Spironolactone Drospirenone

Hyperkalemia Yasmin contains the progestin drospirenone that has antimineralocorticoid activity, including the potential for hyperkalemia in high-risk patients, comparable to a 25 mg dose of spironolactone. Yasmin should not be used in patients with conditions that predispose to hyperkalemia. Women receiving daily, long-term treatment for chronic conditions or diseases with medications that may increase serum potassium should have their serum potassium level checked during the first treatment cycle. 

Androstenolone, 1, can be transformed microbiologically to the 7a,15a-dihy-droxy derivative 2 by the action of Colletotrichium Uni. During formation of the acetal (3), inversion takes place on C-7. Acidic cleavage of 3 results in the triol, 4, which can also be produced by direct acidic catalysis from 2 [12,13]. After selective protection to the 3/l,15a-dipivalate (5), the 15/1,16/1-methylene compound, 6, can be synthetized, and then stereoselectively transformed to the 5/ ,6/ -epoxide, 7. This reacts with triphenylphosphine and tetrachloromethane in pyridine to produce the 7a-chloro derivative, 8. On treatment with zinc and acetic acid, 8 can be converted to the key compound 9, which has a 5/i-hydroxy-6-ene structure. Compound 9 can then be methylenated stereoselectively in the 6/1,7/1 position by the Simmons-Smith method. The last three steps - 10 —> 11 —> 12 — drospirenone -include the build-up of the spironolactone ring, after which water is lost from the molecule and oxidation affords drospirenone. 

In some cases, the simple modification of a drug structure can essentially modify the biological activity profile, whilst preserving some part of the original activity. Drospirenone (see Chapter 11-17), an orally active progestin contraceptive with antimineralcorticoid properties, is an example of an analogue-based drug discovery process that started from the diuretic spironolactone. 

ACE INHIBITORS, ANGIOTENSIN II RECEPTOR ANTAGONISTS PROGESTOGENS t risk of hyperkalaemia Drospirenone (component of the Yasmin brand of combined contraceptive pill) is a progestogen derived from spironolactone that can cause potassium retention Monitor serum potassium weekly until stable, then eveiy 6 months... 

Drospirenone, a derivative of spironolactone, has been introdnced in Europe as another antiandrogen agent that may prove to be useful in some patients. ... 

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