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.
30-877: [REDACTED] Look up ARA in Wiktionary, the free dictionary. ARA may refer to: Media and the arts [ edit ] American-Romanian Academy of Arts and Sciences Artistička Radna Akcija , compilation album released in former Yugoslavia Associate of the Royal Academy , denoting membership in the British Royal Academy of Arts ARA News , an online Arabic and English language news service focussed on Syrian and Kurdish events Organisations [ edit ] Academic Research Alliance, an organization created to involve students in scientific activities Alliance for Retired Americans ,
60-449: A 9α,11α- epoxy group . This group is believed to be the reason why eplerenone has a 20-40-fold lower affinity for the mineralocorticoid receptor than spironolactone . Despite the nonsteroidal nature of finerenone which yields a different lipophilicity and polarity profile for this compound, finerenone 's affinity toward mineralocorticoid receptors is equal to that of spironolactone and 500 times that of eplerenone , hinting that
90-657: A British agency for the recovery of the proceeds of crime Athénée Royal d'Auderghem , a school in Brussels, Belgium Australasian Raptor Association , a special interest group of the Royal Australasian Ornithologists Union Military [ edit ] Aerial rocket artillery , helicopter artillery units used by the U.S. Army in the Vietnam War mainly to engage ground targets Armada de la República Argentina ,
120-432: A British agency for the recovery of the proceeds of crime Athénée Royal d'Auderghem , a school in Brussels, Belgium Australasian Raptor Association , a special interest group of the Royal Australasian Ornithologists Union Military [ edit ] Aerial rocket artillery , helicopter artillery units used by the U.S. Army in the Vietnam War mainly to engage ground targets Armada de la República Argentina ,
150-683: A Hungarian-Canadian endocrinologist, studied the effects of aldosterone antagonists on rats and found that the use of one of the first aldosterone antagonists, spironolactone , protected them from aldosterone-induced cardiac necrosis . The same year, 1959, spironolactone was launched as a potassium-sparing diuretic . It became clear years later that aldosterone antagonists inhibit a specific receptor protein. This protein has high affinity for aldosterone but also for cortisol in humans and corticosterone in mice and rats . For this reason, aldosterone antagonists were called mineralocorticoid receptor antagonists. There have been three major waves in
180-570: A senior citizen organization American Relief Administration , a relief mission after World War I Amateur Rowing Association , the governing body of rowing in the United Kingdom, now renamed British Rowing Amateurs Radio Algeriens , the national amateur radio organization of Algeria American Radio Association , a national AFL-CIO affiliated labor union representing U.S. Flag Merchant Marine Licensed Communications and Electronics Officers American Railway Association , precursor to
210-506: A senior citizen organization American Relief Administration , a relief mission after World War I Amateur Rowing Association , the governing body of rowing in the United Kingdom, now renamed British Rowing Amateurs Radio Algeriens , the national amateur radio organization of Algeria American Radio Association , a national AFL-CIO affiliated labor union representing U.S. Flag Merchant Marine Licensed Communications and Electronics Officers American Railway Association , precursor to
240-488: A wireless mesh network routing protocol; see Swarm intelligence AppleTalk Remote Access , a communications protocol Audio Random Access , an extension to audio plug-in interfaces Arachidonic acid (also AA), as found in breast milk and infant formula The Arrow-Pratt measure of absolute risk aversion Askaryan Radio Array (ARA), a GZK neutrino detector based on the Askaryan effect and will be positioned in
270-432: A wireless mesh network routing protocol; see Swarm intelligence AppleTalk Remote Access , a communications protocol Audio Random Access , an extension to audio plug-in interfaces Arachidonic acid (also AA), as found in breast milk and infant formula The Arrow-Pratt measure of absolute risk aversion Askaryan Radio Array (ARA), a GZK neutrino detector based on the Askaryan effect and will be positioned in
300-425: Is excreted 47-51% through kidneys . Patients with chronic kidney disease therefore require close monitoring when taking the drug. Spironolactone is also eliminated through feces (35-41%). The excretion of eplerenone is 67% through kidneys and 32% through feces. The information about excretion plays a critical role when determining the appropriate doses for patients with renal and/or hepatic dysfunction. It
330-444: Is a commonly reported side effect, particularly during the initial phase following treatment initiation; this is mostly transient and tends to reduce with sustained treatment. Common side effects for antimineralocorticoid medications include nausea and vomiting, stomach cramps and diarrhoea. Clinically significant hyperkalemia is possible, and warrants serum potassium monitoring on a periodic basis. The pathophysiology of hyperkalemia
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#1732773368155360-414: Is clear that the two drugs differ. Spironolactone has shorter half-life (t1/2 = 1.3-1.4 hours) than eplerenone (t1/2 = 4–6 hours). Eplerenone goes through rapid metabolism by the liver to inactive metabolites (t1/2 = 4–6 hours). However, spironolactone is metabolized to three active metabolites , which give it prolonged activity (13.8 – 16. 5 hours). Spironolactone has a long half-life and
390-477: Is dependent on the presence of a y-lactone ring on the C-17 position. The C-7 position is also important for activity as substituents there sterically hinder the interaction of C-7-unsubstituted agonists such as aldosterone . Eplerenone is a newer drug that was developed as a spironolactone analog with reduced adverse effects. In addition to the y-lactone ring and the substituent on C-7, eplerenone has
420-407: Is that antimineralocorticoid medications reduce potassium (K) excretion . Aldosterone is a mineralocorticoid which is synthesized in the adrenal glands . When aldosterone is secreted from the adrenal glands , it binds to the mineralocorticoid receptor in the renal tubule cell and forms a complex. This complex enhances transcription of specific DNA segments in the nucleus , leading to
450-459: Is very important to adjust the doses for patients with renal dysfunction because if they fail to eliminate the drug through their kidneys it could accumulate in the body, causing high concentration of potassium in the blood. Spironolactone and Eplerenone competitively block the binding of aldosterone to the mineralocorticoid receptor and hindering the reabsorption of sodium and chloride ions. The activity of mineralocorticoid antagonists
480-403: The blood pressure . Mineralocorticoid receptor antagonists decrease the aldosterone effect by binding to the mineralocorticoid receptor inhibiting aldosterone . This leads to higher levels of potassium in serum and increased sodium excretion, resulting in decreased body fluid and lower blood pressure . When comparing the pharmacokinetic properties of spironolactone and eplerenone , it
510-689: 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 beneficial in some cardiovascular conditions . Mineralocorticoid receptor antagonists have been used for many clinical conditions in the cardiovascular system . It has proven beneficial for diseases like primary aldosteronism , primary and resistant hypertension , heart failure and chronic kidney disease . They are often used with other medications, such as ACE inhibitors or beta blockers . Increased urination
540-692: The pharmaceutical industry when it comes to research and development of mineralocorticoid receptor antagonists: The first wave took place within Searle Laboratories . This company identified, shortly after the purification of aldosterone , steroid -based spironolactone as the first anti-mineralocorticoid. The second wave was all about discovering much more specific steroidal anti-mineralocorticoids. The main active companies were Searle , Ciba-Geigy , Roussel Uclaf and Schering AG . Around 50 years after Selye's work, several pharmaceutical companies began drug discovery programs. Their goal
570-428: The steroidal core component of most antimineralocorticoids is not essential for mineralocorticoid receptor affinity. The main goal of the identification of the first aldosterone antagonists, which happened during the 1950s, was to identify inhibitors of aldosterone activity. In those times, the main use of aldosterone was recognized as the control of renal sodium and the excretion of potassium . Hans Selye ,
600-515: The Antarctic ice sheet Computer science [ edit ] Application release automation People [ edit ] Amedeo Rocco Armentano (1886–1966), Italian esotericist and musician See also [ edit ] Ara (disambiguation) Topics referred to by the same term [REDACTED] This disambiguation page lists articles associated with the title ARA . If an internal link led you here, you may wish to change
630-458: The Antarctic ice sheet Computer science [ edit ] Application release automation People [ edit ] Amedeo Rocco Armentano (1886–1966), Italian esotericist and musician See also [ edit ] Ara (disambiguation) Topics referred to by the same term [REDACTED] This disambiguation page lists articles associated with the title ARA . If an internal link led you here, you may wish to change
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#1732773368155660-869: The Argentine Navy (Argentine Navy ships use ARA as a name prefix, just as the US Navy uses USS) Armenian Revolutionary Army , an armed militant group Aryan Republican Army , white nationalist criminal group Australian Regular Army Government [ edit ] Auckland Regional Authority , a former local government council in New Zealand Sciences [ edit ] Angiotensin II receptor antagonist , more often called angiotensin receptor blocker (ARB) Aldosterone receptor antagonist (mineralocorticoid receptor antagonist, that is, antimineralocorticoid ) Ant-based Routing Algorithm,
690-630: The Argentine Navy (Argentine Navy ships use ARA as a name prefix, just as the US Navy uses USS) Armenian Revolutionary Army , an armed militant group Aryan Republican Army , white nationalist criminal group Australian Regular Army Government [ edit ] Auckland Regional Authority , a former local government council in New Zealand Sciences [ edit ] Angiotensin II receptor antagonist , more often called angiotensin receptor blocker (ARB) Aldosterone receptor antagonist (mineralocorticoid receptor antagonist, that is, antimineralocorticoid ) Ant-based Routing Algorithm,
720-881: The Association of American Railroads American Rally Association , governing body of rallying and championship in the United States Anti-Racist Action , a network of anti-racist activists Anti-Racist Alliance , a defunct anti-racist organisation in the United Kingdom Applied Research Associates , a research and engineering company Arab Rescue Army , a volunteer army during the 1948 Palestine war Arcade and Attica Railroad , from its reporting mark Archives and Records Association , professional body for UK and Irish archivists, archive conservators and records managers Assets Recovery Agency ,
750-632: The Association of American Railroads American Rally Association , governing body of rallying and championship in the United States Anti-Racist Action , a network of anti-racist activists Anti-Racist Alliance , a defunct anti-racist organisation in the United Kingdom Applied Research Associates , a research and engineering company Arab Rescue Army , a volunteer army during the 1948 Palestine war Arcade and Attica Railroad , from its reporting mark Archives and Records Association , professional body for UK and Irish archivists, archive conservators and records managers Assets Recovery Agency ,
780-425: The formation of two protein transporters, Na+/K+ ATPase pump at the basolateral membrane and Na+ channel called ENaC, located at the apical membrane of the renal tubule cell. These protein transporters increase sodium reabsorption and potassium excretion in the distal tubule and the collecting duct of the kidneys . This helps the body to maintain normal volume and electrolyte balance , increasing
810-593: The free dictionary. ARA may refer to: Media and the arts [ edit ] American-Romanian Academy of Arts and Sciences Artistička Radna Akcija , compilation album released in former Yugoslavia Associate of the Royal Academy , denoting membership in the British Royal Academy of Arts ARA News , an online Arabic and English language news service focussed on Syrian and Kurdish events Organisations [ edit ] Academic Research Alliance, an organization created to involve students in scientific activities Alliance for Retired Americans ,
840-436: The link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=ARA&oldid=1251343645 " Category : Disambiguation pages Hidden categories: Short description is different from Wikidata All article disambiguation pages All disambiguation pages ARA [REDACTED] Look up ARA in Wiktionary,
870-447: The link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=ARA&oldid=1251343645 " Category : Disambiguation pages Hidden categories: Short description is different from Wikidata All article disambiguation pages All disambiguation pages Antimineralocorticoid Mineralocorticoid receptor antagonists are diuretic drugs that work primarily on
900-408: Was to discover novel non-steroidal mineralocorticoid receptor antagonists for use as efficacious and safe drugs with the pharmacodynamics and pharmacokinetics well defined. Their goal was to use these candidates for a broad spectrum of diseases. This was essentially the third wave. The first mineralocorticoid receptor antagonists were all discovered and identified by in vivo experiments whereas
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