These are all on the same topic. I just have to formulate different responses to my classmates forum posts. These are what they wrote. find articles relating to what they wrote and ask them a question to respond to to promote discussion. Here is the original question that was asked. Come up with a paragraph response and be sure to ask them a question back.
What are the benefits of spironolactone for the obvious indications of HTN and CHF- what are the more nontradtional usage of this steroidal agent and if patients develop side effects- do we have competitor medications that will accomplish the desired therapeutic goals? FILLER TEXT
Classmate response 1: Spironolactone works as a diuretic to reduce water retention in HTN and CHF. Spironolactone binds to the mineral corticosteroid receptor to block aldosterone. This prevents Na+ reabsorption as Na+ stays in the lumen and takes water with it which causes the diuretic effect. Since the Na+ does not enter the cell in exchange for potassium, the potassium does not leave the cell. Thus, ‘sparing’ the potassium. A more non-traditional use of Spironolactone is for Acne Vulgaris in women. Acne takes advantage of Spironolactone’s anti-androgen ability. Spironolactone works to reduce testosterone production as it prevents testosterone form binding to androgen receptors in the skin. Potential side effects of Spironolactone include fluid imbalance, gout, and hyperkalemia. If using Spironolactone for acne vulgaris, consult the American Academy of Dermatology. The academy recommends a topical agent like benzoyl peroxide or tretinoin as1st line therapy for mild acne vulgaris. If the acne is moderate to severe, the preferred treatment is benzoyl peroxide, tretinoin and oral antibiotics depending on the severity.FILLER TEXT
FILLER TEXTClassmate response 2: The main uses of spironolactone are for hypertension, chronic heart failure, and the edema that can be associated with them. Spironolactone is an aldosterone antagonist that allows sodium and water to be excreted while preserving potassium. It is going to help with lowering blood pressure and also reducing volume so that you can decrease hypertension. It is also going to put a little bit less stress on the heart which is key when someone has had heart failure. It is not first line for hypertension or heart failure but can be used for resistance of either one of them.
Along with the traditional uses are nontraditional or off label uses. This consists of acne in women, hirsutism, and hormone therapy for transgender females. I found these uses on lexicomp, which will lead me into more in depth research on PubMed. In regards to acne, spironolactone is a non-selective mineralocorticoids receptor antagonist which has moderate affinity for both progesterone and androgen receptors. A reduction in acne is thought to be by blocking the dihydrotestosterone binding to the androgen receptor. There isn’t much concrete evidence in this systematic review on the benefits and potential harms of spironolactone for acne use in women. There is “statistically highly significant evidence though that 200 mg/day effectively reduces inflamed lesions”. There are no specified guidelines for spironolactone use for acne in women, so it is recommended the clinicians use their best judgment for this off label use.
Hirsutism is another off label use with spironolactone. Spironolactone is not first line for this indication. rather combined oral contraceptive is. While spironolactone is not recommended as first line therapy or monotherapy for hirsutism there is an exception for women with an intrauterine device. It can be used for monotherapy in these women as they have a very low risk for accidental pregnancy. This use for hirsutism doesn’t have a whole lot of evidence for use but it is thought to work in a similar way as it is for acne in women with antagonizing the androgen receptors.
The last off label use that was mentioned on lexicomp is hormone therapy for transgender females. Transgender people seem to be more and more prevalent in our day and age so I could see this becoming something that starts to get more and more light as we continue throughout our careers. This article is looking to compare two anti androgenic drugs in transgender females that don’t want androgenic physical characteristics. The comparison is between cyproterone acetate and spironolactone. They also mention how there isn’t much evidence about which one is more beneficial than the other. What we do know is that spironolactone has anti-androgenic effects to help these people. We don’t have enough evidence yet to recommend one over the other but hopefully as we continue to see more of these scenarios, more research can be done for the exact mechanisms and how to use these medications for theses other indications. As with any off label use of a medication, clinicians should use their professional judgment on how to dose and use these medications.
FILLER TEXTClassmate response 3
Spironolactone and hypertension
Spironolactone is used to treat hypertension by lowering blood pressure. This occurs through the competitive binding of sodium-potassium transporters. The effect takes place in the distal convoluted tube. This causes sodium to be excreted which is followed by water. It also allows for the potassium to stay within the body. The excretion of water through urine decreased blood pressure. In the article “Spironolactone for Resistant Hypertension”, a study found that spironolactone lowered average home systolic blood pressure by 8.7mm Hg when compared to a placebo. This was compared to 4.5 mm Hg for bisoprolol and 4.0 mm Hg for doxazosin. This shows that spironolactone is an important medication for the treatment of hypertension. The same article states that evidence is indicating that resistant hypertension is caused in large part by sodium retention. Because of the potassium sparing nature of spironolactone, it could be a great help to treating this.
Congestive heart failure
The excretion of sodium and retention of potassium are believed to be how spironolactone helps in CHF. This is similar to the effect in hypertension. The aldosterone antagonist activity also potentially helps with CHF. By competitively binding aldosterone sites, the medication is helping prevent secondary aldosteronism. According to information acquired on the FDA website, spironolactone helped reduce the risk of cardiac death, primarily sudden death, and death by progressive heart failure by 31%.
Nontraditional uses of spironolactone
Hormone therapy for transgender females (male-to-female)
When an individual is a transitioning female (male-to-female), they will undergo a hormone therapy schedule. These hormones are used to block the production of testosterone, which leads to male secondary sex characteristics. Generally, the patient will also begin an estrogen hormone therapy. This will be done in order to increase the prevalence of female secondary sex characteristics. Spironolactone is used early in the process, during the feminizing hormone therapy. When beginning the therapy, spironolactone is used to block endogenous testosterone (androgen). There are other medications that can and have been used for this, however, with hyperkalemia being the most likely adverse effect it is generally considered to be safer than alternatives.
Hirsutism and acne vulgaris
Hirsutism is the excessive growth of hair in females and can also be treated with spironolactone. It is commonly caused by the increasing of secondary sex characteristics by endogenous male sex hormones or androgens. In this treatment, spironolactone is used in the exact same way as the previously discussed hormone therapy. Spironolactone blocks the androgen receptors, causing the secondary sex characteristics to not become so pronounced. This helps prevent the excessive hair. Acne vulgaris is believed to be treated in the same fashion. However, in the article “Spironolactone versus placebo or in combination with steroids for hirsutism and/or acne”, it was suggested that while the treatment is effective for hirsutism, it is not effective in the treatment of acne.
There are not very many alternatives for the off-label indications that I found. Usually the blockage of the androgen receptors is the necessary function, which I couldn’t find many alternatives. The only one I found suggested was 5?-reductase inhibitors (finasteride). This was not considered strongly because of its side effects.