Prostaglandin E1 Explained

Prostaglandin E₁ (PGE₁) is a naturally occurring prostaglandin and is also used as a medication (alprostadil).

In infants with congenital heart defects, it is delivered by slow injection into a vein to open the ductus arteriosus until surgery can be carried out.^[1] By injection into the penis or placement in the urethra, it is used to treat erectile dysfunction.^[2]

Common side effects when given to babies include decreased breathing, fever, and low blood pressure. When injected into the penis for erectile dysfunction; side effects may include penile pain, bleeding at the site of injection, and prolonged erection (priapism). Prostaglandin E₁ is in the vasodilator family of medications. It works by opening blood vessels and relaxing smooth muscle.^[3]

Prostaglandin E₁ was isolated in 1957 and approved for medical use in the United States in 1981.^{[3] [4]} It is on the World Health Organization's List of Essential Medicines.^[5]

Biosynthesis

Prostaglandin E₁ is biosynthesized on an as-needed basis from dihomo-γ-linolenic acid (an omega-6 fatty acid) in healthy humans without coronary artery disease^[6] and/or a genetic disorder.

Medical uses

Patent ductus arteriosus

Alprostadil is also used in maintaining a patent ductus arteriosus in newborns, primarily for an infant with ductal-dependent congenital heart disease, including cyanotic lesions and acyanotic lesions.

Sexual dysfunction

Alprostadil is sold in the United States as urethral suppositories (brand name Muse^[7]) and in injectable form (brand names: Edex^[8] and Caverject^[9]). As a penile suppository, the medication is inserted into the urethra at least ten minutes before the erection is needed. Other forms similarly fast-acting, but instead are injected by the syringe directly into the corpus cavernosum of the penis.

Alprostadil is also available as a generic. It must be mixed by a compounding pharmacy. The different formulations, including Bimix and Trimix, may include papaverine and/or phentolamine. A typical mix might be 30 mg of papaverine, 2 mg of phentolamine, and 20 μg alprostadil.The compound has been made into an applicable topical cream form known as Vitaros,^[10] made by Takeda UK Ltd., it contains either 200 or 300 μg of alprostadil in 100mg of cream. The tip of the device is placed in the urethral meatus, and the cream is delivered into the urethra.

Off-brand Uses, Interactions

Clinical trials for the treatment showed positive results in around 3,000 men that it was tested on; it is said to be usable by men with diabetes or heart problems and those who have undergone a prostatectomy.^[11] It has no known interactions with food, alcohol or other medications.

Misoprostol is another synthetic prostaglandin E1 analog used to prevent gastric ulcers when taken on a continuous basis,^[12] to treat missed miscarriage,^[13] to induce labor,^[14] and to induce abortion.^[15]

Critical limb ischemia

Prostanoids, including alprostadil, do not reduce the risk of limb amputation but may offer a slight improvement in rest-pain and leg ulcer healing in persons with critical limb ischemia.^[16]

Contrast-induced nephropathy

Preventative administration of alprostadil may reduce the risk of kidney injury (specifically contrast-induced nephropathy) in persons having cardiac angiography or percutaneous coronary intervention.^{[17] [18]}

Adverse effects

• Accidental injury (Muse only)
• Apnea
• Bleeding:
  • Cerebral
  • Urethral
• Bradycardia
• Cardiac arrest
• Congestive heart failure
• Cortical proliferation of long bones
• Diarrhea
• Disseminated intravascular coagulation
• Edema
• Fever
• Flushing
• Hyperemia
• Hypotension
• Injection-site haematoma
• Injection-site ecchymosis (Caverject only)
• Pain:
  • Back
  • Pelvic
  • Penile
  • Testicular (Muse only)
  • Urethral
• Prolonged erection
• Penile fibrosis
• Second-degree heart block
• Seizures
• Sepsis
• Shock
• Spasm of right ventricle infundibulum
• Supraventricular tachycardia
• Tachycardia
• Ventricular fibrillation
• Urethral burning
• Uterine rupture

Notes and References

1. Book: Northern Neonatal Network. Neonatal Formulary: Drug Use in Pregnancy and the First Year of Life. 208. John Wiley & Sons. 9780470750353. 2010. 5. en. live. https://web.archive.org/web/20170113131748/https://books.google.ca/books?id=aumIBqHmChwC&pg=PA210. 13 January 2017.
2. Book: British National Formulary (BNF) . 2015. British Medical Association . 9780857111562 . 569 . 69th.
3. Web site: Alprostadil. The American Society of Health-System Pharmacists. 8 January 2017. live. https://web.archive.org/web/20170116185111/https://www.drugs.com/monograph/alprostadil.html. 16 January 2017.
4. Book: Sneader W . Drug Discovery: A History. 2005. John Wiley & Sons. 9780470015520. 185. en. live. https://web.archive.org/web/20170113131638/https://books.google.ca/books?id=jglFsz5EJR8C&pg=PA185. 13 January 2017.
5. Book: ((World Health Organization)) . World Health Organization model list of essential medicines: 21st list 2019 . 2019 . 10665/325771 . World Health Organization . World Health Organization . Geneva . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO .
6. Meller SM, Stilp E, Walker CN, Mena-Hurtado C. The link between vasculogenic erectile dysfunction, coronary artery disease, and peripheral artery disease: role of metabolic factors and endovascular therapy. . J Invasive Cardiol . 2013 . 25 . 6 . 313–9 . 23735361 .
7. Web site: Muse Suppository - Facts and Comparisons . live . https://web.archive.org/web/20130119131710/http://www.drugs.com/cdi/muse-suppository.html . 19 January 2013 . 4 January 2013 . Drugs.com.
8. Web site: Edex - Facts and Comparisons . https://web.archive.org/web/20121026073759/http://www.drugs.com/cdi/edex.html . 26 October 2012 . Drugs.com.
9. Web site: Caverject - Facts and Comparisons . https://web.archive.org/web/20121026075757/http://www.drugs.com/cdi/caverject.html . 26 October 2012 . Drugs.com.
10. Web site: Vitaros 3 mg/g cream - Summary of Product Characteristics . https://web.archive.org/web/20150211142552/https://www.medicines.org.uk/emc/medicine/28866 . 11 February 2015 . Medicines.org.uk .
11. Web site: Vitaros- New Erectile Dysfunction Topical Treatment . https://web.archive.org/web/20150211141258/http://www.meds4all.co.uk/blog/Sexual%20Health/vitaros-erectile-dysfunction.html . 11 February 2015 . Meds4All.co.uk .
12. Walt RP . November 1992 . Misoprostol for the treatment of peptic ulcer and antiinflammatory-drug-induced gastroduodenal ulceration . The New England Journal of Medicine . 327 . 22 . 1575–1580 . 10.1056/NEJM199211263272207 . 1435885.
13. Wu HL, Marwah S, Wang P, Wang QM, Chen XW . May 2017 . Misoprostol for medical treatment of missed abortion: a systematic review and network meta-analysis . Scientific Reports . 7 . 1 . 1664 . 2017NatSR...7.1664W . 10.1038/s41598-017-01892-0 . 5431938 . 28490770.
14. Book: Misoprostol for Cervical Ripening and Induction of Labour: A Review of Clinical Effectiveness, Cost-Effectiveness and Guidelines . Chatsis V, Frey N . 2018 . Canadian Agency for Drugs and Technologies in Health . CADTH Rapid Response Reports . Ottawa (ON) . 30907996.
15. Web site: Medical abortion . 28 April 2022 . Mayo Clinic . en.
16. Vietto V, Franco JV, Saenz V, Cytryn D, Chas J, Ciapponi A . Prostanoids for critical limb ischaemia . The Cochrane Database of Systematic Reviews . 1 . 1 . CD006544 . January 2018 . 29318581 . 6491321 . 10.1002/14651858.CD006544.pub3 .
17. Ye Z, Lu H, Guo W, Dai W, Li H, Yang H, Li L . The effect of alprostadil on preventing contrast-induced nephropathy for percutaneous coronary intervention in diabetic patients: A systematic review and meta-analysis . Medicine . 95 . 46 . e5306 . November 2016 . 27861357 . 5120914 . 10.1097/MD.0000000000005306 .
18. Xie J, Jiang M, Lin Y, Deng H, Li L . Effect of Alprostadil on the Prevention of Contrast-Induced Nephropathy: A Meta-Analysis of 36 Randomized Controlled Trials . Angiology . 70 . 7 . 594–612 . August 2019 . 30669852 . 10.1177/0003319719825597 . 58950588 .