Definition
Description
Top Gene Interactions
Related Pathways
General Information
- 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%.
Toxicity
- 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 |
---|---|---|
Estrogen receptor Glucocorticoid receptor Androgen receptor Progesterone receptor Peroxisome proliferator-activated receptor gamma Nuclear receptor subfamily 1 group I member 2 Delta-type opioid receptor Sex hormone-binding globulin Cytochrome P450 2C19 Mineralocorticoid receptor Cytochrome P450 11B2, mitochondrial 17alpha-hydroxylase 17,20-desmolase Voltage-dependent calcium channel Dihydrotestosterone receptor |
17881754 976190 11791081 10942165 14978157 2972662 872489 15554912 15808807 15947888 14664717 23611293 15128471 984618 11752352 |