Spironolactone is a so-called competitive antagonist to the receptor for mineralocorticoids. The active ingredient spironolactone belongs to the pharmacological group of diuretics, which have potassium-sparing properties. The drug counts as an essential drug on the WHO list.
What is spironolactone?
Spironolactone causes increased flushing of water from the body. Spironolactone is a pharmacological agent that is used as a medication for the therapy of various complaints and diseases. It causes an increased excretion of water from the body. By taking it, the effect of the steroid homone aldosterone is reduced, which is why sodium excretion is reduced as a result. For this reason, it is possible that a higher proportion of potassium is retained. This is because aldosterone impedes or completely prevents its incorporation into the sodium channel. As a result of this mechanism, increased excretion of water occurs.
Pharmacologic action
The mechanism of action of spironolactone is primarily based on the fact that the substance blocks aldosterone receptors. As a result, water and sodium are excreted in greater amounts. At the same time, a greater amount of potassium is retained. If the drug spironolactone is taken orally, its bioavailability is over 90 percent. First, the substance is absorbed in the small intestine. Subsequently, the drug is metabolized into the active ingredient canrenoate. In the majority of cases, the half-life of the active substance is around 90 minutes. In principle, however, the complete effect of spironolactone is only seen after a few days. This is because it is necessary for the active metabolites to accumulate in sufficient quantities. In most cases, the greatest possible diuretic effect of the drug occurs after about five days. It should be noted that the onset of the effect of spironolactone cannot be brought about more quickly even by increasing the dose. Spironolactone leads to a blockage of the collecting tubes in the kidneys. The substance aldosterone is thus no longer able to bind to its receptor. The sodium channels are hindered in their installation, while at the same time the luminal membrane on the principal cells is blocked. As a result, the reabsorption of sodium is severely impaired. As a consequence, water is not drawn into the so-called collecting tubes of the kidneys. As a result, no further water enters the blood either. Instead, there is an increased excretion of sodium and water. Therefore, the amount of blood in the organism also decreases. Thus, the heart is relieved, which is why blood pressure decreases. In addition, accumulations of water in the tissues are also flushed out. The loss of potassium, which is a consequence of numerous diuretics, is compensated by combined therapy with spironolactone. Clinical studies have shown that treatment with the active substance spironolactone has a positive effect on prognosis and survival in chronic heart failure. Following oral administration, the substance spironolactone is generally well absorbed. After one hour, the active substance is completely eliminated in the plasma. However, various metabolites remain. In principle, these metabolites are largely responsible for the effect of the drug. In principle, the metabolism of the drug is complex. The substance canrenone plays a significant role in this process and shows up both in the urine and in the blood. Numerous metabolites of this process are excreted in the stool and bile.
Medical use and application
The drug spironolactone is used in the majority of cases for the treatment of liver cirrhosis and heart failure. Depending on the individual indication, the attending physician prescribes dosages of 25 to 100 milligrams per day. In addition, the drug spironolactone is also used in cases of elevated concentrations of aldosterone. The underlying diseases here are usually liver cirrhosis or primary hyperaldosteronism. Spironolactone is very effective in chronic heart failure. However, it tends to be used rather rarely for this purpose in Europe, whereas it is used as a standard drug in the USA. Spironolactone is also used in endocrinology in people with transsexualism.In this process, the drug acts as a testosterone blocker by interfering with the synthesis of the hormone as well as its binding to the corresponding androgen receptors.
Risks and side effects
In the course of therapy with the drug, various undesirable side effects and complaints are possible, which differ depending on the patient and the individual case. The most common is an increased level of potassium in the blood. For this reason, patients must be monitored by a physician while taking the drug. Hormonal disturbances are also possible with high doses of the drug. These are manifested, for example, in the absence of menstruation in women. Male patients may experience erectile dysfunction or changes in their voice. In transsexual people, exactly these effects are sometimes desired. Interactions are seen, for example, when the active ingredient digoxin is taken at the same time. Increased concentrations of the cardiac glycoside in the plasma are possible. Other side effects may include hyperkalemia, gynecomastia, or impotence. Some side effects of spironolactone lead to the drug being used as a doping agent in sports. It should be noted that misuse of the drug, as well as overdose, significantly increases the risk of damage to the kidneys.
