Spironolactone

An aldosterone antagonist.

Oral agent with 90% protein binding, hepatic metabolism, urine and biliary excretion, half-life 1.3-2 hours.

A synthetic, steroidal antimineralocorticoid agent with additional antiandrogen and weak progestogen properties.

Competes with aldosterone to bind to the mineralocorticoid receptor, which is expressed in the distal convoluted tubule cells of the kidney.

This  binding inhibits aldosterone dependent sodium- potassium exchange, leading to excretion of sodium and water and retention of potassium.

It is considered to be a weak diarrhetic, and is usually administered with another drug that targets the proximal tubule in order to increase diuresis.

It an  be associated with hyperkalemia.

it non-selectively, binds to androgen and progesteronereceptors, leading to off target effects, such as gynecomastia.

Has some indirect estrogen and glucocorticoid effects.

Used primarily as a diuretic and antihypertensive

Also used to reduce elevated or unwanted androgen activity in the body.

Acts predominantly as a competitive antagonist of the aldosterone receptor, and belongs to a class of pharmaceutical drugs known as potassium-sparing diuretics.

Anti-androgens like spironolactone block androgen receptors in the body, preventing cells from absorbing androgen hormones.

Limits hormonal fluctuations that can contribute to acne breakouts.

Can help women who have hormonal acne.

Only women whose acne has a hormonal basis will see benefits with this medication.

It is an inexpensive generic oral agent that is generally well tolerated and modulates one of the fundamental defects leading to acne: testosterone stimulation.

Response is usually seen within a 1 to 3 months in acne.

It has been used successfully in both genders to treat refractory acne.

Up to 66% of women on spironolactone had excellent improvement or complete clearing acne and when used in combination with oral contraceptives this number jumps to 85%, according to one study.

Used primarily to treat heart failure, ascites in patients with liver disease, low-renin hypertension, hypokalemia, secondary hyperaldosteronism, and Conn’s syndrome.

When used alone it is only a weak diuretic because its effects target the distal nephron collecting tubule, where urine volume can only be slightly modified.

When combined with other diuretics they increase its efficacy.

Concomitant use with loop diuretics decreases heart failure hospitalizations and mortality among patients with heart failure with reduced ejection fraction: its use in patients with heart failure with preserved ejection fraction is less established

Reduces production of testosterone and blocks androgen receptors, and can cause effects associated with low testosterone levels and hypogonadism.

It’s usefulness for long term therapy is therefore limited in men

Potassium levels need to be carefully monitored because of the potential danger of hyperkalemia.

In patients with severe congestive heart failure, the use of this agent has a relative risk of death of 0.7 or 30% relative risk reduction compared to placebo group, indicating a significant benefit in both mortality and morbidity.

Use improves the prognosis for patients with heart failure and reduced left ventricular ejection fraction.

In patients with heart failure and preserved ejection fraction use does not significantly reduce the incidence of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure (TOPCAT Investigators).

Antiandrogen effects make it useful to treat hirsutism, androgenic alopecia, acne, and seborrhea in females, and male pattern baldness in either low doses or as a topical formulation in males.

At high doses presents risks of feminization in males.

Its use in heart failure is associated with a higher risk of hyperkalemia and acute kidney injury.

Commonly used to treat symptoms of hyperandrogenism in polycystic ovarian syndrome.

Frequently used as a component of hormone replacement therapy in male-to-female transsexuals undergoing sex change therapy.

Inhibits the effects of mineralocorticoids including aldosterone and corticosterone by competing for intracellular mineralocorticoid receptors in the collecting duct of the kidney.

Decreases the reabsorption of sodium and water, while decreasing the secretion of potassium.

Has a slow onset of action and takes several days to develop because steroid receptors are nuclear receptors which work by regulating gene transcription.

May directly inactivate of steroid 11β-hydroxylase and aldosterone synthase (18-hydroxylase), enzymes involved in the biosynthesis of the mineralocorticoids.

Spironolactone inhibits steroid 11β-hydroxylase, essential for the production of the glucocorticoid hormone cortisol, yet it increases cortisol levels with acute and chronic administration.

Spironolactone is not a pure antagonist of the androgen receptor, but is actually a weak partial agonist with the capacity for both agonist and antagonist effects.

Contraindicated in prostate cancer, as the drug has been shown in vitro to significantly accelerate carcinoma growth in the absence of any other androgens.

Accelerates the metabolic clearance rate of testosterone by an enhancement of the rate of peripheral conversion of testosterone to estradiol.

Spironolactone has weak progestogenic properties, thought to be responsible for menstrual irregularities seen in women, serum lipid profile changes, and gynecomastia and breast tenderness.

Has some estrogenic effects which it mediates via several indirect actions.

Has half-life of about 1–2 hours, but may act as a prodrug to active metabolites with much longer half-lives.

Highly plasma protein bound.

Whille metabolized by the liver, it is eliminated mostly by the kidneys, with only minimal biliary excretion.

The bioavailability improves significantly when it is taken with food.

Most common side effect is urinary frequency.

Other side effects include ataxia, drowsiness, dry skin, rashes, gastrointestinal bleeding, gynecomastia, feminization, testicular atrophy, and sexual dysfunction consisting of loss of libido and erectile dysfunction, menstrual irregularities and breast tenderness and enlargement.

Commonly increases serum potassium levels.

Patients should avoid potassium supplements and salt substitutes containing potassium, and have periodic

laboratory testing for potassium levels.

Incidence of serious hyperkalemia about 5-8%.

Can interfere with the effectiveness of antidepressant treatment by interfering with normalization of the hypothalamic-pituitary-adrenal axis.

Should not be taken under any circumstance by pregnant women due to the high risk of feminization of male fetuses.

Long-term administration of spironolactone results in spironolactone bodies in the adrenal cortex, which are eosinophilic, round, concentrically laminated cytoplasmic inclusions surrounded by clear halos in preparations stained with hematoxylin and eosin.