There is a third class of diuretic that is referred to as potassiumsparing diuretics. Dont forget to take the thiazide diuretics quiz after. In addition, current hypertension treatment guidelines in the usa recommend thiazide diuretics as a firstline treatment for most patients with essential hypertension. Diuretic dosing and adverse effects are discussed separately. Their mechanism of action involves inhibition of the nacl cotransporter channel in the proximal part of the distal convoluted tubule, leading to increased sodium and chloride secretion. Some of these effects can be used to treat disorders like hypercalcemia, hypocalcemia or hyperaldosteronism. Pharmacokinetics of the thiazide diuretics wiley online library. Thiazide diuretics uses, list, thiazide mechanism of. Effects of these agents on the renal excretion of water, sodium, chloride. The mechanism of the hypercalcemia may involve the action of thiazide diuretics to increase proximal tubular calcium reabsorption as a secondary consequence of direct action of thiazides on the distal tubule.
Introduction the thiazides are the most widely used of the diuretic drugs thiazide diuretics are sulfonamide derivatives all thiazides affect the distal tubule, and all have equal maximum diuretic effects are moderately potent diuretics. Because loop and thiazide diuretics increase sodium delivery to the distal segment of the. Thiazide diuretics are used as monotherapy, or they can be administered adjunctively with other antihypertensive agents. Thiazide diuretics were developed during the 1950s, when chemists and physiologists at merck sharpe and dohme tested derivatives of sulfonamidebased carbonic anhydrase inhibitors, with the goal of discovering drugs that enhance the excretion of sodium with chloride rather than sodium bicarbonate. The consistency of torsemides absorption and its longer duration of action are distinguishing pharmacologic features among loop diuretics. Diuretic agents major site of action mechanism of action clinical use. Thus the various compounds differ in the amount of drug required to achieve a given effect, but not.
Pdf thiazide diuretics were the first tolerated efficient antihypertensive drugs. Medscape s clinical reference is the most authoritative and accessible pointofcare medical reference for physicians and healthcare professionals, available online and via all major mobile devices. Thiazide and thiazidelike diuretics act on the nephron mainly at the proximal part of the distal tubule. Diuretics are tools of considerable therapeutic importance. Thiazide diuretics enhance the effectiveness of most other antihypertensive agents, especially vasodilators such as hydralazine and minoxidil, which by themselves promote volume expansion. Mechanisms for blood pressure lowering and metabolic effects of. Their effects on reducing peripheral vascular resistance further contribute to their antihypertensive properties, in addition to. Thiazide diuretics are some of the most common diuretics currently in use. Based on the call for research and issues raised in this article, future research is needed help to better elucidate the mechanisms of thiazides. Thiazide diuretics are medications that help remove extra fluid volume from the blood through increased urination. The high efficacy of loop diuretics is due to the unique site of action involving the loop of henle a portion of the renal tubule in the kidneys. The first of these, chlorothiazide, was soon accompanied by a large number of other sulfonamide derivatives, including chlorthalidone. Action increases excretion of sodium and water by inhibiting sodium reabsorption in the distal tubule.
The other major group of diuretics is the thiazide group mentioned earlier and this description includes the thiazide like diuretics figure 2, which are not true benzothiazides but are heterocyclic variants e. Combination diuretic therapy to overcome resistance to ld. Although loop diuretics have diuretic efficacy greater than that of thiazide or thiazide like agents, effects on blood pressure are relatively brief and reflex stimulation. Like acetazolamide, these drugs are secreted into the tubular fluid and block the electro neutral sodium and chloride transport symport in the distal convoluted tubule by. Some drugs in this class antagonize the actions of aldosterone aldosterone receptor antagonists at the distal segment of the distal tubule. Diuretics are a group of drugs that induce increased production of urine. Severe, chronic diarrhea with substantial weight loss has been reported in patients taking olmesartan months to years after drug initiation.
Chlorothiazide is the thiazide commonly used chlorothiazide is also known as diuril thiazide diuretics act on the distal tubule the exact mechanism of action is unknown thiazides tend to bind chloride which interrupts the transport of sodium thiazides do not increase urinary calcium loss. Coadministration of thiazides increases the efficacy of loop diuretics. The end result is an elevation in the concentration of nacl in tubular fluid, without any disturbances of the acidbase balance. 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. As a result, there is increased excretion of sodium and water and an associated loss of potassium. Thiazide diuretics were the first tolerated efficient antihypertensive drugs and have been used as a part of treatment strategies in numerous clinical trials involving hypertension. Review of the available evidence on thiazides diuretics in the. The carbonic anhydrase inhibitor acetazolamide has been extensively studied using a variety of techniques.
Urine output in such patients can be reduced with a low sodium diet, nsaids and thiazide diuretics. Site of action of diuretic drugs kidney international. Hf,renaldysfunction,cirrhosis,glucocorticoidtherapy,estrogentherapy. Illustration of the mechanism of action of thiazide diuretics in the distal convoluted tubule. Thiazides compete for the same secretory process by which uric acid is secreted into the proximal tubule. Thiazide diuretics also exert an additional vasodilator effect on arterial smooth muscle by a still poorly understood mechanism.
Mechanism of action loop diuretics act on the nephron mainly in the thick ascending links of the loop of henle. Thiazide diuretics increase the elimination of sodium and chloride in approximately equivalent amounts. Domenic sica discusses the mechanisms of action of thiazide type diuretics, comparability to loop diuretics, and the basis for combining them with nondiuretic antihypertensive medication classes. Thiazide type diuretics have enjoyed a considerable success in the management of hypertension. In conclusion, thiazide diuretics markedly potentiate the natriuretic and chloruretie action of loop diuretics even in patients with advanced renal failure. Distal convoluted tubule diuretics thiazides and thiazide like drugs are also organic anions that act in much the same manner, but bind to the thiazide sensitive nacl cotransporter ncc, encoded by slc12a3 along the distal convoluted tubule. Pdf thiazide diuretics in the treatment of hypertension. The netter collection of medical illustrations urinary. Unlike loop and thiazide diuretics, some of these drugs do not act directly on sodium transport. Clinical pharmacology in diuretic use american society. Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus.
Theoretical mechanisms of thiazideinduced chronic blood pressure lowering. Intestinal biopsies of patients often demonstrated villous atrophy. Thiazide and loop diuretics sica 2011 the journal of. Sodium excretion and urine volume are increased by interference with transfer across cell membranes. Thiazide diuretics were introduced in the united states for the treatment of hypertension in 1957.
Pharmacology and clinical use of diuretics katie herndon, pharm. 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. Ongoing considerations on mechanism of action article in journal of clinical hypertension 611. The ability to induce negative fluid balance has made diuretics useful in the treatment of a variety of conditions, particularly edematous states and hypertension. Several of the other mechanisms of action of different diuretic classes are summarized in table 1 16.
Thiazide diuretics tzd are one of the most widely prescribed therapeutic agents for treatment of hypertension and are also used in the treatment of heart failure and stroke olde engberink et al. 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. Diuretic thiazide diuretics increase urinary excretion of sodium and water by inhibiting sodium reabsorption in the early distal tubules 04. Diuretics knowledge for medical students and physicians. Thiazide refers to both a class of sulfurcontaining organic molecules and a class of diuretics. Their mechanism depends on renal prostaglandin production. However, the mechanism by which these drugs chronically lower blood pressure is poorly. However, the mechanism underlying chronic reduction of arterial pressure to tzd remains unclear despite investigations over greater than five decades. Such questions include issues of mechanism of action. Thiazides are sulfonamide related organic acids that are secreted into the proximal tubule by an organic secretory mechanism. Combination of loop diuretics with thiazidetype diuretics. Rasblocking drugs or, conversely, to the negative action of.
Thiazide diuretics can also mobilize mild edema and are sometimes used for this purpose, but loop diuretics are generally used to treat edema. Mechanisms for blood pressure lowering and metabolic. Overview of the transport systems in the renal nephron, and major sites of action of diuretics. This mechanism of action accounts for a key aspect of loop and distal convoluted tubule diuretic. Despite the widespread use of this drug class, the mechanism by which thiazide diuretics lower blood pressure remains poorly understood.
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. 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 thiazide like diuretics. Mechanism of action illustration of the mechanism of action of thiazide diuretics in the distal convoluted tubule of nephrons. Choose from 303 different sets of thiazide diuretics flashcards on quizlet. Thiazide diuretics inhibit reabsorption of sodium and chloride mostly in. Learn thiazide diuretics with free interactive flashcards.
Which medications in the drug class diuretics, thiazide. 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. Thiazide like chlortalidone indapamide mechanism of action thiazide and thiazide like diuretics act on the nephron mainly at the proximal part of the distal tubule. 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. Mechanism of thiazide diuretic arterial pressure reduction. These drugs have assumed a standardofcare position in the minds of many health care providers.