Potassium-sparing Diuretics

Overview

Definition

Potassium-sparing diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication are medications that act in the principal cells Principal cells Tubular System in the collecting ducts (CDs) to induce diuresis that does not result in excretion of potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia.

Overview of antihypertensive agents

Drugs in the potassium-sparing diuretic class

Drugs in this class include: 

• Aldosterone antagonists Aldosterone antagonists Drugs that bind to and block the activation of mineralocorticoid receptors by mineralocorticoids such as aldosterone. Heart Failure and Angina Medication:
  • Spironolactone
  • Eplerenone
• Sodium channel blockers Sodium Channel Blockers A class of drugs that act by inhibition of sodium influx through cell membranes. Blockade of sodium channels slows the rate and amplitude of initial rapid depolarization, reduces cell excitability, and reduces conduction velocity. Myotonic Dystrophies:
  • Triamterene
  • Amiloride Amiloride A pyrazine compound inhibiting sodium reabsorption through sodium channels in renal epithelial cells. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with diuretics to spare potassium loss. Liddle Syndrome

Chemistry and Pharmacodynamics

Chemical structure

• Spironolactone and eplerenone: synthetic steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors 
• Triamterene: pteridine derivative
• Amiloride Amiloride A pyrazine compound inhibiting sodium reabsorption through sodium channels in renal epithelial cells. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with diuretics to spare potassium loss. Liddle Syndrome: pyrazine Pyrazine Antimycobacterial Drugs derivative

Mechanism of action (MOA) and physiologic effects

Aldosterone antagonists Aldosterone antagonists Drugs that bind to and block the activation of mineralocorticoid receptors by mineralocorticoids such as aldosterone. Heart Failure and Angina Medication (spironolactone, eplerenone):

• Also called mineralocorticoid receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors antagonists (MRAs)
• MOA: binds to the basolateral mineralocorticoid receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors in the collecting duct Collecting duct Straight tubes commencing in the radiate part of the kidney cortex where they receive the curved ends of the distal convoluted tubules. In the medulla the collecting tubules of each pyramid converge to join a central tube (duct of bellini) which opens on the summit of the papilla. Renal Cell Carcinoma as a competitive aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors antagonist, blocking the effects of aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia 
• Effects of aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia: 
  • Aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia stimulates production of the following proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis within the principle cells in the CD:
    • Na⁺/K⁺-ATPase on the basolateral side
    • ENaC ENaC Sodium channels found on salt-reabsorbing epithelial cells that line the distal nephron; the distal colon; salivary ducts; sweat glands; and the lung. They are amiloride-sensitive and play a critical role in the control of sodium balance, blood volume, and blood pressure. Liddle Syndrome ( epithelial sodium channel Epithelial sodium channel Sodium channels found on salt-reabsorbing epithelial cells that line the distal nephron; the distal colon; salivary ducts; sweat glands; and the lung. They are amiloride-sensitive and play a critical role in the control of sodium balance, blood volume, and blood pressure. Liddle Syndrome) on the lumen side: allows Na⁺ reabsorption from the lumen into the principal cells Principal cells Tubular System
    • Renal outer medullary potassium channel Renal outer medullary potassium channel Renal Potassium Regulation (ROMK) on the lumen side: allows excretion of K⁺ into the urine
  • Aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia stimulates Na⁺ reabsorption from the renal tubules:
    • Water follows the Na⁺
    • Creates a negative electrical gradient Electrical gradient Renal Potassium Regulation across the lumen, promoting the secretion Secretion Coagulation Studies of K⁺ and H⁺ into the urine
• Results of aldosterone antagonists Aldosterone antagonists Drugs that bind to and block the activation of mineralocorticoid receptors by mineralocorticoids such as aldosterone. Heart Failure and Angina Medication:
  • ↓ Na⁺ reabsorption → water stays in the tubular lumen with the Na⁺ → diuresis
  • ↓ K⁺ excretion → potassium-sparing
  • ↓ H⁺ excretion → trend toward metabolic acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis
• Antiandrogenic effects:
  • Spironolactone (significant antiandrogenic effects):
    • Nonselective MRA MRA Imaging of the Heart and Great Vessels, which also can bind BIND Hyperbilirubinemia of the Newborn estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy and progesterone Progesterone The major progestational steroid that is secreted primarily by the corpus luteum and the placenta. Progesterone acts on the uterus, the mammary glands and the brain. It is required in embryo implantation; pregnancy maintenance, and the development of mammary tissue for milk production. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Gonadal Hormones receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors → can ↑ aromatization of testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens to estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins
    • ↓ Testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens production
    • Binds to androgen receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors and competitively inhibits testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens and dihydrotestosterone Dihydrotestosterone A potent androgenic metabolite of testosterone. It is produced by the action of the enzyme 3-oxo-5-alpha-steroid 4-dehydrogenase. Gonadal Hormones
    • Can help improve acne, but also causes gynecomastia Gynecomastia Gynecomastia is a benign proliferation of male breast glandular ductal tissue, usually bilateral, caused by increased estrogen activity, decreased testosterone activity, or medications. The condition is common and physiological in neonates, adolescent boys, and elderly men. Gynecomastia, impotence, decreased libido, and menstrual irregularities
  • Eplerenone:
    • More selective for the mineralocorticoid receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors, with much fewer antiandrogenic effects
    • Better tolerated
• Antiinflammatory effects (low-dose eplerenone):
  • ↓ Myocardial perfusion defects after an MI MI MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction → ↓ cardiac mortality Mortality All deaths reported in a given population. Measures of Health Status
  • May slow the progression of albuminuria Albuminuria The presence of albumin in the urine, an indicator of kidney diseases. Kidney Function Tests in diabetic patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship

Sodium channel blockers Sodium Channel Blockers A class of drugs that act by inhibition of sodium influx through cell membranes. Blockade of sodium channels slows the rate and amplitude of initial rapid depolarization, reduces cell excitability, and reduces conduction velocity. Myotonic Dystrophies (triamterene, amiloride Amiloride A pyrazine compound inhibiting sodium reabsorption through sodium channels in renal epithelial cells. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with diuretics to spare potassium loss. Liddle Syndrome):

• Cations Cations Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. Electrolytes that bind BIND Hyperbilirubinemia of the Newborn to and directly block the ENaCs on the apical side of cells lining the distal convoluted tubules (DCTs) and CDs.
• Results:
  • ↓ Na⁺ reabsorption 
  • ↓ K⁺ excretion 
  • Water always follows Na⁺ → water stays with Na⁺ in the tubules (rather than being reabsorbed).
• Physiologic effects:
  • Diuresis results from the osmotic effect of Na⁺ in the tubules.
  • No significant loss of potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia

Pharmacokinetics

• Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption:
  • All are absorbed well orally.
  • Peak activity occurs at about 2–4 hours.
• Metabolism:
  • Spironolactone and triamterene are metabolized to active metabolites.
  • Eplerenone is metabolized to inactive metabolites.
  • Amiloride Amiloride A pyrazine compound inhibiting sodium reabsorption through sodium channels in renal epithelial cells. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with diuretics to spare potassium loss. Liddle Syndrome is not metabolized hepatically.
• Excretion: primarily via the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy; secondarily via the bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy/feces

Indications

General indications

The potassium-sparing diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication are most useful for treating edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema related to states of mineralocorticoid excess Mineralocorticoid excess A hereditary disease characterized by childhood onset hypertension, hypokalemic alkalosis, and low renin and aldosterone secretion. It results from a defect in the activity of the 11-beta-hydroxysteroid dehydrogenase type 2 enzyme which results in inadequate conversion of cortisol to cortisone. The build up of unprocessed cortisol to levels that stimulate mineralocorticoid receptors creates the appearance of having excessive mineralocorticoids. Metabolic Alkalosis, which may be either primary or secondary. Indications include:

• Edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema due to primary causes of mineralocorticoid excess Mineralocorticoid excess A hereditary disease characterized by childhood onset hypertension, hypokalemic alkalosis, and low renin and aldosterone secretion. It results from a defect in the activity of the 11-beta-hydroxysteroid dehydrogenase type 2 enzyme which results in inadequate conversion of cortisol to cortisone. The build up of unprocessed cortisol to levels that stimulate mineralocorticoid receptors creates the appearance of having excessive mineralocorticoids. Metabolic Alkalosis:
  • Conn syndrome Conn Syndrome Hyperaldosteronism
  • Ectopic adrenocorticotropic hormone Adrenocorticotropic hormone An anterior pituitary hormone that stimulates the adrenal cortex and its production of corticosteroids. Acth is a 39-amino acid polypeptide of which the n-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotropic activity. Upon further tissue-specific processing, acth can yield alpha-msh and corticotropin-like intermediate lobe peptide (clip). Adrenal Hormones (ACTH) production
• Edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema due to states of depleted intravascular volume resulting in secondary mineralocorticoid excess Mineralocorticoid excess A hereditary disease characterized by childhood onset hypertension, hypokalemic alkalosis, and low renin and aldosterone secretion. It results from a defect in the activity of the 11-beta-hydroxysteroid dehydrogenase type 2 enzyme which results in inadequate conversion of cortisol to cortisone. The build up of unprocessed cortisol to levels that stimulate mineralocorticoid receptors creates the appearance of having excessive mineralocorticoids. Metabolic Alkalosis:
  • Heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR)/post-MI (especially eplerenone)
  • Cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis
  • Nephrotic syndrome Nephrotic syndrome Nephrotic syndrome is characterized by severe proteinuria, hypoalbuminemia, and peripheral edema. In contrast, the nephritic syndromes present with hematuria, variable loss of renal function, and hypertension, although there is sometimes overlap of > 1 glomerular disease in the same individual. Nephrotic Syndrome
  • Resistant hypertension Resistant hypertension Blood pressure that remains uncontrolled despite concurrent use of 3 antihypertensive agents of different classes. Uncontrolled Hypertension (typically in addition to 1st-line antihypertensive agents)

Unique indications of spironolactone

Spironolactone has additional indications owing to its antiandrogenic properties:

• States of hyperandrogenism in females, including:
  • Acne vulgaris Acne vulgaris Acne vulgaris, also known as acne, is a common disorder of the pilosebaceous units in adolescents and young adults. The condition occurs due to follicular hyperkeratinization, excess sebum production, follicular colonization by Cutibacterium acnes, and inflammation. Acne Vulgaris 
  • Hirsutism Hirsutism A condition observed in women and children when there is excess coarse body hair of an adult male distribution pattern, such as facial and chest areas. It is the result of elevated androgens from the ovaries, the adrenal glands, or exogenous sources. The concept does not include hypertrichosis, which is an androgen-independent excessive hair growth. Polycystic Ovarian Syndrome
  • Polycystic ovary syndrome
  • Congenital Congenital Chorioretinitis adrenal hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation
• Hormone therapy for transgender Transgender Persons having a sense of persistent identification with, and expression of, gender-coded behaviors not typically associated with one’s anatomical sex at birth, with or without a desire to undergo sex reassignment procedures. Gender Dysphoria women (male-to-female)

Adverse Effects and Contraindications

Adverse effects of potassium-sparing diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication

• Fluid and electrolyte abnormalities:
  • Hyperkalemia Hyperkalemia Hyperkalemia is defined as a serum potassium (K+) concentration >5.2 mEq/L. Homeostatic mechanisms maintain the serum K+ concentration between 3.5 and 5.2 mEq/L, despite marked variation in dietary intake. Hyperkalemia can be due to a variety of causes, which include transcellular shifts, tissue breakdown, inadequate renal excretion, and drugs. Hyperkalemia (↑ K⁺)
  • Hyperchloremic metabolic acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis
  • Hyponatremia Hyponatremia Hyponatremia is defined as a decreased serum sodium (sNa+) concentration less than 135 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled via antidiuretic hormone (ADH) release from the hypothalamus and by the thirst mechanism. Hyponatremia (↓ Na⁺) 
  • Hypomagnesemia Hypomagnesemia A nutritional condition produced by a deficiency of magnesium in the diet, characterized by anorexia, nausea, vomiting, lethargy, and weakness. Symptoms are paresthesias, muscle cramps, irritability, decreased attention span, and mental confusion, possibly requiring months to appear. Deficiency of body magnesium can exist even when serum values are normal. In addition, magnesium deficiency may be organ-selective, since certain tissues become deficient before others. Electrolytes (↓ Mg²⁺)
  • Hypocalcemia Hypocalcemia Hypocalcemia, a serum calcium < 8.5 mg/dL, can result from various conditions. The causes may include hypoparathyroidism, drugs, disorders leading to vitamin D deficiency, and more. Calcium levels are regulated and affected by different elements such as dietary intake, parathyroid hormone (PTH), vitamin D, pH, and albumin. Presentation can range from an asymptomatic (mild deficiency) to a life-threatening condition (acute, significant deficiency). Hypocalcemia (↓ Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)²⁺)
  • Hypovolemia Hypovolemia Sepsis in Children
• Symptoms:
  • Dizziness Dizziness An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. Lateral Medullary Syndrome (Wallenberg Syndrome)
  • Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
  • Muscle cramps Cramps Ion Channel Myopathy
  • GI distress: abdominal cramping Abdominal cramping Norovirus, nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
  • Photosensitivity Photosensitivity Tetracyclines (triamterene)
• Additional effects specific to spironolactone (related to its antiandrogenic properties):
  • Gynecomastia Gynecomastia Gynecomastia is a benign proliferation of male breast glandular ductal tissue, usually bilateral, caused by increased estrogen activity, decreased testosterone activity, or medications. The condition is common and physiological in neonates, adolescent boys, and elderly men. Gynecomastia
  • Impotence and ↓ libido
  • Menstrual abnormalities

Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation

• Hyperkalemia Hyperkalemia Hyperkalemia is defined as a serum potassium (K+) concentration >5.2 mEq/L. Homeostatic mechanisms maintain the serum K+ concentration between 3.5 and 5.2 mEq/L, despite marked variation in dietary intake. Hyperkalemia can be due to a variety of causes, which include transcellular shifts, tissue breakdown, inadequate renal excretion, and drugs. Hyperkalemia
• Addison disease/ adrenal insufficiency Adrenal Insufficiency Conditions in which the production of adrenal corticosteroids falls below the requirement of the body. Adrenal insufficiency can be caused by defects in the adrenal glands, the pituitary gland, or the hypothalamus. Adrenal Insufficiency and Addison Disease
• Anuria Anuria Absence of urine formation. It is usually associated with complete bilateral ureteral (ureter) obstruction, complete lower urinary tract obstruction, or unilateral ureteral obstruction when a solitary kidney is present. Acute Kidney Injury or severe/progressive CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease
• Severe hepatic disease
• Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care (especially the aldosterone antagonists Aldosterone antagonists Drugs that bind to and block the activation of mineralocorticoid receptors by mineralocorticoids such as aldosterone. Heart Failure and Angina Medication, which may cause feminization of a male fetus)

Precautions

• Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus (especially triamterene and amiloride Amiloride A pyrazine compound inhibiting sodium reabsorption through sodium channels in renal epithelial cells. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with diuretics to spare potassium loss. Liddle Syndrome)
• Gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. Gout
• Lactation Lactation The processes of milk secretion by the maternal mammary glands after parturition. The proliferation of the mammary glandular tissue, milk synthesis, and milk expulsion or let down are regulated by the interactions of several hormones including estradiol; progesterone; prolactin; and oxytocin. Breastfeeding

Comparison of Medications

Some of the other most common diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication include thiazide Thiazide Heterocyclic compounds with sulfur and nitrogen in the ring. This term commonly refers to the benzothiadiazines that inhibit sodium-potassium-chloride symporters and are used as diuretics. Hyponatremia diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication (e.g., hydrochlorothiazide Hydrochlorothiazide A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It is used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism. Thiazide Diuretics), loop diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication (e.g., furosemide Furosemide A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for edema and chronic renal insufficiency. Loop Diuretics), carbonic anhydrase Carbonic anhydrase A family of zinc-containing enzymes that catalyze the reversible hydration of carbon dioxide. They play an important role in the transport of carbon dioxide from the tissues to the lung. Carbonic Anhydrase Inhibitors inhibitors (e.g., acetazolamide Acetazolamide One of the carbonic anhydrase inhibitors that is sometimes effective against absence seizures. It is sometimes useful also as an adjunct in the treatment of tonic-clonic, myoclonic, and atonic seizures, particularly in women whose seizures occur or are exacerbated at specific times in the menstrual cycle. However, its usefulness is transient often because of rapid development of tolerance. Its antiepileptic effect may be due to its inhibitory effect on brain carbonic anhydrase, which leads to an increased transneuronal chloride gradient, increased chloride current, and increased inhibition. Carbonic Anhydrase Inhibitors), and osmotic diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication (e.g., mannitol Mannitol A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity. Osmotic Diuretics).