Prostaglandin E1 and prostacyclin, both of which belong to the prostaglandin homologue, have distinctly different pharmacological effects and clinical treatment directions. 1. Prostaglandin physiology in vivo Prostaglandin is an unsaturated fatty acid derivative with 20 carbon atoms widely present in the body. 1935 Euler was first discovered in sheep semen and mistakenly thought to be secreted by the prostate gland, hence the name Prostaglandins. It has been shown that prostaglandins in semen come from the seminal vesicles, and many tissues and organs such as the lungs, brain, heart, kidneys, stomach and intestines can also produce prostaglandins. The chemical structure of prostaglandins all contain a common basic structural unit – prostatic acid. The prostaglandin congeners are classified into A, B, C, D, E, F, G, H and I according to the five-carbon ring and the various substituents on the five-carbon ring; they are also classified into 1, 2 and 3 types according to the number of side chains. Prostaglandin E1 is the first strong vasoactive substance with broad-spectrum effects, which was discovered to be generated by the twenty-carbon unsaturated fatty acids of the body cells as precursors. The phospholipids of the cell membrane generate arachidonic acid under the action of phospholipase A2, the latter is catalyzed by cyclooxygenase to form PGG2, which is subsequently transformed into PGH2, and PGH2 is transformed into PGI2 under the action of prostacyclin synthase, which carries a double ring, with an oxygen-containing five-atom ring in addition to cyclopentane, and is therefore called prostacyclin. Lung and liver are the main inactivation sites of prostacyclin. Except for PGA2 and PGI2, which can function in the circulatory system in the form of hormones throughout the body, the rest can only function near the site of release and are local hormones. 2. The pharmacological effects of prostaglandin E1 and prostacyclin are similar. Both have similar chemical structures; both have short half-lives; both have no biological activity when taken orally; both have powerful vasodilatory effects; both require continuous intravenous infusion for clinical application. In addition, they have inhibition of platelet aggregation, mild positive inotropic effects and cytoprotective effects. Differences 1) Prostaglandin E1 was the first prostaglandin to be isolated and purified; prostacyclin was a prostaglandin congener discovered in the 1980s. 2) Prostaglandin E1 is mainly metabolized in the lungs and has a greater effect on vasodilatation in the body circulation than in the pulmonary circulation; prostacyclin has a greater effect on vasodilation in the pulmonary vasculature than in the body circulation. The dose of prostaglandin E1 is several times higher than that of prostacyclin to achieve the same pulmonary vasodilatory effect. 3) Prostaglandin E1 has no effect on the hypoxic pulmonary vasoconstriction response; prostacyclin reduces the hypoxic pulmonary vasoconstriction response. 4) Prostaglandin E1 is weaker than prostacyclin in inhibiting platelet aggregation. 3) Prostaglandin E1 and prostacyclin in the treatment of pulmonary hypertension The clinical application: Prostaglandin E1 and prostacyclin are both vasodilators, so both have the effect of lowering pulmonary artery pressure. However, in the treatment of pulmonary hypertension, prostacyclin has obvious advantages over prostaglandin E1, mainly: 1) Prostacyclin has a definite efficacy in the treatment of severe pulmonary hypertension and is now the first choice internationally; whereas prostaglandin E1 is not mentioned in the latest WHO guidelines for the treatment of pulmonary hypertension. 2) Prostacyclin not only reduces pulmonary vascular resistance in patients with pulmonary hypertension, but also causes a decrease in pulmonary vascular resistance in normal subjects. Prostacyclin has been shown to reduce pulmonary vascular resistance in patients with pulmonary hypertension, but also in normal subjects, whereas the effect of prostaglandin E1 on pulmonary vascular resistance in normal subjects is reduced, unchanged or increased. 3) Prostacyclin activates platelets to a lesser extent than prostaglandin E1, and platelet function recovers more rapidly, thus posing a lower risk of bleeding complications than prostaglandin E1. 4) Although both prostacyclin and prostaglandin E1 can cause congenital heart disease, congestive heart failure, acute adult respiratory distress syndrome, and other conditions, prostaglandin E1 has been shown to reduce the risk of bleeding. The risk of bleeding complications is lower with prostacyclin than with prostaglandin E1. 4) Although both prostacyclin and prostaglandin E1 can decrease pulmonary vascular resistance, increase cardiac output, and improve systemic blood oxygen delivery in pulmonary hypertension and idiopathic pulmonary hypertension combined with congenital heart disease, congestive heart failure, acute adult respiratory distress syndrome, and mitral stenosis, prostacyclin acts mainly by dilating the pulmonary vasculature, whereas prostaglandin E1 produces these effects mainly by dilating the veins of the body circulation, which can easily cause hypotension and make the patient’s condition worse. 5) The half-life of prostacyclin is only 1-2 minutes, and once the side effects occur, it can be recovered after stopping the drug; while prostaglandin still has 34% of the drug in the bloodstream 20 minutes after the drug is administered. 6) Prostacyclin is significantly better tolerated than prostaglandin. It is important to emphasize that the application of vasodilators such as prostacyclin for the treatment of pulmonary hypertension needs to be continued over a long period of time, because if the drug is effective, sudden discontinuation can lead to pulmonary hypertensive crisis, causing serious consequences. The more the symptoms rebound after stopping the drug, the more effective the vasodilator is. On the contrary, if the patient’s symptoms do not worsen after stopping the drug but improve, it reflects that the drug used actually does not have the effect of reducing pulmonary arterial resistance. At present, many physicians in China still use prostaglandin E1 to treat pulmonary hypertension, and often stop the drug in about 1 week to observe the efficacy, which should be absolutely avoided in the clinical application. Generally, benign remodeling of the pulmonary vasculature occurs after 1 year of treatment, when the hemodynamics become stable and the prostacyclin can be slowly reduced on the basis of the application of endothelin receptor antagonists, sildenafil and other oral drugs, and some patients can even stop using it.
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