Action and Spectrum

Actions and Spectrum: 

The action of spironolactone is primarily to increase the excretion of salt and water by kidneys, while reducing the loss of potassium. This results in a decrease in fluid build-up in the body, which is beneficial in conditions such as congestive heart failure, liver cirrhosis, and nephrotic syndrome. spironolactone can also be used to treat high blood pressure, as it reduces the constriction of blood vessels, thereby decreasing blood pressure. 

Apart from its diuretic effects, spironolactone also has anti-androgenic properties, meaning it can block the effects of male sex hormones (androgens) in the body. This makes it useful in the treatment of conditions such as hirsutism (excessive hair growth) and acne in women, as well as in transgender hormone therapy to help suppress testosterone levels. 

Overall, spironolactone’s action is to increase the excretion of salt and water by the kidneys, while reducing the loss of potassium, and it also has anti-androgenic properties. 

Drug Interaction

Adverse Reaction

Frequency not defined 

• Stevens-Johnson Syndrome 
• Abdominal cramping 
• Gynecomastia 
• Headache 
• Drowsiness 
• Rash 
• Nausea/vomiting 
• Lethargy 
• Gastritis 
• Urticaria 
• Menstrual disorders 
• Toxic epidermal necrolysis 
• Diarrhea 
• Impotence 

Black Box Warning

Black Box Warning: 

spironolactone has a black box warning for tumors in chronic toxicity studies in rats. This means that in animal studies, chronic use of high doses of spironolactone has been associated with the development of tumors in rats.

While there is no evidence that spironolactone causes tumors in humans, this warning is included to caution against long-term use of high doses of the medication. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

• Hyperkalemia: spironolactone can cause potassium levels in the blood to rise, which can lead to a condition called hyperkalemia. Hyperkalemia can be life-threatening and can cause heart rhythm disturbances. spironolactone should not be used in patients with hyperkalemia or in patients taking other medications that can cause hyperkalemia. 
• Severe kidney disease: spironolactone is metabolized and excreted by the kidneys. Patients with severe kidney disease may not be able to clear the medication from their system, leading to a buildup of spironolactone and its metabolites in the body. 
• Addison’s disease: spironolactone can interfere with the diagnosis and treatment of Addison’s disease, a condition where the adrenal glands do not make adequate hormones. spironolactone can cause false-negative results in tests for adrenal insufficiency and can also interfere with the effectiveness of replacement therapy. 
• Pregnancy and breastfeeding: spironolactone should not be used during pregnancy or breastfeeding due to the risk of harm to the fetus or infant. 
• Allergic reaction: spironolactone can cause an allergic reaction in some patients. Symptoms of an allergic reaction may involve rash, hives, itching, swelling, difficulty breathing, and anaphylaxis. 

Caution 

• Liver disease: spironolactone is metabolized by the liver, so patients with liver disease may not be able to clear the medication from their system, leading to a build-up of spironolactone and its metabolites in the body. Patients with liver disease should be monitored closely while taking spironolactone. 
• Electrolyte imbalances: spironolactone can cause changes in the levels of electrolytes in the body, such as potassium, sodium, and magnesium. Patients with electrolyte imbalances or those taking other medications that can cause electrolyte imbalances should be monitored closely while taking spironolactone. 
• Heart disease: spironolactone can cause changes in the heart’s electrical activity, particularly in patients with heart disease. Patients with heart disease should be monitored closely while taking spironolactone. 
• Diabetes: spironolactone can cause changes in blood sugar levels, particularly in patients with diabetes. Patients with diabetes should monitor their blood sugar levels closely while taking spironolactone. 
• Surgery: spironolactone can interfere with the effectiveness of anesthesia, so patients who are scheduled for surgery should inform their healthcare provider that they are taking spironolactone. 
• Elderly patients: Elderly patients may be more sensitive to the effects of spironolactone, particularly in terms of electrolyte imbalances and changes in blood pressure 

Pregnancy / Lactation

Pregnancy consideration:  

AU TGA pregnancy category: B3
US FDA pregnancy category: C 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies do not show risk to the fetus in the first/later trimester.        
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women        
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.       
• Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.        
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.        
• Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

spironolactone is classified as an aldosterone antagonist medication that operates by obstructing the actions of aldosterone, a hormone make by the adrenal glands that governs sodium and potassium balance in the body. 

In addition to its effects on aldosterone, spironolactone also has anti-androgenic properties, meaning it can block the effects of male hormones (androgens) in the body. This makes it useful for treating conditions such as hormonal acne and hirsutism (excessive hair growth) in women. 

Pharmacodynamics: 

Mechanism of Action: 

spironolactone is an aldosterone antagonist that has diuretic and antihypertensive effects. It competitively binds to receptors at the aldosterone-dependent Na-K exchange site in distal tubules, leading to an increase in the excretion of Na+, Cl-, and H2O and retention of K+ and H+. 

Pharmacokinetics: 

Absorption 

spironolactone is well-absorbed after oral administration and reaches peak plasma levels within 2-3 hours. Food does not significantly affect its absorption. 

Distribution 

spironolactone is highly protein-bound (more than 90%) and distributes throughout the body, including the liver, kidneys, and heart. It can also cross the blood-brain barrier and the placenta. 

Metabolism 

spironolactone is metabolized in the liver to its active metabolite, canrenone. Canrenone has a longer half-life than spironolactone and is responsible for most of the drug’s activity. spironolactone and canrenone are primarily excreted in the urine. 

Elimination and Excretion 

spironolactone has a half-life of about 1.4 hours, while the half-life of canrenone is about 16.5 hours. The majority of the drug and its metabolites are eliminated in the urine, with a smaller amount excreted in the feces. 

Adminstartion

Administration: 

Oral Administration 

Consistency in taking Spironolactone with respect to food is important, as it can be taken either with or without food. 

Missed Dose 

If a dose is missed, it is recommended to take it as soon as possible. However, if the next scheduled dose is missed, it should be skipped and the following dose should be taken at the appropriate time. It is important to avoid taking a double dose of the medication to compensate for the missed dose. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: spironolactone 

Pronounced: [ spir-ON-oh-LAK-tone ] 

Why do we use spironolactone? 

spironolactone is a medication that is commonly prescribed for high blood pressure and heart failure. By lowering high blood pressure, it can help prevent strokes, heart attacks, and kidney problems.

Additionally, it is used to alleviate swelling (edema) caused by certain conditions such as heart failure and liver disease, withdrawal the excess fluid and improving symptoms like breathing problems. 

Moreover, this medication is also used to treat conditions in which the body is producing an excess amount of a natural substance called aldosterone. spironolactone is categorized as a “water pill” or potassium-sparing diuretic