Top Gene Interactions
- Metabolism: Rapidly and extensively metabolized. The metabolic pathway of spironolactone is complex and can be divided into two main routes: those in which the sulfur moiety is retained and those in which the sulfur moiety is removed by dethioacetylation. Spironolactone is transformed to a reactive metabolite that can inactivate adrenal and testicular cytochrome P450 enzymes. It also has anti-androgenic activity. Route of Elimination: The metabolites are excreted primarily in the urine and secondarily in bile. Half Life: 10 minutes
- Uses/Sources: Used primarily to treat low-renin hypertension, hypokalemia, and Conn's syndrome.
- Symptoms: Acute overdosage of spironolactone may be manifested by drowsiness, mental confusion, maculopapular or erythematous rash, nausea, vomiting, dizziness, or diarrhea. Spironolactone has been shown to be a tumorigen in chronic toxicity studies in rats.
- Route of Exposure: Fairly rapidly absorbed from the gastrointestinal tract. Food increases the bioavailability of unmetabolized spironolactone by almost 100%.
- Carcinogenicity: 3, not classifiable as to its carcinogenicity to humans. (L135)
- Toxicity: The oral LD<sub>50</sub> of spironolactone is greater than 1,000 mg/kg in mice, rats, and rabbits.
Mechanism of Action
|Target Name||Mechanism of Action||References|
Peroxisome proliferator-activated receptor gamma
Nuclear receptor subfamily 1 group I member 2
Delta-type opioid receptor
Sex hormone-binding globulin
Cytochrome P450 2C19
Cytochrome P450 11B2, mitochondrial
Voltage-dependent calcium channel