Spironolactone

Spironolactone is a medicine that belongs to the class of aldosterone antagonists. It is used to treat high blood pressure (hypertension), heart failure, and to reduce fluid and salt levels in the body. Spironolactone may also be used in the treatment of some other conditions, such as polycystic ovary syndrome in women and hormone-dependent cosmetic acne in men and women. It works by blocking the action of aldosterone, a hormone that regulates fluid and salt levels in the body.

Indications Spironolactone

1. Hypertension (high blood pressure): Spironolactone may be prescribed as a component of the comprehensive treatment of hypertension, especially in the presence of high aldosterone levels or when other antihypertensive drugs are ineffective.
2. Heart Failure: Spironolactone may be used to treat heart failure, especially in combination with other medications, to reduce swelling and improve heart function.
3. Polycystic ovarian syndrome (PCOS): In women with PCOS, Spironolactone may help reduce androgen levels in the body, which can improve symptoms of hyperandrogenism such as excess body hair, reduced acne, and improved hair condition.
4. Hormonal acne: Spironolactone may be used to treat acne, especially in women whose acne is associated with elevated levels of androgens in the blood.
5. Liver cirrhosis and ascites: In some cases, spironolactone may be used to reduce ascites (fluid buildup in the abdomen) in cirrhosis of the liver.

Release form

1. Pills

• Dosage: The most common dosages in tablet form are 25 mg, 50 mg, and 100 mg.
• Description: The tablets may be coated or uncoated. They are intended for oral administration and should be swallowed whole.

2. Oral suspensions

• Description: A liquid form of spironolactone that may be prescribed when patients have difficulty swallowing tablets.
• Use: Especially useful for children or adults with swallowing disorders.

3. Capsules

• Dosages: Spironolactone is sometimes available in capsule form, which may provide an alternative way to take the medication, especially if individualized dosage adjustments are required.

Pharmacodynamics

1. Aldosterone receptorantagonism: Spironolactone is an antagonist of aldosterone receptors in the kidneys, blocking their effects. Aldosterone is a hormone that increases reabsorption of sodium and water in the kidneys, resulting in increased blood volume and blood pressure. Blocking aldosterone receptors results in decreased sodium and water retention and increased potassium excretion.
2. Diuretic action: Due to its effect on sodium reabsorption in the kidneys, spironolactone increases the excretion of sodium and water in the urine, which helps to reduce circulating blood volume and blood pressure.
3. Decreased blood potassium levels: Although spironolactone blocks sodium reabsorption, it also blocks potassium excretion, which may lead to hyperkalemia (increased blood potassium levels). This may require monitoring of blood potassium levels while taking the drug.
4. Antiandrogenic action: Spironolactone also has antiandrogenic properties and may be used to treat hyperandrogenic conditions such as hormonal disorders and acne in women.
5. Antiedema: In addition to its diuretic action, spironolactone may be effective in the treatment of edema associated with hepatic cirrhosis and heart failure.

Pharmacokinetics

1. Absorption: Spironolactone is usually rapidly and completely absorbed from the gastrointestinal tract after oral administration.
2. Distribution: It has a large volume of distribution, penetrating into various tissues and organs, including the kidneys.
3. Metabolism: Spironolactone is metabolized in the liver to form active metabolites such as canrenion. Metabolites of spironolactone have anti-aldosterone action.
4. Excretion: Spironolactone and its metabolites are mainly excreted through the kidneys. Approximately 80-85% of the dose is excreted as metabolites, the remainder is unchanged.
5. Half-life: The half-life of spironolactone is approximately 1.4 hours, compared to approximately 16.5 hours for its main active metabolite canrenion.

The pharmacokinetics of spironolactone may be altered in the presence of pathologic conditions such as hepatic or renal insufficiency, as well as in the concomitant use of other drugs that may affect its metabolism or excretion.

Dosing and administration

Heart failure

• Dosage: The starting dose is usually 12.5 mg to 25 mg daily. The dose can be gradually increased at intervals of several weeks up to a maximum daily dose of 50 mg.

Arterial hypertension

• Dosage: The initial dose is 50 mg per day, which may be increased to a maximum daily dose of 100 mg if the effect is insufficient and the drug is well tolerated.

Primary hyperaldosteronism

• Dosage: For diagnostic purposes, the initial dose may be 400 mg per day for 4 days. For therapeutic purposes, the dose is adapted individually.

Cirrhosis with ascites.

• Dosage: The initial dose is 100 mg per day, which can be adjusted depending on the response to treatment and the state of electrolyte balance. Usually the dose is in the range of 25-200 mg per day.

Polycystic ovary syndrome and other hormonal disorders

• Dosage: 50-100 mg daily, depending on clinical response and tolerability of the drug.

Method of admission

• Tablets and capsules should be taken orally, preferably in the morning to prevent nocturnal diuretic effect, with a small amount of water, after meals to reduce gastric irritation.

Important notes

• Regular monitoring of electrolyte levels, especially potassium, is necessary, as spironolactone can cause hyperkalemia (high potassium levels).
• To avoid dehydration and electrolyte imbalances, excessive amounts of water should not be consumed.
• Potassium supplements or other potassium-saving diuretics should be avoided without a doctor's prescription.
• During treatment with spironolactone, caution should be exercised when driving and operating machinery, as side effects such as dizziness or fatigue may occur.

Use Spironolactone during pregnancy

The use of spironolactone during pregnancy can be dangerous and requires special caution. First, spironolactone is FDA Category D for use during pregnancy. This means that there is a potential risk to the fetus, but the benefits of using it when needed may justify the potential risks.

The use of spironolactone during pregnancy may be associated with the risk of various side effects in both mother and fetus. In the mother, these may include hyperkalemia (increased potassium levels in the blood), hypotension (low blood pressure) and other adverse events. In the fetus, the development of the kidneys and other organs may be affected.

Contraindications

1. Hyperkalemia: Because spironolactone may cause potassium retention in the body, it should not be used in patients with already elevated blood potassium levels (hyperkalemia).
2. Renal insufficiency: In patients with severe renal insufficiency the use of spironolactone may be contraindicated due to the risk of exacerbation of this condition.
3. Hormonally active tumors: The drug may be contraindicated in the presence of hormonally active tumors, such as breast cancer or kidney cancer, due to possible increased hormonal activity.
4. Allergy: People with known hypersensitivity to spironolactone or other components of the drug should avoid its use.
5. Pregnancy and lactation: The use of spironolactone may be contraindicated during pregnancy and lactation due to its potential effects on the development of the fetus or breast milk.
6. Reduced blood pressure: In patients with low blood pressure, the use of spironolactone may lead to an additional drop in blood pressure and associated complications.
7. Diabetes mellitus: Caution is required when using spironolactone in patients with diabetes mellitus due to its effect on blood glucose levels.
8. Use with other medicines: Spironolactone may interact with other medicines, including some antihypertensive medicines and medicines that increase the level of potassium in the blood.

Side effects Spironolactone

1. Hyperkalemia: Spironolactone may cause an increase in blood potassium levels, which can be dangerous, especially for people with kidney disease or those taking other medications that increase this effect.
2. Urinary effects: Taking spironolactone may increase the frequency of urination and diuresis (volume of urine).
3. Dizzinessand weakness: Some patients may experience dizziness, weakness, or drowsiness.
4. GI disorders: Dyspeptic symptoms such as nausea, vomiting, diarrhea or decreased appetite may occur.
5. Electrolyte balance disorders: The content of sodium, calcium and magnesium in the body may be disturbed.
6. Gynecomastia: Men may experience enlargement of the breast glands.
7. Menstrual disorders: Menstrual disorders may occur in women.
8. Gynecologic side effects: Enlargement or sensitivity of the mammary glands, menstrual irregularities, and libido problems may occur.
9. Increased uric acid levels: This can aggravate or trigger a gout attack.
10. Allergic reactions: In rare cases, allergic reactions such as urticaria, pruritus, edema or angioedema may occur.
11. Other side effects: Other reactions are possible and may vary depending on individual body characteristics.

Overdose

Spironolactone overdose can cause serious electrolyte imbalance, especially hyperkalemia (increased blood potassium levels), which can lead to cardiac arrhythmias and other dangerous conditions. Other possible effects of overdose include drowsiness, dizziness, headache, heart rhythm disturbances, seizures, and various gastrointestinal disorders.

In case of suspected spironolactone overdose, medical attention should be sought immediately. Treatment of overdose may include therapeutic measures to restore electrolyte balance and control cardiac activity.

Interactions with other drugs

1. Potassium-boosting drugs: Spironolactone may increase potassium levels in the body. In concomitant use with other drugs such as ACE-inhibitors (e.g. Lisinopril) or antihypertensive agents of the "arbiter" class (e.g. Losartan), which may also increase potassium, the risk of hyperkalemia may increase.
2. Potassium-lowering drugs: Drugs such as thiazide diuretics (e.g. Hydrochlorthiazide) may decrease potassium levels in the body. Concurrent use with thiazide diuretics may reduce the risk of hyperkalemia with spironolactone.
3. Non-steroidal anti-inflammatory drugs (NSAIDs): Some NSAIDs, such as ibuprofen or diclofenac, may reduce the effectiveness of spironolactone, especially with respect to its diuretic action.
4. Drugs affecting renal function: Concomitant use with drugs affecting renal function, such as nephrotoxic antibiotics or some nephrotoxic anti-inflammatory drugs, may increase the risk of renal failure.
5. Drugs affecting hormonal balance: Spironolactone may interact with other drugs affecting hormonal balance, such as hormonal contraceptives or hormone replacement therapy, which may potentially alter the efficacy or toxicity of these drugs.