Intracavernosal injection or transurethral suppository therapy with alprostadil (PGE1) is a second-line treatment for erectile dysfunction. Injected doses are 2.5–25 mcg; suppositories are recommended to start at 125 mcg or 250 mcg, up to 1000 mcg. Penile pain is a frequent side effect, which may be related to the algesic effects of PGE derivatives; however, only a few patients discontinue the use because of pain. Prolonged erection and priapism are side effects that occur in less than 4% of patients and are minimized by careful titration to the minimal effective dose. When given by injection, alprostadil may be used as monotherapy or in combination with either papaverine or phentolamine.
Increased biosynthesis of prostaglandins has been associated with one form of Bartter’s syndrome. This is a rare disease characterized by low-to-normal blood pressure, decreased sensitivity to angiotensin, hyperreninemia, hyperaldosteronism, and excessive loss of K+. There also is an increased excretion of prostaglandins, especially PGE metabolites, in the urine. After long-term administration of COX inhibitors, sensitivity to angiotensin, plasma renin values, and the concentration of aldosterone in plasma return to normal. Although plasma K+ rises, it remains low, and urinary wasting of K+ persists. Whether an increase in prostaglandin biosynthesis is the cause of Bartter’s syndrome or a reflection of a more basic physiologic defect is not yet known.
A. Pulmonary Hypertension
PGI2 lowers peripheral, pulmonary, and coronary vascular resistance. Pulmonary hypertension is characterized by an increase in vascular resistance in the pulmonary blood vessels. PGI2 has been used to treat pulmonary hypertension arising from primary lung disease and that arising from heart or systemic diseases. In addition, prostacyclin has been used successfully to treat portopulmonary hypertension, which arises secondary to liver disease. The first commercial preparation of PGI2 approved for treatment of pulmonary hypertension (epoprostenol) improves symptoms, prolongs survival, and delays or prevents the need for lung or lung-heart transplantation. Side effects include flushing, headache, hypotension, nausea, and diarrhea. The extremely short plasma half-life (3–5 minutes) of epoprostenol necessitates continuous intravenous infusion through a central line for longterm treatment. Intravenous infusion dosage of epoprostenol is increased in a graded dose-dependent manner, based on recurrence, persistence, or worsening of symptoms. Several prostacyclin analogs with longer half-lives have been developed and used clinically. Iloprost (half-life about 30 minutes) is usually inhaled six to nine times per day (2.5–5 mcg/dose), although it has been delivered by intravenous administration outside the USA. Treprostinil (half-life about 4 hours) may be delivered by subcutaneous or intravenous infusion or by inhalation. Recently, two oral prostacyclin receptor agonists were approved by the US Food and Drug Administration (FDA): selexipag (a prodrug rapidly converted to active prostacyclin agonist) and an oral preparation of treprostinil. Other drugs used in pulmonary hypertension are discussed in Chapter 17.
B. Peripheral Vascular Disease
A number of studies have investigated the use of PGE1 and PGI2 compounds in Raynaud’s phenomenon and peripheral arterial disease. However, these studies are mostly small and uncontrolled. Currently, these therapies do not have an established place in the treatment of peripheral vascular disease.
C. Patent Ductus Arteriosus