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Potassium-sparing Diuretics
Potassium-sparing diuretics or antikaliuretics refer 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 ...
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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 w ...
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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, heart failure, kidney failure and myocardial infarction. Evidence suggests that a reduction of blood pressure by 5 mmHg can decrease the risk of stroke by 34% and of ischaemic heart disease by 21%. It 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, angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin II receptor blockers or 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 goa ...
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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 * C-type natriuretic peptide Natriuretic pepti ...
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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 in humans 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). The opposite state is called hyperkalemia that means high level of potassium in the blood serum. The speed at which potassium should be replaced depends on whether or not there are symptom ...
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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 podocyte foot processes 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 wit ...
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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 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 these may join to form cortical collecting ...
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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 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 blood pressure was observed between both p ...
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Finerenone
Finerenone, marketed under the brand name Kerendia among others, 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. It is taken orally (swallowed by mouth). Common side effects include abnormally high levels of potassium in the bloodstream, abnormally low levels of sodium in the bloodstream, and abnormally low blood pressure. Finerenone was approved for medical use in the United States in July 2021, and in the European Union in February 2022. The US Food and Drug Administration considers it to be a first-in-class medication. 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 fo ...
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Eplerenone
Eplerenone, marketed under brand name Inspa or Espler, is an aldosterone antagonist used primarily in the treatment of heart failure with reduced ejection fraction (HFrEF), particularly following myocardial infarction. It may also be considered as an add-on therapy in resistant hypertension; however, the majority of evidence in this setting supports the use of spironolactone (another drug in a same class), with fewer studies directly evaluating eplerenone. It is also a steroidal antimineralocorticoid of the spirolactone group and a selective aldosterone receptor antagonist (SARA). Medical uses Heart failure Eplerenone and other Mineralocorticoid receptor antagonists have been demonstrated to reduce the risk of death and hospitalisation in patients with heart failure with reduced ejection fraction (HFrEF) who have a left ventricular ejection fraction (LVEF) of 40% or less. It has also been demonstrated to increase LVEF by an average of 4.95%. These benefits are seen when used w ...
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Mineralocorticoid Receptor Antagonist
A mineralocorticoid receptor antagonist (MRA or MCRA) or aldosterone antagonist, is a diuretic drug which antagonizes the action of aldosterone at mineralocorticoid receptors. This group of drugs is often used as adjunctive therapy, in combination with other drugs, for the management of chronic heart failure. Spironolactone, the first member of the class, is also used in the management of hyperaldosteronism (including Conn's syndrome) and female hirsutism (due to additional antiandrogen actions). Most antimineralocorticoids, including spironolactone, are steroidal spirolactones. Finerenone is a nonsteroidal antimineralocorticoid. Medical uses Mineralocorticoid receptor antagonists are diuretic drugs that work primarily on the kidneys. They decrease sodium reabsorption, which leads to increased water excretion by the kidneys. By regulating water excretion, mineralocorticoid receptor antagonists lower blood pressure and reduce fluid around the heart which can be very benefici ...
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