There may be an increased risk of angioedema in those concurrently taking ACE inhibitors. Pharmacology
Pharmacodynamics
EMP, also known as estradiol normustine phosphate, is a combined estrogen ester and nitrogen mustard ester. It consists of estradiol, an estrogen, linked with a phosphate ester as well as an ester of normustine, a nitrogen mustard. In terms of its pharmacodynamic effects, EMP is a prodrug of estramustine, estromustine, and estradiol. As a prodrug of estradiol, EMP is an estrogen and hence an agonist of the estrogen receptors. EMP itself has only very weak affinity for the estrogen receptors. The medication is of about 91% higher molecular weight than estradiol due to the presence of its C3 normustine and C17β phosphate esters. Because EMP is a prodrug of estradiol, it may be considered to be a natural and bioidentical form of estrogen, although it does have additional cytostatic activity via estramustine and estromustine.EMP acts by a dual mechanism of action: 1) direct cytostatic activity via a number of actions; and 2) as a form of high-dose estrogen therapy via estrogen receptor-mediated antigonadotropic and functional antiandrogenic effects. The antigonadotropic and functional antiandrogenic effects of EMP consist of strong suppression of gonadal androgen production and hence circulating levels of androgens such as testosterone; greatly increased levels of sex hormone-binding globulin and hence a decreased fraction of free androgens in the circulation; and direct antiandrogenic actions in prostate cells. The free androgen index with oral EMP has been found to be on average 4.6-fold lower than with orchiectomy.
Acid–base balance
The pH of the extracellular fluid, including the blood plasma, is normally tightly regulated between 7.32 and 7.42 by the chemical buffers, the respiratory system, and the renal system. The normal pH in the fetus differs from that in the adult. In the fetus, the pH in the umbilical vein pH is normally 7.25 to 7.45 and that in the umbilical artery is normally 7.18 to 7.38.Aqueous buffer solutions will react with strong acids or strong bases by absorbing excess H+ ions, or OH− ions, replacing the strong acids and bases with weak acids and weak bases. This has the effect of damping the effect of pH changes, or reducing the pH change that would otherwise have occurred. But buffers cannot correct abnormal pH levels in a solution, be that solution in a test tube or in the extracellular fluid. Buffers typically consist of a pair of compounds in solution, one of which is a weak acid and the other a weak base. The most abundant buffer in the ECF consists of a solution of carbonic acid (H2CO3), and the bicarbonate (HCO−3) salt of, usually, sodium (Na+). Thus, when there is an excess of OH− ions in the solution carbonic acid partially neutralizes them by forming H2O and bicarbonate (HCO−3) ions.