Carboprost (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway. Before the advent of motorized transportation, they also provided accomm ...

, trade names for the tromethamine salts Hemabate, Tham) is a synthetic

prostaglandin Prostaglandins (PG) are a group of physiology, physiologically active lipid compounds called eicosanoids that have diverse hormone-like effects in animals. Prostaglandins have been found in almost every Tissue (biology), tissue in humans and ot ...

analogue of PGF_2α (specifically, it is 15-methyl-PGF_2α) with

oxytocic A uterotonic, also known as an oxytocic or ecbolic, is a type of medication used to induce contraction or greater tonicity of the uterus. Uterotonics are used both to induce labor and to reduce postpartum hemorrhage. Labor induction in the thi ...

properties. Carboprost's main use is to reduce

postpartum bleeding Postpartum bleeding or postpartum hemorrhage (PPH) is often defined as the loss of more than 500 ml or 1,000 ml of blood following childbirth. Some have added the requirement that there also be signs or symptoms of low blood volume f ...

during the obstetrical emergency of

postpartum hemorrhage Postpartum bleeding or postpartum hemorrhage (PPH) is often defined as the loss of more than 500 ml or 1,000 ml of blood following childbirth. Some have added the requirement that there also be signs or symptoms of low blood volume fo ...

Indication

Carboprost is used in postpartum hemorrhage caused by uterine atony not controlled by other methods. One study has shown that carboprost tromethamine is more effective than oxytocin in preventing postpartum hemorrhage in high-risk patients undergoing cesarean delivery. Carboprost was the first drug widely used for

medication abortion A medical abortion, also known as medication abortion or non-surgical abortion, occurs when drugs (medication) are used to bring about an abortion. Medical abortions are an alternative to surgical (also called procedural or instrumentation) a ...

s. It is still sometimes used for second trimester abortions, but has generally been supplanted by the

mifepristone Mifepristone, and also known by its developmental code name RU-486, is a drug typically used in combination with misoprostol to bring about a medical abortion during pregnancy. This combination is 97% effective during the first 63 days (9 wee ...

misoprostol Misoprostol is a synthetic prostaglandin medication used to prevent and treat stomach and duodenal ulcers, induce labor, cause an abortion, and treat postpartum bleeding due to poor contraction of the uterus. It is taken by mouth when used ...

combination.Hemabate ackage Insert New York, NY: Pharmacia and Upjohn Company; 2014."Carboprost" - Drug fact sheet, Mayo Clinic. Last updated: July 01, 2024 https://www.mayoclinic.org/drugs-supplements/carboprost-intramuscular-route/proper-use/drg-20067975Vukelić J. Second trimester pregnancy termination in primigravidas by double application of dinoprostone gel and intramuscular administration of carboprost tromethamine. Med Pregl. 2001 Jan-Feb;54(1-2):11-6. English, Croatian. PMID: 11436877.Bygdeman, M., & Gemzell-Danielsson, K. (2008). An Historical Overview of Second Trimester Abortion Methods. Reproductive Health Matters, 16(sup31), 196–204. https://doi.org/10.1016/S0968-8080(08)31385-8Schwallie PC, Lamborn KR. Induction of abortion by intramuscular administration of (15S)-15-methyl PGF2 alpha. An overview of 815 cases. J Reprod Med. 1979 Dec;23(6):289-93. PMID: 392084.Bhaskar A, Dimov V, Baliga S, Kinra G, Hingorani V, Laumas KR. Plasma levels of 15 (S) 15-methyl-PGF 2 alpha-methyl ester following vaginal administration for induction of abortion in women. ''Contraception''. 1979 Nov;20(5):519-31. doi: 10.1016/0010-7824(79)90057-x. PMID: 527343.

Contraindication

Carboprost is contraindicated in severe cardiovascular, renal, and hepatic disease. It is also contraindicated in acute pelvic inflammatory disease. Hypersensitivity to carboprost or any of its components is also a contraindication.

Precautions

* asthma * anemia * jaundice * diabetes mellitus * seizure disorders * past uterine surgery

Adverse effects

* diarrhea (most common, may be sudden in onset) * flushing or hot flashes * fever * chills * nausea/vomiting

Storage and availability

Carboprost is supplied with its salt derivative tromethamine in 1-milliliter ampules containing a 250 mcg/mL solution of the active drug. The drug must be kept refrigerated at .

Synthesis

A significant deactivating metabolic transformation of natural prostaglandins is enzymatic oxidation of the C-15 hydroxyl to the corresponding ketone. This is prevented, with retention of activity, by methylation to give the C-15 tertiary carbinol series. Carboprost synthesis

This molecular feature is readily introduced at the stage of the Corey lactone (1) by reaction with methyl

Grignard reagent Grignard reagents or Grignard compounds are chemical compounds with the general formula , where X is a halogen and R is an organic group, normally an alkyl or aryl. Two typical examples are methylmagnesium chloride and phenylmagnesium bromi ...

trimethylaluminium Trimethylaluminium or TMA is one of the simplest examples of an organoaluminium compound. Despite its name it has the formula (abbreviated as , where Me stands for methyl), as it exists as a dimer. This colorless liquid is pyrophoric. It is an ...

. The resulting mixture of tertiary carbinols (2) is transformed to oxytocic carboprost (3) by standard transformations, including separation of diastereomers, so that the final product is the C-15 analogue. This diastereomer is reputably freeer of prostaglandin side effects than the C-15 (S) isomer.

References

External links

* {{Prostanoidergics Orphan drugs Drugs developed by Pfizer Medication abortion Prostaglandins Uterotonics