spironolactone

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A steroid derivative, C₂₄H₃₂O₄S, that blocks the action of aldosterone, used as a diuretic primarily in the treatment of hypertension.

[Alteration of spirolactone : Latin spīra, coil; see spiral + LACTONE.]

trade names: Aldactone, Spirozide; drug class: potassium-sparing diuretic; action: competes with aldosterone at receptor sites in distal tubule, resulting in excretion of sodium chloride and water and retention of potassium and phosphate; uses: treatment for edema, hypertension, diuretic-induced hypokalemia, and cirrhosis of the liver with ascites.

Brand names: Aldactone®Spirono™

Chemical formula:

Español:
• Espironolactona, Tableta oral

Spironolactone Oral tablet

What is this medicine?

SPIRONOLACTONE is a diuretic. It helps you make more urine and to lose excess water from your body. This medicine is used to treat high blood pressure, and edema or swelling from heart, kidney, or liver disease. It is also used to treat patients who make too much aldosterone or have low potassium.

This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:
•high blood level of potassium
•kidney disease or trouble making urine
•liver disease
•an unusual or allergic reaction to spironolactone, other medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should I use this medicine?

Take this medicine by mouth with a drink of water. Follow the directions on your prescription label. You may take this medicine with or without food. If it upsets your stomach, take it with food or milk. Do not take your medicine more often than directed. Remember that you will need to pass more urine after taking this medicine. Do not take your doses at a time of day that will cause you problems. Do not take at bedtime.

Talk to your pediatrician regarding the use of this medicine in children. While this drug may be prescribed for selected conditions, precautions do apply.

Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.
NOTE: This medicine is only for you. Do not share this medicine with others.

What may interact with this medicine?

Do not take this medicine with any of the following medications:
•eplerenone

This medicine may also interact with the following medications:
•corticosteroids
•digoxin
•lithium
•medicines for high blood pressure like ACE inhibitors
•skeletal muscle relaxants like tubocurarine
•NSAIDs, medicines for pain and inflammation, like ibuprofen or naproxen
•potassium products like salt substitute or supplements
•pressor amines like norepinephrine
•some diuretics

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

What should I watch for while using this medicine?

Visit your doctor or health care professional for regular checks on your progress. Check your blood pressure as directed. Ask your doctor what your blood pressure should be, and when you should contact them.

You may need to be on a special diet while taking this medicine. Ask your doctor. Also, ask how many glasses of fluid you need to drink a day. You must not get dehydrated.

This medicine may make you feel confused, dizzy or lightheaded. Drinking alcohol and taking some medicines can make this worse. Do not drive, use machinery, or do anything that needs mental alertness until you know how this medicine affects you. Do not sit or stand up quickly.

What side effects may I notice from receiving this medicine?

Side effects that you should report to your doctor or health care professional as soon as possible:
•allergic reactions such as skin rash or itching, hives, swelling of the lips, mouth, tongue, or throat
•black or tarry stools
•fast, irregular heartbeat
•fever
•muscle pain, cramps
•numbness, tingling in hands or feet
•trouble breathing
•trouble passing urine
•unusual bleeding
•unusually weak or tired

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):
•change in voice or hair growth
•confusion
•dizzy, drowsy
•dry mouth, increased thirst
•enlarged or tender breasts
•headache
•irregular menstrual periods
•sexual difficulty, unable to have an erection
•stomach upset

This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Where should I keep my medicine?

Keep out of the reach of children.

Store below 25 degrees C (77 degrees F). Throw away any unused medicine after the expiration date.

Last updated: 7/1/2002

Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.

A competitive antagonist of aldosterone, used as a diuretic. It increases resorption of sodium in the distal renal tubules.

Spironolactone
Systematic (IUPAC) name
7α-Acetylthio-3-oxo-17α-pregn-4-ene-21,17-carbolactone OR (1' S,2R,2' R,9' R,10' R,11' S,15' S)-9'-(acetylsulfanyl)-2',15'-dimethylspiro[oxolane-2,14'-tetracyclo[8.7.0.02,7.011,15]heptadecan]-6'-ene-5,5'-dione
Identifiers
CAS number	52-01-7
ATC code	C03DA01
PubChem	5833
DrugBank	APRD01234
ChemSpider	5628
Chemical data
Formula	C24H32O4S
Mol. mass	416.574 g/mol
SMILES	eMolecules & PubChem
Synonyms	Aldactone Spirotone Spirolactone
Pharmacokinetic data
Bioavailability	?
Metabolism	Hepatic
Half life	10 minutes
Excretion	Urine, bile
Therapeutic considerations
Pregnancy cat.	B3(AU) C(US)
Legal status	POM(UK)
Routes	Oral

Spironolactone (marketed under the trade names Aldactone, Novo-Spiroton, Aldactazide, Spiractin, Spirotone, Verospiron or Berlactone) is a diuretic and is used as an antiandrogen.

It is a synthetic 17-lactone drug that is a renal competitive aldosterone antagonist in a class of pharmaceuticals called potassium-sparing diuretics, used primarily to treat heart failure, ascites in patients with liver disease, low-renin hypertension, hypokalemia and Conn's syndrome. On its own, spironolactone is only a weak diuretic, but it can be combined with other diuretics. About one person in one hundred with hypertension has elevated levels of aldosterone; in these persons the antihypertensive effect of spironolactone may exceed that of complex combined regimens of other antihypertensives. Due to its anti-androgen effect, it can also be used to treat hirsutism, and it is a common component in hormone therapy for male-to-female transsexual and transgender people. It is also used for treating hair loss and acne in women and can be used as a topical medication for treatment of male baldness. It is commonly used to treat symptoms of Polycystic ovary syndrome(PCOS) such as excess facial hair and acne.

Contents 1 Mechanism of action 2 Pharmacokinetics 3 Mortality and morbidity benefit in severe heart failure 4 Adverse effects and interactions 4.1 Carcinogenicity 5 Other potential benefits 6 See also 7 References 8 External links

Mechanism of action

Spironolactone inhibits the effect of aldosterone by competing for intracellular aldosterone receptors in the distal tubule cells (it actually works on aldosterone receptors in the collecting duct). This increases the excretion of water and sodium, while decreasing the excretion of potassium. Spironolactone has a fairly slow onset of action, taking several days to develop, and similarly the effect diminishes slowly. Spironolactone has anti-androgen activity by binding to the androgen receptor and preventing it from interacting with dihydrotestosterone.^[1]

Pharmacokinetics

Spironolactone is a synthetic steroid that acts as a competitive antagonist to aldosterone. Its onset and duration of action are determined by the kinetics of the aldosterone response in the target tissue. Substantial inactivation of spironolactone occurs in the liver. Over all, spironolactone has a rather slow onset of action, requiring several days before full therapeutic effect is achieved.

Mortality and morbidity benefit in severe heart failure

Spironolactone was shown to have a significant mortality and morbidity benefit in the Randomized Aldactone Evaluation Study (RALES), which studied people with severe congestive heart failure (New York Heart Association functional class III or IV).^[2] Patients in the study arm of the trial (those receiving spironolactone) had a relative risk of death (when compared to the placebo group) equal to 0.70 or a 30% relative risk reduction. Patients in the study arm also had fewer symptoms of CHF and were hospitalized less frequently.

The mechanism of this effect is also mediated by inhibiting aldosterone, which in conjunction with heart failure leads to myocardial fibrosis, sodium retention, and vascular dysfunction.

Adverse effects and interactions

Spironolactone is associated with an increased risk of bleeding from the stomach and duodenum, but a causal relationship between the two has not been established.^[3] Because it also affects androgen receptors and other steroid receptors, it can cause gynecomastia, menstrual irregularities and testicular atrophy. Other side effects include ataxia, erectile dysfunction, drowsiness and rashes. A carcinogenic effect has been demonstrated in rats. Spironolactone has been shown to be immunosuppressive in the treatment of sarcoidosis.^[4]

Spironolactone often increases serum potassium levels and can cause hyperkalemia, a potentially serious condition. Therefore, it is recommended that people using this drug avoid potassium supplements and salt substitutes containing potassium. ^[5] Doctors usually recommend periodic screening of serum potassium levels and some patients may be advised to limit dietary consumption of potassium.

Research has also shown that spironolactone can interfere with the effectiveness of antidepressant treatment. The drug is actually (among its other receptor interactions) a mineralocorticoid (MR) antagonist, and has been found to reduce the effectiveness of antidepressant drugs in the treatment of major depression, presumably by interfering with normalization of the hypothalamic-pituitary-adrenal axis in patients receiving antidepressant therapy. ^[6]

Carcinogenicity

Studies of spironolactone and the related compound potassium canrenoate (which, like spironolactone, metabolizes to canrenone) in rats for one to two year periods show an increase in carcinogenesis in the thyroid gland, testes, liver, breasts, and myelocytic leukocytes. Mammalian cells, depending on the presence of metabolic activation, show mixed results for mutagenicity in vitro.^[7] In light of this research, Sandoz has recommended that unnecessary use of spironolactone be avoided.

Other potential benefits

It has been suggested that spironolactone can reduce the risk of Alzheimer's disease. In one study ^[8], researchers observed a reduction in the risk of Alzheimer's specifically associated with potassium-sparing diuretics. Unpublished findings from other studies, including the Gothenberg Study have suggested that higher potassium levels may be associated with a lower risk of dementia.

It is widely reported that most American diets contain more sodium than is necessary and lack the optimal daily intake of potassium. Therefore, spironolactone could theoretically counter the effects of the typical American diet as it tends to promote sodium excretion and potassium retention. However, there is no proof that it is beneficial for persons whose serum potassium and sodium levels are within the normal range. Few if any doctors would recommend using spironolactone in the absence of conditions for which it is normally indicated.

Spironolactone has also been shown to help prevent certain types of acne in females when taken in combination with oral contraceptives.

See also

• Baldness treatments

References

1. ^ Berardesca, E; Gabba P, Ucci G, Borroni G, Rabbiosi G. (1988). "Topical spironolactone inhibits dihydrotestosterone receptors in human sebaceous glands: an autoradiographic study in subjects with acne vulgaris". Int J Tissue React. 10 (2): 115–119. PMID 2972662. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2972662&dopt=Abstract. Retrieved on 2007-03-15. 
2. ^ Pitt B, Zannad F, Remme W, Cody R, Castaigne A, Perez A, Palensky J, Wittes J (1999). "The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators". N Engl J Med 341 (10): 709–17. doi:10.1056/NEJM199909023411001. PMID 10471456. http://content.nejm.org/cgi/content/full/341/10/709. 
3. ^ Verhamme KMC, Mosis G, Dieleman JP, et al. (2006). "Spironolactone and risk of upper gastrointestinal events: population based case-control study". Brit Med J 333 (7563): 330–3. doi:10.1136/bmj.38883.479549.2F. PMID 16840442. 
4. ^ Wandelt-Freerksen E. (1977). "Aldactone in the treatment of sarcoidosis of the lungs". JZ Erkr Atmungsorgane. 149(1): 156–9. PMID 607621. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=607621&query_hl=22&itool=pubmed_DocSum. Retrieved on 2007-05-02. 
5. ^ "Advisory Statement" (pdf). Klinge Chemicals / LoSalt. http://www.losalt.com/docs/lo_salt_web_advice.pdf. Retrieved on 2007-03-15. 
6. ^ Holsboer, F. The Rationale for Corticotropin-Releasing Hormone Receptor (CRH-R) Antagonists to Treat Depression and Anxiety. J. Psychiatr. Res. 33, 181–214 (1999)
7. ^ "Spironolactone RX Monograph" (html). Sandoz Inc.. http://dailymed.nlm.nih.gov/dailymed/fdaDrugXsl.cfm?id=2479&type=display. Retrieved on 2007-05-02. 
8. ^ [Antihypertensive Medication Use and Incident Alzheimer Disease http://archneur.ama-assn.org/cgi/content/full/63.5/noc60013v1]

External links

• nih.gov information site
• Aldactone patient info leaflet

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