Gemeprost

Chemical Name 11,15-Dlhydroxy-16,16-dimethyl-9-oxoprosta-2,13-dien-1-oil acid methyl ester 

Ethyl 9a-hydroxy-11a,15a-bis(2-tetrahydropyranyloxy)-16,16-dimethyl-prosta-trans-2,trans-l3-dienoate Potassium hydroxide Manganese sulfate Acetic acid 

Synthesis of 9-oxo-11 CH,1 Sol-bis-(2-tetrahydropyranytoxy)-16,16-dimethyl-prosta-trans-2, trans-13-dienoicacid 4gof ethyl 9a-hydroxy-1 la,1 5a-bis-(2-tetrahydropyranyloxy )-16,16-dimethyl-prosta-trans-2,trans-13-dienoate were dissolved In 130 ml of a mixture of ethanol-water (3 1), mixed with 3.9 g of potassium hydroxide and stirred at 25°C for 2 hours. The reaction mixture was acidified with aqueous solution of oxalic acid to pH 5, and diluted with 100 ml of water, extracted with ethyl acetate. The extracts were washed with water, dried over sodium sulfate and concentrated under reduced pressure to obtain 3,88 g of 90 -hydroxy-11a,15a-bis-(2-tetrahydropyranyloxy)-16,16-dimethyl-prosta-trans-2,trans-13-dienoic acid. 

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Gemeprost (73 16.16-dimethvl-trans-A -prostaglandin-E]) is dramatically more potent on a dosage basis as an abortifacient than prostaglandin E2 itself and has fewer side effects. The gem-dimethyl groups at C-16 protect the alcohol moiety at C-15 from rapid metabolic oxidation. 

Thong KJ, Robertson AJ, Baird DT. A retrospective study of 932 second trimester terminations using gemeprost (16,16 dimethyl-trans delta 2 PGE1 methyl ester). Prostaglandins 1992 44(l) 65-74. 

In a double-blind, randomized, controlled trial, 896 healthy women requesting a medical abortion (57-63 days gestation, mean age 25 years) were randomized to a single oral dose of mifepristone 200 or 600 mg, both followed in 48 hours by gemeprost 1 mg vaginally (2). The complete abortion rates were similar with the lower and higher doses of mifepristone (92 versus 92%). The incidences of adverse effects were similar, with the exception of nausea at 1 week, which was less frequent in the low-dose group (3.6 versus 7.6%). 

Two women developed myocardial ischemia during treatment with gemeprost for termination of pregnancy (3). 

A 32-year-old woman, a smoker, had an evacuation after the death of her fetus at 18 weeks. Two pessaries of gemeprost 1 mg were inserted 7.25 hours apart, and about 90 minutes later she became unconscious, apneic, and cyanotic, and had dilated pupils and no detectable blood pressure or pulse. She was given 100% oxygen, intravenous adrenaline and dobutamine, and a crystalloid infusion. Her systolic pressure rose to 100 mmHg. Coronary angiography showed left and circumflex coronary artery spasm. 

The author commented that the myocardial ischemia experienced by both of these patients was thought to be due to prostaglandin-induced coronary spasm. It would be prudent to monitor every woman treated with gemeprost during the course of an abortion. 

Toxic epidermal necrolysis has been attributed to mife-pristone/gemeprost (4). 

Lecorvaisier-Pieto C, Joly P, Thomine E, Tanasescu S, Noblet C, Lauret P. Toxic epidermal necrolysis after mife-pristone/gemeprost-induced abortion. J Am Acad Dermatol 1996 35(1) 112. 

Misoprostol, an analogue of PGE1 is licensed for use in the management of gastroduodenal ulceration. It is an effective myometrial stimulant of the pregnant uterus and is used for the induction of labor and as abortifacient, both alone and in combination with other substances (for example mifepristone). It provides an effective alternative to gemeprost, the most widely used prostaglandin pessaries in combination with mifepristone. 

Vaginal misoprostol is more effective and better tolerated than oral misoprostol for induction of first and second trimester abortions after the administration of mifepristone (1,2). It is more effective than either gemeprost or sulprostone combined with mifepristone for induction of first trimester abortion, although uterine rupture has been reported (3). 

Ripening of the cervix was started with a pessary of gemeprost 1 mg. After 3 hours, when the cervix was 1 cm dilated, an intramuscular injection of sulprostone 500 mg was given. After 30 minutes she developed persistent abdominal pain, which became a continuous cramping and then a shooting pain a male fetus of 170 g was aborted. There was a 3 cm longitudinal cervical rupture located posteriorly that reached the posterior fornix. 

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