Diuretics also known as water pills increases the excretion of water and electrolytes (Na+) in
urine.
Natriuresis – large amount of sodium excreted in urine due to the action of kidneys.
Promoted by – ventricular and atrial natriuretic as well as calcitonin.
Inhibited by chemicals such as aldosterone. The drugs which increases sodium excretion are
known as natriuretic.
Diuresis – increased or excessive production of urine. The drugs which enhances the excretion
of water without loss of electrolyte is called as aquaretic.
The document summarizes different classes of diuretic drugs, including their mechanisms of action, pharmacokinetics, uses, and side effects. It discusses loop diuretics like furosemide that act in the loop of Henle, thiazide diuretics like hydrochlorothiazide that act in the distal tubule, potassium-sparing diuretics like spironolactone that antagonize aldosterone, and osmotic diuretics like mannitol that cause water diuresis through osmosis. Loop and thiazide diuretics can cause hypokalemia and metabolic alterations while potassium-sparing diuretics risk hyperkalemia if not carefully monitored. Di
Diuretics : Dr Renuka Joshi MD,DNB, (FNB )Renuka Buche
This document discusses different classes of diuretic drugs, including their mechanisms of action, examples, effects, dosages, and interactions. It covers loop diuretics like furosemide and bumetanide that act in the thick ascending loop of Henle; thiazide diuretics like hydrochlorothiazide that act in the distal convoluted tubule; and potassium-sparing diuretics like spironolactone and amiloride that act in the collecting duct. It provides recommendations for diuretic use and combinations in the treatment of heart failure and fluid overload.
Loop diuretics work by selectively inhibiting sodium chloride reabsorption in the thick ascending limb of Henle's loop. This makes them highly effective diuretic agents. They are rapidly absorbed and eliminated by the kidneys. Common loop diuretics include furosemide, bumetanide, and torsemide. Loop diuretics are used to treat conditions causing edema such as heart failure, as well as hyperkalemia and acute renal failure. Potential side effects include hypokalemia, ototoxicity, and hypomagnesemia with prolonged use.
Any substance that promotes the production of urine
All diuretics increase the excretion of water from bodies
Alternatively, an antidiuretic such as vasopressin, or antidiuretic hormone.
Diuretics are used to treat heart failure, liver cirrhosis, hypertension, water poisoning, and certain kidney diseases
This document discusses different types of diuretic drugs, how they work, and their uses. It covers high-ceiling loop diuretics which inhibit sodium reabsorption; thiazide diuretics which inhibit sodium transport in the distal convoluted tubule; carbonic anhydrase inhibitors which reduce hydrogen ion secretion; potassium-sparing diuretics which act in the cortical collecting duct; and osmotic diuretics like mannitol. Diuretics are used to treat conditions causing fluid retention like heart failure and liver disease. Side effects include electrolyte abnormalities and dehydration. Loop diuretics are commonly used for heart failure but may require intravenous administration for severe cases.
Lecture №6-1.pptx..Asian Medical InstituteVijitaPriya
1) Diuretics are drugs that increase urine output. The main classes are thiazide diuretics, loop diuretics, and potassium-sparing diuretics.
2) Thiazide diuretics such as hydrochlorothiazide are commonly used to treat hypertension. They increase the excretion of sodium and chloride but can cause hypokalemia with prolonged use.
3) Loop diuretics like furosemide have the strongest diuretic effect and are used for acute edema. However, they can cause dehydration, electrolyte imbalances, and hearing loss.
4) Potassium-sparing diuretics counteract potassium loss from other diure
Diuretics work by inhibiting sodium reabsorption in the kidney, which increases water excretion and urine output. They are classified based on their site of action along the nephron. Loop diuretics like furosemide act in the ascending loop of Henle. Thiazides such as hydrochlorothiazide act in the distal convoluted tubule. Potassium-sparing diuretics including spironolactone and amiloride act in the collecting duct. Each class of diuretic has distinct mechanisms of action, pharmacokinetics, indications, and toxicities.
The document summarizes different classes of diuretic drugs, including their mechanisms of action, pharmacokinetics, uses, and side effects. It discusses loop diuretics like furosemide that act in the loop of Henle, thiazide diuretics like hydrochlorothiazide that act in the distal tubule, potassium-sparing diuretics like spironolactone that antagonize aldosterone, and osmotic diuretics like mannitol that cause water diuresis through osmosis. Loop and thiazide diuretics can cause hypokalemia and metabolic alterations while potassium-sparing diuretics risk hyperkalemia if not carefully monitored. Di
Diuretics : Dr Renuka Joshi MD,DNB, (FNB )Renuka Buche
This document discusses different classes of diuretic drugs, including their mechanisms of action, examples, effects, dosages, and interactions. It covers loop diuretics like furosemide and bumetanide that act in the thick ascending loop of Henle; thiazide diuretics like hydrochlorothiazide that act in the distal convoluted tubule; and potassium-sparing diuretics like spironolactone and amiloride that act in the collecting duct. It provides recommendations for diuretic use and combinations in the treatment of heart failure and fluid overload.
Loop diuretics work by selectively inhibiting sodium chloride reabsorption in the thick ascending limb of Henle's loop. This makes them highly effective diuretic agents. They are rapidly absorbed and eliminated by the kidneys. Common loop diuretics include furosemide, bumetanide, and torsemide. Loop diuretics are used to treat conditions causing edema such as heart failure, as well as hyperkalemia and acute renal failure. Potential side effects include hypokalemia, ototoxicity, and hypomagnesemia with prolonged use.
Any substance that promotes the production of urine
All diuretics increase the excretion of water from bodies
Alternatively, an antidiuretic such as vasopressin, or antidiuretic hormone.
Diuretics are used to treat heart failure, liver cirrhosis, hypertension, water poisoning, and certain kidney diseases
This document discusses different types of diuretic drugs, how they work, and their uses. It covers high-ceiling loop diuretics which inhibit sodium reabsorption; thiazide diuretics which inhibit sodium transport in the distal convoluted tubule; carbonic anhydrase inhibitors which reduce hydrogen ion secretion; potassium-sparing diuretics which act in the cortical collecting duct; and osmotic diuretics like mannitol. Diuretics are used to treat conditions causing fluid retention like heart failure and liver disease. Side effects include electrolyte abnormalities and dehydration. Loop diuretics are commonly used for heart failure but may require intravenous administration for severe cases.
Lecture №6-1.pptx..Asian Medical InstituteVijitaPriya
1) Diuretics are drugs that increase urine output. The main classes are thiazide diuretics, loop diuretics, and potassium-sparing diuretics.
2) Thiazide diuretics such as hydrochlorothiazide are commonly used to treat hypertension. They increase the excretion of sodium and chloride but can cause hypokalemia with prolonged use.
3) Loop diuretics like furosemide have the strongest diuretic effect and are used for acute edema. However, they can cause dehydration, electrolyte imbalances, and hearing loss.
4) Potassium-sparing diuretics counteract potassium loss from other diure
Diuretics work by inhibiting sodium reabsorption in the kidney, which increases water excretion and urine output. They are classified based on their site of action along the nephron. Loop diuretics like furosemide act in the ascending loop of Henle. Thiazides such as hydrochlorothiazide act in the distal convoluted tubule. Potassium-sparing diuretics including spironolactone and amiloride act in the collecting duct. Each class of diuretic has distinct mechanisms of action, pharmacokinetics, indications, and toxicities.
This document provides information about different types of diuretic drugs, including their mechanisms of action, therapeutic uses, and side effects. It discusses loop diuretics like furosemide that act in the thick ascending limb of the loop of Henle, thiazide diuretics like hydrochlorothiazide that act in the distal convoluted tubule, potassium-sparing diuretics like spironolactone that act in the collecting duct, and carbonic anhydrase inhibitors like acetazolamide. The document explains how each class of diuretic increases urine output and outlines their applications in conditions like heart failure, hypertension, and edema. It also notes common adverse effects like hypokalemia, hy
Diuretics are drugs that promote the excretion of sodium and water from the body by acting on the kidney. They work by interfering with sodium transport mechanisms in different segments of the nephron. The main types are loop diuretics which act on the thick ascending limb of the loop of Henle, thiazide diuretics which act on the early distal tubule, and potassium-sparing diuretics which act on the late distal tubule and collecting duct. Diuretics are important drugs used to treat hypertension, heart failure, and edema.
This document discusses various classes of diuretic drugs including loop diuretics, thiazide diuretics, thiazide-like diuretics, potassium-sparing diuretics, carbonic anhydrase inhibitors, and osmotic diuretics. It describes the mechanisms of action, pharmacokinetics, uses, and adverse effects of these diuretic classes with a focus on furosemide, hydrochlorothiazide, acetazolamide, spironolactone, triamterene, and mannitol. Key sites of action in the nephron are identified for each drug class.
Hello friends. In this PPT I am talking about diuretics. If you like it, please do let me know in the comments section. A single word of appreciation from you will encourage me to make more of such videos. Thanks. Enjoy and welcome to the beautiful world of pharmacology where pharmacology comes to life. This video is intended for MBBS, BDS, paramedical and any person who wishes to have a basic understanding of the subject in the simplest way.
The document discusses kidney function and urine formation processes. It then summarizes the key functions of the kidneys, which include regulating electrolyte and fluid balance and removing waste from the blood. It describes the three main processes involved in urine formation - filtration, reabsorption, and secretion. The document then focuses on hypertension, describing classifications of blood pressure and types of hypertension. It outlines mechanisms for blood pressure control and discusses non-pharmacological and pharmacological approaches to hypertension management.
Hyperphosphatemia, hypomagnesemia, hypermagnesemia, and hypertension were discussed. Hyperphosphatemia can be caused by transcellular shift, increased intake, or decreased renal excretion and treated with dietary restrictions, phosphate binders, and dialysis. Hypomagnesemia can be caused by impaired absorption, increased renal excretion, or transcellular shift and treated with oral supplementation or IV therapy. Hypermagnesemia can be iatrogenic or due to renal failure and treated with calcium, saline, and dialysis if severe. Hypertension was defined and stages and emergencies discussed.
The document discusses diuretic drugs, which increase urine output. It describes the mechanisms of urine formation through glomerular filtration, tubular reabsorption and secretion. It then classifies and describes various diuretic drugs based on their site of action in the nephron (loop, distal tubule, etc.), speed/duration of action, and relative potency. Common diuretics discussed include furosemide, hydrochlorothiazide, spironolactone, and mannitol. Their indications, mechanisms, effects and side effects are summarized.
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.
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
This document provides guidelines for the management of hypokalemia according to NICE guidelines. It defines hypokalemia as a serum potassium level below 3.5 mmol/L. The major causes are decreased intake, increased losses through the kidneys or GI tract, and shifts in distribution. Treatment involves identifying and correcting the underlying cause, monitoring for magnesium deficiency, and replacing potassium orally or intravenously depending on the severity. Close monitoring of serum potassium levels, ECG, renal function, and for side effects is important when replacing potassium.
A detailed information about the diuretics - classification of drugs, mechanism of action, side effects, dosage and indications.
Classification based on the efficacy of the diuretics.
1. High
2. Moderate
3. Weak
A brief introduction given about the nephron structure and its indications.
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.
Acute renal failure is a clinical syndrome where sudden deterioration of renal function results in the kidneys' inability to maintain fluid and electrolyte homeostasis. It has various etiologies like pre-renal, intrinsic renal, and post-renal factors. Management involves treating the underlying cause, fluid resuscitation, controlling electrolyte abnormalities, and starting dialysis for refractory volume overload, hyperkalemia, acidosis, or neurological symptoms. The healthcare team works to stabilize the patient and prevent long-term kidney damage.
Acute renal failure develops when renal function is diminished such that fluid homeostasis can no longer be maintained. It can be oliguric or nonoliguric. Causes include prerenal issues like decreased perfusion, direct renal problems, and postrenal obstruction. Treatment involves fluid management, electrolyte control like treating hyperkalemia, and correcting acidosis while avoiding tetany from rapid changes. Dialysis may be needed for persistent issues.
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.
This document provides information about diuretic drugs, including their classification, mechanisms of action, effects, uses, and challenges. It discusses diuretics that act at different sites in the nephron (proximal tubule, thick ascending loop of Henle, distal convoluted tubule), including carbonic anhydrase inhibitors, loop diuretics, thiazides, potassium-sparing diuretics, and osmotic diuretics. It also lists examples of prescribed diuretic drugs, drugs that have been withdrawn, and summarizes some clinical studies on diuretic use.
The document provides an overview of acute renal failure (ARF), including its anatomy, physiology, definitions, epidemiology, causes, pathogenesis, clinical features, investigations, complications, management, prognosis and prevention. It discusses ARF in various contexts such as pre-renal, renal and post-renal causes. Key points covered include classification of ARF, common causes like sepsis and nephrotoxins, treatment approaches involving fluid management and dialysis indications. Newborn-specific ARF is also briefly addressed.
Dr. Sachin Verma is a young, diligent and dynamic physician. He did his graduation from IGMC Shimla and MD in Internal Medicine from GSVM Medical College Kanpur. Then he did his Fellowship in Intensive Care Medicine (FICM) from Apollo Hospital Delhi. He has done fellowship in infectious diseases by Infectious Disease Society of America (IDSA). He has also done FCCS course and is certified Advance Cardiac Life support (ACLS) and Basic Life Support (BLS) provider by American Heart Association. He has also done a course in Cardiology by American College of Cardiology and a course in Diabetology by International Diabetes Centre. He specializes in the management of Infections, Multiorgan Dysfunctions and Critically ill patients and has many publications and presentations in various national conferences under his belt. He is currently working in NABH Approved Ivy super-specialty Hospital Mohali as Consultant Intensivists and Physician.
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
This document provides information about different types of diuretic drugs, including their mechanisms of action, therapeutic uses, and side effects. It discusses loop diuretics like furosemide that act in the thick ascending limb of the loop of Henle, thiazide diuretics like hydrochlorothiazide that act in the distal convoluted tubule, potassium-sparing diuretics like spironolactone that act in the collecting duct, and carbonic anhydrase inhibitors like acetazolamide. The document explains how each class of diuretic increases urine output and outlines their applications in conditions like heart failure, hypertension, and edema. It also notes common adverse effects like hypokalemia, hy
Diuretics are drugs that promote the excretion of sodium and water from the body by acting on the kidney. They work by interfering with sodium transport mechanisms in different segments of the nephron. The main types are loop diuretics which act on the thick ascending limb of the loop of Henle, thiazide diuretics which act on the early distal tubule, and potassium-sparing diuretics which act on the late distal tubule and collecting duct. Diuretics are important drugs used to treat hypertension, heart failure, and edema.
This document discusses various classes of diuretic drugs including loop diuretics, thiazide diuretics, thiazide-like diuretics, potassium-sparing diuretics, carbonic anhydrase inhibitors, and osmotic diuretics. It describes the mechanisms of action, pharmacokinetics, uses, and adverse effects of these diuretic classes with a focus on furosemide, hydrochlorothiazide, acetazolamide, spironolactone, triamterene, and mannitol. Key sites of action in the nephron are identified for each drug class.
Hello friends. In this PPT I am talking about diuretics. If you like it, please do let me know in the comments section. A single word of appreciation from you will encourage me to make more of such videos. Thanks. Enjoy and welcome to the beautiful world of pharmacology where pharmacology comes to life. This video is intended for MBBS, BDS, paramedical and any person who wishes to have a basic understanding of the subject in the simplest way.
The document discusses kidney function and urine formation processes. It then summarizes the key functions of the kidneys, which include regulating electrolyte and fluid balance and removing waste from the blood. It describes the three main processes involved in urine formation - filtration, reabsorption, and secretion. The document then focuses on hypertension, describing classifications of blood pressure and types of hypertension. It outlines mechanisms for blood pressure control and discusses non-pharmacological and pharmacological approaches to hypertension management.
Hyperphosphatemia, hypomagnesemia, hypermagnesemia, and hypertension were discussed. Hyperphosphatemia can be caused by transcellular shift, increased intake, or decreased renal excretion and treated with dietary restrictions, phosphate binders, and dialysis. Hypomagnesemia can be caused by impaired absorption, increased renal excretion, or transcellular shift and treated with oral supplementation or IV therapy. Hypermagnesemia can be iatrogenic or due to renal failure and treated with calcium, saline, and dialysis if severe. Hypertension was defined and stages and emergencies discussed.
The document discusses diuretic drugs, which increase urine output. It describes the mechanisms of urine formation through glomerular filtration, tubular reabsorption and secretion. It then classifies and describes various diuretic drugs based on their site of action in the nephron (loop, distal tubule, etc.), speed/duration of action, and relative potency. Common diuretics discussed include furosemide, hydrochlorothiazide, spironolactone, and mannitol. Their indications, mechanisms, effects and side effects are summarized.
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.
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
This document provides guidelines for the management of hypokalemia according to NICE guidelines. It defines hypokalemia as a serum potassium level below 3.5 mmol/L. The major causes are decreased intake, increased losses through the kidneys or GI tract, and shifts in distribution. Treatment involves identifying and correcting the underlying cause, monitoring for magnesium deficiency, and replacing potassium orally or intravenously depending on the severity. Close monitoring of serum potassium levels, ECG, renal function, and for side effects is important when replacing potassium.
A detailed information about the diuretics - classification of drugs, mechanism of action, side effects, dosage and indications.
Classification based on the efficacy of the diuretics.
1. High
2. Moderate
3. Weak
A brief introduction given about the nephron structure and its indications.
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.
Acute renal failure is a clinical syndrome where sudden deterioration of renal function results in the kidneys' inability to maintain fluid and electrolyte homeostasis. It has various etiologies like pre-renal, intrinsic renal, and post-renal factors. Management involves treating the underlying cause, fluid resuscitation, controlling electrolyte abnormalities, and starting dialysis for refractory volume overload, hyperkalemia, acidosis, or neurological symptoms. The healthcare team works to stabilize the patient and prevent long-term kidney damage.
Acute renal failure develops when renal function is diminished such that fluid homeostasis can no longer be maintained. It can be oliguric or nonoliguric. Causes include prerenal issues like decreased perfusion, direct renal problems, and postrenal obstruction. Treatment involves fluid management, electrolyte control like treating hyperkalemia, and correcting acidosis while avoiding tetany from rapid changes. Dialysis may be needed for persistent issues.
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.
This document provides information about diuretic drugs, including their classification, mechanisms of action, effects, uses, and challenges. It discusses diuretics that act at different sites in the nephron (proximal tubule, thick ascending loop of Henle, distal convoluted tubule), including carbonic anhydrase inhibitors, loop diuretics, thiazides, potassium-sparing diuretics, and osmotic diuretics. It also lists examples of prescribed diuretic drugs, drugs that have been withdrawn, and summarizes some clinical studies on diuretic use.
The document provides an overview of acute renal failure (ARF), including its anatomy, physiology, definitions, epidemiology, causes, pathogenesis, clinical features, investigations, complications, management, prognosis and prevention. It discusses ARF in various contexts such as pre-renal, renal and post-renal causes. Key points covered include classification of ARF, common causes like sepsis and nephrotoxins, treatment approaches involving fluid management and dialysis indications. Newborn-specific ARF is also briefly addressed.
Dr. Sachin Verma is a young, diligent and dynamic physician. He did his graduation from IGMC Shimla and MD in Internal Medicine from GSVM Medical College Kanpur. Then he did his Fellowship in Intensive Care Medicine (FICM) from Apollo Hospital Delhi. He has done fellowship in infectious diseases by Infectious Disease Society of America (IDSA). He has also done FCCS course and is certified Advance Cardiac Life support (ACLS) and Basic Life Support (BLS) provider by American Heart Association. He has also done a course in Cardiology by American College of Cardiology and a course in Diabetology by International Diabetes Centre. He specializes in the management of Infections, Multiorgan Dysfunctions and Critically ill patients and has many publications and presentations in various national conferences under his belt. He is currently working in NABH Approved Ivy super-specialty Hospital Mohali as Consultant Intensivists and Physician.
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1. P a g e | 1
Pharmacology of Drugs acting on Renal System
• Diuretics
• Antidiuretics
DIURETICS:
Diuretics also known as water pills increases the excretion of water and electrolytes (Na+
) in
urine.
Natriuresis – large amount of sodium excreted in urine due to the action of kidneys.
Promoted by – ventricular and atrial natriuretic as well as calcitonin.
Inhibited by chemicals such as aldosterone. The drugs which increases sodium excretion are
known as natriuretic.
Diuresis – increased or excessive production of urine. The drugs which enhances the excretion
of water without loss of electrolyte is called as aquaretic.
CLASSIFICATION
1. High efficacy (Inhibitors of Na+
- K+
- 2 Cl-
cotransport)
Drugs acting at thick ascending limb of loop of Henle.
❖ High ceiling or loop diuretics
→ Furosemide
→ Bumetanide
→ Torsemide
Historical high ceiling diuretics includes ethacrynic acid and organomercurials.
2. Medium efficiency (inhibitors of Na+
- Cl+
symport)
Drugs acting on early distal tubule.
❖ Thiazides
→ Hydrochlorothiazide
→ Hydro flumethiazide
→ Benzthiazide
❖ Thiazide-like
→ Chlorthalidone
→ Metolazone
→ Xipamide
→ Indapamide
→ Clopamide
sulfonamide derivative
2. P a g e | 2
High ceiling or loop diuretics:
Loop diuretics are the diuretics that act at the ascending limb of loop of Henle in the kidney.
It includes – Furosemide (Frusemide); Bumetanide and Torsemide.
Mechanism of action –
3. Weak/Adjunction diuretics
❖ Carbonic – anhydrase inhibitor
Drugs acting on proximal convoluted tubule.
→ Acetazolamide
→ Methazolamide
→ Dorzolamide
❖ Osmotic diuretic
Drugs acting on entire nephron (main site in loop of Henle).
→ Mannitol
→ Isosorbide
→ Glycerol
❖ Potassium sparing diuretics
Drugs acting at distil convulated tubule and collecting duct.
→ Aldosterone antagonists
• Spironolactone
• Eplerenone
→ Renal epithelial Na+
channel inhibitors
• Amiloride
• Triamterene
Na+
Na+
Na+
2Cl-
Cl-
Cl-
K+
K+
K+
Na+
K+
ATPase
Ascending limb of Henle’s loop
Lumen Blood
3. P a g e | 3
➢ Loop diuretics act on the Na2+
- K+
- 2Cl-
symporter in the thick ascending limb of
loop of Henle to inhibit Na+
, Cl-
and K+
reabsorption.
➢ The excretion of Na+
and Cl_ in the urine increases.
➢ More Na+
exchanges with K+
, as the tubular fluid reaching the distal convulated
tubule contains large amount of Na+
, which leads to K+
loss.
➢ Loop diuretics also increases the excretion of Ca2+
, and Mg2+
– (but Ca2+
is
reabsorbed back in distal tubule).
➢ They increase the reabsorption of uric acid in the proximal tubule.
➢ In case of, Frusemide, the excretion of HCO3
−
increases, as it has weak carbonic
anhydrous-inhibiting activity.
Loop diuretics are highly efficacious – i.e., they have maximal Na+
excreting capacity when
compared to thiazide and potassium sparing diuretics. Hence, are called high ceiling diuretics.
Pharmacokinetic:
Rapidly absorbed through the gastro intestinal tract.
Frusemide is administered by oral, IV or IM route.
On set of action – 20 to 40 minutes orally; 10 to 20 minutes when given intramuscularly; 2-5
minutes intravenously.
The duration of action of frusemide is short (2-4 hours) hence, it requires twice daily dosing.
Plasma half-life (𝑡1
2
⁄ ) is 1
1
2
hours. They cannot enter the glomerular filtrate as they are
extensively and firmly bound to plasma proteins. By organic acid transport system, loop
diuretics are secreted in the proximal tubule and reach ascending limb of loop of Henle.
They are partly metabolized in the liver and the metabolites are excreted by the kidney by
glomerular filtration, and tubular secretion.
Bumetanide and Torsemide are more potent then frusemide.
Bumetanide is 40 times more potent than frusemide (i.e., 1 mg bumetanide = 40 mg of
Frusemide). It can also be administered orally, intravenously or intramuscularly. It has better
oral bioavailability (80-100%) than frusemide and the onset of action is faster than frusemide.
It is bound to plasma proteins, and partly metabolized and excreted unchanged in urine. Plasma
𝑡1
2
⁄ is 60 mins, but in renal and hepatic insufficiency it is prolonged.
The adverse effects like hypokalaemia, ototoxicity, hyperglycaemia and hyperuricemia are
milder and hence, better tolerated. But may cause muscular weakness (myopathy).
Bumetanide may be used in patients not responding to frusemide.
LASIX 40mg tab, 20 mg/2 ml inj. LASIX HIGH DOSE 500 mg tab, 250 mg/25
ml inj; (solution degrades spontaneously on exposure to light), SALINEX 40 mg
tab, FRUSENEX 40, 100 mg tab,
Doses:
Usually 20-80 mg once daily in the morning. In renal insufficiency, up to 200 mg
6 hourly has been given by i.m./i.v. route. In pulmonary edema, 40-80 mg may be
injected i.v.
4. P a g e | 4
Torsemide – recently introduced loop diuretics. It is 2 times more potent than frusemide.
Torsemide is administered by oral and IV route. Bioavailability is 80-90%. It is highly bound
to (>90%). It is mostly metabolized in the liver (80%), therefore, in case of liver failure, the
dose should be decreased. Is the first-long acting loop diuretics and therefore, can be given
once a day.
Ethacrynic acid:
Onset of action is rapid within 30 minutes after an oral dose; within 5 minutes when given
intravenously. Ethacrynic acid is not commonly used because it is more likely to cause adverse
effect partially. It is used in patients allergic to sulphonamides.
Adverse effects:
1. Electrolyte disturbances are the most common adverse effects
❖ Hypokalemia and metabolic alkalosis (due to H+
loss) is dose-dependent. In patients
with low dietary intake of potassium or patients with cardiac failure and cirrhosis
hypokalaemia is troublesome in higher doses or prolonged use of diuretics.
Serum potassium levels less than 2.5 mEq/L indicates hypokalaemia. Symptoms of
Hypokalaemia include weakness, fatigue, muscle cramps; cardiac arrythmia are serious
complications.
Hypokalaemia can be prevented and treated with-
a) High dietary K+
intake or
b) KCl supplements (24-72 mEq/day) or
c) Combining loop diuretics with K+
sparing diuretics
(b) and (c) measures are indicated in elderly, cirrhotic and post MI patients, those receiving
digoxin, antiarrhythmics, or tricyclic antidepressant.
❖ Hyponatraemia (Loop diuretics can increase Na+
excretion from the body) dehydration,
hypovolemia and hypotension—all these are due to diuresis and natriuresis.
Can be treated with saline infusion
BUMET, 1mg tab., 0.25 mg/ml inj.
Doses:
1-5 mg oral OD in the morning, 2-4 mg IM/IV; in renal failure 15 mg/day
DIURETOR 10, 20 mg tabs, DYTOR, TIDE 5, 10, 20, 100 mg tabs, 10 mg/2 ml
inj.
Doses:
2.5-5 mg once daily in Hypertension
5-20 mg/day in oedema
100 mg twice daily in renal failure
Not indicated routinely because they may
cause gut ulceration by releasing KCl at one spot
5. P a g e | 5
❖ Hypocalcaemia (increased excretion of Ca2+
in urine)- On prolonged use loop diuretics
may cause hypocalcaemia- this may result in osteoporosis.
❖ Hypomagnesaemia (increased urinary excretion of Mg2+
)- In patients with dietary
magnesium deficiency prolonged use of diuretics can cause hypomagnesaemia.
Hypomagnesaemia increase the risk of ventricular arrhythmias, especially after MI or in
patients receiving digitalis.
Oral magnesium supplements are needed. Adding K+
sparing diuretics minimise Mg2+
loss.
2. The metabolic disturbances include
❖ Hyperuricemia- Frusemide produces lower incidence of hyperuricemia by decreasing
the renal excretion of uric acid and may precipitate acute attacks of gout.
This effect can be counteracted by Allopurinol. Avoid Probenecid as it may interfere with the
diuretic response.
❖ Hyperglycaemia- due to decreased insulin secretion.
❖ Hyperlipidaemia- increase plasma triglycerides and LDL cholesterol levels.
3. Ototoxicity- Cause hearing loss due to damage to hair cells in the inner ear. Deafness,
vertigo and tinnitus may occur. More common with ethacrynic acid.
Ototoxicity is seen in higher doses, common on IV administration, increased risk in patients
with renal impairment and in those receiving other ototoxic drugs like cyclosporine and
aminoglycoside. Frusemide enhances the toxicity of lithium.
Reversible on stoppage of medication except in case of ethacrynic acid.
4. GIT disturbances like nausea, vomiting and diarrhoea
5. CNS disturbances like giddiness, weakness, headache, paraesthesia, impotence can
occasionally occur.
6. Hypersensitivity reactions like skin rashes, eosinophilia, photosensitivity is common with
sulfonamide derivative. Blood dyscrasias are rare.
Therapeutic uses:
• Highly effective for the relief of cardiac, hepatic or renal oedema.
• In chronic congestive cardiac failure, it reduces venus and pulmonary congestion.
• In cerebral oedema frusemide is used as an alternative to mannitol or in combination with
osmotic diuretics to improve efficacy.
• Loop diuretic are used in impending acute renal failure and may decrease the need for
dialysis as the urine output and potassium excretion is increased. Large doses are required
in chronic renal failure.
• In the presence of renal insufficiency, heart failure or in resistant cases and in hypertensive
emergencies loop diuretics are indicated in hypertension.
• Intravenous administration of frusemide quickly relieves acute pulmonary oedema and
acute left ventricular failure following MI, due to its immediate vasodilator effect.
Decrease in blood volume and venous return are responsible for the improvement.
• Frusemide is administered during blood transfusion to prevent volume overload in
severely anaemic patients.
• It is used in acute hypercalcaemia and hyperkalaemia by intravenous furosemide (as it
promotes the excretion of Ca2+
and K+
in urine) along with hypertonic saline (to prevent
volume depletion).
Forced diuresis with frusemide and saline infusion is no more recommended to treat
poisoning.
Mild in
therapeutic
doses
6. P a g e | 6
Thiazide and thiazide-related diuretics:
All thiazide has sulfonamide group. The first thiazide synthesized was chlorothiazide (as a
Carbonic anhydrase inhibitor variant) which unlike acetazolamide produced urine rich in 𝐶𝑙−
,
and diuresis occurred in acidosis as well as alkalosis.
Mechanism of Action-
Thiazides in early distal tubule (primary site of action) bind to 𝐶𝑙−
site of Na+
𝐶𝑙−
symport and
inhibit the system and thus, increases the excretion of Na+
and 𝐶𝑙−
in the early distal tubule.
There will be increased delivery of Na+
to late distal tubule, which leads to, increased exchange
of Na+
- K+
resulting in K+
and Mg2+
loss. Thiazide also have weak carbonic anhydrase
inhibitory action and increases HCO3
−
loss. In comparison to loop diuretics, thiazide decrease
the excretion of Ca2+
and uric acid in urine which may result in hypercalcaemia and
hyperuricaemia.
Usually given once daily in morning to avoid diuresis during night
Contraindications
• Electrolyte depletion
• Anuria
• Hypersensitivity to sulfonamide
• Hepatic coma
• Severe renal failure
• Pregnancy and lactation
Thiazide act in the early distal tubule where loop diuretics deliver a large amount of
sodium, therefore, concurrent use of thiazide and loop diuretics have a synergistic effect
Na+
Na+
Thiazide
Cl-
Na+
Cl-
symporter
K+
K+
K+
K+
Cl- Cl-
Na+
K+
ATPase
Distal Tubular Cell
Lumen Blood
Cl-
7. P a g e | 7
Pharmacokinetics-
Thiazide and related drugs are well absorbed orally. There are no parenteral preparations of
thiazide. These are rapidly acting—action starts within 1 hour, but the duration of action varies
from 6 — 48 hrs. In more lipid-soluble agents, larger volume of distribution (some also bound
in tissues) and high tubular reabsorption are seen, thus these agents are longer acting. Most of
the agents are partly metabolized in the liver and excreted unchanged.
Bendroflumethiazide, polythiazide and indapamide are metabolised in liver; chlorothiazide,
hydrochlorothiazide, hydroflumethiazide and chlorthalidone are excreted in urine.
Adverse effects-
1. Electrolyte disturbances like hypokalaemia, metabolic alkalosis, hyponatraemia,
hypovolaemia hypotension, dehydration, hypochloremic, hypomagnesaemia and
hypercalcaemia are often seen with thiazide use.
❖ Hypokalaemia is the common adverse effect seen in thiazide than loop diuretics
because thiazide have long duration of action.
❖ Hypercalcaemia occurs due to decreased excretion of Ca2+
in urine.
2. Metabolic disturbances include
❖ Hyperglycaemia- due to the inhibition of insulin release (which maybe secondary to
hypokalaemia) hyperglycaemia may precipitate diabetes mellitus in borderline
hyperglycaemic patients.
Correction of hypokalaemia will also reduce hypoglycaemia.
❖ Hyperuricaemia In hypertension, long term use of thiazide in high dose causes rise in
blood urate level. It is now rare due to use of lower dose.
❖ Hyperlipidaemia
3. Thiazide can cause impotence in men. Therefore, it is not preferred in young males.
4. GI disturbances, hypersensitivity reactions (skin rashes and photosensitivity), weakness,
fatigue and anorexia
Uses:
• Chlorthalidone and indapamide are one of the first line thiazide diuretics used in
hypertension.
• Combination of thiazide and loop diuretics are used in management of oedema due to
congestive heart failure. Less effective in renal and hepatic oedema. In the presence of renal
failure, except metolazone other thiazides are not effective.
• Hypercalciuria and renal stones- thiazides are used as they reduce calcium excretion.
• Thiazide are only effective drugs used in nephrogenic diabetes insipidus.
Contraindications
• Allergy of sulpha drugs
• Hyposensitivity
• Hypotension
• Gout
• Hypokalaemia
• Renal failure and liver disease
• Pregnancy and lactation
8. P a g e | 8
Commonly used Thiazide and related diuretics
Name Tablet (mg) Daily dose as
diuretics (mg)
Duration
of action
(hr)
Elimination
𝐭𝟏
𝟐
⁄
Chlorothiazide DIURIL,
SODIUM
DIURIL
500- 1000;
Child-20 mg/kg
6-12 45-120 mins
Hydrochlorothiazide AQUAZIDE,
HYDRIDE
THIAZIDE (12.5,
25, 50),
ESIDREX (50)
25-200;
Child-2 mg/kg
6-12 6-15 hrs
Hydroflumethiazide DIUCARDIN
(50)
25-200 mg 18-24 17 hrs (normal
subjects);
10 hrs (in
patients with
cardiac failure)
Benzthiazide 25 mg 50-200 mg 12-18
Cyclopenthiazide NAVIDREX
(0.5)
0.5-1 mg 18-24 1.5-2.5 hr
Bendroflumethiazide NATURETIN (5) 2.5-5 mg 18-24
Polythiazide 1, 2, 4 mg 1-4 mg 24-48
Chlorthalidone HYTHALTON
(50, 100),
HYDRAZIDE,
THALIZIDE
(12.5, 25)
50-100 mg 48-72 40-50 hrs
Quinethazone 50-200 mg 18-24 3-4 hrs
Metolazone XAROXOLYN
(5, 10),
DIUREM,
METORAL (2.5,
5, 10)
5-10 mg 18-24 14 hrs
Xipamide XIPAMID (20) 20-60 mg 12 5.8-8.2 hrs
Indapamide LORVAS (2.5) 2.5- 5 mg 8-12 15-18 hrs
Clopamide BRINALDIX
(20)
10- 60 mg 12-18 10 hrs (approx.)
Benzthiazide (25 mg) + Triamterene (50 mg) used in the treatment of hypertension.
Carbonic anhydrase inhibitors: (Weak diuretic)
The formation of carbonic acid which spontaneously ionises to H+
and HCO3
−
, is catalysed by
an enzyme Carbonic anhydrase (reversible reaction). This enzyme is present in the renal
tubular cell (proximal tubule), gastric mucosa, exocrine pancreas, ciliary body of eye, brain
and RBC.
H2O + CO2 ⇌ H2CO3
H2CO3 is then split into H+
and H2CO3. This H2CO3 combines with Na+
and is reabsorbed.
H2CO3 ⇌ H+ + 𝐇𝐂𝐎𝟑
−
9. P a g e | 9
Mechanism of action:
Acetazolamide (Carbonic anhydrase inhibitor) block NaHCO3 reabsorption by inhibiting the
enzyme (carbonic anhydrase) and cause HCO3
−
diuresis. Thus, carbonic anhydrase is not
formed, preventing the formation of H+
ions for luminal Na+
exchange. Na+
is excreted in urine
along with HCO3
−
. The main site of action is proximal tubule; it also acts in the collecting duct.
Due to increase of Na+
-K+
exchange in distal convulated tubule, it leads to K+
loss. Therefore,
there will be net loss of Na+
, K+
, HCO3
−
and water in urine resulting in alkaline urine.
Other actions:
• Eye: The ciliary body of the eye contains carbonic anhydrase which produces aqueous
humour, which is high in bicarbonate content. The enzyme is inhibited by Acetazolamide
which reduces the intraocular pressure.
• CNS: Acetazolamide reduces the formation of CSF.
Pharmacokinetic:
Acetazolamide is well absorbed orally and excreted unchanged in the urine. Onset of action
within 60-90 mins and duration of action is 8-12 hrs.
Adverse effects:
• Metabolic acidosis due to HCO3
−
loss
• Hypokalaemia
• Drowsiness, Paresthesias and Fatigue may occur occasionally.
• Abdominal discomfort
• Hypersensitivity reaction –fever, rashes and blood dyscrasias (rare)
DIAMOX, SYNOMAX 250 mg tab. IOPAR-SR 250 mg SR cap.
ACETAZOLAMIDE 0.25 g tablet
Doses:
250 mg OD or BD in divided doses. Sodium acetazolamide can be given parenterally.
ATP
Na+
Na+
Na+
K+
Cl-
Base-
Sodium-hydrogen
exchanger 3
H+
+ HCO3
−
H2CO3
HCO3
−
+ H+
H2CO3
H2O + CO2
CO2 + H2O
CA CA
+
Lumen urine Intrestitinum-blood
10. P a g e | 10
• Hypercalciuria (since Ca2+
is lost with HCO3
−
) may lead to renal calcium and phosphorus
calculi formation
• Bone marrow depression is rare but serious.
• Salicylates inhibits its plasma protein binding and interfere with its renal tubular secretion,
hence, increasing the toxicity.
Therapeutic uses
The use of acetazolamide is restricted due to the self-limiting action, production of acidosis
and hypokalaemia. Currently it is used in following conditions-
• Glaucoma: Acetazolamide decrease intraocular pressure (IOP) by reducing the formation
of aqueous humour. It is administered by oral and IV route. Systemic Carbonic anhydrase
inhibitor includes Methazolamide (50—100mg, 8 hrly) and Dichlorphenamide (50 mg
OD—TDS); Dorzolamide and Brinzolamide are topical carbonic anhydrase (better
tolerated and available as eye drops) used in Glaucoma.
• In UTI or overdosage of acidic drugs acetazolamide is used to alkalinize urine.
• Acetazolamide increases the excretion of HCO3
−
. In patients with heart failure, metabolic
alkalosis due to excess diuretics respond to acetazolamide.
• Acetazolamide may be used in both for symptomatic relief and prophylaxis of mountain
sickness. Acetazolamide relieve symptoms by decreasing the pH and formation
cerebrospinal fluid. Hence, it is better to use prophylactically (250 mg 12 hrly the day
before, during and 5 days after the ascent).
• Used in prevention of periodic paralysis attacks.
• Epilepsy- When primary drugs are not effective, acetazolamide is used as an adjuvant as it
enhances the seizure threshold.
• Acetazolamide can be used in severe hyperphosphatemia to increase urinary phosphate
excretion.
Osmotic diuretics:
Main site of action: Descending limb of loop of Henle
Osmotic diuretics are solutes which include mannitol, isosorbide and glycerol. They have
following properties:
▪ Pharmacologically inert substances
▪ Generally, nonmetabolized
▪ Increase osmolality of plasma and tubular fluid
▪ Freely filtered at the glomerulus
▪ Insignificantly reabsorbed by the renal tubule
Contraindications
• Hepatic coma may be precipitated in patients with cirrhosis by
interfering with urinary excretion of NH3 (due to alkaline urine)
• Metabolic acidosis occurs in patients with COPD
11. P a g e | 11
Mannitol is administered intravenously (as 10-20% solution) in sufficiently large doses to raise
the osmolarity and renal tubular fluid. Elimination t1
2
⁄ is 0.5-1.5 hrs.
Adverse effects include headache, nausea, chills, excess thirst (polydipsia), confusion, pain in
chest, dizziness, cellular dehydration (on rapid infusion of mannitol), hyponatraemia (due to
volume expansion), visual disturbances, hypersensitivity reaction; extravasation may cause
oedema, skin necrosis, thrombophlebitis; rarely acute renal failure in large doses. It can cross
BBB and can cause rise in intracranial tension.
Precaution: Solutions containing more than 15% mannitol gets crystalized on storage,
therefore the solution should be warmed before use to redissolve crystals and shouldn’t be used
if any crystals remain; intravenous administration sets must have filter; mannitol should not be
administered with whole blood because agglutination and irreversible crenation of RBCs may
occur.
Uses:
• Mannitol is used to reduce Intracranial and Intraocular pressure—following head injury or
tumour, acute congestive glaucoma, stroke etc. Fluid from brain parenchyma, CSF and
aqueous humour is drawn into the circulation by osmotic effect and thus, reducing
Intracranial pressure. Similarly, lowering Intraocular pressure.
To reduce plasma osmolarity, 1-1.5 g/kg is infused over 1 hour as 20% solution to raise
plasma osmolarity.
To prevent acute rise in IOP/ICP, mannitol is infused before and after ocular or brain
surgery.
Mannitol i.v.
Plasma Osmolarity Gets freely filtered by
glomerulus but not reabsorbed
Shifts fluid from intracellular fluid
to extracellular fluid which leads to
extracellular fluid
osmolarity of
tubular fluid
Water retained in proximal
convulated tubule and descending
limb of Henle’s loop
Urine formation
urine volume
sed urinary excretion of Na+
, K+
, Ca2+
, Mg2+
, Cl-
, HCO3
−
and PO4
3−
MANNITOL 10%, 20% in 100, 350- and 500-ml vac
12. P a g e | 12
• To prevent acute renal failure by maintaining urine volume and prevent oliguria in shock,
cardiac surgery, severe trauma, Rhabdomyolysis and massive haemolysis. Slow infusion
of mannitol 500-1000 ml of 10-20% solution over 24 hours is given, after a test dose of
12.5 g IV, since, all patients with oliguria may not respond to mannitol.
Mannitol is contraindicated in patients who have already gone into renal failure because it can cause
pulmonary oedema and heart failure due to volume expansion.
• In cerebral oedema, 25-50 g IV every 3-5 hrs to a max of 2 g/kg/day mannitol is given.
• To maintain osmolality of ECF during rapid dialysis.
Isosorbide and Glycerol is used to reduce IOP and ICP. Glycerol is also used in the presence
of dehydration and cardiac failure where mannitol is not effective. Used topically to relieve
oedema including corneal oedema.
Dose: 0.5-1.5 g/kg as 50-75% oral solution; max dose 120 g/ day
Rapid infusion of higher doses can cause haemolysis and it can also cause hyperglycaemia.
Potassium sparing diuretics:
In the late distal tubule and collecting duct, potassium sparing diuretics inhibit Na+
absorption,
which indirectly suppress the secretion of H+
and K+
preventing potassium loss. These act in
two ways:
▪ Aldosterone antagonist: Spironolactone, Eplerenone
▪ Renal epithelial Na+
channel inhibitor: Triamterene, Amiloride
Spironolactone- It is a synthetic steroid and chemically mineralocorticoid aldosterone.
Mechanism of action:
Aldosterone enters into late distal tubule and collecting duct cells and binds to specific
mineralocorticoid receptor (MR). The hormone receptor complex (MR-AL) enters the cell
nucleus inducing the formation of Aldosterone-induced protein (AIPs). The AIPs promotes
Na+
reabsorption and potassium excretion.
Spironolactone acts from the interstitial side (all other diuretics act by luminal side) of the
tubular cell and combines with MR, inhibiting the formation of AIPs. Under normal
circumstances, it increases Na+
and decreases K+
excretion, whereas, in the absence of
aldosterone it has no effect on Na+
and K+
transport.
Contraindications
• Anuria
• Pulmonary oedema
• Renal insufficiency
• Acute tubular necrosis
• Acute left ventricular failure
• Congestive heart failure
• Cerebral haemorrhage
Xanthine as diuretics
Methylxanthine, like theophylline (most
effective xanthine diuretic) has weak diuretic
action and acts by increasing blood flow by
both cardiac and vascular action, also by
inhibiting the tubular reabsorption of sodium.
Slow infusion of 0.25-0.5g diluted in 10-20
ml of 5% glucose over 20 mins is effective.
13. P a g e | 13
When circulating aldosterone level are high, spironolactone’s are most effective. More amount
of Na+
is reabsorbed in the proximal tubule, hence it has low efficiency. Other diuretics reduce
K+
loss. Excretion of Ca2+
increases, by direct action of renal tubules.
Pharmacokinetics:
Spironolactone is administered orally as microfine powder tablet to increase bioavailability
(75%). It is highly bound to plasma proteins and completely metabolized in the liver and
converts into Canrenone and other active metabolites in the liver. The onset of action is slow
and the plasma t-half of spironolactone is 1-2 hours; Canrenone has long t1
2
⁄ of 18 hours.
Adverse effects:
1. Endocrine side effects are seen with
• Gynaecomastia and impotence in men
• Hirsutism and menstrual irregularities in women
• Spironolactone interacts with progestin and androgen receptors and interferes with
steroidogenesis.
2. In patients with renal in sufficiency, hyperkalaemia and metabolic acidosis can occur. ACE
inhibitor or beta-blockers increases the risk of hyperkalaemia.
ALDACTONE 25, 50, 100 mg tabs.
ALDACTONE: Spironolactone 25 mg + hydroflumethiazide 25 mg tab,
LACILACTONE, SPIROMIDE: Spironolactone 50 mg + furosemide 20 mg tab,
TORLACTONE Spironolactone 50 mg + torsemide 10 mg tab.
Dose: 25-50 mg BD-QID: max 400 mg/day
14. P a g e | 14
3. Drowsiness, Ataxia, mental confusion, epigastric distress and diarrhoea can occur.
4. Spironolactone can increase blood urea nitrogen and serum uric acid levels. Hence, should
be monitored and discontinued in case of hyperkalaemia.
5. NSAIDs inhibits the excretion of these drugs.
Therapeutic uses:
1. Used in combination with thiazide/loop diuretics to counteract K+
loss.
2. Spironolactone are used in cirrhotic and nephrotic oedema, where aldosterone levels are
high.
3. Spironolactone is used along with thiazide to avoid hyperkalaemia and additive effect in
the treatment of hypertension.
4. Spironolactone are used in primary and secondary hyper aldosterone (Conn’s syndrome).
5. Spironolactone is used as additional drug to conventional therapy in moderate to serve
CHF; it prevents disease progression and lower mortality.
Eplerenone, a more selective aldosterone antagonist. Hence, it is less likely to cause
gynaecomastia, impotence and menstrual irregularities. It is therefore. Used in long- term
therapy of hypertension and CHF.
Renal epithelial Na+ channel inhibitors-
Amiloride and Triamterene (directly acting agents)- are two nonsteroidal organic bases with
similar action. It binds to Na+
channel on distal convulated tubule and collecting duct and
blocks Na+
channels in the luminal membrane of the cell which increases Na+
excretion and
reduces K+
loss (since, K+
secretion is dependent on Na+
entry).
Contraindications
• Pregnancy
• Breast feeding
• Hyperkalaemia
• Hyponatraemia
• Severe renal impairment
• Addison disease
EPLERAN, EPTUS, ALRISTA 25, 50 mg tab
Dose: 25-50 BD
15. P a g e | 15
Pharmacokinetics:
Triamterene is partially absorbed orally, partly bound to plasma proteins, largely metabolized
in liver to an active metabolite and excreted in urine. Duration of action is 6-8 hrs; plasma t1/2
is 4 hours.
Side effects include nausea, muscle cramps, dizziness and rise in blood urea. Photosensitivity
and impaired glucose tolerance can also occur infrequently—but urate level is not increased.
Amiloride, only 1
4
⁄ th
of the oral dose is absorbed. It is 10 times more potent than triamterene
i.e. duration of action is longer than triamterene and t1
2
⁄ = 20 hrs. It reduces Ca2+
and Mg2+
excretion and increases urate excretion. It is not metabolized and not bound to plasma protein.
Side effects include GI disturbances, metabolic acidosis, hyperkalaemia and headache.
Amiloride blocks entry of Li+
through Na+
channels in the cells and makes diabetes insipidus
induced by lithium less severe.
Contraindicated in hyperkalaemia and renal failure.
Collecting tubular cell
DITIDE, triamterene 50 mg + Benzthiazide 25 mg tab; FRUSEMENE, triamterene
50 mg + furosemide 20 mg tab.
Dose: 50-100 mg daily
BIDURET, KSPAR: Amiloride 5 mg + hydrochlorothiazide 50 mg tab, LASIRIDE,
AMIFRU amiloride 5 mg + frusemide 40 mg tab
Dose: 5-10 mg once or twice daily
H2O H2O H2O
H2O
Na+
Na+
Na+
Na+
K+
K+
K+
K+
Aqueous
channels
ADH+
Na+
channel
K+
channel
Amiloride
Triamterene
Lumen Blood
Aldosterone
16. P a g e | 16
Diuretics Resistance:
Diuretics resistance is inability to reduce plasma sodium levels despite using full therapeutic
dose of diuretics.
Reasons for diuretic resistance:
• Reduced absorption of the diuretics
• Higher sodium intake
• Inadequate renal blood flow
• Long term therapy with thiazide and loop diuretics
Diuretic resistance is mainly seen in elderly patients due to decreased glomerular filtration rate
(GFR) and decreased renal function. Other factors like chronic renal failure, heart failure, liver
diseases and administration of diuretics with a NSAID may develop diuretic resistance.
• Frusemide + digoxin: Digoxin oral increases K+ levels wheras frusemide
decreases potassium levels in the blood; may increase the effect of
digoxin.
• Loop diuretics + Aminoglycoside: Increased risk of ototoxicity and
nephrotoxicity as both are ototoxicity drugs.
• Frusemide/ethacrynic acid + Warfarin and clofibrate: Compete for protien
binding sites as they are highly protien bound, resulting in therapeutic
failure.
• Loop/thiazide diuretics + adrenal steroids: Severe hypokalaemia.
• Thiazide + Chlorpropamide: Hyponatremia
• Loop and thiazide diuretics + NSAIDs: Decreased diuretic effect
• Loop and thiazide diuretics + Probenecid: Decreased diuretic effect
• Loop and thiazide diuretics + Lithium: Increased plasma (Lithium)
Drug Interactions:
17. P a g e | 17
ANTIDIURETICS (anti-aquaretic drugs):
Antidiuretics are drugs that reduces urine volume, particularly in diabetes insipidus (DI) which
is one of their primary indication.
→ Increasing the dose and frequency of a diuretic.
→ Using suitable combination.
→ Reduced salt intakes.
→ Intake of diuretics half an hour to 1 hour before meal.
→ Avoiding NSAIDs
Antidiuretics hormone, also known as vasopressin, regulates the body’s retention of water. It
is non-peptide secreted by posterior pituitary gland along with oxidation.
Synthesis and Storage
It is synthesized in the supraoptic ana paraventricular nuclei in the hypothalamus. It is then
transported to the posterior pituitary gland along the hypothalamus hypophyseal tract. The
synthesis is completed in the posterior pituitary gland and is stored here until it is secreted into
circulation.
Vasopressin receptors and their action:
ADH acts on vasopressin receptors. These are G-protein coupled cell membrane receptors – V1
and V2.
V1 receptors- Except those on renal CD cells, thick ascending limb of loop of Henle cells and
vascular endothelium, all other vasopressin receptors are of V1 type. They are of two sub types:
V1a and V1b
Antidiuretics
Antidiuretic hormone
and its analogues
Vasopressin (ADH)
Desmopressin
Lypressin
Terlipressin
Natriuretics
Thiazide
Amiloride
Miscellaneous
Chlorpropamide
Carbamazepine
Indomethacin
Analogues
The release of ADH is controlled by various factors. Changes in plasma osmotic
pressure and contraction of ECF volume are the two most influential factors. Exercise,
angiotensin II and emotional states such as pain are other factors that promote the
release of ADH.
18. P a g e | 18
V2 receptors – primarily located on the principle cells of collecting duct in the kidney and
mediate water retention.
Pharmacokinetics:
Vasopressin is administered parentally SC/IM/IV injection and intranasal route orally AVP is
destroyed by trypsin, therefore not preferred for oral use.
It is metabolized in the liver and excreted by kidney. Plasma t-half is ~ 25 minutes. Aqueous
vasopressin lasts for 3-4 hours.
V1
V1a
Blood vessels - Vasoconstriction
Gut - Increases peristalsis
Liver - Glycogenolysis
Platelets - Addredation
Uterus - Contraction of the smooth muscle
Brain
V1b
CNS: Release of ACTH from anterior
pituitary
V2
1. Renal tubules (CD): Enhance water reabsorption, therefore
reducing urinary output
2. Vascular endothesium: Release of clothing factor VIII and
von Willebrands factor from vascular endothelium.
V2 receptors are more sensitive to
arginine vasopressin (AVP) than V1
receptors i.e., they respond at lower
concentration.
Aqueous vasopressin (AVP inj: POSTACTON 10 U inj; for IV, IM or SC
administration)
19. P a g e | 19
Lypressin is a 8-lysine vasopressin. It is less potent than AVP but have longer duration of action
(4-6 hours). It acts on both V1 as well as V2 receptors. It is used in place of AVP (mostly for V1
receptors). It is administered parenterally (IV/IM/SC).
Desmopressin is a selective V2 against and is 12 times more potent than AVP; but has negligible
vasoconstrictor activity.
t-half: 1-2 hours and duration of action is 8-12 hours. Given intranasally, the bioavailability is
10-20% whereas on oral administration the bioavailability is 1-2%, hence oral dose is 10-15
times higher than the intranasal dose.
Terlipressin is a synthetic prodrug of vasopressin and is used for bleeding oesophageal varies.
It has less adverse effects compared to lypressin. It is a longer acting drug.
Contraindicated in pregnancy.
Felypressin is short acting and used with local anaesthetics to prolong the duration of action
because of its vasoconstrictor properties.
Adverse effects:
→ On intranasal administration ADH can cause allergy, rhinitis, nasal irritation and atrophy
of the nasal mucosa.
→ Nausea, abdominal cramps (due to contractions of the uterus) belching, pallor, urge
defecate and back pain systemic effects.
→ Fluid retention and hyponatraemia may develop. Hence, should not be given in patients
with acute renal failure.
→ AVP can cause bradycardia, increase cardiac after load and precipitate angina by
constricting coronary vessels.
PETRESIN, VASOPIN 20 IU/ml inj;
10 IU IM or SC or 20 IU diluted in 100-200 ml of dextrose solution and infused IV
over 10-20 minutes.
MINIRIN 100 µg/ml nasal spray (10 µg per actuation); 100 µg/ml intranasal
solution in 2.5 ml bottle with applicator; 0.1 mg tablets; 4 µg/ml inj.; D-VOID
100 µg/ml nasal spray.
Dose: Intranasal: Adults 10-40 µg/day in 2-3 divided doses, children (for bed
wetting) 5-10 µg at bed time.
Oral: 0.1-0.2 mg TDS.
Parenteral (SC or IV) 2-3 divided doses.
GLYPRESSIN 1mg freeze dried powder with 5 ml diluent for inj, T-PRESSIN,
TERLINIS 1 mg/ 10 ml inj.
Dose: 2 mg IV repeat 1-2 mg every 4-6 hours as needed.
20. P a g e | 20
Therapeutic Uses:
1. Based on V1 receptor action
• Bleeding oesophageal varies– Vasopressin/Terlipressin constricts mesenteric blood
vessels and reduce blood flow through the liver to the varies, forming clot.
Terlipressin is safer than vasopressin and stops bleeding in ~ 80%, improving survival
rate.
• AVP/ Lypressin is used before abdominal radiography to expel intestinal gases from
bowel.
• Asystolic cardiac arrest- single dose of 40IU, IM vasopressin is found to be effective.
• In acute haemorrhagic gastritis.
2. Based on V2 receptor action
• Diabetes insipidus (DI) of pituitary origin (central DI or neurogenic DI) is treated with
Desmopressin, but is not effective in renal DI (nephrogenic DI), because the renal
tubules (collecting duct) fails to respond to ADH. It requires life-long therapy except in
case of head injury or neurosurgery, where DI occurs for short time.
• Nocturnal enuresis (bedwetting or loss of bladder control at night)—administration of
desmopressin orally or intranasally at bedtime reduces urine volume, thus, controlling
primary nocturia. Fluid intake should be restricted 1 hour before and till 8 hours after
the dose to avoid fluid retention. BP and body weight should be monitored periodically
to avoid fluid overload. The treatment should be withheld for a week every 3 months for
reassessment.
• Renal concentration test—5-10 U IM of aqueous vasopressin or 2 µg of desmopressin
can enhance the urine concentration which is measured by urinary specific gravity.
Thiazides
Benzothiadiazine are found to be effective in controlling both neurogenic as well as
nephrogenic DI. The exact mechanism of action is not known—they probably act by causing a
negative sodium balance and reducing the GFR, leading to an increase concentration of urine
and decrease in volume. Polythiazide, a long acting drug is usually preferred. K+
sparing
diuretics are needed as hypokalaemia is usually associated with this therapy.
Hydrochlorothiazide, 25-50 mg TDS or equivalent dose of a longer acting agent is commonly
use. It is less effective than AVP, but more convenient and cheat.
In nephrogenic DI, where renal tubule (CD) fail to respond to the action of desmopressin,
thiazides are effective. They are combined with low sodium diet and PG synthesis inhibitors
such as Indomethacin, to reduce renal DI.
Amiloride is the drug of choice for lithium induced nephrogenic DI because they block Li+
entry along with Na+
in the principal cells of CD.
Contraindications
• Ischaemic Heart disease
• Hypertension
• Chronic nephritis
• Psychogenic polydipsia
• Bleeding disorder—Haemophilia and
von Willebrand’s disease—
Desmopressin 0.3 µg/kg diluted in 50 ml
saline and infused IV over 30 mins,
controls bleeding by promoting release of
factor VIII and von Willebrand factor.
21. P a g e | 21
Chlorpropamide, reduces urine volume in DI of pituitary origin but not in renal DI. It is long
acting sulfonyl oral hypoglycaemic, which sensitizes the kidney to ADH action.
Carbamazepine, an antiepileptic, reduces urine volume in DI of pituitary origin, but exact
mechanism of action is not clear—it probably acts by stimulating vasopressin release from the
neurohypophysis. Higher doses are required—400-600 mg/day. It is effective in patients with
partial DI.
Vasopressin antagonist
Conivaptan (V1a + V2 antagonist)- is a competitive, non-selective vasopressin-which causes
decreased permeability of the renal collecting ducts to water, leading to excretion of free
water.
99% is protein-bounded and metabolised by CYP3A4 in the liver.
It is used in the short-term treatment of euvolemic hyponatraemia caused by SIADH,
hypothyroidism and adrenocortical insufficiency.
It is administered parentally, and is well tolerated but may cause dry mouth, thirst, vomiting,
headache, hypokalaemia and hypotension.
Tolvaptan is a benzazepine derivative and has more selective V2 antagonistic action. It is
effective orally. It is used in the treatment of euvolemic and hypervolemic hyponatraemia in
patients with cirrhosis, CHF and SIADH.
In clinical trials symptoms of severe heart failure are improved. However, thrombotic
complications can occur due to haemoconcentration, if rapid correction of hyponatraemia is
attempted.
Tolvaptan is metabolised by CYP3A4 in liver; therefore could not be given in patients
receiving inhibitors of this isoenzyme; t-half is 6-8 hours, given once daily.
Side effects:
→ Thirst
→ Fever
→ Hyperglycaemia
→ Dry mouth
→ Gastrointestinal upset
Mozavaptan, V2 selective antagonist is used clinically.
Syndrome of Inappropriate Antidiuretics Hormone (SIADH) Secretion:
There is an impaired water excretion along with hyponatraemia and low plasma
osmolality due to inappropriate ADH secretion. Conditions associated with
SIADH include head injury, brain humour, meningitis, brain humour, pulmonary
diseases etc.
Signs and Symptoms:
➢ Nausea
➢ Vomiting
➢ Lethargy
➢ Muscle cramps
➢ Convulsion
➢ Coma
SIADH may result in death of the patient.