Prostaglandin E2

verifiedfields	changed
watchedfields	changed
verifiedrevid	394516799
image2	Prostaglandin-E2-from-xtal-3D-bs-17.png
tradename	Prostin E2, Cervidil, Propess, others
medlineplus	a682512
licence eu	yes
dailymedid	Dinoprostone
pregnancy au	C
pregnancy au comment	‡R1R‡
pregnancy us	C (gel and suppository) / X (subcutaneous) / N (insert)
pregnancy us comment	‡R1R‡
routes of administration	Intravaginal, IV
atc prefix	G02
atc suffix	AD02
legal uk	POM
legal us	Rx-only
legal eu	Rx-only
cas number	363-24-6
pubchem	5280360
iuphar ligand	1883
drugbank	DB00917
chemspiderid	4444059
unii	K7Q1JQR04M
kegg	D00079
chebi	15551
chembl	548
synonyms	PGE2, (5Z,11α,13E,15S)-11,15-Dihydroxy-9-oxo-prosta-5,13-dien-1-oic acid
iupac name	(5Z,11α,13E,15S)-7-[3-hydroxy-2-(3-hydroxyoct-1-enyl)- 5-oxo-cyclopentyl] hept-5-enoic acid
c	20
h	32
o	5
smiles	CCCCC[C@@H](/C=C/[C@H]1[C@@H](CC(=O)[C@@H]1C/C=C\CCCC(=O)O)O)O
stdinchi	1S/C20H32O5/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/h4,7,12-13,15-17,19,21,23H,2-3,5-6,8-11,14H2,1H3,(H,24,25)/b7-4-,13-12+/t15-,16+,17+,19+/m0/s1
stdinchikey	XEYBRNLFEZDVAW-ARSRFYASSA-N

Prostaglandin E2 (PGE2), also known as dinoprostone, is a naturally occurring prostaglandin with oxytocic properties that is used as a medication. Dinoprostone is used in labor induction, bleeding after delivery, termination of pregnancy, and in newborn babies to keep the ductus arteriosus open.[2] In babies it is used in those with congenital heart defects until surgery can be carried out.[2] It is also used to manage gestational trophoblastic disease. It may be used within the vagina or by injection into a vein.[3]

PGE2 synthesis within the body begins with the activation of arachidonic acid (AA) by the enzyme phospholipase A2. Once activated, AA is oxygenated by cyclooxygenase (COX) enzymes to form prostaglandin endoperoxides. Specifically, prostaglandin G2 (PGG2) is modified by the peroxidase moiety of the COX enzyme to produce prostaglandin H2 (PGH2) which is then converted to PGE2.[4]

Physiological effects

Dinoprostone has important effects in labor by inducing softening of the cervix and causing uterine contraction, and also stimulates osteoblasts to release factors that stimulate bone resorption by osteoclasts.[9]

Natural prostaglandins, including PGE1 and PGE2, are important in the structure and function of the ductus arteriosus in fetuses and newborns.[10] They allow the ductus arteriosus to remain open, providing the necessary connection between the pulmonary artery and descending aorta that allows the blood to bypass the fetus's underdeveloped lungs and be transported to the placenta for oxygenation.[10] The ductus arteriosus normally begins to close upon birth due to an increase of PGE2 metabolism, but in newborns with congenital heart disease, prostaglandins can be used to keep the ductus arteriosus open longer than normal to sustain healthy oxygen saturation levels in the blood.[4][10] Although PGE1 is more commonly used in this setting, there has been a report of oral PGE2 being used to treat ductus-dependent congenital heart diseases in newborns to delay surgical treatment until the pulmonary arteries grew.[11] In addition, PGE2 was used in another report to dilate the ductus arteriosus in newborns with various cardiovascular defects to allow for better perfusion of the lungs and kidneys.[12] On the other hand, the post-partal synthesis of PGE2 in newborns is considered one cause of patent ductus arteriosus.[13]

When administered in aerosol form, PGE2 serves as a bronchodilator, but its use in this setting is limited by the fact that it also causes coughing.[4]

PGE2, similarly to PGE1, acts as a direct vasodilator by acting on smooth muscle to cause dilation of blood vessels.[4] In addition, PGE2 inhibits platelet aggregation.[4]

PGE2 also suppresses T cell receptor signaling and proliferation, and may play a role in resolution of inflammation.[4][14] In addition, PGE2 limits the immune response by preventing B-lymphocyte differentiation and their ability to present antigens.[4]

Central and peripheral nervous systems effects

Prostaglandin E2 (PGE2) has a variety of functions within the central nervous system and peripheral nervous system. When PGE2 interacts with EP3 receptors, it increases body temperature, resulting in fever.[15][16] PGE2 is also a predominant prostanoid that contributes to inflammation via enhancing edema and leukocyte infiltration from increased vascular permeability (allowing more blood flow into an inflamed area of the body) when acting on EP2 receptors. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) blocks the activity of COX-2, resulting in a decrease of PGE2 production. NSAIDs blocking COX-2 and decreasing the production of PGE2 remediates fever and inflammation.[4][17]

Additionally, PGE2 acting on EP1 and EP4 receptors are a component in feeling pain via inflammatory

Medical uses

Cervical ripening

In the setting of labor and delivery, cervical ripening (also known as cervical effacement) is a natural process that occurs before labor, in which the cervix becomes softer, thinner, and dilated, enabling the fetus to pass through the cervix.[25] A ripe cervix is favorable prior to induction of labor, which is a common obstetric practice, and increases the chances for a successful induction.[26] Pharmacological methods are sometimes required to induce cervical ripening that does not occur naturally.[27] The natural ripening of the cervix is mediated by prostaglandins, thus a common pharmacological method is to use external prostaglandins such as PGE2, or dinoprostone.[25] Results of a systematic review and meta-analysis of the literature found that outpatient cervical ripening with dinoprostone or single-balloon catheters did not increase the risk of cesarean deliveries.[28][29]

Prostaglandin E2 (PGE2) achieves cervical ripening and softening by stimulating uterine contractions as well as directly acting on the collagenase present in the cervix to soften it.[4] There are currently two formulations of PGE2 analog available for use in cervical ripening: Prepidil, a vaginal gel, and Cervidil, a vaginal insert.[26] PGE2 is similar to oxytocin in terms of successful labor induction and the time from induction to delivery.[4]

Termination of intrauterine pregnancy

PGE2 is a common pharmacological method of termination of pregnancy, particularly in the second trimester or for missed abortion, which is a miscarriage in which the fetus did not evacuate the uterus.[4][30][31] However, PGE2 is not feticidal, and only induces abortion by stimulating uterine contractions. It is recommended that 20 mg of dinoprostone vaginal suppository be administered every three to five hours to evacuate the uterus.[4] The abortion should occur within 24 hours after the beginning of administration of dinoprostone; if it does not, dinoprostone should no longer be given and other interventions would be required, such as dilation and curettage.[4]

References

Dinoprostone topical Use During Pregnancy Drugs.com, 17 December 2019, retrieved 27 July 2020^

Northern Neonatal Network. Neonatal Formulary: Drug Use in Pregnancy and the First Year of Life John Wiley & Sons, 2007^

British national formulary: BNF 69 British Medical Association, 2015^

Basic & Clinical Pharmacology McGraw-Hill Education, 2017^

Enzymes of the cyclooxygenase pathways of prostanoid biosynthesis Chemical Reviews, October 2011^

Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition Jones & Bartlett Learning, 2015^

Dinoprostone The American Society of Health-System Pharmacists, retrieved 8 January 2017^

World Health Organization model list of essential medicines: 21st list 2019 World Health Organization, 2019^

Dinoprostone PubChem, U.S. National Library of Medicine, retrieved 2020-07-27^

Prostaglandins in Congenital Heart Disease Medical Journal, Armed Forces India, April 2001^

Oral prostaglandin E2 in ductus-dependent pulmonary circulation Circulation, March 1981^

[Prostaglandin E2 in newborns with congenital heart disease] Zeitschrift für Kardiologie, July 1982^

Textbook of Pathology Jaypee Brothers Medical Publishers Pvt. Limited, 2015^

A live imaging cell motility screen identifies prostaglandin E2 as a T cell stop signal antagonist Journal of Immunology, October 2011^

Impaired febrile response in mice lacking the prostaglandin E receptor subtype EP3 Nature, 1998-09-17^

Prostaglandin EP3 receptor–expressing preoptic neurons bidirectionally control body temperature via tonic GABAergic signaling Science Advances, 2022-12-23^

Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials Lancet, August 2013^

Acute Pain Current Medical Diagnosis and Treatment 2020, McGraw-Hill Education, 2020, retrieved 2020-08-04^

Regulation of immune responses by prostaglandin E2 Journal of Immunology, January 2012^

Prostaglandins as the Agents That Modulate the Course of Brain Disorders Degenerative Neurological and Neuromuscular Disease, 2020^

The Rostral Raphe Pallidus Nucleus Mediates Pyrogenic Transmission from the Preoptic Area The Journal of Neuroscience, 2002-06-01^

Stress responses: the contribution of prostaglandin E(2) and its receptors Nature Reviews. Endocrinology, March 2011^

The role of prostaglandin E2 in human vascular inflammation Prostaglandins, Leukotrienes, and Essential Fatty Acids, August 2013^

The PGE2-EP2-mast cell axis: an antiasthma mechanism Molecular Immunology, January 2015^

Dinoprostone Vaginal Insert: A Review in Cervical Ripening Drugs, October 2018^

Methods for cervical ripening and induction of labor American Family Physician, May 2003^

ACOG Committee on Practice Bulletins -- Obstetrics. ACOG Practice Bulletin No. 107: Induction of labor Obstetrics and Gynecology, August 2009^

A Tribute to Nancy C. Chescheir, MD Obstetrics and Gynecology, January 2021^

Cervical Ripening in the Outpatient Setting AHRQ Comparative Effectiveness Reviews, Agency for Healthcare Research and Quality (US), 2021-03-22^

Prostaglandins: overview in obstetrics and gynecology Journal of Reproduction and Fertility, May 1974^

The use of prostaglandins and their analogues for abortion Clinics in Obstetrics and Gynaecology, December 1984^

StatPearls StatPearls Publishing, 2020^

Improving induction of labour - a quality improvement project addressing Caesarean section rates and length of process in women undergoing induction of labour BMJ Quality Improvement Reports, 2015^

Administration and Dosing www.cervidil.com, retrieved 2020-07-31^

Prostin E2 Pfizer Monograph retrieved 2020-07-31^

Review of Propess--a controlled release dinoprostone (prostaglandin E2 ) pessary Journal of Obstetrics and Gynaecology, September 1997^

Dinoprostone dosage forms confused Institute for Safe Medication Practices, 2013^

Prostaglandin metabolism. II. Identification of two 15-hydroxyprostaglandin dehydrogenase types J. Biol. Chem., 1975^

Prostaglandin E2 American Chemical Society^

Success of prostaglandin E2 in structure-function is a challenge for structure-based therapeutics Proceedings of the National Academy of Sciences of the United States of America, July 2003^

Drugs@FDA: FDA-Approved Drugs www.accessdata.fda.gov^

Prostaglandin E2

Physiological effects

Central and peripheral nervous systems effects

Medical uses

Cervical ripening

Termination of intrauterine pregnancy

Side effects

Mechanism of action

Administration

Contraindications

Toxicity

Pharmacokinetics

History

External links

References

Immunity

Neurological effects

Smooth muscle effects

Kidney effects