1. The document discusses diuretics, which are drugs that increase renal excretion of water and sodium. They are commonly used to treat edema and hypertension.
2. Diuretics work by inhibiting sodium reabsorption in different segments of the renal tubule. Carbonic anhydrase inhibitors like acetazolamide specifically inhibit sodium bicarbonate reabsorption in the proximal tubule.
3. The renal tubule transports solutes like sodium via active transport mechanisms like the sodium-potassium pump and secondary active transporters, which diuretics can inhibit to reduce sodium reabsorption.
Loop diuretics, thiazides, and other diuretic classes are summarized. Loop diuretics act in the thick ascending limb of Henle's loop by inhibiting the Na-K-2Cl transporter. Thiazides act in the distal convoluted tubule by blocking coupled Na and Cl reabsorption. Carbonic anhydrase inhibitors inhibit bicarbonate absorption in the proximal tubule. Osmotic diuretics like mannitol are filtered but not reabsorbed, drawing water out of cells. Potassium-sparing diuretics like amiloride act late in the distal nephron to inhibit Na reabsorption. Diuretic combinations can have synergistic effects.
A diuretic is a chemical that increases urine production by inhibiting sodium reabsorption in the nephron at four major sites. The primary sites are the proximal tubule, thick ascending limb of Henle's loop, distal convoluted tubule, and connecting tubule/cortical collecting tubule. Diuretics work by blocking sodium transport mechanisms like cotransporters at these sites, causing increased excretion of sodium and water. The specific transport mechanisms and diuretic drug targets vary between nephron segments.
Diuretics are chemicals that increase urine formation by increasing sodium and chloride ion excretion. There are several classes of diuretics that act at different sites along the nephron. Loop diuretics act in the ascending loop of Henle by inhibiting sodium-potassium-chloride transport. Thiazides act in the distal convoluted tubule by inhibiting sodium and chloride transport. Carbonic anhydrase inhibitors act in the proximal tubule by inhibiting the enzyme carbonic anhydrase. Potassium-sparing diuretics act in the collecting duct and do not promote potassium secretion. Osmotic diuretics act by increasing osmotic pressure in the proximal tubule and loop of Henle to prevent water
This document provides information on loop diuretics and potassium sparing diuretics. It begins with an overview of normal urine formation and sites of renal reabsorption. It then classifies diuretics and discusses the mechanisms and sites of action of loop diuretics like furosemide and torsemide as well as potassium sparing diuretics like spironolactone and amiloride. It notes their therapeutic uses, interactions, and resistance. In recent years, new loop diuretic compounds like CRE 10904 have been developed.
This document provides an overview of diuretics, including their definition, classification, mechanisms of action, and side effects. It discusses the physiology of urine formation and the roles of the kidney in homeostasis. Specific sections cover thiazide diuretics, loop diuretics, their mechanisms in inhibiting sodium reabsorption in the distal tubule and thick ascending limb, respectively. Adverse effects include hypokalemia, hyperuricemia, and effects on calcium and magnesium levels. The document compares the potencies and durations of action of different diuretic classes and individual drugs.
Diuretic agents work by increasing urine output and sodium excretion. There are several classes of diuretics including carbonic anhydrase inhibitors, loop diuretics, osmotic diuretics, potassium-sparing diuretics, and thiazide diuretics. Nursing care involves monitoring for therapeutic and adverse effects such as hypokalemia, hypotension, and fluid imbalance.
Loop diuretics, thiazides, and other diuretic classes are summarized. Loop diuretics act in the thick ascending limb of Henle's loop by inhibiting the Na-K-2Cl transporter. Thiazides act in the distal convoluted tubule by blocking coupled Na and Cl reabsorption. Carbonic anhydrase inhibitors inhibit bicarbonate absorption in the proximal tubule. Osmotic diuretics like mannitol are filtered but not reabsorbed, drawing water out of cells. Potassium-sparing diuretics like amiloride act late in the distal nephron to inhibit Na reabsorption. Diuretic combinations can have synergistic effects.
A diuretic is a chemical that increases urine production by inhibiting sodium reabsorption in the nephron at four major sites. The primary sites are the proximal tubule, thick ascending limb of Henle's loop, distal convoluted tubule, and connecting tubule/cortical collecting tubule. Diuretics work by blocking sodium transport mechanisms like cotransporters at these sites, causing increased excretion of sodium and water. The specific transport mechanisms and diuretic drug targets vary between nephron segments.
Diuretics are chemicals that increase urine formation by increasing sodium and chloride ion excretion. There are several classes of diuretics that act at different sites along the nephron. Loop diuretics act in the ascending loop of Henle by inhibiting sodium-potassium-chloride transport. Thiazides act in the distal convoluted tubule by inhibiting sodium and chloride transport. Carbonic anhydrase inhibitors act in the proximal tubule by inhibiting the enzyme carbonic anhydrase. Potassium-sparing diuretics act in the collecting duct and do not promote potassium secretion. Osmotic diuretics act by increasing osmotic pressure in the proximal tubule and loop of Henle to prevent water
This document provides information on loop diuretics and potassium sparing diuretics. It begins with an overview of normal urine formation and sites of renal reabsorption. It then classifies diuretics and discusses the mechanisms and sites of action of loop diuretics like furosemide and torsemide as well as potassium sparing diuretics like spironolactone and amiloride. It notes their therapeutic uses, interactions, and resistance. In recent years, new loop diuretic compounds like CRE 10904 have been developed.
This document provides an overview of diuretics, including their definition, classification, mechanisms of action, and side effects. It discusses the physiology of urine formation and the roles of the kidney in homeostasis. Specific sections cover thiazide diuretics, loop diuretics, their mechanisms in inhibiting sodium reabsorption in the distal tubule and thick ascending limb, respectively. Adverse effects include hypokalemia, hyperuricemia, and effects on calcium and magnesium levels. The document compares the potencies and durations of action of different diuretic classes and individual drugs.
Diuretic agents work by increasing urine output and sodium excretion. There are several classes of diuretics including carbonic anhydrase inhibitors, loop diuretics, osmotic diuretics, potassium-sparing diuretics, and thiazide diuretics. Nursing care involves monitoring for therapeutic and adverse effects such as hypokalemia, hypotension, and fluid imbalance.
Diuretics are drugs that cause a net loss of sodium and water in urine. They are classified as high efficacy loop diuretics, medium efficacy thiazide diuretics, and weak adjunctive diuretics. Loop diuretics act in the thick ascending limb of the loop of Henle to inhibit sodium reabsorption. Thiazide diuretics act in the distal convoluted tubule. Carbonic anhydrase inhibitors act in the proximal convoluted tubule. Potassium sparing diuretics act in the late distal tubule and collecting duct. Common uses include treating hypertension, heart failure, kidney disease, calcium disorders, and poisoning. Adverse effects can include hypokalemia, hy
This document discusses diuretics, which are medications that increase urine output. It covers the four anatomical sites in the nephron where diuretics act: the proximal convoluted tubule, the thick ascending loop of Henle, the distal tubule, and the connecting tubule and collecting duct. It provides details on the classes of diuretics that act at each site, including their mechanisms of action, structure-activity relationships, examples of medications, uses, and adverse effects. Thorough understanding of diuretic medicinal chemistry helps clinicians appropriately tailor diuretic therapy to individual patients.
The document discusses various classes of diuretic drugs, including their mechanisms of action, therapeutic uses, and adverse effects. It focuses on loop diuretics, which act on the thick ascending limb of the loop of Henle to inhibit sodium and chloride reabsorption, resulting in increased urinary excretion of sodium, chloride, potassium, magnesium, and calcium. Loop diuretics are potent and commonly used to treat edema associated with congestive heart failure or liver/kidney disease but can cause electrolyte imbalances and other adverse effects if not carefully monitored.
This document discusses different classes of diuretic drugs, including their sites of action in the nephron, mechanisms of action, therapeutic uses, and side effects. It covers osmotic diuretics, carbonic anhydrase inhibitors, thiazide diuretics, loop diuretics, and potassium-sparing diuretics. The main points are that diuretics work by inhibiting transport in different parts of the nephron like the proximal tubule, loop of Henle, or distal convoluted tubule. They are used to treat conditions like edema, hypertension, and heart failure. Common side effects among the classes include electrolyte imbalances and metabolic alterations.
Diuretics work by inhibiting reabsorption of sodium and water in the kidneys, increasing urine output. There are several types of diuretics that act in different parts of the kidney: loop diuretics act in the ascending limb of Henle's loop, thiazide diuretics act in the distal convoluted tubule, and potassium-sparing diuretics act in the cortical collecting tubule. Diuretics are used to treat conditions like heart failure, liver failure, renal failure, and hypertension by mobilizing edema fluid and maintaining urine volume. Common side effects include hypokalemia, hyperglycemia, and increased uric acid levels.
Loop diuretics are high efficacy diuretics that act by inhibiting sodium transport in the loop of Henle, causing increased excretion of sodium, chloride, potassium, magnesium, and water in urine. They are used to treat severe or refractory edema and acute heart failure. Adverse effects include hypokalemia, hypomagnesemia, and ototoxicity when combined with other ototoxic drugs. Loop diuretics increase renal blood flow, unlike thiazides, making them preferable for hypertension in patients with renal impairment.
The document provides an overview of renal pharmacology and physiology, with a focus on diuretic drugs. It discusses how the kidney regulates fluid and electrolytes and introduces different classes of diuretics, including loop diuretics, thiazides, and osmotic agents. It describes the mechanisms of action and sites of action for different diuretics in renal structures like the proximal tubule, loop of Henle, and collecting duct. Key effects of diuretics include increased sodium, water, and electrolyte excretion. The document also reviews toxicity concerns for different diuretic classes.
Use of diuretics in congestive heart failure. pptxJimmy Potter
This document discusses the use of diuretics in congestive heart failure (CHF). It defines CHF and describes the signs, symptoms, and pathophysiology. The main therapeutic objectives for CHF are to relieve symptoms, enhance quality of life, prevent complications, and prolong life. Diuretics are effective for symptomatic relief in CHF patients with edema by rapidly relieving dyspnea. The document reviews the different classes of diuretics, their mechanisms of action, pharmacokinetic profiles, dosages, adverse effects, interactions, and considerations for resistance. Combination diuretic therapy can be effective for patients who do not respond to single agents.
Diuretics work by interfering with electrolyte reabsorption in the kidney to promote excretion of sodium and water. They are classified based on where in the nephron they act: carbonic anhydrase inhibitors act in the proximal convoluted tubule; loop diuretics act on the ascending loop of Henle; thiazide diuretics act in the distal convoluted tubule; and aldosterone inhibitors act on the collecting tubule. Common diuretics include acetazolamide, furosemide, hydrochlorothiazide, and spironolactone. They are used to treat conditions like hypertension, heart failure, and edema. Adverse effects can include electrolyte imbalances like hyp
Diuretics are drugs that increase urine output by inhibiting reabsorption of sodium, chloride and water in the kidneys. There are several classes of diuretics including thiazide diuretics, loop diuretics, carbonic anhydrase inhibitors, and potassium-sparing diuretics. Thiazide diuretics such as chlorothiazide and hydrochlorothiazide act by inhibiting sodium reabsorption in the distal convoluted tubule. Loop diuretics like furosemide act in the loop of Henle and are the most potent class. Carbonic anhydrase inhibitors including acetazolamide inhibit bicarbonate reabsorption in the proximal tubule. Potassium-spar
Diuretics
Pharmacology
Katzung
Abnormalities in fluid volume and electrolyte composition are common and important clinical disorders. Drugs that block specific transport functions of the renal tubules are valuable clinical tools in the treatment of these disorders. Although various agents that increase urine volume (diuretics) have been described since antiquity, it was not until 1937 that carbonic anhydrase inhibitors were first described and not until 1957 that a much more useful and powerful diuretic agent (chlorothiazide) became available. Technically, a “diuretic” is an agent that increases urine volume, whereas a “natriuretic” causes an increase in renal sodium excretion and an “aquaretic” increases excretion of solute-free water. Because natriuretics almost always also increase water excretion, they are usually called diuretics. Osmotic diuretics and antidiuretic hormone antagonists (see Agents That Alter Water Excretion) are aquaretics that are not directly natriuretic.
This document discusses different types of diuretic drugs, which cause increased urination by reducing sodium and water reabsorption in the kidneys. It describes carbonic anhydrase inhibitors which act in the proximal tubule; osmotic diuretics like glycerin and mannitol which act in the loop of Henle; high-ceiling diuretics like furosemide that inhibit sodium reabsorption in the thick ascending limb; thiazide diuretics which inhibit sodium-chloride symporters in the distal tubule; potassium-sparing diuretics like amiloride that inhibit sodium channels in the late distal tube and collecting duct; and mineralocorticoid receptor antagonists like
This document discusses the mechanism of action and classification of diuretic drugs. It begins by explaining the normal physiology of urine formation in the kidney and sites of tubular reabsorption. It then classifies diuretics based on potency and site of action. Loop diuretics such as furosemide are described as very potent diuretics that act in the thick ascending loop of Henle by inhibiting sodium-potassium-chloride reabsorption. Their pharmacological effects and mechanisms are explained in detail. Other loop diuretics including torsemide and bumetanide are also briefly discussed. The document concludes by noting some important drug interactions with loop diuretics.
This document provides information on diuretics, including what they are, the conditions they can treat, their mechanisms of action, and classifications. The main points are:
1. Diuretics promote urine production and can treat conditions like heart failure, kidney issues, hypertension, and liver cirrhosis. They work by either increasing glomerular filtration or decreasing tubular reabsorption of water and ions in the kidneys.
2. Diuretics can be classified as mercurial or non-mercurial. Common non-mercurial classes include thiazides, carbonic anhydrase inhibitors, and loop diuretics which act at different parts of the nephron.
3. Thiaz
This document provides an overview of diuretics, including their classification, mechanisms of action, pharmacology, and uses. It discusses urine formation through the nephron and covers various diuretic drug classes like carbonic anhydrase inhibitors, loop diuretics, thiazides, and potassium-sparing diuretics. Key points include that diuretics act primarily by inhibiting sodium transport at different nephron sites and that their primary effects impact electrolyte excretion patterns and secondary effects.
The document discusses the sites of action and mechanisms of various diuretic drugs. It begins by describing the role of the kidneys in volume homeostasis and the general principles of diuretic action. It then details the specific sites where different classes of diuretics act - in the proximal convoluted tubule, loop of Henle, distal convoluted tubule, and cortical collecting duct. Loop diuretics like furosemide act in the thick ascending limb of the loop of Henle. Thiazides act in the distal convoluted tubule. Potassium-sparing diuretics like spironolactone act in the collecting duct. The summary focuses on the key sites and classes of diuretics.
This document provides information on diuretic drugs, including their mechanisms and sites of action, indications for use, and adverse effects. It discusses loop diuretics like furosemide and bumetanide that act in the thick ascending loop of Henle, thiazide diuretics like hydrochlorothiazide that act in the distal tubule, and potassium-sparing diuretics like amiloride and spironolactone that act in the collecting ducts. It also covers carbonic anhydrase inhibitors and osmotic diuretics. Non-diuretic uses and combinations with other drugs are mentioned. Resistance, interactions, and specific adverse effects are summarized for each drug class.
in this presentation i have tried to briefly discuss about diuretics (water pills), their classification, mechanism of action, pharmacokinetics and pharmacodynamics of these drugs
Mechanism of urine formation
Definition and classification of diuretics
MOA and SAR of each class
Their dose and adverse effects
Pharmacologicaol uses
all about diuretics
This document provides an overview of diuretic agents, including their definition, purposes, side effects, mechanisms of action, and types. It discusses how diuretics work by inhibiting sodium and water reabsorption in the renal tubule system. The major types of diuretics are described along with their mechanisms and sites of action, including carbonic anhydrase inhibitors, osmotic diuretics, loop diuretics, thiazides, and potassium-sparing diuretics. The renal tubule transport system and characteristics of different tubule segments are also summarized.
I. The proximal tubule reabsorbs sodium, bicarbonate, glucose and other solutes. Carbonic anhydrase and NHE3 transporters facilitate reabsorption. Carbonic anhydrase inhibitors and adenosine receptor antagonists act in the proximal tubule.
II. In the loop of Henle, the thin descending limb is water permeable while the thick ascending limb actively transports sodium via NKCC2 transporters. Loop diuretics block NKCC2.
III. The distal convoluted tubule reabsorbs sodium and chloride via NCC transporters. Thiazide diuretics block NCC.
IV. The collecting duct regulates sodium, potassium and water balance.
Diuretics are drugs that cause a net loss of sodium and water in urine. They are classified as high efficacy loop diuretics, medium efficacy thiazide diuretics, and weak adjunctive diuretics. Loop diuretics act in the thick ascending limb of the loop of Henle to inhibit sodium reabsorption. Thiazide diuretics act in the distal convoluted tubule. Carbonic anhydrase inhibitors act in the proximal convoluted tubule. Potassium sparing diuretics act in the late distal tubule and collecting duct. Common uses include treating hypertension, heart failure, kidney disease, calcium disorders, and poisoning. Adverse effects can include hypokalemia, hy
This document discusses diuretics, which are medications that increase urine output. It covers the four anatomical sites in the nephron where diuretics act: the proximal convoluted tubule, the thick ascending loop of Henle, the distal tubule, and the connecting tubule and collecting duct. It provides details on the classes of diuretics that act at each site, including their mechanisms of action, structure-activity relationships, examples of medications, uses, and adverse effects. Thorough understanding of diuretic medicinal chemistry helps clinicians appropriately tailor diuretic therapy to individual patients.
The document discusses various classes of diuretic drugs, including their mechanisms of action, therapeutic uses, and adverse effects. It focuses on loop diuretics, which act on the thick ascending limb of the loop of Henle to inhibit sodium and chloride reabsorption, resulting in increased urinary excretion of sodium, chloride, potassium, magnesium, and calcium. Loop diuretics are potent and commonly used to treat edema associated with congestive heart failure or liver/kidney disease but can cause electrolyte imbalances and other adverse effects if not carefully monitored.
This document discusses different classes of diuretic drugs, including their sites of action in the nephron, mechanisms of action, therapeutic uses, and side effects. It covers osmotic diuretics, carbonic anhydrase inhibitors, thiazide diuretics, loop diuretics, and potassium-sparing diuretics. The main points are that diuretics work by inhibiting transport in different parts of the nephron like the proximal tubule, loop of Henle, or distal convoluted tubule. They are used to treat conditions like edema, hypertension, and heart failure. Common side effects among the classes include electrolyte imbalances and metabolic alterations.
Diuretics work by inhibiting reabsorption of sodium and water in the kidneys, increasing urine output. There are several types of diuretics that act in different parts of the kidney: loop diuretics act in the ascending limb of Henle's loop, thiazide diuretics act in the distal convoluted tubule, and potassium-sparing diuretics act in the cortical collecting tubule. Diuretics are used to treat conditions like heart failure, liver failure, renal failure, and hypertension by mobilizing edema fluid and maintaining urine volume. Common side effects include hypokalemia, hyperglycemia, and increased uric acid levels.
Loop diuretics are high efficacy diuretics that act by inhibiting sodium transport in the loop of Henle, causing increased excretion of sodium, chloride, potassium, magnesium, and water in urine. They are used to treat severe or refractory edema and acute heart failure. Adverse effects include hypokalemia, hypomagnesemia, and ototoxicity when combined with other ototoxic drugs. Loop diuretics increase renal blood flow, unlike thiazides, making them preferable for hypertension in patients with renal impairment.
The document provides an overview of renal pharmacology and physiology, with a focus on diuretic drugs. It discusses how the kidney regulates fluid and electrolytes and introduces different classes of diuretics, including loop diuretics, thiazides, and osmotic agents. It describes the mechanisms of action and sites of action for different diuretics in renal structures like the proximal tubule, loop of Henle, and collecting duct. Key effects of diuretics include increased sodium, water, and electrolyte excretion. The document also reviews toxicity concerns for different diuretic classes.
Use of diuretics in congestive heart failure. pptxJimmy Potter
This document discusses the use of diuretics in congestive heart failure (CHF). It defines CHF and describes the signs, symptoms, and pathophysiology. The main therapeutic objectives for CHF are to relieve symptoms, enhance quality of life, prevent complications, and prolong life. Diuretics are effective for symptomatic relief in CHF patients with edema by rapidly relieving dyspnea. The document reviews the different classes of diuretics, their mechanisms of action, pharmacokinetic profiles, dosages, adverse effects, interactions, and considerations for resistance. Combination diuretic therapy can be effective for patients who do not respond to single agents.
Diuretics work by interfering with electrolyte reabsorption in the kidney to promote excretion of sodium and water. They are classified based on where in the nephron they act: carbonic anhydrase inhibitors act in the proximal convoluted tubule; loop diuretics act on the ascending loop of Henle; thiazide diuretics act in the distal convoluted tubule; and aldosterone inhibitors act on the collecting tubule. Common diuretics include acetazolamide, furosemide, hydrochlorothiazide, and spironolactone. They are used to treat conditions like hypertension, heart failure, and edema. Adverse effects can include electrolyte imbalances like hyp
Diuretics are drugs that increase urine output by inhibiting reabsorption of sodium, chloride and water in the kidneys. There are several classes of diuretics including thiazide diuretics, loop diuretics, carbonic anhydrase inhibitors, and potassium-sparing diuretics. Thiazide diuretics such as chlorothiazide and hydrochlorothiazide act by inhibiting sodium reabsorption in the distal convoluted tubule. Loop diuretics like furosemide act in the loop of Henle and are the most potent class. Carbonic anhydrase inhibitors including acetazolamide inhibit bicarbonate reabsorption in the proximal tubule. Potassium-spar
Diuretics
Pharmacology
Katzung
Abnormalities in fluid volume and electrolyte composition are common and important clinical disorders. Drugs that block specific transport functions of the renal tubules are valuable clinical tools in the treatment of these disorders. Although various agents that increase urine volume (diuretics) have been described since antiquity, it was not until 1937 that carbonic anhydrase inhibitors were first described and not until 1957 that a much more useful and powerful diuretic agent (chlorothiazide) became available. Technically, a “diuretic” is an agent that increases urine volume, whereas a “natriuretic” causes an increase in renal sodium excretion and an “aquaretic” increases excretion of solute-free water. Because natriuretics almost always also increase water excretion, they are usually called diuretics. Osmotic diuretics and antidiuretic hormone antagonists (see Agents That Alter Water Excretion) are aquaretics that are not directly natriuretic.
This document discusses different types of diuretic drugs, which cause increased urination by reducing sodium and water reabsorption in the kidneys. It describes carbonic anhydrase inhibitors which act in the proximal tubule; osmotic diuretics like glycerin and mannitol which act in the loop of Henle; high-ceiling diuretics like furosemide that inhibit sodium reabsorption in the thick ascending limb; thiazide diuretics which inhibit sodium-chloride symporters in the distal tubule; potassium-sparing diuretics like amiloride that inhibit sodium channels in the late distal tube and collecting duct; and mineralocorticoid receptor antagonists like
This document discusses the mechanism of action and classification of diuretic drugs. It begins by explaining the normal physiology of urine formation in the kidney and sites of tubular reabsorption. It then classifies diuretics based on potency and site of action. Loop diuretics such as furosemide are described as very potent diuretics that act in the thick ascending loop of Henle by inhibiting sodium-potassium-chloride reabsorption. Their pharmacological effects and mechanisms are explained in detail. Other loop diuretics including torsemide and bumetanide are also briefly discussed. The document concludes by noting some important drug interactions with loop diuretics.
This document provides information on diuretics, including what they are, the conditions they can treat, their mechanisms of action, and classifications. The main points are:
1. Diuretics promote urine production and can treat conditions like heart failure, kidney issues, hypertension, and liver cirrhosis. They work by either increasing glomerular filtration or decreasing tubular reabsorption of water and ions in the kidneys.
2. Diuretics can be classified as mercurial or non-mercurial. Common non-mercurial classes include thiazides, carbonic anhydrase inhibitors, and loop diuretics which act at different parts of the nephron.
3. Thiaz
This document provides an overview of diuretics, including their classification, mechanisms of action, pharmacology, and uses. It discusses urine formation through the nephron and covers various diuretic drug classes like carbonic anhydrase inhibitors, loop diuretics, thiazides, and potassium-sparing diuretics. Key points include that diuretics act primarily by inhibiting sodium transport at different nephron sites and that their primary effects impact electrolyte excretion patterns and secondary effects.
The document discusses the sites of action and mechanisms of various diuretic drugs. It begins by describing the role of the kidneys in volume homeostasis and the general principles of diuretic action. It then details the specific sites where different classes of diuretics act - in the proximal convoluted tubule, loop of Henle, distal convoluted tubule, and cortical collecting duct. Loop diuretics like furosemide act in the thick ascending limb of the loop of Henle. Thiazides act in the distal convoluted tubule. Potassium-sparing diuretics like spironolactone act in the collecting duct. The summary focuses on the key sites and classes of diuretics.
This document provides information on diuretic drugs, including their mechanisms and sites of action, indications for use, and adverse effects. It discusses loop diuretics like furosemide and bumetanide that act in the thick ascending loop of Henle, thiazide diuretics like hydrochlorothiazide that act in the distal tubule, and potassium-sparing diuretics like amiloride and spironolactone that act in the collecting ducts. It also covers carbonic anhydrase inhibitors and osmotic diuretics. Non-diuretic uses and combinations with other drugs are mentioned. Resistance, interactions, and specific adverse effects are summarized for each drug class.
in this presentation i have tried to briefly discuss about diuretics (water pills), their classification, mechanism of action, pharmacokinetics and pharmacodynamics of these drugs
Mechanism of urine formation
Definition and classification of diuretics
MOA and SAR of each class
Their dose and adverse effects
Pharmacologicaol uses
all about diuretics
This document provides an overview of diuretic agents, including their definition, purposes, side effects, mechanisms of action, and types. It discusses how diuretics work by inhibiting sodium and water reabsorption in the renal tubule system. The major types of diuretics are described along with their mechanisms and sites of action, including carbonic anhydrase inhibitors, osmotic diuretics, loop diuretics, thiazides, and potassium-sparing diuretics. The renal tubule transport system and characteristics of different tubule segments are also summarized.
I. The proximal tubule reabsorbs sodium, bicarbonate, glucose and other solutes. Carbonic anhydrase and NHE3 transporters facilitate reabsorption. Carbonic anhydrase inhibitors and adenosine receptor antagonists act in the proximal tubule.
II. In the loop of Henle, the thin descending limb is water permeable while the thick ascending limb actively transports sodium via NKCC2 transporters. Loop diuretics block NKCC2.
III. The distal convoluted tubule reabsorbs sodium and chloride via NCC transporters. Thiazide diuretics block NCC.
IV. The collecting duct regulates sodium, potassium and water balance.
I. The proximal tubule reabsorbs sodium, bicarbonate, glucose and other solutes. Carbonic anhydrase and NHE3 transporters facilitate reabsorption. Carbonic anhydrase inhibitors and adenosine receptor antagonists act in the proximal tubule.
II. In the loop of Henle, the thin descending limb is water permeable while the thick ascending limb actively transports sodium via NKCC2 transporters. Loop diuretics inhibit this transporter.
III. The distal convoluted tubule reabsorbs sodium and chloride via NCC cotransporters and regulates calcium reabsorption. Thiazide diuretics act on the NCC transporter.
IV
This document discusses the classification and mechanisms of different types of diuretic drugs. It describes high efficacy diuretics that inhibit sodium-potassium-chloride cotransport, medium efficacy diuretics that inhibit sodium-chloride symport like thiazide diuretics, and weak diuretics including carbonic anhydrase inhibitors, potassium sparing diuretics, and osmotic diuretics. It also covers the sites of action and transport mechanisms affected by these diuretic classes in different parts of the nephron like the thick ascending limb of Henle's loop and distal convoluted tubule.
Loop of Henle with its complex anatomy and even more complicated physiology has long remained an enigma to researchers all around the world. Here we discuss about the functional anatomy and the transport characteristics of Loop of Henle.
Reabsorption In Renal Tubule (The Guyton and Hall physiology)Maryam Fida
Features of PCTPCT have high capacity of active & passive re-absorption.
This is due to special cellular features of epithelial cells.
They have increased no. of mitochondria due to high metabolic activity.
brush border on luminal (apical) side.
Brush border contains protein carrier molecules to transport Na+ by co-transport mechanism with other substances (a.acids, glucose etc).
Additional sodium is transported by COUNTER-TRANSPORT that reabsorb sodium while secreting hydrogen.
About 65 % of filtered load of Na+ & water is reabsorbed in PCT.
A lower % age of Cl- is also absorbed.
In 1st half of PC tubules, Na+ is re-absorbed by co-transport along with glucose, a.acids and other solutes.
In 2nd half of PC tubules, mainly Na+ is reabsorbed with Cl- and some of glucose + a.acids remain un-absorbed.
2nd half of PCT has high conc of Cl- (140 mEq/L) as compared to 1st half (105 mEq/L).
1) The document discusses the structure and function of the nephron, the functional unit of the kidney.
2) Key processes in the nephron include filtration at the bowman's capsule and reabsorption and secretion of substances at the proximal convoluted tubule and distal convoluted tubule.
3) Waste products are secreted and useful materials like sodium, chloride, and bicarbonate are reabsorbed through complex exchange mechanisms involving protein transporters and ion pumps.
This document discusses different classes of diuretic medications, their mechanisms of action, indications, and side effects. It describes:
1) Loop diuretics which inhibit sodium reabsorption in the loop of Henle, causing increased excretion of sodium, chloride, and water. Their main indications include heart failure and edema.
2) Thiazide diuretics which inhibit sodium reabsorption in the distal convoluted tubule. They are used to treat hypertension and have fewer side effects than loop diuretics.
3) Carbonic anhydrase inhibitors which inhibit bicarbonate reabsorption in the proximal tubule, causing a metabolic acidosis. Their main use is for glaucoma.
This document provides an overview of renal physiology, covering the following key points in 3 sentences:
The kidneys have excellent blood supply and filter plasma to remove waste and regulate water/ion balance through processes of glomerular filtration, tubular reabsorption and secretion; the nephron is the functional unit where filtration occurs at the glomerulus and capillaries aid reabsorption; precise control of filtration, reabsorption of substances like sodium, glucose and water, and secretion of potassium allows the kidneys to maintain electrolyte and fluid homeostasis.
The kidneys lie on the posterior abdominal wall, one on each side of the vertebral column, behind the peritoneum and below the diaphragm
The nephron consists of a tubule closed at one end, the other end opening into a collecting tubule
Continuing from the glomerular capsule the remainder of the nephron is about 3 cm long and is described in three parts:
the proximal convoluted tubule
the medullary loop (loop of Henle)
the distal convoluted tubule, leading into a collecting duct
High efficacy diuretics (Inhibitors of Na-+K+-2Cl¯ cotransport)
Sulphamoyl derivatives : Furosemide, Bumetanide, Torasemide
2. Medium efficacy diuretics (Inhibitors of Na+-Cl¯ symport)
Benzothiadiazines (thiazides) Hydrochlorothiazide, Benzthiazide, Hydroflumethiazide, Bendroflumethiazide
Thiazide like (related heterocyclics) Chlorthalidone, Metolazone, Xipamide, Indapamide, Clopamide
3. Weak or adjunctive diuretics
(a) Carbonic anhydrase inhibitors : Acetazolamide
(b) Potassium sparing diuretics
Aldosterone antagonist: Spironolactone, Eplerenone
Inhibitors of renal epithelial Na+ channel: Triamterene, Amiloride.
(c) Osmotic diuretics :Mannitol, Isosorbide, Glycerol
Carbonic anhydrase and glutaminase are key enzymes involved in renal acid-base regulation in the proximal tubule cells. Carbonic anhydrase generates protons and bicarbonate ions from carbon dioxide and water to facilitate proton secretion and bicarbonate reabsorption. Glutaminase produces ammonium ions from glutamine that are secreted, along with protons, to buffer acids. Together these reactions help maintain blood pH within a normal range. The proximal tubule also efficiently reabsorbs amino acids, glucose and other filtered solutes using sodium-coupled active transport mechanisms.
The proximal tubule reabsorbs approximately 60-65% of the filtered load, including sodium, chloride, bicarbonate, potassium, glucose, and amino acids. Transport occurs through both transcellular and paracellular pathways. Glucose is actively transported across the apical membrane via sodium-glucose co-transporters and exits across the basolateral membrane. Sodium is reabsorbed primarily via the sodium-potassium ATPase pump. Bicarbonate is reabsorbed through secretion of hydrogen ions via sodium-hydrogen exchange and reabsorption of bicarbonate. The proximal tubule also plays an important role in reabsorption of other substances like phosphate, calcium, magnesium and
The document provides an overview of renal pharmacology. It discusses the structure and function of the renal corpuscle and nephron. It describes the processes of filtration, reabsorption, and secretion that occur along the nephron to produce urine. It also discusses the sites and mechanisms of action of various classes of diuretic drugs, including loop diuretics, thiazide diuretics, and potassium-sparing diuretics.
The document summarizes key aspects of the loop of Henle and distal tubule in the kidney nephron. It discusses how the loop of Henle regulates salt concentration in urine by reabsorbing sodium, chloride, potassium and other electrolytes. The descending limb is permeable to water but not solutes, increasing osmolality. The thick ascending limb reabsorbs 25% of filtered sodium load. The distal tubule and collecting duct further regulate urine concentration and composition by reabsorbing substances like sodium, water, calcium and secreting drugs and uric acid, controlled by hormones like aldosterone and ADH.
The document describes renal physiology and the transport of solutes across renal tubules. It discusses how solutes like sodium, glucose, and water are reabsorbed or secreted at different parts of the nephron through passive and active transport mechanisms. Countercurrent exchange in the loop of Henle and the actions of hormones help generate the osmotic gradients needed to concentrate urine from plasma filtrate.
The document describes renal physiology and the transport of solutes across renal tubules. It discusses how solutes like sodium, glucose, and water are reabsorbed or secreted at different parts of the nephron through passive and active transport mechanisms. Countercurrent multiplication in the loop of Henle and the actions of hormones like ADH and aldosterone help generate concentrated urine by regulating solute and water transport across tubular cells.
The document describes renal physiology and the processes of urine formation in the nephron. It discusses how solutes are transported across renal tubules through passive and active transport mechanisms. Key parts of the nephron, including the proximal tubule, loop of Henle, and collecting duct, reabsorb water and solutes like sodium, chloride, and glucose to varying degrees. The countercurrent multiplier system in the loop of Henle and transport of urea in the medullary interstitium allow the kidney to concentrate urine up to 1200-1400 mOsm/L.
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Webinar Recording: https://www.panagenda.com/webinars/hcl-notes-und-domino-lizenzkostenreduzierung-in-der-welt-von-dlau/
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Wir erklären Ihnen, wie Sie häufige Konfigurationsprobleme lösen können, die dazu führen können, dass mehr Benutzer gezählt werden als nötig, und wie Sie überflüssige oder ungenutzte Konten identifizieren und entfernen können, um Geld zu sparen. Es gibt auch einige Ansätze, die zu unnötigen Ausgaben führen können, z. B. wenn ein Personendokument anstelle eines Mail-Ins für geteilte Mailboxen verwendet wird. Wir zeigen Ihnen solche Fälle und deren Lösungen. Und natürlich erklären wir Ihnen das neue Lizenzmodell.
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Presentation of the OECD Artificial Intelligence Review of Germany
Diuretics
1. 1
Diuretics
Xiaoping Du, MD, PhD., Department of Pharmacology
Phone: (312) 355 0237; Email: xdu@uic.edu
I. Overview
1. Definition:
Diuretic agents are drugs that increase renal excretion of water and solutes (mainly sodium
salt).
2. Purpose of diuretic therapy:
Major purposes of diuretic therapy are to decrease fluid volume of the body, and to adjust the
water and electrolyte balance.
Diuretics are often used in the management of pathological conditions such as edema (e.g. in
congestive heart failure and certain renal diseases) and hypertension.
3. Commonly seen side effects:
The most common side effect associated with most diuretics is the distortion of water and
electrolyte balance (such as hypokalemia, hyperkalemia, metabolic alkalosis, acidosis, and
hyponatremia). Specific side effects of each diuretic are mainly determined by its mechanism of
action and conditions of the patient.
4. Mechanisms of action:
Most diuretics exert their effects by inhibiting tubular sodium and water reabsorption by
epithelial cells lining the renal tubule system. Certain diuretics (such as carbonic anhydrase
inhibitors, loop diuretics, thiazide-like diuretics and potassium-sparing diuretics) suppress sodium
and water reabsorption by inhibiting the function of specific proteins that are responsible for (or
participate in) the transportation of electrolytes across the epithelial membrane; osmotic diuretics
inhibit water and sodium reabsorption by increasing intratubular osmotic pressure. Different types
of diuretics may inhibit different transporters in different segments of the tubular system.
5. Different types of diuretics
Type Example Site of action Mechanism
Carbonic anhydrase (CA) acetazolamide Proximal tubule inhibition of CA
inhibitors
Osmotic Mannitol Loop of Henle (DTL) Osmotic action
Proximal tubule
Loop diuretics furosemide Loop of Henle (TAL) inhibition of Na+-K+-
2Cl- symport
Thiazides hydrochlorothiazide Distal convoluted inhibition of Na+-Cl-
tubule symport
Potassium-sparing diuretics
(1) Na+ channel triamterene, Cortical collecting tubule inhibition of Na+
inhibitors amiloride channel
(2) aldosterone spironolactone Cortical collecting tubule inhibition of
2. 2
antagonists aldosterone receptor
II. Renal tubule transport mechanisms
1. Basic mechanisms for transmembrane transport of solutes
A Active transport
a. Primary active transport: Na+-K+ ATPase (sodium pump) in the basolateral membrane
of epithelial cells is the major driving force for the transport of solutes in kidney.
b. Secondary active transport: Secondary active transport utilizes energy available from
the transmembrane Na+ gradient established by sodium pump to transport other solutes against
their electrochemical gradient. Secondary active transport includes symport (co-transport) which
transports sodium and other solutes in the same direction, and antiport (counter-transport) which
exchanges movement of sodium for the counter movement of other solutes.
B Passive transport
a. Convection.
b. Simple diffusion.
c. Channel-mediated diffusion.
d. Carrier-mediated diffusion.
2. Characteristics of different segments of the renal tubule.
A. Proximal tubule
Proximal tubule reabsorbs 40% of filtered salt and 60% filtered water.
Proximal tubule is the major site for sodium carbonate reabsorption (85%), which requires
sodium-proton exchanger (antiport) and carbonic anhydrase. Inhibitors of carbonic anhydrase exert
diuretic effects by inhibition of sodium carbonate transport.
The proximal tubule is the major site for the secretion of the organic acid and bases to the
tubular lumen. This is the mechanism by which most diuretics reach their sites of action.
B Loop of Henle
Descending thin limb (DTL) of loop of Henle is highly permeable to water but non-permeable
to sodium. Water is extracted from DTL by osmotic pressure from the hypertonic medullary
interstitium.
Thick ascending limb (TAL) of loop of Henle actively reabsorbs NaCl and KCl via the Na+-
K+-2Cl- symport (35% of salt absorption). TAL is not permeable to water and thus is a urine-diluting
segment. Active sodium reabsorption at TAL contributes to the hypertonicity in medullary
interstitium.
Loop diuretics inhibit the Na+-K+--2Cl- symport.
Na+-K+-2Cl- symport and sodium pump together generate a positive lumen potential that
drives the reabsorption of Ca++ and Mg++.
C. Distal convoluted tubule
3. 3
Distal convoluted tubule absorbs about 10% of NaCl via Na+-Cl- symport, which is a different
protein from the Na+-K+-2Cl- symport.
Thiazides inhibit Na+-Cl- symport.
D. Collecting tubule
The collecting tubule is the final site for NaCl reabsorption (2-5% NaCl).
Sodium reabsorption in the
collecting tubule is regulated by
aldosterone. Aldosterone antagonists
exert diuretic effect by inhibiting
aldosterone receptor.
Sodium reabsorption in the
collecting tubule is mediated by a sodium
channel, which can be inhibited by
amiloride and triamterene.
The collecting tubule is the major
site for K+ secretion. K+ secretion is
driven by a negative lumen potential
established by Na+ reabsorption. Drugs
that inhibit Na+ reabsorption in the
collecting tubule thus also inhibit K+
secretion. These drugs are called K+-
sparing diuretics. Diuretics that act on
Tub ule Transp o r t syst em
upstream segments of the tubular system
increase Na+ concentration in the tubular
fluid, resulting in increased Na+ absorption in the collecting tubule. These diuretics may thus cause
increased K+ secretion, and hypokalemia.
Water permeability in the collecting tubule is regulated by anti-diuretic hormone (ADH).
III. Pharmacology of diuretics
1. Carbonic anhydrase (CA) inhibitors
A. Chemistry
Sulfonamide derivatives (See the table below).
Sulfonamide group (-SO2NH2) is essential for activity.
4. 4
Inhibitors of Carbonic Anhydrase
Acetazolamide
Dichlorphenamide
Methazolamide
B. Mechanism of action
This class of diuretics inhibits carbonic
anhydrase in the membrane and cytoplasm of the
epithelial cells. The primary site of action is in
proximal tubules. Na +
In the proximal tubule, Na+-H+ antiport in N a+
ATP
K+
the apical membrane of epithelial cells transports H CO + H +
3
-
H + + HC - O3
H + into tubular lumen in exchange for Na+ Na +
movement into the cytoplasm. Na + in the CA C A
cytoplasm is pumped out to the interstitium by CA In h ib i t o rs
sodium pump. H+ in the lumen reacts with H O + CO 2 2
H O + CO
2 2
HCO3- to form H2CO3. H2CO3 is dehydrated to
CO2 and H2O. This reaction is catalyzed by
carbonic anhydrase in the luminal membrane.
Both CO2 and H2O can permeate into cells, and Pr o x i al co nvolu t ed t ub u le
m
Int erst it ium
rehydrate to form H2CO3. The rehydration is
Lumen
epit heli l cell
a
catalyzed by the cytoplasmic carbonic anhydrase.
H2CO3 dissociates to form H+ which is secreted
into lumen, and HCO3- which is transported into
interstitium. Inhibition of anhydrase thus inhibits HCO3- reabsorption. Accumulation of HCO3- in
the tubular lumen subsequently inhibits Na+-H+ exchange and Na+ reabsorption.
The increase in sodium concentration in the tubular fluid may be compensated partially by
increased NaCl reabsorption in later segments of the tubule. Thus, the diuretic effect of the carbonic
anhydrase inhibitors is mild.
C. Clinical indications
(i) Glaucoma
(ii) Treatment of cystinuria, and enhance excretion of uric acid and other organic acids.
(iii) Metabolic alkalosis
5. 5
(iv) Acute mountain sickness
D. Major side effects and toxicity
(i) Electrolyte imbalance: Hyperchloremic metabolic acidosis is the most common side
effect.
(ii) Renal stones
(iii) Central nerve system effects: drowsiness and paresthesias.
(iv) Allergic reactions to sulfonamides such as rash, fever, and interstitial nephritis.
2. Osmotic diuretics
A. Chemistry
Osmotic Diuretics
Glycerin
Isosorbide
Mannitol
Urea
R, renal excretion; M metabolism; ID, insufficient data.
6. 6
B. Mechanism of action
Osmotic diuretics are substances to which the tubule epithelial cell membrane has limited
permeability. When administered (often in a large dosage), osmotic diuretics significantly increase
the osmolarity of plasma and tubular fluid. The osmotic force thus generated prevents water
reabsorption, and also extracts water from the intracellular compartment, expands extracellular fluid
volume and increases renal blood flow resulting in reduced medulla tonicity. The primary sites of
action for osmotic diuretics are the Loop of Henle and the proximal tubule where the membrane is
most permeable to water.
C. Clinical indications
(i) To increase urine volume in some patients with acute renal failure caused by ischemia,
nephrotoxins, hemoglobinuria and myoglobinuria (test for responsiveness).
(ii) Reduction of intracranial pressure before and after neurosurgery and in neurological
conditions.
(iii) Reduction of intraocular pressure before ophthalmologic procedures and during acute
attack of glaucoma.
D. Major side effect and toxicity
(i) Water and electrolyte imbalance: excessive loss of more water relative to sodium may
cause dehydration and hypernatremia.
(ii) Expansion of extracellular fluid volume may result in hyponatremia causing central
nerve system symptoms such as nausea, headache, and vomiting. In patients with congestive heart
failure, expansion of extracellular volume may produce pulmonary edema.
3. Loop diuretics
A. Chemistry
Two major classes of loop diuretics: 1) sulfonamide derivatives such as furosemide,
bumetanide and torsemide; and 2) non-sulfonamide loop diuretic such as ethacrynic acid.
7. 7
B. Mechanism of action
Loop diuretics inhibit reabsorption of NaCl and KCl by inhibiting the Na+-K+-2Cl- symport in
the luminal membrane of the thick ascending limb (TAL) of loop of Henle. As TAL is responsible for
the reabsorption of 35% of filtered sodium, and there are no significant downstream compensatory
reabsorption mechanisms, loop diuretics are highly efficacious and are thus called high ceiling
diuretics.
As the Na+-K+-2Cl- symport and sodium pump together generate a positive lumen potential
that drives the reabsorption of Ca++ and Mg++, inhibitors of the Na+-K+-2Cl- symport also inhibit
reabsorption of Ca++ and Mg++.
By unknown mechanisms (possibly prostaglandin-mediated), loop diuretics also have direct
effects on vasculature including increase in renal blood flow, and increase in systemic venous
capacitance.
8. 8
C. Major Clinical indications
(i) Acute pulmonary edema
(ii) Chronic congestive heart failure when
diminution of extracellular fluid volume is desirable to
Na+ reduce venous and pulmonary edema.
Na+ ATP
K+
(iii) Treatment of hypertension when patients
K+
2Cl - do not response satisfactorily to thiazide diuretics and
anti-hypertensive drugs.
K+
(iv) Hypercalcemia
L o o p d iu r e t ics
N a+ (v) Treatment of hyperkalemia in combination
with isotonic NaCl administration.
K+ C-
l
(vi) Used in acute renal failure to increase the
C-
l
urine flow and K+ secretion.
+
(vii) Treatment of toxic ingestions of bromide,
-
Ca 2 +
Mg2 +
fluoride and iodide (with simultaneous saline
Lum en
T h i k asce n d in g lmb
c i Int erst i i m
tu
administration).
epith elal cell
i
D. Major side effects and toxicity
(i) Hypokalemic metabolic alkalosis
(ii) Ototoxicity
(iii) Hyperuricemia
(iv) Hypomagnesemia
(v) Allergic reactions
4. Thiazides
A. Chemistry
Thiazides are also called benzothiadiazides. Thiazides are sulfonamide derivatives.
B. Mechanism of action
Thiazides inhibit a Na+-Cl- symport in the luminal membrane of the epithelial cells in the
distal convoluted tubule. Thus, Thiazides inhibit NaCl reabsorption in the distal convoluted tubule,
and may have a small effect on the NaCl reabsorption in the proximal tubule.
Thiazides enhance Ca++ reabsorption in the distal convoluted tubule by inhibiting Na+ entry
and thus enhancing the activity of Na+-Ca++ exchanger in the basolateral membrane of epithelial
cells.
C. Major clinical indications
(i) Hypertension.
(ii) Edema associated with congestive heart failure, hepatic cirrhosis and renal diseases.
(iii) Nephrolithiasis due to hypercalciuria
(iv) Nephrogenic diabetes insipidus.
D. Major side effects and toxicity
(i) Water and electrolyte imbalance is the major side effect.
9. 9
Hypokalemic metabolic alkalosis, and hyperuricemia. Also may cause extracellular volume
depletion, hypotension, hypochloremia, and hypomagnesemia. These effects are similar to that
caused by loop diuretics.
Hypercalcemia.
Hyponatremia is more common with thiazides than with loop diuretics.
(ii) Thiazides may impair glucose tolerance and hyperglycemia. Hyperglycemia can be
reduced when K+ is administered together with thiazides, suggesting that hyperglycemia may be
related to hypokelemia.
(iii) Thiazides may cause hyperlipidemia. Plasma LDL, cholesterol and triglycerides are
increased.
(iv) Allergic reactions to sulfonamides
(v) CNS symptoms and impotence can be seen but not common.
10. 10
Drug
Bendroflumethiazide
Chlorothiazide
Hydrochlorothiazide
Chlothalidone
Indapamide
Metolazone
Quinethazone
R, renal
ID, insufficient data
11. 11
Lum en Coll ct i g t ubu l
e n e Int erst i i m
tu
N a + Ch a nn e l
Pri ncip a l cell
in h ib it o rs
Na+ Na+ Na+ N a+
A TP A TP
Cl - K+ K+
K+
K+
T h ia z id e s -
AR +
Na + Na +
A DH- R
Ca2 + C a2 + H 2O
Cl -
- S p ironola c tone +
C-
l
Int ercalat ed cell
D i st al co nv o l t e d t u b u l
u e
Lum en Int erst i i m
tu
H C O3 -
epith elal cell
i
ATP Cl -
H+
Cl -
5. Potassium-sparing diuretics
(1) Na+ channel inhibitors
A. Chemistry
Amiloride and triamterene are the only two drugs in this class.
Sodium Channel Inhibitors
Amiloride
Triamterene
B. Mechanism of action
Amiloride and triamterene inhibit the sodium channel in the luminal membrane of the
collecting tubule and collecting duct. This sodium channel is critical for Na+ entry into cells down
12. 12
the electrochemical gradient created by sodium pump in the basolateral membrane, which pumps
Na+ into interstitium. This selective transepithelial transport of Na+ establishes a luminal negative
transepithelial potential which in turn drives secretion of K+ into the tubule fluid. The luminal
negative potential also facilitates H+ secretion via the proton pump in the intercalated epithelial cells
in collecting tubule and collecting duct. Inhibition of the sodium channel thus not only inhibits Na+
reabsorption but also inhibits secretion of K+ and H+, resulting in conservation of K+ and H+.
C. Major clinical indications
(i) Na+ channel inhibitors are mainly used in combination with other classes of diuretics
such as loop diuretics and thiazides in order to enhance Na+ excretion and to counteract K+ wasting
induced by these diuretics.
(ii) Pseudo-hyperaldosteronism (Liddle's syndrome).
(iii) Amiloride is used to treat Lithium-induced nephrogenic diabetes insipidus by blocking
Li+ transport into tubular epithelial cells.
(iv) Amiloride also inhibits Na+ channel in airway epithelial cells, and is used to improve
mucociliary clearance in patients with cystic fibrosis.
D. Major side effects and toxicity
(i) The major side effect is hyperkalemia.
(ii) CNS symptoms such as nausea, vomiting, headache.
(iii) Triamterene may reduce glucose tolerance.
(iv) Triamterene may induce interstitial nephritis and renal stone.
(2) Aldosterone antagonists
A. Chemistry
Spironolactone is the only available aldosterone antagonist in US. An metabolite of
spironolactone, canrenone, is also active and has a half-life of about 16 hours.
B. Mechanism of action
13. 13
Aldosterone, by binding to its receptor in the cytoplasm of epithelial cells in collecting tubule
and duct, increases expression and function of Na+ channel and sodium pump, and thus enhances
sodium reabsorption (see " Na+ channel inhibitors" above). Spironolactone competitively inhibits the
binding of aldosterone to its receptor and abolishes its biological effects.
C. Major clinical indications
(i) Used in combination with loop diuretics and thiazides in treatment of edema and
hypertension. Spironolactone enhances Na+ excretion and reduces K+ wasting.
(ii) Treatment of primary hyperaldosteronism (such as adrenal adenomas).
(iii) Treatment of edema associated with secondary hyperaldosteronism (such as cardiac
failure, hepatic cirrhosis and nephrotic syndrome). Spironolactone is the diuretic of choice in
patients with hepatic cirrhosis.
D. Major side effects and toxicity
(i) Hyperkalemia
(ii) Metabolic acidosis in cirrhotic patients
(iii) Due to its steroid structure, Spironolactone may cause gynecomastia, impotence, and
hirsutism.
(iv) CNS symptoms.