primarily by blocking reabsorption of sodium at four major sites in the nephron. Mechanism of action of carbonic anhydrase inhibitor diuretics. Potassiumsparing diuretics an overview sciencedirect. The mechanism of action of aldosterone antagonists explains their association with hyponatremia and hyperkalemia in the present study.
Diuretics 1 free download as powerpoint presentation. 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. Starting with the physiology of the kidney, it progresses to explain how diuretics actually work, via symports on the inside of the renal tubules. Despite their unproven effect on survival, their indisputable efficacy in relieving congestive symptoms makes them first line therapy for most patients. Certain classes of diuretic are in this category, such as the thiazides. The loop diuretics furosemide, bumetanide, and torsemide act from the lumen to inhibit the nak2cl cotransporter nkcc2, encoded by. Potassiumsparing diuretics are diuretics that result in increased urine production and also lower blood pressure while increasing serum levels of potassium. 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. 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. The mechanisms of action of antihypertensive drugs. Thus, they must be excreted into the tubular fluid to be active, so that a decrease in renal function makes thiazide diuretics much less effective. However, at low doses the use of potassiumsparing diuretics has not been found to produce a clinically significant reduction in. If the kidney excretes more sodium, then water excretion will also increase.
Diuretic drugs increase urine output by the kidney i. Loop diuretics, or highceiling diuretics, such as furosemide, are the most potent and rapidly produce an intense dosedependent diuresis of relatively short duration. Cellular mechanism of action of furosemidelike diuretics in the thick ascending limb of the loop of henle. Diuretics are tools of considerable therapeutic importance. They work via antagonism of vasopressin or antidiuretic hormone and enable your body to secrete electrolyte free water. Potassiumsparing like spironolactone or amiloride both act on the collecting tubules but employ different mechanisms of action. Diuretic dosing and adverse effects are discussed separately. Fifty years of thiazide diuretic therapy for hypertension. The list of available and currently investigated agents is quite long. Diuretic effect of the different classes of diuretics varies considerably, varying from less than 2% for the weak potassium sparing diuretics to over 20% for the potent loop diuretics. This is accomplished by altering how the kidney handles sodium. Even in hypoalbuminuria, there is not enough free drug at one time to get across.
Thiazides such as bendroflumethiazide and hydrochlorothiazide are structurally related to sulphonamides. Agents such as acetazolamide that act in the proximal convoluted tubule cause an enhancement of solute. The association between hypernatremia and loop diuretic use is explained by the mechanism of action of loop diuretics where the excretion of electrolyte free water exceeds the increased natriuresis. Pharmacology of diuretics free download as powerpoint presentation. 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. Clinical pharmacology in diuretic use american society of. Mannitol is used with diuretics to regain the balance. Kirchner, effect of prostaglandin inhibition on the action of diuretic agents. In the treatment of more advanced stages of heart failure diuretics may fail to control. Most diuretics act from the luminal side of the membrane.
588 1179 622 922 930 1457 1059 615 906 696 940 410 1342 42 1194 16 318 1572 258 128 326 1032 882 76 506 1107 514 443 804