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Potassium-sparing Diuretics
Potassium-sparing diuretics refers to drugs that cause diuresis without causing potassium loss in the urine. They are typically used as an adjunct in management of hypertension, cirrhosis, and congestive heart failure. The steroidal aldosterone antagonists can also be used for treatment of primary hyperaldosteronism. Spironolactone, a steroidal aldosterone antagonist, is also used in management of female hirsutism and acne from PCOS or other causes. Types of Potassium-Sparing Diuretics * Epithelial sodium channel blockers: ** Amiloride - better tolerated than triamterene ** Triamterene - increased renal side-effects * Aldosterone antagonists, also known as mineralocorticoid receptor antagonists: ** Spironolactone - most widespread use, inexpensive ** Eplerenone - more selective so reduced side-effects but more expensive and less potent ** Finerenone - non-steroidal, more selective and potent than spironolactone and eplerenone ** Canrenone - very limited use Mechanism of action ...
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Potassium-sparing Diuretics
Potassium-sparing diuretics refers to drugs that cause diuresis without causing potassium loss in the urine. They are typically used as an adjunct in management of hypertension, cirrhosis, and congestive heart failure. The steroidal aldosterone antagonists can also be used for treatment of primary hyperaldosteronism. Spironolactone, a steroidal aldosterone antagonist, is also used in management of female hirsutism and acne from PCOS or other causes. Types of Potassium-Sparing Diuretics * Epithelial sodium channel blockers: ** Amiloride - better tolerated than triamterene ** Triamterene - increased renal side-effects * Aldosterone antagonists, also known as mineralocorticoid receptor antagonists: ** Spironolactone - most widespread use, inexpensive ** Eplerenone - more selective so reduced side-effects but more expensive and less potent ** Finerenone - non-steroidal, more selective and potent than spironolactone and eplerenone ** Canrenone - very limited use Mechanism of action ...
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Epithelial Sodium Channel
The epithelial sodium channel (ENaC), (also known as amiloride-sensitive sodium channel) is a membrane-bound ion channel that is selectively permeable to sodium ions (). It is assembled as a heterotrimer composed of three homologous subunits α or δ, β, and γ, These subunits are encoded by four genes: SCNN1A, SCNN1B, SCNN1G, and SCNN1D. The ENaC is involved primarily in the reabsorption of sodium ions at the collecting ducts of the kidney's nephrons. In addition to being implicated in diseases where fluid balance across epithelial membranes is perturbed, including pulmonary edema, cystic fibrosis, COPD and COVID-19, proteolyzed forms of ENaC function as the human salt taste receptor. The apical membranes of many tight epithelia contain sodium channels that are characterized primarily by their high affinity for the diuretic blocker amiloride. These channels mediate the first step of active sodium reabsorption essential for the maintenance of body salt and water homeostasis. In ...
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Anti-hypertensives
Antihypertensives are a class of drugs that are used to treat hypertension (high blood pressure). Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34% and of ischaemic heart disease by 21%, and can reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease. There are many classes of antihypertensives, which lower blood pressure by different means. Among the most important and most widely used medications are thiazide diuretics, calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists (ARBs), and beta blockers. Which type of medication to use initially for hypertension has been the subject of several large studies and resulting national guidelines. The fundamental goal of treatment should be the prevention of the important endpoints of hypert ...
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Natriuretic
Natriuresis is the process of sodium excretion in the urine through the action of the kidneys. It is promoted by ventricular and atrial natriuretic peptides as well as calcitonin, and inhibited by chemicals such as aldosterone. Natriuresis lowers the concentration of sodium in the blood and also tends to lower blood volume because osmotic forces drag water out of the body's blood circulation and into the urine along with the sodium. Many diuretic drugs take advantage of this mechanism to treat medical conditions like hypernatremia and hypertension, which involve excess blood volume. Excess natriuresis can be caused by: *Medullary cystic disease *Bartter syndrome *Diuretic phase of acute tubular necrosis *Some diuretics *Primary renal diseases *Congenital adrenal hyperplasia *Syndrome of inappropriate antidiuretic hormone hypersecretion Endogenous natriuretic hormones include: * Atrial natriuretic peptide * Brain natriuretic peptide Brain natriuretic peptide 32 (BNP), also kno ...
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Hypokalemia
Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an abnormal heart rhythm, which is often too slow and can cause cardiac arrest. Causes of hypokalemia include vomiting, diarrhea, medications like furosemide and steroids, dialysis, diabetes insipidus, hyperaldosteronism, hypomagnesemia, and not enough intake in the diet. Normal potassium levels are between 3.5 and 5.0 mmol/L (3.5 and 5.0 mEq/L) with levels below 3.5 mmol/L defined as hypokalemia. It is classified as severe when levels are less than 2.5 mmol/L. Low levels may also be suspected based on an electrocardiogram (ECG). Hyperkalemia is a high level of potassium in the blood serum. The speed at which potassium should be replaced depends on whether or not there are symptoms or abnormalities on an electrocardiogram. Potas ...
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Nephron
The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structure called Bowman's capsule. The renal tubule extends from the capsule. The capsule and tubule are connected and are composed of epithelial cells with a lumen. A healthy adult has 1 to 1.5 million nephrons in each kidney. Blood is filtered as it passes through three layers: the endothelial cells of the capillary wall, its basement membrane, and between the foot processes of the podocytes of the lining of the capsule. The tubule has adjacent peritubular capillaries that run between the descending and ascending portions of the tubule. As the fluid from the capsule flows down into the tubule, it is processed by the epithelial cells lining the tubule: water is reabsorbed and substances are exchanged (some are added, others are removed); first with t ...
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Collecting Tubule
The collecting duct system of the kidney consists of a series of tubules and ducts that physically connect nephrons to a minor calyx or directly to the renal pelvis. The collecting duct system is the last part of nephron and participates in electrolyte and fluid balance through reabsorption and excretion, processes regulated by the hormones aldosterone and vasopressin (antidiuretic hormone). There are several components of the collecting duct system, including the connecting tubules, cortical collecting ducts, and medullary collecting ducts. Structure Segments The segments of the system are as follows: Connecting tubule With respect to the renal corpuscle, the connecting tubule (CNT, or junctional tubule, or arcuate renal tubule) is the most proximal part of the collecting duct system. It is adjacent to the distal convoluted tubule, the most distal segment of the renal tubule. Connecting tubules from several adjacent nephrons merge to form cortical collecting tubules, and th ...
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Canrenone
Canrenone, sold under the brand names Contaren, Luvion, Phanurane, and Spiroletan, is a steroidal antimineralocorticoid of the spirolactone group related to spironolactone which is used as a diuretic in Europe, including in Italy and Belgium. It is also an important active metabolite of spironolactone, and partially accounts for its therapeutic effects. Medical uses Canrenone is mainly used as a diuretic. Canrenone has been found to be effective in the treatment of hirsutism in women. Heart failure Two studies of canrenone in people with heart failure have shown a mortality benefit compared to placebo. In the evaluation which studied people with chronic heart failure (CHF), people that were treated with canrenone displayed a lower number of deaths compared to the placebo group, indicating a death and morbidity benefit of the medication. One study compared 166 treated with canrenone to 336 given conventional therapy lasting 10 years. Differences in systolic and diastolic b ...
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Finerenone
Finerenone, sold under the brand name Kerendia, is a medication used to reduce the risk of kidney function decline, kidney failure, cardiovascular death, non-fatal heart attacks, and hospitalization for heart failure in adults with chronic kidney disease associated with type2 diabetes. Finerenone is a non-steroidal mineralocorticoid receptor antagonist (MRA). Common side effects include hyperkalemia (high levels of potassium), hypotension (low blood pressure), and hyponatremia (low levels of sodium). Finerenone was approved for medical use in the United States in July 2021, and in the European Union in February 2022. Medical uses In the United States, finerenone is indicated to reduce the risk of kidney function decline, kidney failure, cardiovascular death, non-fatal heart attacks, and hospitalization for heart failure in adults with chronic kidney disease associated with type2 diabetes. In the European Union, finerenone is indicated for the treatment of chronic kidney dis ...
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Eplerenone
Eplerenone, sold under the brand name Inspra, is an aldosterone antagonist type of potassium-sparing diuretic that is used to treat chronic heart failure and high blood pressure, particularly for patients with resistant hypertension due to elevated aldosterone. It is a steroidal antimineralocorticoid of the spirolactone group and a selective aldosterone receptor antagonist (SARA). Eplerenone is more selective than spironolactone at the mineralocorticoid receptor relative to binding at androgen, progestogen, glucocorticoid, or estrogen receptors. Medical uses Heart failure Eplerenone reduces risk of death in patients with heart failure, particularly in patients with recent myocardial infarction (heart attack). Hypertension Eplerenone lowers blood pressure in patients with primary hypertension. Eplerenone also reduces arterial stiffness and vascular endothelial dysfunction. For persons with resistant hypertension, eplerenone is safe and effective for reducing blood pressure, p ...
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Mineralocorticoid Receptor Antagonist
Mineralocorticoids are a class of corticosteroids, which in turn are a class of steroid hormones. Mineralocorticoids are produced in the adrenal cortex and influence salt and water balances (electrolyte balance and fluid balance). The primary mineralocorticoid is aldosterone. Physiology The name mineralocorticoid derives from early observations that these hormones were involved in the retention of sodium, a mineral. The primary endogenous mineralocorticoid is aldosterone, although a number of other endogenous hormones (including progesterone and deoxycorticosterone) have mineralocorticoid function. Aldosterone acts on the kidneys to provide active reabsorption of sodium and an associated passive reabsorption of water, as well as the active secretion of potassium in the principal cells of the cortical collecting tubule and active secretion of protons via proton ATPases in the lumenal membrane of the intercalated cells of the collecting tubule. This in turn results in an increase ...
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