Carboprost

Carboprost

File:Carboprost.svg
Systematic (IUPAC) name
(5Z,9α,11α,13E,15S)-9,11,15-trihydroxy-15- methylprosta-5,13-dien-1-oic acid
Clinical data
AHFS/Drugs.com	Micromedex Detailed Consumer Information
MedlinePlus	a600042
Pregnancy category	c
Legal status	℞ (Prescription only)
Routes of administration	Intramuscular
Identifiers
CAS Number	58551-69-2 Y
ATC code	G02AD04 (WHO)
PubChem	CID: 5281075
DrugBank	DB00429 N
ChemSpider	4444532 Y
UNII	U4526F86FJ Y
ChEMBL	CHEMBL1237122 N
Chemical data
Formula	C21H36O5
Molecular mass	368.508 g/mol
SMILES O=C(O)CCC/C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1/C=C/[C@](O)(C)CCCCC
InChI InChI=1S/C21H36O5/c1-3-4-9-13-21(2,26)14-12-17-16(18(22)15-19(17)23)10-7-5-6-8-11-20(24)25/h5,7,12,14,16-19,22-23,26H,3-4,6,8-11,13,15H2,1-2H3,(H,24,25)/b7-5-,14-12+/t16-,17-,18+,19-,21+/m1/s1 Y Key:DLJKPYFALUEJCK-IIELGFQLSA-N Y
NY (what is this?)  (verify)

Carboprost (INN, trade names for the tromethamine salts Hemabate, Tham) is a synthetic prostaglandin analogue of PGF_2α (specifically, it is 15-methyl-PGF_2α) with oxytocic properties.

Carboprost induces contractions and can trigger abortion in early pregnancy. It also reduces postpartum bleeding.

Indication

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 caesarian delivery. Carboprost is also used for the termination of pregnancy in the 2nd trimester.

Unlabeled use:

• Hemorrhagic Cystitis
• PID

Contraindication

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 Exert caution in asthmatic patients as carboprost may cause bronchospasm.

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 microgram/milliliter solution of the active drug. The drug must be refrigerated at a temperature between 2 – 8 degrees Celsius.

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.

File:Carboprost synthesis.svg

Carboprost synthesis: G. L. Bundy et al., DE 2121980 ; G. L. Bundy, U.S. Patent 3,728,382 (1971, 1973 both to Upjohn).

This molecular feature is readily introduced at the stage of the Corey lactone (1) by reaction with methyl Grignard reagent or trimethylaluminium. The resulting mixture of tertiary carbinols (2) is transformed to oxytocic carboprost (3) by standard transformations, including sepoaration of diastereomers, so that the final product is the C-15 analogue. This diastereomer is reputably freeer of porstaglandin side effects than the C-15 (S) isomer.

See also

• Arbaprostil

External links

• Carboprost at the US National Library of Medicine Medical Subject Headings (MeSH)