اسپیرنولاکتون

Spironolactone, sold under the brand name Aldactone among others, is a medication that is primarily used to treat fluid build-up due to heart failure, liver scarring, or kidney disease.[4] It is also used in the treatment of high blood pressure, low blood potassium that does not improve with supplementation, early puberty in boys, acne and excessive hair growth in women, and as a part of transgender hormone therapy in transgender women.[4][17][18] Spironolactone is taken by mouth.[4]

Common side effects include electrolyte abnormalities, particularly high blood potassium, nausea, vomiting, headache, rashes, and a decreased desire for sex.[4] In those with liver or kidney problems, extra care should be taken.[4] Spironolactone has not been well studied in pregnancy and should not be used to treat high blood pressure of pregnancy.[3] It is a steroid that blocks the effects of the hormones aldosterone and testosterone and has some estrogen-like effects.[4][19] Spironolactone belongs to a class of medications known as potassium-sparing diuretics.[4]

Spironolactone was discovered in 1957, and was introduced in 1959.[20][21][22] It is on the World Health Organization’s List of Essential Medicines.[23] It is available as a generic medication.[4] In 2017, it was the 69th most commonly prescribed medication in the United States, with more than eleven million prescriptions.[24][25]

Spironolactone is used primarily to treat heart failure, edematous conditions such as nephrotic syndrome or ascites in people with liver disease, essential hypertension, low blood levels of potassium, secondary hyperaldosteronism (such as occurs with liver cirrhosis), and Conn’s syndrome (primary hyperaldosteronism). The most common use of spironolactone is in the treatment of heart failure.[26] On its own, spironolactone is only a weak diuretic because it primarily targets the distal nephron (collecting tubule), where only small amounts of sodium are reabsorbed, but it can be combined with other diuretics to increase efficacy. The classification of spironolactone as a “potassium-sparing diuretic” has been described as obsolete.[27] Spironolactone is also used to treat Bartter’s syndrome due to its ability to raise potassium levels.[28]اسپیرنولاکتون

Spironolactone has antiandrogenic activity. For this reason, it is frequently used to treat a variety of dermatological conditions in which androgens play a role. Some of these uses include acne, seborrhea, hirsutism, and pattern hair loss in women.[29] Spironolactone is the most commonly used medication in the treatment of hirsutism in the United States.[30] High doses of spironolactone, which are needed for considerable antiandrogenic effects, are not recommended for men due to the high risk of feminization and other side effects. Spironolactone is also commonly used to treat symptoms of hyperandrogenism, such as due to polycystic ovary syndrome, in women.[31]

While loop diuretics remain first-line for most people with heart failure, spironolactone has shown to reduce both morbidity and mortality in numerous studies and remains an important agent for treating fluid retention, edema, and symptoms of heart failure. Current recommendations from the American Heart Association are to use spironolactone in patients with NYHA Class II-IV heart failure who have a left ventricular ejection fraction of less than 35%.[32]

In a randomized evaluation which studied people with severe congestive heart failure, people treated with spironolactone were found to have a relative risk of death of 0.70 or an overall 30% relative risk reduction compared to the placebo group, indicating a significant death and morbidity benefit of the medication. People in the study’s intervention arm also had fewer symptoms of heart failure and were hospitalized less frequently.[33] Likewise, it has shown benefit for and is recommended in patients who recently suffered a heart attack and have an ejection fraction less than 40%, who develop symptoms consistent with heart failure, or have a history of diabetes mellitus. Spironolactone should be considered a good add-on agent, particularly in those patients “not” yet optimized on ACE inhibitors and beta-blockers.[32] Of note, a recent randomized, double-blinded study of spironolactone in patients with symptomatic heart failure with “preserved” ejection fraction (i.e. >45%) found no reduction in death from cardiovascular events, aborted cardiac arrest, or hospitalizations when spironolactone was compared to placebo.[34]

It is recommended that alternatives to spironolactone be considered if serum creatinine is greater than 2.5 mg/dL (221 µmol/L) in males or greater than 2 mg/dL (176.8 µmol/L) in females, if glomerular filtration rate is below 30 mL/min or with a serum potassium of greater than 5.0 mEq/L given the potential for adverse events detailed elsewhere in this article. Doses should be adjusted according to the degree of kidney function as well.[32]

According to a systematic review, in heart failure with preserved ejection fraction, treatment with spironolactone did not improve patient outcomes. This is based on the TOPCAT Trial examining this issue, which found that of those treated with placebo had a 20.4% incidence of negative outcome vs 18.6% incidence of negative outcome with spironolactone. However, because the p-value of the study was 0.14, and the unadjusted hazard ratio was 0.89 with a 95% confidence interval of 0.77 to 1.04, it is determined the finding had no statistical significance. Hence the finding that patient outcomes are not improved with use of spironolactone.[35] More recently, when blood samples from 366 patients in the TOPCAT study were analyzed for presence of canrenone (an active metabolite of spironolactone), 30% of blood samples from Russia lacked detectable residues of canrenone. This led to the conclusion that the TOPCAT trial results in Russia do not reflect actual clinical experience with spironolactone in patients with preserved ejection fraction.[36] The TOPCAT study results are now considered to have been invalidated. The study’s prime investigator and other prominent research cardiologists are now advising physicians treating heart failure with preserved ejection fraction to consider prescribing spironolactone pending outcome of two multicenter trials of newer medications.[37]

Due to its antiandrogenic properties, spironolactone can cause effects associated with low androgen levels and hypogonadism in males. For this reason, men are typically not prescribed spironolactone for any longer than a short period of time, e.g., for an acute exacerbation of heart failure. A newer medication, eplerenone, has been approved by the U.S. Food and Drug Administration for the treatment of heart failure, and lacks the antiandrogenic effects of spironolactone. As such, it is far more suitable for men for whom long-term medication is being chosen. However, eplerenone may not be as effective as spironolactone or the related medication canrenone in reducing mortality from heart failure.[38]

The clinical benefits of spironolactone as a diuretic are typically not seen until 2–3 days after dosing begins. Likewise, the maximal antihypertensive effect may not be seen for 2–3 weeks.[medical citation needed]

Unlike with some other diuretics, potassium supplementation should not be administered while taking spironolactone, as this may cause dangerous elevations in serum potassium levels resulting in hyperkalemia and potentially deadly abnormal heart rhythms.[medical citation needed]

About 1 in 100 people with hypertension have elevated levels of aldosterone; in these people, the antihypertensive effect of spironolactone may exceed that of complex combined regimens of other antihypertensives since it targets the primary cause of the elevated blood pressure. However, a Cochrane review found adverse effects at high doses and little effect on blood pressure at low doses in the majority of people with high blood pressure.[39] There is no evidence of person-oriented outcome at any dose in this group.[39]

Androgens like testosterone and DHT play a critical role in the pathogenesis of a number of dermatological conditions including oily skin, acne, seborrhea, hirsutism (excessive facial/body hair growth in women), and male pattern hair loss (androgenic alopecia).[40][41] In demonstration of this, women with complete androgen insensitivity syndrome (CAIS) do not produce sebum or develop acne and have little to no body, pubic, or axillary hair.[42][43] Moreover, men with congenital 5α-reductase type II deficiency, 5α-reductase being an enzyme that greatly potentiates the androgenic effects of testosterone in the skin, have little to no acne, scanty facial hair, reduced body hair, and reportedly no incidence of male-pattern hair loss.[44][45][46][47][48] Conversely, hyperandrogenism in women, for instance due to polycystic ovary syndrome (PCOS) or congenital adrenal hyperplasia (CAH), is commonly associated with acne and hirsutism as well as virilization (masculinization) in general.[40] In accordance with the preceding, antiandrogens are highly effective in the treatment of the aforementioned androgen-dependent skin and hair conditions.[49][50]

Because of the antiandrogenic activity of spironolactone, it can be quite effective in treating acne in women.[51] In addition, spironolactone reduces oil that is naturally produced in the skin and can be used to treat oily skin.[52][53][41] Though not the primary intended purpose of the medication, the ability of spironolactone to be helpful with problematic skin and acne conditions was discovered to be one of the beneficial side effects and has been quite successful.[52][53] Oftentimes, for women treating acne, spironolactone is prescribed and paired with a birth control pill.[52][53] Positive results in the pairing of these two medications have been observed, although these results may not be seen for up to three months.[52][53] Spironolactone has been reported to produce a 50 to 100% improvement in acne at sufficiently high doses.[54] Response to treatment generally requires 1 to 3 months in the case of acne and up to 6 months in the case of hirsutism.[54] Ongoing therapy is generally required to avoid relapse of symptoms.[54] Spironolactone is commonly used in the treatment of hirsutism in women, and is considered to be a first-line antiandrogen for this indication.[55] Spironolactone can be used in the treatment of female-pattern hair loss (pattern scalp hair loss in women).[56] There is tentative low quality evidence supporting its use for this indication.[57] Although apparently effective, not all cases of female-pattern hair loss are dependent on androgens.[58]

Antiandrogens like spironolactone are male-specific teratogens which can feminize male fetuses due to their antiandrogenic effects.[49][59][60] For this reason, it is recommended that antiandrogens only be used to treat women who are of reproductive age in conjunction with adequate contraception.[49][59][60] Oral contraceptives, which contain an estrogen and a progestin, are typically used for this purpose.[49] Moreover, oral contraceptives themselves are functional antiandrogens and are independently effective in the treatment of androgen-dependent skin and hair conditions, and hence can significantly augment the effectiveness of antiandrogens in the treatment of such conditions.[49][61]

Spironolactone is not generally used in men for the treatment of androgen-dependent dermatological conditions because of its feminizing side effects, but it is effective for such indications in men similarly.[56] As an example, spironolactone has been reported to reduce symptoms of acne in males.[62] An additional example is the usefulness of spironolactone as an antiandrogen in transgender women.[63][64][65]

Topical spironolactone has been found to be effective in the treatment of acne as well.[66] As a result, topical pharmaceutical formulations containing 2% or 5% spironolactone cream became available in Italy for the treatment of acne and hirsutism in the early 1990s.[67][68] The products were discontinued in 2006 when the creams were added to the list of doping substances with a decree of the Ministry of Health that year.[68]

Spironolactone, the 5α-reductase inhibitor finasteride, and the nonsteroidal antiandrogen flutamide all appear to have similar effectiveness in the treatment of hirsutism.[55][69][70] However, some clinical research has found that the effectiveness of spironolactone for hirsutism is greater than that of finasteride but is less than that of flutamide.[55] The combination of spironolactone with finasteride is more effective than either alone for hirsutism and the combination of spironolactone with a birth control pill is more effective than a birth control pill alone.[55] One study showed that spironolactone or the steroidal antiandrogen cyproterone acetate both in combination with a birth control pill had equivalent effectiveness for hirsutism.[55] Spironolactone is considered to be a first-line treatment for hirsutism, finasteride and the steroidal antiandrogen cyproterone acetate are considered to be second-line treatments, and flutamide is no longer recommended for hirsutism due to liver toxicity concerns.[55] The nonsteroidal antiandrogen bicalutamide is an alternative option to flutamide with improved safety.[71][72]

The combination of spironolactone with a birth control pill in the treatment of acne appears to have similar effectiveness to a birth control pill alone and the combination of a birth control pill with cyproterone acetate, flutamide, or finasteride.[52] However, this was based on low- to very-low-quality evidence.[52] Spironolactone may be more effective than birth control pills in the treatment of acne, and the combination of spironolactone with a birth control pill may have greater effectiveness for acne than either alone.[73] In addition, some clinical research has found that flutamide is more effective than spironolactone in the treatment of acne.[52] In one study, flutamide decreased acne scores by 80% within 3 months, whereas spironolactone decreased symptoms by only 40% in the same time period.[74][75][76] However, the use of flutamide for acne is limited by its liver toxicity.[77][78][79][80] Bicalutamide is a potential alternative to flutamide for acne as well.[81][82] Spironolactone can be considered as a first-line treatment for acne in those who have failed other standard treatments such as topical therapies and under certain other circumstances, although this is controversial due to the side effects of spironolactone and its teratogenicity.[73][50]

There is insufficient clinical evidence to compare the effectiveness of spironolactone with other antiandrogens for female-pattern hair loss.[83] The effectiveness of spironolactone in the treatment of both acne and hirsutism appears to be dose-dependent, with higher doses being more effective than lower doses.[73][84][85] However, higher doses also have greater side effects, such as menstrual irregularities.[52]

Spironolactone is frequently used as a component of feminizing hormone therapy in transgender women, especially in the United States (where cyproterone acetate is not available), usually in addition to an estrogen.[63][64][65] Other clinical effects include decreased male pattern body hair, the induction of breast development, feminization in general, and lack of spontaneous erections.[65] The medication is not approved for use as an antiandrogen by the Food and Drug Administration; instead, it is used off-label for such purposes.[86]

Spironolactone is typically used at a low dosage of 25 to 50 mg/day in the treatment of heart failure,[87][88][89][90] while it is used at low to high dosages of 25 to 200 mg/day in the treatment of essential hypertension,[87][90] and at high dosages of 100 to 400 mg/day for hyperaldosteronism and ascites due to cirrhosis.[91][92][93][94] The medication is typically used at high dosages of 100 to 200 mg/day in the treatment of skin and hair conditions in women,[95][96][97][98][99] and at high dosages of 100 to 400 mg/day in feminizing hormone therapy for transgender women.[100][101][102]

Spironolactone is available in the form of tablets (25 mg, 50 mg, 100 mg; brand name Aldactone, others) and suspensions (25 mg/5 mL; brand name CaroSpir) for use by mouth.[103][104][105][106][107] It has also been marketed in the form of 2% and 5% topical cream in Italy for the treatment of acne and hirsutism under the brand name Spiroderm, but this product is no longer available.[5][108] The medication is also available in combination with other medications, such as hydrochlorothiazide (brand name Aldactazide, others).[107][109] Spironolactone has poor water solubility, and for this reason, only oral and topical formulations have been developed; other routes of administration such as intravenous injection are not used.[6] The only antimineralocorticoid that is available as a solution for parenteral use is the related medication potassium canrenoate.[110]

Contraindications of spironolactone include hyperkalemia (high potassium levels), severe and end-stage kidney disease (due to high hyperkalemia risk, except possibly in those on dialysis), Addison’s disease (adrenal insufficiency and low aldosterone levels), and concomitant use of eplerenone.[111][112] It should also be used with caution in people with some neurological disorders, no urine production, acute kidney injury, or significant impairment of kidney excretory function with risk of hyperkalemia.[111]

One of the most common side effects of spironolactone is frequent urination. Other general side effects include dehydration, hyponatremia (low sodium levels), mild hypotension (low blood pressure),[74]ataxia (muscle incoordination), drowsiness, dizziness,[74]dry skin, and rashes. Because of its antiandrogenic activity, spironolactone can, in men, cause breast tenderness, gynecomastia (breast development), feminization in general, and demasculinization, as well as sexual dysfunction including loss of libido and erectile dysfunction, although these side effects are usually confined to high doses of spironolactone.[113] At very high doses (400 mg/day), spironolactone has also been associated with testicular atrophy and reversibly reduced fertility, including semen abnormalities such as decreased sperm count and motility in men.[114][115] However, such doses of spironolactone are rarely used clinically.[115] In women, spironolactone can cause menstrual irregularities, breast tenderness, and breast enlargement.[29][52][95] Aside from these adverse effects, the side effects of spironolactone in women taking high doses are minimal, and it is well tolerated.[52][74][116]

The most important potential side effect of spironolactone is hyperkalemia (high potassium levels), which, in severe cases, can be life-threatening.[111] Hyperkalemia in these people can present as a non anion-gap metabolic acidosis.[111] Spironolactone may put people at a heightened risk for gastrointestinal issues like nausea, vomiting, diarrhea, cramping, and gastritis.[111][117] In addition, there has been some evidence suggesting an association between use of the medication and bleeding from the stomach and duodenum,[111] though a causal relationship between the two has not been established.[118] Also, spironolactone is immunosuppressive in the treatment of sarcoidosis.[119]

Most of the side effects of spironolactone are dose-dependent.[51] Low-dose spironolactone is generally very well tolerated.[51] Even higher doses of spironolactone, such as 100 mg/day, are well tolerated in most individuals.[51] Dose-dependent side effects of spironolactone include menstrual irregularities, breast tenderness and enlargement, orthostatic hypotension, and hyperkalemia.[51] The side effects of spironolactone are usually mild and rarely result in discontinuation.[51]

Spironolactone can cause hyperkalemia, or high blood potassium levels.[115] Rarely, this can be fatal.[115] Of people with heart disease prescribed typical dosages of spironolactone, 10 to 15% develop some degree of hyperkalemia, and 6% develop severe hyperkalemia.[115] At a higher dosage, a rate of hyperkalemia of 24% has been observed.[120] An abrupt and major increase in the rate of hospitalization due to hyperkalemia from 0.2% to 11% and in the rate of death due to hyperkalemia from 0.3 per 1,000 to 2.0 per 1,000 between early 1994 and late 2001 has been attributed to a parallel rise in the number of prescriptions written for spironolactone upon the publication of the Randomized Aldactone Evaluation Study (RALES) in July 1999.[115][120][121][26] However, another population-based study in Scotland failed to replicate these findings.[122][123] The risk of hyperkalemia with spironolactone is greatest in the elderly, in people with renal impairment (e.g., due to chronic kidney disease or diabetic nephropathy), in people taking certain other medications (including ACE inhibitors, angiotensin II receptor blockers, nonsteroidal anti-inflammatory drugs, and potassium supplements), and at higher dosages of spironolactone.[115][26]

Although spironolactone poses an important risk of hyperkalemia in the elderly, in those with kidney or cardiovascular disease, and/or in those taking medications or supplements which increase circulating potassium levels, a large retrospective study found that the rate of hyperkalemia in young women without such characteristics who had been treated with high doses of spironolactone for dermatological conditions did not differ from that of controls.[52][53][124] This was the conclusion of a 2017 hybrid systematic review of studies of spironolactone for acne in women as well, which found that hyperkalemia was rare and was invariably mild and clinically insignificant.[52] These findings suggest that hyperkalemia may not be a significant risk in such individuals, and that routine monitoring of circulating potassium levels may be unnecessary in this population.[52][53][124] However, other sources have claimed that hyperkalemia can nonetheless also occur in people with more normal renal function and presumably without such risk factors.[26] Occasional testing on a case-by-case basis in those with known risk factors may be justified.[52] Side effects of spironolactone which may be indicative of hyperkalemia and if persistent could justify serum potassium testing include nausea, fatigue, and particularly muscle weakness.[52] Notably, non-use of routine potassium monitoring with spironolactone in young women would reduce costs associated with its use.[52]

Spironolactone frequently causes breast pain and breast enlargement in women.[99][125] This is “probably because of estrogenic effects on target tissue.”[115] At low doses, breast tenderness has been reported in only 5% of women, but at high doses, it has been reported in up to 40% of women.[126][51] Breast enlargement may occur in 26% of women at high doses and is described as mild.[74] Some women regard spironolactone-induced breast enlargement as a positive effect.[52]

Spironolactone also commonly and dose-dependently produces gynecomastia (breast development) as a side effect in men.[114][125][127][128] At low doses, the rate is only 5 to 10%,[128] but at high doses, up to or exceeding 50% of men may develop gynecomastia.[114][125][127] In the RALES, 9.1% of men taking 25 mg/day spironolactone developed gynecomastia, compared to 1.3% of controls.[129] Conversely, in studies of healthy men given high-dose spironolactone, gynecomastia occurred in 3 of 10 (30%) at 100 mg/day, in 5 of 8 (62.5%) at 200 mg/day, and in 6 of 9 (66.7%) at 400 mg/day, relative to none of 12 controls.[130][131] The severity of gynecomastia with spironolactone varies considerably, but is usually mild.[114] As with breast enlargement caused by spironolactone in women, gynecomastia due to spironolactone in men is often although inconsistently accompanied by breast tenderness.[114] In the RALES, only 1.7% of men developed breast pain, relative to 0.1% of controls.[129]

The time to onset of spironolactone-induced gynecomastia has been found to be 27 ± 20 months at low doses and 9 ± 12 months at high doses.[129] Gynecomastia induced by spironolactone usually regresses after a few weeks following discontinuation of the medication.[114] However, after a sufficient duration of gynecomastia being present (e.g., one year), hyalinization and fibrosis of the tissue occurs and drug-induced gynecomastia may become irreversible.[132][133]

Spironolactone at higher doses can cause menstrual irregularities as a side effect in women.[51] These irregularities include metrorrhagia (intermenstrual bleeding), amenorrhea (absence of menstruation), and breakthrough bleeding.[51] They are common during spironolactone therapy, with 10 to 50% of women experiencing them at moderate doses and almost all experiencing them at a high doses.[74][115] For example, about 20% of women experienced menstrual irregularities with 50 to 100 mg/day spironolactone, whereas about 70% experienced menstrual irregularities at 200 mg/day.[51] Most women taking moderate doses of spironolactone develop amenorrhea, and normal menstruation usually returns within two months of discontinuation.[115] Spironolactone produces an irregular and anovulatory pattern of menstrual cycles.[74] It is also associated with metrorrhagia and menorrhagia (heavy menstrual bleeding) in large percentages of women,[99] as well as with polymenorrhea (short menstrual cycles).[134][135] The medication reportedly has no birth control effect.[136]

It has been suggested that the weak progestogenic activity of spironolactone is responsible for these effects, although this has not been established and spironolactone has been shown to possess insignificant progestogenic and antiprogestogenic activity even at high dosages in women.[74][137][138] An alternative proposed cause is inhibition of 17α-hydroxylase and hence sex steroid metabolism by spironolactone and consequent changes in sex hormone levels.[114] Indeed, CYP17A1 genotype is associated with polymenorrhea.[139] Regardless of their mechanism, the menstrual disturbances associated with spironolactone can usually be controlled well by concomitant treatment with a birth control pill, due to the progestin component.[74][140]

Research is mixed on whether antimineralocorticoids like spironolactone have positive or negative effects on mood.[141][142][143] In any case, it is possible that spironolactone might have the capacity to increase the risk of depressive symptoms.[141][142][143] However, a 2017 hybrid systematic review found that the incidence of depression in women treated with spironolactone for acne was less than 1%.[52] Likewise, a 10-year observational study found that the incidence of depression in 196 transgender women taking high-dose spironolactone in combination with an estrogen was less than 1%.[144]

Aside from hyperkalemia, spironolactone may rarely cause adverse reactions such as anaphylaxis, kidney failure,[145]hepatitis (two reported cases, neither serious),[146]agranulocytosis, DRESS syndrome, Stevens–Johnson syndrome or toxic epidermal necrolysis.[147][148] Five cases of breast cancer in patients who took spironolactone for prolonged periods of time have been reported.[115][128]

Long-term administration of spironolactone gives the histologic characteristic of “spironolactone bodies” in the adrenal cortex. Spironolactone bodies are eosinophilic, round, concentrically laminated cytoplasmic inclusions surrounded by clear halos in preparations stained with hematoxylin and eosin.[149]

In the United States, spironolactone is considered pregnancy category C meaning that it is unclear if it is safe for use during pregnancy.[3][4] It is able to cross the placenta.[99] Likewise, it has been found to be present in the breast milk of lactating mothers and, while the effects of spironolactone or its metabolites have not been extensively studied in breastfeeding infants, it is generally recommended that women also not take the medication while nursing.[111] However, only very small amounts of spironolactone and its metabolite canrenone enter breast milk, and the amount received by an infant during breastfeeding (<0.5% of the mother's dose) is considered to be insignificant.[150]اسپیرنولاکتون

A study found that spironolactone was not associated with teratogenicity in the offspring of rats.[151][152][153] Because it is an antiandrogen, however, spironolactone could theoretically have the potential to cause feminization of male fetuses at sufficient doses.[151][152] In accordance, a subsequent study found that partial feminization of the genitalia occurred in the male offspring of rats that received doses of spironolactone that were five times higher than those normally used in humans (200 mg/kg per day).[151][153] Another study found permanent, dose-related reproductive tract abnormalities rat offspring of both sexes at lower doses (50 to 100 mg/kg per day).[153]

In practice however, although experience is limited, spironolactone has never been reported to cause observable feminization or any other congenital defects in humans.[151][152][154][155] Among 31 human newborns exposed to spironolactone in the first trimester, there were no signs of any specific birth defects.[155] A case report described a woman who was prescribed spironolactone during pregnancy with triplets and delivered all three (one boy and two girls) healthy; there was no feminization in the boy.[155] In addition, spironolactone has been used at high doses to treat pregnant women with Bartter’s syndrome, and none of the infants (three boys, two girls) showed toxicity, including feminization in the male infants.[150][151] There are similar findings, albeit also limited, for another antiandrogen, cyproterone acetate (prominent genital defects in male rats, but no human abnormalities (including feminization of male fetuses) at both a low dose of 2 mg/day or high doses of 50 to 100 mg/day).[155] In any case, spironolactone is nonetheless not recommended during pregnancy due to theoretical concerns relating to feminization of males and also to potential alteration of fetal potassium levels.[151][156]

A 2019 systematic review found insufficient evidence that spironolactone causes birth defects in humans.[157] However, there was also insufficient evidence to be certain that it does not.[157]

Spironolactone is relatively safe in acute overdose.[111]Symptoms following an acute overdose of spironolactone may include drowsiness, confusion, maculopapular or erythematous rash, nausea, vomiting, dizziness, and diarrhea.[111] In rare cases, hyponatremia, hyperkalemia, or hepatic coma may occur in individuals with severe liver disease.[111] However, these adverse reactions are unlikely in the event of an acute overdose.[111] Hyperkalemia can occur following an overdose of spironolactone, and this is especially so in people with decreased kidney function.[111] Spironolactone has been studied at extremely high oral doses of up to 2,400 mg per day in clinical trials.[110][158] Its oral median lethal dose (LD50) is more than 1,000 mg/kg in mice, rats, and rabbits.[111]

There is no specific antidote for overdose of spironolactone.[111] Treatment may consist of induction of vomiting or stomach evacuation by gastric lavage.[111] The treatment of spironolactone overdose is supportive, with the purpose of maintaining hydration, electrolyte balance, and vital functions.[111] Spironolactone should be discontinued in people with impaired kidney function or hyperkalemia.[111]

Spironolactone often increases serum potassium levels and can cause hyperkalemia, a very serious condition. Therefore, it is recommended that people using this medication avoid potassium supplements and salt substitutes containing potassium.[159] Physicians must be careful to monitor potassium levels in both males and females who are taking spironolactone as a diuretic, especially during the first twelve months of use and whenever the dosage is increased. Doctors may also recommend that some patients may be advised to limit dietary consumption of potassium-rich foods. However, recent data suggests that both potassium monitoring and dietary restriction of potassium intake is unnecessary in healthy young women taking spironolactone for acne.[160] Spironolactone together with trimethoprim/sulfamethoxazole increases the likelihood of hyperkalemia, especially in the elderly. The trimethoprim portion acts to prevent potassium excretion in the distal tubule of the nephron.[161]

Spironolactone has been reported to induce the enzymes CYP3A4 and certain UDP-glucuronosyltransferases (UGTs), which can result in interactions with various medications.[12][162][163] However, it has also been reported that metabolites of spironolactone irreversibly inhibit CYP3A4.[164] In any case, spironolactone has been found to reduce the bioavailability of oral estradiol, which could be due to induction of estradiol metabolism via CYP3A4.[165] Spironolactone has also been found to inhibit UGT2B7.[166] Spironolactone can also have numerous other interactions, most commonly with other cardiac and blood pressure medications, for instance digoxin.[111]

Licorice, which has indirect mineralocorticoid activity by inhibiting mineralocorticoid metabolism, has been found to inhibit the antimineralocorticoid effects of spironolactone.[167][168][169] Moreover, the addition of licorice to spironolactone has been found to reduce the antimineralocorticoid side effects of spironolactone in women treated with it for hyperandrogenism, and licorice hence may be used to reduce these side effects in women treated with spironolactone as an antiandrogen who are bothered by them.[167][168] On the opposite end of the spectrum, spironolactone is useful in reversing licorice-induced hypokalemia.[170][171]Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) have been found to attenuate the diuresis and natriuresis induced by spironolactone, but, not to affect its antihypertensive effect.[28][172]

Some research has suggested that spironolactone might be able to interfere with the effectiveness of antidepressant treatment. As the medication acts as an antimineralocorticoid, it is thought that it might be able to reduce the effectiveness of certain antidepressants by interfering with normalization of the hypothalamic–pituitary–adrenal axis and by increasing levels of glucocorticoids such as cortisol.[173][174] However, other research contradicts this hypothesis and has suggested that spironolactone might actually produce antidepressant effects, for instance studies showing antidepressant-like effects of spironolactone in animals.[175]

The pharmacodynamics of spironolactone are characterized by high antimineralocorticoid activity, moderate antiandrogenic activity, and weak steroidogenesis inhibition, among other more minor activities.[110][113][130] Spironolactone is a prodrug, so most of its actions are actually mediated by its various active metabolites.[110] The major active forms of spironolactone are 7α-thiomethylspironolactone (7α-TMS) and canrenone (7α-desthioacetyl-δ6-spironolactone).[6][110]

Spironolactone is a potent antimineralocorticoid.[6] That is, it is an antagonist of the mineralocorticoid receptor (MR), the biological target of mineralocorticoids like aldosterone and 11-deoxycorticosterone.[6] By blocking the MR, spironolactone inhibits the effects of mineralocorticoids in the body.[6] The antimineralocorticoid activity of spironolactone is responsible for its therapeutic efficacy in the treatment of edema, high blood pressure, heart failure, hyperaldosteronism, and ascites due to cirrhosis.[178][179] It is also responsible for many of the side effects of spironolactone, such as urinary frequency, dehydration, hyponatremia, low blood pressure, fatigue, dizziness, metabolic acidosis, decreased kidney function, and its risk of hyperkalemia.[180] Due to the antimineralocorticoid activity of spironolactone, levels of aldosterone are significantly increased by the medication, probably reflecting an attempt of the body to maintain homeostasis.[49][74]

Spironolactone is a moderate antiandrogen.[113][137][163] That is, it is an antagonist of the androgen receptor (AR), the biological target of androgens like testosterone and dihydrotestosterone (DHT).[113][137][163] By blocking the AR, spironolactone inhibits the effects of androgens in the body.[113][137][163] The antiandrogenic activity of spironolactone is mainly responsible for its therapeutic efficacy in the treatment of androgen-dependent skin and hair conditions like acne, seborrhea, hirsutism, and pattern hair loss and hyperandrogenism in women, precocious puberty in boys with testotoxicosis, and as a component of feminizing hormone therapy for transgender women.[137][165][181] It is also primarily responsible for some of its side effects, like breast tenderness, gynecomastia, feminization, and demasculinization in men.[114][181] Blockade of androgen signaling in the breast disinhibits the actions of estrogens in this tissue.[182] Although useful as an antiandrogen in women, who have low testosterone levels compared to men,[183][184] spironolactone is described as having relatively weak antiandrogenic activity.[96][181][185][186]

Spironolactone is a weak steroidogenesis inhibitor.[113][130][137][187] That is, it inhibits steroidogenic enzymes, or enzymes involved in the production of steroid hormones.[113][130][137][187] Spironolactone and/or its metabolites have been found in vitro to weakly inhibit a broad array of steroidogenic enzymes including cholesterol side-chain cleavage enzyme, 17α-hydroxylase, 17,20-lyase, 5α-reductase, 3β-hydroxysteroid dehydrogenase, 11β-hydroxylase, 21-hydroxylase, and aldosterone synthase (18-hydroxylase).[137][187][188][189] However, although very high doses of spironolactone can considerably decrease steroid hormone levels in animals, spironolactone has shown mixed and inconsistent effects on steroid hormone levels in clinical studies, even at high clinical doses.[52][113][130][137][163] In any case, the levels of most steroid hormones, including testosterone and cortisol, are usually unchanged by spironolactone in humans, which may in part be related to compensatory upregulation of their synthesis.[113][130][190] The weak steroidogenesis inhibition of spironolactone might contribute to its antiandrogenic efficacy to some degree and may explain its side effect of menstrual irregularities in women.[113][114] However, its androgen synthesis inhibition is probably clinically insignificant.[54]

Spironolactone has been found in some studies to increase levels of estradiol, an estrogen, although many other studies have found no changes in estradiol levels.[113][130] The mechanism of how spironolactone increases estradiol levels is unclear, but it may involve inhibition of the inactivation of estradiol into estrone and enhancement of the peripheral conversion of testosterone into estradiol.[191][192] It is notable that spironolactone has been found in vitro to act as a weak inhibitor of 17β-hydroxysteroid dehydrogenase 2, an enzyme that is involved in the conversion of estradiol into estrone.[193][194] Increased levels of estradiol with spironolactone may be involved in its preservation of bone density and in its side effects such as breast tenderness, breast enlargement, and gynecomastia in women and men.[191][195][196]

In response to the antimineralocorticoid activity spironolactone, and in an attempt to maintain homeostasis, the body increases aldosterone production in the adrenal cortex.[197][198][199] Some studies have found that levels of cortisol, a glucocorticoid hormone that is also produced in the adrenal cortex, are increased as well.[198][199][200] However, other clinical studies have found no change in cortisol levels with spironolactone,[137][201][85][202] and those that have found increases often have observed only small changes.[203] In accordance, spironolactone has not been associated with conventional glucocorticoid medication effects or side effects.[204][205]

Other activities of spironolactone may include very weak interactions with the estrogen and progesterone receptors and agonism of the pregnane X receptor.[85][206] These activities could contribute to the menstrual irregularities and breast side effects of spironolactone and to its drug interactions, respectively.[207][208][209]

The pharmacokinetics of spironolactone have not been studied well, which is in part because it is an old medication that was developed in the 1950s.[131] Nonetheless, much has been elucidated about the pharmacokinetics of spironolactone over the decades.[210][211][212][213][214][215][216][217]

The bioavailability of spironolactone when taken by mouth is 60 to 90%.[6][7][8] The bioavailability of spironolactone and its metabolites increases significantly (+22–95% increases in levels) when spironolactone is taken with food, although it is uncertain whether this further increases the therapeutic effects of the medication.[219][220][221] The increase in bioavailability is thought to be due to promotion of the gastric dissolution and absorption of spironolactone, as well as due to a decrease of the first-pass metabolism.[219][222][223] The relationship between a single dose of spironolactone and plasma levels of canrenone, a major active metabolite of spironolactone, has been found to be linear across a dose range of 25 to 200 mg spironolactone.[96]Steady-state concentrations of spironolactone are achieved within 8 to 10 days of treatment initiation.[177][224]

Little or no systemic absorption has been observed with topical spironolactone.[225]

Spironolactone and its metabolite canrenone are highly plasma protein bound, with percentages of 88.0% and 99.2%, respectively.[6][9] Spironolactone is bound equivalently to albumin and α1-acid glycoprotein, while canrenone is bound only to albumin.[6][9] Spironolactone and its metabolite 7α-thiospironolactone show very low or negligible affinity for sex hormone-binding globulin (SHBG).[226][227] In accordance, a study of high-dosage spironolactone treatment found no change in steroid binding capacity related to SHBG or to corticosteroid-binding globulin (CBG), suggesting that spironolactone does not displace steroid hormones from their carrier proteins.[228] This is in contradiction with widespread statements that spironolactone increases free estradiol levels by displacing estradiol from SHBG.[85][229]

Spironolactone appears to cross the blood–brain barrier.[230][231]

Spironolactone is rapidly and extensively metabolized in the liver upon oral administration and has a very short terminal half-life of 1.4 hours.[6][7] The major metabolites of spironolactone are 7α-thiomethylspironolactone (7α-TMS), 6β-hydroxy-7α-thiomethylspironolactone (6β-OH-7α-TMS), and canrenone (7α-desthioacetyl-δ6-spironolactone).[6][7][176] These metabolites have much longer elimination half-lives than spironolactone of 13.8 hours, 15.0 hours, and 16.5 hours, respectively, and are responsible for the therapeutic effects of the medication.[6][7] As such, spironolactone is a prodrug.[233] The 7α-thiomethylated metabolites of spironolactone were not known for many years and it was originally thought that canrenone was the major active metabolite of the medication, but subsequent research identified 7α-TMS as the major metabolite.[6][176][177] Other known but more minor metabolites of spironolactone include 7α-thiospironolactone (7α-TS), which is an important intermediate to the major metabolites of spironolactone,[12] as well as the 7α-methyl ethyl ester of spironolactone and the 6β-hydroxy-7α-methyl ethyl ester of spironolactone.[10]

Spironolactone is hydrolyzed or deacetylated at the thioester of the C7α position into 7α-TS by carboxylesterases.[12][234] Following formation of 7α-TS, it is S-oxygenated by flavin-containing monooxygenases to form an electrophilic sulfenic acid metabolite.[12] This metabolite is involved in the CYP450 inhibition of spironolactone, and also binds covalently to other proteins.[12] 7α-TS is also S-methylated into 7α-TMS, a transformation catalyzed by thiol S-methyltransferase.[12] Unlike the related medication eplerenone, spironolactone is said to not be metabolized by CYP3A4.[235] However, hepatic CYP3A4 is likely responsible for the 6β-hydroxylation of 7α-TMS into 6β-OH-7α-TMS.[13][236] 7α-TMS may also be hydroxylated at the C3α and C3β positions.[14] Spironolactone is dethioacetylated into canrenone.[15] Finally, the C17 γ-lactone ring of spironolactone is hydrolyzed by the paraoxonase PON3.[16][237] It was originally thought to be hydrolyzed by PON1, but this was due to contamination with PON3.[16]

The majority of spironolactone is eliminated by the kidneys, while minimal amounts are handled by biliary excretion.[238]

Spironolactone, also known as 7α-acetylthiospirolactone, is a steroidal 17α-spirolactone, or more simply a spirolactone.[110] It can most appropriately be conceptualized as a derivative of progesterone,[129][239][224] itself also a potent antimineralocorticoid, in which a hydroxyl group has been substituted at the C17α position (as in 17α-hydroxyprogesterone), the acetyl group at the C17β position has been cyclized with the C17α hydroxyl group to form a spiro 21-carboxylic acid γ-lactone ring, and an acetylthio group has been substituted in at the C7α position.[240][241][242] These structural modifications of progesterone confer increased oral bioavailability and potency,[243] potent antiandrogenic activity, and strongly reduced progestogenic activity.[244] The C7α substitution is likely responsible for or involved in the antiandrogenic activity of spironolactone, as 7α-thioprogesterone (SC-8365), unlike progesterone,[245] is an antiandrogen with similar affinity to the AR as that of spironolactone.[246] In addition, the C7α substitution appears to be responsible for the loss of progestogenic activity and good oral bioavailability of spironolactone, as SC-5233, the analogue of spironolactone without a C7α substitution, has potent progestogenic activity but very poor oral bioavailability similarly to progesterone.[245][247][248]

Spironolactone is also known by the following equivalent chemical names:[240][241][242]

Spironolactone is closely related structurally to other clinically used spirolactones such as canrenone, potassium canrenoate, drospirenone, and eplerenone, as well as to the never-marketed spirolactones SC-5233 (6,7-dihydrocanrenone; 7α-desthioacetylspironolactone), SC-8109 (19-nor-6,7-dihydrocanrenone), spiroxasone, prorenone (SC-23133), mexrenone (SC-25152, ZK-32055), dicirenone (SC-26304), spirorenone (ZK-35973), and mespirenone (ZK-94679).[110]

Chemical syntheses of spironolactone and its analogues and derivatives have been described and reviewed.[249]

The natriuretic effects of progesterone were demonstrated in 1955, and the development of spironolactone as a synthetic antimineralocorticoid analogue of progesterone shortly followed this.[129][239][250][251] Spironolactone was first synthesized in 1957,[20][250][251] was patented between 1958 and 1961,[252][253] and was first marketed, as an antimineralocorticoid, in 1959.[254][255] Gynecomastia was first reported with spironolactone in 1962,[110][256] and the antiandrogenic activity of the medication was first described in 1969.[257] This shortly followed the discovery in 1967 that gynecomastia is an important and major side effect of AR antagonists.[258][259] Spironolactone was first studied in the treatment of hirsutism in women in 1978.[260][167][261][262][263] It has since become the most widely used antiandrogen for dermatological indications in women in the United States.[106][264][265][266] Spironolactone was first studied as an antiandrogen in transgender women in 1986, and has since become widely adopted for this purpose as well, particularly in the United States where cyproterone acetate is not available.[267][268][269]

Early oral spironolactone tablets showed poor absorption.[270] The formulation was eventually changed to a micronized formulation with particle sizes of less than 50 μg, which resulted in approximately 4-fold increased potency.[270]

The English, French, and generic name of the medication is spironolactone and this is its INN, USAN, USP, BAN, DCF, and JAN.[108][109][240][271] Its name is spironolactonum in Latin, spironolacton in German, espironolactona in Spanish and Portuguese, and spironolattone in Italian (which is also its DCIT).[108][109][271]

Spironolactone is also known by its developmental code names SC-9420 and NSC-150339.[108][109][240]

Spironolactone is marketed under a large number of brand names throughout the world.[108][109] The major brand name of spironolactone is Aldactone.[108][109] Other important brand names include Aldactone-A, Berlactone, CaroSpir, Espironolactona, Espironolactona Genfar, Novo-Spiroton, Prilactone (veterinary), Spiractin, Spiridon, Spirix, Spiroctan, Spiroderm (discontinued),[5] Spirogamma, Spirohexal, Spirolon, Spirolone, Spiron, Spironolactone Actavis, Spironolactone Orion, Spironolactone Teva, Spirotone, Tempora (veterinary), Uractone, Uractonum, Verospiron, and Vivitar.[108][109]

Spironolactone is also formulated in combination with a variety of other medications, including with hydrochlorothiazide as Aldactazide, with hydroflumethiazide as Aldactide, Lasilacton, Lasilactone, and Spiromide, with altizide as Aldactacine and Aldactazine, with furosemide as Fruselac, with benazepril as Cardalis (veterinary), with metolazone as Metolactone, with bendroflumethiazide as Sali-Aldopur, and with torasemide as Dytor Plus, Torlactone, and Zator Plus.[109]

Spironolactone is marketed widely throughout the world and is available in almost every country, including in the United States, Canada, the United Kingdom, other European countries, Australia, New Zealand, South Africa, Central and South America, and East and Southeast Asia.[108][109]

There was a total of 17.2 million prescriptions for spironolactone in the United States between the beginning of 2003 and the end of 2005.[272] There was a total of 12.0 million prescriptions for spironolactone in the United States in 2016 alone.[273] It was the 66th top prescribed medication in the United States in 2016.[273]

Spironolactone has been studied at a high dosage in the treatment of benign prostatic hyperplasia (BPH; enlarged prostate).[274][275][276] It was found to be better than placebo in terms of symptom relief following three months of treatment.[274][275] However, this was not maintained after six months of treatment, by which point the improvements had largely disappeared.[274][275][276] Moreover, no difference was observed between spironolactone and placebo with regard to volume of residual urine or prostate size.[274][275] Gynecomastia was observed in about 5% of people.[275] On the basis of these results, it has been said that spironolactone has no place in the treatment of BPH.[275]

Spironolactone has been studied and used limitedly in the treatment of prostate cancer.[277][278][28]

Spironolactone has been found to block Epstein–Barr virus (EBV) production and that of other human herpesviruses by inhibiting the function of an EBV protein SM, which is essential for infectious virus production.[279] This effect of spironolactone was determined to be independent of its antimineralocorticoid actions.[279] Thus, spironolactone or compounds based on it have the potential to yield novel antiviral medications with a distinct mechanism of action and limited toxicity.[279]

Spironolactone has been studied in the treatment of rosacea in both males and females.[280][281][282][62][283]

Spironolactone has been studied in fibromyalgia in women.[284][285] It has also been studied in bulimia nervosa in women, but was not found to be effective.[286]

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“Spironolactone for heart failure with preserved ejection fraction”

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“Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People”

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the original

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“Advisory Statement”

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the original

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“Pharmacology of estrogens and progestogens: influence of different routes of administration”

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Archived

زمينه و هدف: اسپيرنولاكتون يك داروي ديورتيك و ضد آندروژني است كه در درمان پرفشاري خون، هيپرآلدوسترونيسم ثانويه، نارسايي احتقاني قلب، سيروز كبدي، سندرم نفروتيك و غيره از آن استفاده مي شود. در اين پژوهش تاثير اين دارو بر ميزان هورمونهاي هيپوفيزي- گنادي يعني FSH, LH، تستوسترون، دي هيدروتستوسترون و همچنين تغييرات وزن بدن و بافت بيضه، در موش صحرايي نر بالغ مورد بررسي قرار گرفت.روش كار: 40 سرموش صحرايي نر بالغ از نژاد ويستار، با وزن تقريبي 10±190 گرم انتخاب و با 5 گروه 8 تايي تقسيم شدند. گروه ها شامل گروه كنترل، شاهد تزريق (دريافت كننده آب مقطر) و گروههاي تجربي با مقادير حداقل دارو 25 ميلي گرم بر كيلوگرم، متوسط دارو 50 ميلي گرم بر كيلوگرم و حداكثر دارو 100 ميلي گرم بر كيلوگرم بودن. داروي اسپيرونولاكتون به صورت دهاني و به مدت 14 روز به طور روزانه به حيوانات خورانده شد. در پايان دوره آزمايش پس از تعيين وزن آنها، عمل خون گيري انجام شد و غلظت هورمون هاي FSH, LH، تستوسترون و دي هيدروتستوسترون (DHT) اندازه گيري شد، سپس بيضه هاي حيوان جهت بررسي تغييرات بافتي از بدن خارج و توزين شدند و پس از تهيه مقاطع بافتي و رنگ آميزي با روش هماتوكسيلين- ائوزين، مورد بررسي و مطالعه قرار گرفتند.يافته ها: مصرف داروي اسپيرنولاكتون در مقدار حداكثر به مدت 14 روز افزايش معني داري در غلظت هورمون LH و كاهش معني داري در غلظت هورمون هاي تستوسترون و دي هيدروتستوسترون نشان داد (p£0.05). در هيچ يك از مقادير دارو اختلاف معني داري درميزان هورمون FSH، وزن بدن و وزن بيضه مشاهده شد.نتيجه گيري: مصرف خوراكي داروي اسپيرنولاكتون با مقدار حداكثر يعني 100 ميلي گرم بر كيلوگرم به مدت 14 روز در افزايش هورمون LH و كاهش هورمونهاي تستوسترون و دي هيدروتستوسترون موثر است.

نشانی: تهران، بزرگراه اشرفی اصفهانی، نرسیده به پل بزرگراه شهید همت، خیابان شهید قموشی، خیابان بهار، نبش کوچه چهارم، پلاک 1

کدپستی: 1461965381

اسپیرنولاکتون

تلفن و دورنگار: 4 الی 44265001

کارگاه های آموزشی

اخبار

JCR

خبرگزاری سیناپرس

پیوندهای مرتبط

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اسپیرونولاکتون چیست؟ اسپیرونولاکتون جهت درمان ادم (در اصطلاح علمی ورم اندام ها) در اثر بیماری های کبدی، مشکلات کلیوی یا نارسایی قلبی تجویز می شود.

( قرص اسپیداکتون محصول شرکت تهران شیمی )

ورم یا ادم وقتی اتفاق می افتد که مایع از میان سلول های عروق خونی خارج می شود و به فضای بین سلول ها وارد می شود.این مساله باعث متورم شدن بافت سلولی در ریه ها ،پا یا مچ می شود.
این عارضه در ریه تنفس را با مشکل مواجه می کند یا پاها را متورم و سنگین می کند.
اسپیرونولاکتون با افزایش حجم ادرار ،دفع آب را افزایش می دهد و در نتیجه ورم کاهش می یابد.
این دارو همچنین در موارد دیگری مانند افزایش آلدوسترون در بدن و برخی مشکلات دیگر مانند پرمویی(هیرسوتیسم) و برخی از اختلالات هورمونی زنان کاربرد دارد.
اسپیرونولاکتون یک داروی ادرار آور حافظ پتاسیم می باشد و برخلاف سایر داروهای ادرار آور این دارو سبب کاهش پتاسیم بدن بیمار نمی شود.
این دارو به تنهایی یا همراه با داروهای ادرار آور در یک محصول موجود می باشد.بطور مثال لاسیکتون یک داروی ترکیبی از فروزماید و اسپیرونولاکتون می باشد.این محصولات ترکیبی ،تعداد قرص مصرفی در روز را کاهش می دهند و دارودرمانی را تسهیل می نمایند.

پیش از مصرف اسپیرونولاکتون_در صورت بارداری یا قصد باردار شدن و یا شیردهی،مشکلات کلیوی و غدد آدرنال (فوق کلیوی) ،پزشک خودرا مطلع نمایید.
_سابقه ی هرگونه حساسیت دارویی را به پزشک خود اعلام کنید.
-از آنجا که این دارو می تواند در عملکرد داروهای دیگر در بدن اختلال ایجاد کند لازم است پیش از شروع مصرف لیستی از کلیه ی داروهای مصرفی خود در اختیار پزشک یا داروساز خود قرار دهید.نحوه ی مصرف اسپیرنولاکتون_مقدار مصرف روزانه ی این دارو از 25 تا 200 میلی گرم بسته به شرایط و نیاز بیمار در روز می تواند متفاوت باشد لذا دارو را دقیقا مطابق با تجویز پزشک خود مصرف کنید و از کم یا زیاد کردن آن خودداری نمایید.
_بهترین زمان مصرف دارو همراه یا پس از غذا می باشد . در صورتی که یک بار در روز تجویز شده باشد بهتر است صبح ها پس از صبحانه مصرف شود.در صورتی که بیشتر از یک نوبت در روز تجویز شده باشد،بهتر است دوز دوم پیش از غروب (6 بعد از ظهر) مصرف شود تا افزایش ادرار موجب برهم زدن خواب بیمار نشود.
_در صورت فراموشی یک نوبت مصرف دارو به محض یادآوری ،آن را مصرف نمایید اما در صورتی که از ساعت 6 عصر گذشته باشد ،دارو را مصرف نکنید و نوبت بعدی را طبق برنامه قبلی مصرف نمایید.توصیه های اسپیرونولاکتون_معمولا درمان با این دارو ها طولانی مدت می باشد .در مدت درمان با این دارو،تحت نظر پزشک خود باشید و آزمایشات دوره ای که توسط پزشک برای شما تجویز می شود را به طور منظم انجام دهید .خصوصا انجام آزمایشات خون برای بررسی نمک های موجود درخون مانند سدیم و پتاسیم در مدت درمان با داروهای ادرار آور بسیار مهم است.
_دارو های ادرار آور کمک می کنند تا آب اضافی بدنتان دفع شود . تنفس و حرکت بدنی شما بهتر و راحت تر شود .با این وجود از دست دادن مایعات بیش از حد ،بدن را کم آب می کند و عوارضی مانند تشنگی،خشکی پوست ،کاهش وزن سریع پس از شروع درمان و بی حالی می دهد در صورتی که با این علائم مواجه شدید ،به پزشک اطلاع دهید تا تغییرات لازم را در مقدار مصرفی روزانه ی دارو اعمال کند.
_به علت اینکه اسپیرونولاکتون حافظ پتاسیم در بدن می باشد درصورت مصرف طولانی با دوز بالا، مصرف غذاهای غنی از پتاسیم را مانند نمک های حاوی پتاسیم یا کم سدیم، هندوانه، سیب زمینی، موز، سویا، کدو حلوایی، آلو و… را محدود کنید تا سطح پتاسیم خون افزایش نیابد.عوارض شایع اسپیرونولاکتوناحساس خستگی،گیجی ، خواب آلودگی و تهوع از عوارض شایع این دارو می باشد که با مصرف وعده های غذایی سبک و محدود کردن غذاهای چرب و پر ادویه می توان آن را کاهش داد.
-بدليل اينكه اين دارو ممکن است کمی خواب آورباشد،تا زماني كه اثر خواب آوري آن را احساس مي كنيد از رانندگي و كارهايي كه نياز به احتياط بيشتري دارند خودداري نماييد.
_مصرف این دارو در خانمها ممکن است موجب تغییرات در دوره ماهانه و تغییرات هورمونی مربوط به آن از جمله نا منظم شدن قاعدگی ،ریزش موهای زاید،دل پیچه ،تغییر خلق وخو ،قرمزی پوست و… شود.در صورتی که این مشکلات برای شما بوجود آمد،به پزشک خود اطلاع دهید.
_مصرف داروی اسپیرنولاکتون بر روی جنین ،خصوصا جنین پسر عوارض بدی می تواند داشته باشد.لذا حتما باید حداقل 3 ماه پیش از بارداری قطع شود.به این دلیل خانم ها در سنین باروری که تحت درمان با این دارو می باشند باید یک روش موثر پیشگیری از بارداری طبق نظر پزشک خود در پیش بگیرند.

Reference: www.webmd.com
Reference: www.drugs.com

اسپیرنولاکتون

در شرايط خاص و نظارت ويژه پزشك قابل استفاده است: مطالعات حیوانی مواردی از عارضه جانبی برای جنین نشان داده است و مطالعات انسانی به اندازه کافی در دست نیست. منافع دارو در مقابل خطرات احتمالی، تعیین کننده مصرف یا عدم مصرف این دارو در دوران بارداری است.

چنانچه در خصوص “اسپیرونولاکتون” سوالی دارید، عارضه خاصی مشاهده نموده اید و یا مطلب ویژه ای به نظرتان می رسد با دیگران به اشتراک بگذارید

 

 

URL: http://ijem.sbmu.ac.ir/article-1-118-fa.html

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ساخت و بررسی بالینی کرم اسپیرنولاکتون در درمان هیرسوتیسم

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متن کامل [PDF 219 kb]

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راهنمای نویسندگان

این دارو بهعنوان دارویکمکی در کنترل حالات خیزدار (مانندنارسایی احتقانی قلب، سیروز کبدی،سندرم نفروتیک که اغلب با زیادی ثانویهآلدوسترون همراه است) و خیز بدون علتمشخص و بهعنوان داروی کمکی دردرمان زیادی فشار خون همراه با افزایشآلدوسترون یا بدون آن، بهویژه درمواردی که نیاز به یک مدر نگهدارندهپتاسیم باشد، مصرف میشود.اسپیرونولاکتون برای تشخیص و درمانافزایش اولیه آلدوسترون و پیشگیری یادرمان کمی پتاسیم خون (در بیمارانی کهسایر اقدامات کافی نباشد) مصرفمیشود. این دارو در درمان پرمویی بدندر زنان نیز مورد استفاده قرار گرفتهاست.

این دارو بخوبی پس ازمصرف خوراکی از مجرای گوارش جذبمیشود و فراهمی زیستی آن نیز بیش از90 درصد است. پیوند این دارو به پروتئینبیش از 90 درصد است. متابولیسم ایندارو کبدی است. اثر آن پس از 4 ـ 2 ساعت(با مصرف مقدار واحد) شروع میشود.زمان لازم برای رسیدن به اوج اثر بامصرف مقادیر متعدد 3 ـ 2 روز است.اسپیرونولاکتون بهصورت متابولیت دفعمیشود.

این دارو در زیادیپتاسیم خون، کمی سدیم خون، عیب شدیدکار کلیه و بیماری آدیسون نباید مصرفشود.

1 ـ در موارد زیر باید با احتیاطفراوان مصرف شود: بیادراری یا عیب کار کلیه، افراد مبتلا بهدیابت و بیماری کلیوی، عیب کار کبد. 2 ـ بیمارانی که شدیدا بد حال هستند یاحجم ادرار آنها کم است، بیشتر در معرضخطر زیادی پتاسیم خون هستند. 3 ـ در بیماران سالخورده، خطر بروززیادی پتاسیم خون افزایش مییابد. اسپیرنولاکتون

اختلالات گوارشی، کاهشتوانایی جنسی، بزرگ شدن پستانها،بینظمی قاعدگی، کسالت، سردرد،اغتشاش شعور، بثورات جلدی، افزایشپتاسیم خون، کاهش سدیم خون،مسمومیت کبدی و نرمی استخوان بامصرف این دارو گزارش شده است.

1 ـ مصرف این داروحتی در صورت احساس بهبودی بایدادامه یابد. 2 ـ این دارو زیادی فشارخون را درماننمیکند، بلکه آن را کنترل مینماید. از اینرومصرف این دارو ممکن است تا آخر عمرضروری باشد. 3 ـ از مصرف سایر داروها، بخصوصداروهای مقلد سمپاتیک که نیاز به نسخهندارند، باید خودداری شود. 4 ـ اگر دارو یک بار در روز بهصورتمقدار واحد مصرف میشود، برای اجتناباز افزایش دفعات دفع ادرار در طول شب،بهتر است صبحها مصرف گردد. 5 ـ به منظور کاهش تحریک گوارشی واحتمالا کمک به افزایش فراهمی زیستیدارو، بهتر است دارو با غذا یا پس از آنمصرف شود.

بزرگسالان: بهعنوان مدر در خیز ناشی ازنارسایی احتقانی قلب، سیروز کبدی یاسندرم نفروتیک در بزرگسالان، ابتداmg/day 200 ـ 25 در 4 ـ 2 مقدار منقسم بهمدت حداقل 5 روز مصرف میشود.بهعنوان مقدار نگهدارنده 400 ـ 75 میلیگرم در 4 ـ 2 مقدار منقسممصرف میشود. در درمان افزایشفشارخون در بزرگسالان، ابتدا 100 mg/day ـ 50 بهصورت مقدار واحد یادر 4 ـ 2 مقدار منقسم به مدت حداقل 2 هفتهمصرف میشود. سپس مقدار مصرف هر2 هفته یک بار بر حسب نیاز تنظیم میشودتا به mg/day 200 برسد. در درمان کمیپتاسیم خون ناشی از مصرف سایر مدرهادر بزرگسالان mg/day 100 ـ 25 بهصورتمقدار واحد یا در 4 ـ 2 مقدار منقسم،بهعنوان داروی کمکی در تشخیص زیادیاولیه آلدوسترون در آزمون طولانی مدت،mg/day 400 به مدت 4 ـ 3 هفته، در آزمونکوتاه مدت 400 میلیگرم به مدت 4 روز وبهعنوان آنتاگونیست آلدوسترون 400 ـ 100 میلیگرم در 4 ـ 2 مقدار منقسممصرف میشود. کودکان: بهعنوان مدر یا کاهنده فشارخوندر درمان خیز، آسیت یا زیادی فشارخونمقدار شروع mg/kg 3 ـ 1 در روز است کهبهصورت مقدار واحد یا در 4 ـ 2 مقدارمنقسم مصرف میشود. پس از 5 روزمقدار مصرف مجددا تنظیم میشود.

مصرف همزمان ایندارو با داروهای نگهدارنده پتاسیم،سیکلوسپورین، مکملهای پتاسیم وداروهای مهارکننده آنزیم مبدلآنژیوتانسین ممکن است منجر به زیادیپتاسیم خون شود. اثرات ضد انعقادیهپارین در صورت مصرف همزمان بااسپیرونولاکتون ممکن است کاهش یابد.مصرف همزمان این دارو با لیتیم به علتکاهش کلیرانس کلیوی لیتیم، ممکن استسبب بروز مسمومیت با لیتیم شود.اسپیرونولاکتون ممکن است نیمه عمردیگوکسین را افزایش دهد.

Tablet : 25 mg

داروخانه شبانه روزی دکتر بهروزی

شهر ری، خیابان فدائیان اسلام، نرسیده به میدان شاه عبدالعظیم، ابتدای خیابان شهید قدمی (روشن)، پلاک 20

Copyright © 2019 Dr.Behroozi. All rights reserved.

آرشیو موضوعی وبسایت

تغذیه و سلامتی

سلامت زنان

سلامت مردان

سلامت کودکان

اسپیرنولاکتون

سلامت میانسالان

سلامت روان

سلامت جنسی

اعتیاد و سیگار

پوست و مو

دهان و دندان

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ویتامین و مکمل

انواع دارو ها

انواع بیماری

اسپیرونولاکتون برای درمان فشار خون بالا استفاده می شود. پایین آوردن فشار خون بالا به جلوگیری از سکته مغزی، حملات قلبی و مشکلات کلیوی کمک می کند. همچنین اسپیرونولاکتون برای درمان تورم (ادم) ناشی از شرایط خاص (مانند نارسایی قلبی، بیماری کبد) با حذف مایعات بیش از حد و بهبود علائمی نظیر مشکلات تنفسی استفاده می شود.

 

اسپیرونولاکتون برای درمان سطح پتاسیم پایین و شرایطی که در آنها بدن بیش از حد مواد شیمیایی طبیعی (آلدوسترون) تولید می کند، استفاده می شود.
اسپیرونولاکتون به عنوان قرص آب شناخته شده است (دیورتیک حافظ پتاسیم).

 

طبق دستور پزشک، این دارو را به صورت خوراکی مصرف کنید. در صورت بروز ناراحتی معده، آن را با غذا یا شیر مصرف کنید. به منظور جلوگیری از لزوم تخلیه ادرار در طول شب، بهتر است صبح زود (قبل از ساعت ۶ صبح) این دارو را مصرف کنید. اگر سوالی دارید، با پزشک یا داروساز مشورت کنید.

اگر از شکل مایع این دارو استفاده می کنید، بطری را قبل از هر دوز مصرف خوب تکان دهید. دوز دقیق را با وسیله یا قاشق مخصوص اندازه گیری کنید. از قاشق خانگی استفاده نکنید زیرا ممکن است دوز دقیق را دریافت نکنید. می توانید شکل مایع این دارو را همراه با غذا یا بدون غذا مصرف کنید، اما مهم است که یک روش را انتخاب کنید و همیشه به همان شکل دارو را مصرف کنید.

مصرف دارو بر اساس وضعیت پزشکی و پاسخ به درمان تعیین میشود. در کودکان نیز، دوز بر اساس وزن بدن تعیین میشود.

این دارو را به طور منظم مصرف کنید تا بیشترین بهره را از آن ببرید. به یاد داشته باشید هر روز آنرا در همان زمان (ها) مصرف کنید. ادامه مصرف دارو حائز اهمیت است حتی اگر احساس خوبی داشته باشید. اکثر افراد مبتلا به فشار خون بالا احساس بیماری نمی کنند.

اسپیرونولاکتون را دقیقا طبق تجویز مصرف کنید. بدون تایید پزشک دوز خود را افزایش ندهید و دفعات و دوره مصرف را از نسخه تجویزی بیشتر نکنید. مصرف دارو را به طور ناگهانی قطع نکنید. هنگامی که مصرف این دارو به طور ناگهانی متوقف شود، وضعیت شما ممکن است بدتر شود.

اگر وضعیت شما بدتر شد (به عنوان مثال اگر متوجه افزایش روزافزون فشار خون خود شدید)، به پزشک اطلاع دهید.

 

با مصرف این دارو خواب آلودگی، احساس سبکی سر، سرگیجه، ناراحتی معده، اسهال، تهوع، استفراغ یا سردرد ممکن است رخ دهند. برای به حداقل رساندن سرگیجه، هنگام بلند شدن از موقعیت نشسته یا دراز کشیده، به آرامی بلند شوید. اگر هر کدام از این موارد ادامه پیدا کرد یا بدتر شد، به پزشک یا داروساز خود اطلاع دهید.

به یاد داشته باشید که پزشک این دارو را بدین دلیل تجویز کرده است که نفع آن را بیشتر از خطر عوارض جانبی آن در نظر گرفته است. بسیاری از افرادی که از این دارو استفاده می کنند، عوارض جانبی جدی ندارند.

اگر در معرض خطر جدی باشید، از جمله: تشنگی، علائم مشکلات کلیه (مانند تغییر مقدار ادرار)، تغییرات ذهنی / خلقی، خستگی / ضعف غیر معمول، اسپاسم عضلانی، تغییرات قاعدگی، درد سینه، بزرگ شدن سینه در مردان (gynecomastia)، مشکلات عملکرد جنسی، علائم عفونت (مانند تب، گلودرد مداوم)، درد شدید معده و شکمی، تهوع / استفراغ مداوم، استفراغی که به رنگ قهوه باشد، ادرار تیره، زردی/ پوست چشم، کبودی / خونریزی آسان.

این دارو به ویژه در بیماران مبتلا به نارسایی کلیه، ممکن است به سطح بالایی از پتاسیم منتهی شود. سطوح بسیار بالای پتاسیم در صورتی که درمان نشود، می تواند کشنده باشد. اگر متوجه یکی از موارد جدی زیر شدید، بلافاصله به پزشک خود اطلاع دهید: ضربان قلب آهسته / نامنظم، ضعف عضلانی.

واکنش آلرژیک بسیار جدی به این دارو نادر است. با این حال، اگر متوجه علائم واکنش شدید آلرژیک شدید، از جمله: بثورات، خارش / تورم (به ویژه در صورت / زبان / گلو)، سرگیجه شدید و مشکل تنفسی، فورا به پزشک مراجعه کنید.

در این مقاله از راستینه ارائه لیست کاملی از عوارض جانبی احتمالی امکان پذیر نیست. اگر متوجه عارضه دیگری شدید که در بالا ذکر نشده است، با پزشک یا داروساز خود تماس بگیرید.

 

قبل از مصرف اسپیرونولاکتون ، اگر به این دارو حساسیت دارید، یا اگر آلرژی دیگری دارید، با پزشک یا داروساز خود مطرح کنید. این محصول ممکن است حاوی مواد غیر فعالی باشد که می توانند واکنش های آلرژیک و مشکلات دیگر ایجاد کنند. برای اطلاعات بیشتر با داروساز خود صحبت کنید.

قبل از استفاده از این دارو، پزشک یا داروساز را از سابقه پزشکی خود مطلع سازید، به ویژه سوابقی همچون: مشکلات کلیوی، مشکلات کبدی، عدم تعادل مواد معدنی درمان نشده (مانند پتاسیم بالا، سدیم کم)، کاهش عملکرد غده فوق کلیه (بیماری آدیسون).

قبل از انجام عمل جراحی، پزشک یا دندانپزشک را در مورد تمام محصولاتی که استفاده میکنید (از جمله داروهای تجویزی، داروهای بدون نسخه و محصولات گیاهی) مطلع سازید.اسپیرنولاکتون

این دارو ممکن است سطح پتاسیم شما را افزایش دهد. قبل از استفاده از مکمل های پتاسیم یا جایگزین نمک هایی که حاوی پتاسیم هستند، با پزشک یا داروساز مشورت کنید. خوراکی های حاوی پتاسیم بالا مانند موز، گوجه فرنگی، سیب زمینی و شیر را محدود کنید. برای جزئیات بیشتر، از جمله توصیه های لازم، با پزشک یا داروساز مشورت کنید.

این دارو ممکن است باعث سرگیجه یا خواب آلودگی شود. مصرف الکل یا ماری جوانا می تواند موجب تشدید سرگیجه یا خواب آلودگی شما شود. از رانندگی، استفاده از ماشین آلات یا انجام هر کاری که نیاز به هشیاری دارد تا زمانی که بتوانید چنین کارهایی را با خیال راحت انجام دهید، خودداری کنید. مصرف نوشیدنی های الکلی را محدود کنید.

سالمندان ممکن است نسبت به عوارض جانبی این دارو، به ویژه تاثیر روی میزان پتاسیم، حساسیت بیشتری داشته باشند (به بخش عوارض جانبی مراجعه کنید).

این دارو در دوران بارداری فقط باید در صورت نیاز شدید مصرف شود. در مورد خطرات و مزایای آن با پزشک خود مشورت کنید.

این دارو به شیر مادر منتقل می شود اما بعید است به شیرخوار آسیب برساند. قبل از شیردهی با پزشک خود مشورت کنید.

 

تداخلات دارویی ممکن است نحوه عملکرد داروهای شما را تغییر دهند یا خطر ابتلا به عوارض جدی را افزایش دهند. این مقاله از راستینه شامل تمام تداخلات احتمالی دارو نیست. فهرستی از تمام محصولاتی که استفاده می کنید (از جمله داروهای تجویزی / غیر تجویز و محصولات گیاهی) تهیه و آن را با پزشک و داروساز خود ارائه دهید. بدون تایید پزشک مصرف هیچ دارویی را شروع یا متوقف نکنید و دوز آنها را تغییر ندهید.

برخی از محصولاتی که ممکن است با این دارو تداخل داشته باشند عبارتنداز: لیتیوم و داروهایی که ممکن است سطح پتاسیم را در خون افزایش دهند (مانند آمیلوراید، سیکلوسپورین، اپلرنون، تاکرولیموس، تریامترن، قرص های ضد بارداری حاوی دسپیرنون).

بعضی از محصولات دارای مواد تشکیل دهنده ای هستند که می توانند فشار خون شما را افزایش دهند یا تورم را بدتر کنند. در صورت مصرف هرگونه دارو (به خصوص محصولات سرفه و سرماخوردگی، داروهای رژیم غذایی یا NSAID ها مانند ایبوپروفن / ناپروکسن) با داروساز مطرح کنید.

این دارو ممکن است با آزمایشات آزمایشگاهی خاص (از جمله میزان دیگوکسین یا کورتیزول)، احتمالا باعث نتایج کاذب می شود. اطمینان حاصل کنید که پرسنل آزمایشگاهی و تمام پزشکان شما می دانند که شما از این دارو استفاده می کنید.

اگر از این دارو برای درمان فشار خون بالا استفاده می کنید، تغییرات در شیوه زندگی مانند برنامه های کاهش استرس، تمرینات و تغذیه ممکن است فواید این دارو را افزایش دهند. با پزشک یا داروساز خود در مورد تغییرات شیوه زندگی که ممکن است برای شما مفید باشند، صحبت کنید. در هنگام مصرف این دارو، فشار خون را به طور منظم بررسی کنید. با پزشک خود صحبت کنید و یاد بگیرید که چگونه فشار خون خود را در منزل کنترل کنید. نتایج میزان فشار خون خود را به پزشک اطلاع دهید.

 

در صورتی که دوز بالایی مصرف گردد با مرکز مسمومیت یا اورژانس تماس گیرید. در تهران می توان با مرکز مسمومیت با شماره تلفن ۱۴۹۰ تماس بگیرید. ساکنان دیگر شهر ها می توانند با مرکز کنترل مسمومیت استانی یا اورژانس ۱۱۵ تماس بگیرند.

 

اسپیرونولاکتون را به بقیه افراد جهت مصرف ندهید. این برخلاف قانون است. تست های آزمایشگاهی و یا پزشکی ممکن است به صورت دوره ای برای نشان دادن پیشرفت شما و یا کنترل عوارض جانبی انجام شود. برای جزئیات بیشتر با پزشک خود مشورت کنید.

 

منبع تصاویر 

اطلاعات پزشکی

زیبایی

تغذیه و سلامتی

تغذیه و سلامتی

اطلاعات پزشکی

پوست و مو

پوست و مو

پوست و مو

پوست و مو

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زمینه و هدف: اسپیرنولاکتون یک داروی دیورتیک و ضد آندروژنی است که در درمان پرفشاری خون، هیپرآلدوسترونیسم ثانویه، نارسایی احتقانی قلب، سیروز کبدی، سندرم نفروتیک و غیره از آن استفاده می شود. در این پژوهش تاثیر این دارو بر میزان هورمونهای هیپوفیزی- گنادی یعنی FSH, LH، تستوسترون، دی هیدروتستوسترون و هم چنین تغییرات وزن بدن و بافت بیضه، در موش صحرایی نر بالغ مورد بررسی قرار گرفت.

روش کار: 40 سر موش صحرایی نر بالغ از نژاد ویستار، با وزن تقریبی 10±190 گرم انتخاب و به 5 گروه 8 تایی تقسیم شدند. گروه ها شامل گروه کنترل، شاهد تزریق ( دریافت کننده آب مقطر) و گروه های تجربی با مقادیر حداقل دارو 25 میلی گرم بر کیلوگرم، متوسط دارو 50گرم بر کیلوگرم و حداکثر دارو 100 میلی گرم بر کیلوگرم بودند. داروی اسپیرونولاکتون به صورت دهانی و به مدت 14 روز به طور روزانه به حیوانات خورانده شد. در پاین دوره آزمایش پس از تعیین وزن آن ها، عمل خون گیری انجام شد و غلظت هورمون های FSH, LH تستوسترون و دی هیدروتستوسترون (DHT) اندازه گیری شد. سپس بیضه های حیوان جهت بررسی تغییرات بافتی از بدن خارج و توزین شدند و پس از تهیه مقاطع بافتی و رنگ آمیزی با روش هماتوکلیسین- ائوزین، مورد بررسی و مطالعه قرار گرفتند.

یافته ها: مصرف داروی اسپیرنولاکتون در مقدار حداکثر به مدت 14 روز افزایش معنی داری در غلظت هورمون LH و کاهش معنی داری در غلظت هورمون های تستوسترون و دی هیدروتستوسترون نشان داد (0.05 p≤). در هیچ یک از مقادیر دارو اختلاف معنی داری در میزان هورمون FSH ، وزن بدن و وزن بیضه مشاهده نشد.

نتیجه گیری: مصرف خوراکی داروی اسپیرنولاکتون با مقدار حداکثر یعنی 100 میلی گرم بر کیلوگرم به مدت 14 روز در افزایش هورمون LH و کاهش هورمون های تستوسترون و دی هیدروتستوسترون موثر است.اسپیرنولاکتون

دکتر مختار مختاری
[
استادیار گروه فیزیولوژی دانشگاه آزاد اسلامی واحد کازرون
]

دکتر مهرداد شریعتی
[
استادیار زیست شناسی تکوینی دانشگاه آزاد اسلامی واحد کازرون
]

نازنین تدین
[
کارشناس ارشد علوم جانوری
]

آدرس مستقیم دسترسی به این مقاله

محورهای همایش:

مکان یابی بهینه بیمارستان های شهری با استفاده از سیستم اطلاعات جغرافیایی، پاتوفیزیولوژی، آلزایمر، تأثیر عصاره گیاه بابونه گاوی

حوزه های تحت پوشش :
پزشکی

 قیمت :
رایگان

 تعداد بازدید :
۴۹۶

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