Prostaglandin E1

Prostaglandin E1

Clinical data
Trade names	Caverject, Muse, others
AHFS/Drugs.com	Monograph
MedlinePlus	a695022
License data	US DailyMed: Alprostadil
Routes of administration	Intravenous
ATC code	C01EA01 (WHO) G04BE01 (WHO)
Legal status
Legal status	CA: ℞-only UK: POM (Prescription only) US: WARNING[1]Rx-only
Identifiers
IUPAC name 7-[(1R,3R)-3-hydroxy-2-[(1E,3S)-3-hydroxyoct-1-en-1-yl]-5-oxocyclopentyl]heptanoic acid
CAS Number	745-65-3^Y
PubChem CID	5280723
IUPHAR/BPS	1882
DrugBank	DB00770^N
ChemSpider	4444306^N
UNII	F5TD010360
KEGG	C04741
ChEBI	CHEBI:15544^N
ChEMBL	ChEMBL495^N
CompTox Dashboard (EPA)	DTXSID9022578
ECHA InfoCard	100.010.925
Chemical and physical data
Formula	C20H34O5
Molar mass	354.487 g·mol^−1
3D model (JSmol)	Interactive image
SMILES CCCCC[C@@H](/C=C/[C@H]1[C@@H](CC(=O)[C@@H]1CCCCCCC(=O)O)O)O
InChI InChI=1S/C20H34O5/c1-2-3-6-9-15(21)12-13-17-16(18(22)14-19(17)23)10-7-4-5-8-11-20(24)25/h12-13,15-17,19,21,23H,2-11,14H2,1H3,(H,24,25)/b13-12+/t15-,16+,17+,19+/m0/s1^N Key:GMVPRGQOIOIIMI-DWKJAMRDSA-N^N
^NY (what is this?)  (verify)

Prostaglandin E₁ (PGE₁) is a naturally occurring prostaglandin and is also used as a medication (alprostadil).^[2]

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.^[3] By injection into the penis or placement in the urethra, it is used to treat erectile dysfunction.^[4]

Common side effects when given to babies include decreased breathing, fever, and low blood pressure.^[2] When injected into the penis for erectile dysfunction; side effects may include penile pain, bleeding at the site of injection, and prolonged erection (priapism).^[2] Prostaglandin E₁ is in the vasodilator family of medications.^[2] It works by opening blood vessels and relaxing smooth muscle.^[2]

Prostaglandin E₁ was isolated in 1957 and approved for medical use in the United States in 1981.^[2][5] It is on the World Health Organization's List of Essential Medicines.^[6]

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^[7] 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^[8]) and in injectable form (brand names: Edex^[9] and Caverject^[10]). 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,^[11] 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.^[12] 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,^[13] to treat missed miscarriage,^[14] to induce labor,^[15] and to induce abortion.^[16]

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.^[17]

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.^[18][19]

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

References

1. "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
2. "Alprostadil". The American Society of Health-System Pharmacists. Archived from the original on 16 January 2017. Retrieved 8 January 2017.
3. Northern Neonatal Network (208). Neonatal Formulary: Drug Use in Pregnancy and the First Year of Life (5 ed.). John Wiley & Sons. p. 2010. ISBN 9780470750353. Archived from the original on 13 January 2017.
4. British National Formulary (BNF) (69th ed.). British Medical Association. 2015. p. 569. ISBN 9780857111562.
5. Sneader W (2005). Drug Discovery: A History. John Wiley & Sons. p. 185. ISBN 9780470015520. Archived from the original on 13 January 2017.
6. World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
7. Meller SM, Stilp E, Walker CN, Mena-Hurtado C (2013). "The link between vasculogenic erectile dysfunction, coronary artery disease, and peripheral artery disease: role of metabolic factors and endovascular therapy". J Invasive Cardiol. 25 (6): 313–9. PMID 23735361.
8. "Muse Suppository - Facts and Comparisons". Drugs.com. Archived from the original on 19 January 2013. Retrieved 4 January 2013.
9. "Edex - Facts and Comparisons". Drugs.com. Archived from the original on 26 October 2012.
10. "Caverject - Facts and Comparisons". Drugs.com. Archived from the original on 26 October 2012.
11. "Vitaros 3 mg/g cream - Summary of Product Characteristics". Medicines.org.uk. Archived from the original on 11 February 2015.
12. "Vitaros- New Erectile Dysfunction Topical Treatment". Meds4All.co.uk. Archived from the original on 11 February 2015.
13. 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. doi:10.1056/NEJM199211263272207. PMID 1435885.
14. 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. Bibcode:2017NatSR...7.1664W. doi:10.1038/s41598-017-01892-0. PMC 5431938. PMID 28490770.
15. Chatsis V, Frey N (2018). Misoprostol for Cervical Ripening and Induction of Labour: A Review of Clinical Effectiveness, Cost-Effectiveness and Guidelines. CADTH Rapid Response Reports. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health. PMID 30907996.
16. "Medical abortion". Mayo Clinic. Retrieved 28 April 2022.
17. Vietto V, Franco JV, Saenz V, Cytryn D, Chas J, Ciapponi A (January 2018). "Prostanoids for critical limb ischaemia". The Cochrane Database of Systematic Reviews. 1 (1): CD006544. doi:10.1002/14651858.CD006544.pub3. PMC 6491321. PMID 29318581.
18. Ye Z, Lu H, Guo W, Dai W, Li H, Yang H, et al. (November 2016). "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. doi:10.1097/MD.0000000000005306. PMC 5120914. PMID 27861357.
19. Xie J, Jiang M, Lin Y, Deng H, Li L (August 2019). "Effect of Alprostadil on the Prevention of Contrast-Induced Nephropathy: A Meta-Analysis of 36 Randomized Controlled Trials". Angiology. 70 (7): 594–612. doi:10.1177/0003319719825597. PMID 30669852. S2CID 58950588.