In any case, spironolactone has been found to reduce the bioavailability of oral estradiol, which could be due to induction of estradiol metabolism via CYP3A4. Spironolactone has also been found to inhibit UGT2B7. Spironolactone can also have numerous other interactions, most commonly with other cardiac and blood pressure medications, for instance digoxin.Licorice, which has indirect mineralocorticoid activity by inhibiting mineralocorticoid metabolism, has been found to inhibit the antimineralocorticoid effects of spironolactone. Moreover, the addition of licorice to spironolactone has been found to reduce the antimineralocorticoid side effects of spironolactone in women treated with it for hyperandrogenism, and licorice hence may be used to reduce these side effects in women treated with spironolactone as an antiandrogen who are bothered by them. On the opposite end of the spectrum, spironolactone is useful in reversing licorice-induced hypokalemia. Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) have been found to attenuate the diuresis and natriuresis induced by spironolactone, but, not to affect its antihypertensive effect.Some research has suggested that spironolactone might be able to interfere with the effectiveness of antidepressant treatment. As the medication acts as an antimineralocorticoid, it is thought that it might be able to reduce the effectiveness of certain antidepressants by interfering with normalization of the hypothalamic–pituitary–adrenal axis and by increasing levels of glucocorticoids such as cortisol. However, other research contradicts this hypothesis and has suggested that spironolactone might actually produce antidepressant effects, for instance studies showing antidepressant-like effects of spironolactone in animals.
Toxic megacolon is an acute form of colonic distension. It is characterized by a very dilated colon (megacolon), accompanied by abdominal distension (bloating), and sometimes fever, abdominal pain, or shock. Toxic megacolon is usually a complication of inflammatory bowel disease, such as ulcerative colitis and, more rarely, Crohns disease, and of some infections of the colon, including Clostridium difficile infections, which have led to pseudomembranous colitis. Other forms of megacolon exist and can be congenital (present since birth, such as Hirschsprungs disease). It can also be caused by Entamoeba histolytica and Shigella. It may also be caused by the use of loperamide. Signs and symptoms
Abdominal pain
Abdominal bloating
Abdominal tenderness
Fever
Tachycardia (rapid heart rate)
DehydrationThere may be signs of septic shock. A physical examination reveals abdominal tenderness and possible loss of bowel sounds. An abdominal radiography shows colonic dilation. White blood cell count is usually elevated. Severe sepsis may present with hypothermia or leukopenia. Complications
Perforation of the colon
Sepsis
ShockEmergency action may be required if severe abdominal pain develops, particularly if it is accompanied by fever, rapid heart rate, tenderness when the abdomen is pressed, bloody diarrhea, frequent diarrhea, or painful bowel movements. Colonoscopy is contraindicated, as it may rupture the dilated colon resulting in peritonitis and septic shock. Pathophysiology
The pathological process involves inflammation and damage to the colonic wall with unknown toxins breaking down the protective mucosal barrier and exposing the muscularis propria. There is relative destruction of the ganglion cells and swelling of the nerve fibers in the myenteric plexus, with concomitant damage to the colonic musculature.