carboprost and sulprostone

Postpartum hemorrhage (PPH) remains a common cause of maternal mortality worldwide. Medical intervention plays an important role in the prevention and treatment of PPH. Prostaglandins (PGs) are currently recommended as second-line uterotonics, which are applied in cases of persistent bleeding despite oxytocin treatment.. PG agents that are constantly used in clinical practice include carboprost, sulprostone, and misoprostol, representing the analogs of PGF2α, PGE2, and PGE1, respectively. Injectable PGs, when used to treat PPH, are effective in reducing blood loss but probably induce cardiovascular or respiratory side effects. Misoprostol is characterized by oral administration, low cost, stability in storage, broad availability, and minimal side effects. It remains a treatment option for uterine atony in low-resource settings, but its effectiveness as a uterotonic for independent application may be limited. Key Messages: The present review article discusses the physiological roles of various natural PGs, evaluates the existing evidence of PG analogs in the prevention and treatment of PPH, and finally provides a reference to assist obstetricians in selecting appropriate uterotonics.

Topics: Carboprost; Dinoprostone; Drug Administration Routes; Drug Stability; Female; Humans; Misoprostol; Postpartum Hemorrhage; Prostaglandins; Receptors, Prostaglandin; Uterus

This article outlines the current modalities of pregnancy termination, as well as their risks and complications, in 3 phases of pregnancy: 1) up to 49 days past the last menstrual period, 2) 8-15 weeks, and 3) 16-24 weeks. Before 8 weeks of pregnancy, suction dilatation and curettage (D and C) is the preferred method. However, a medical approach, possibly self-administered, is viewed as more satisfactory and requires only an improvement in side effects. From 8-15 weeks' gestation, suction D and C and dilatation and evacuation (D and E) are the methods of choice. The use of laminaria tents improves both the facility and safety of these procedures in nulliparous patients and perhaps in multiparous patients. Priming of the cervix with prostaglandin could further decrease the difficulty and risks of these procedures. The use of a hydrogel compound is especially worthy of consideration. There is controversy about the preferred method between 16-20 weeks' gestation. D and E appears to have fewer complications and to be more cost-effective than hypertonic saline injection. Urea-prostaglandin has fewer and less severe complications than saline injection, and seems to be more cost-effective than saline injection in terms of duration of hospitalization. The high frequency of failure and side effects, combined with the possibility of expulsion of a live fetus, make prostaglandin-only injection less desirable. After 20 weeks' gestation, urea-prostaglandin injection is probably the safer method. Given the rapid increase in complications with passing weeks, any delay in providing late abortion services should be avoided. 2nd trimester pregnancy terminations, especially those after 18 weeks' gestation, are associated with increased mortality and morbidity and should be performed at specialized centers where providers are better equipped to manage complications.

Topics: 16,16-Dimethylprostaglandin E2; Abortifacient Agents; Abortion, Induced; Alprostadil; Amnion; Anesthesia; Animals; Arbaprostil; Bacterial Infections; Carboprost; Cervix Uteri; Dilatation and Curettage; Dinoprost; Dinoprostone; Female; Humans; Hypertonic Solutions; Oxytocin; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Progestins; Prostaglandins E; Prostaglandins E, Synthetic; Prostaglandins F; Pulmonary Embolism; Risk; Saline Solution, Hypertonic; Time Factors; Urea; Uterine Hemorrhage; Uterine Perforation

The present study included 592 second trimester healthy informed patients admitted to the participating hospitals for termination of pregnancy. In each patient one medium size laminaria tent was introduced into the cervical canal. The laminaria was withdrawn 12 h later and the patients were randomly allocated to either intramuscular infections of 15-methyl-PGF2 alpha (Prostin 15M), 0.25 mg every second hour, or 16-phenoxy-omega-17,18,19,20-tetranor PGE2 methyl sulfonylamide (Nalodor), 0.5 mg every fourth hour. Both treatment schedules were equally effective. The success rate was 95.6% and 94.5% for the E and F analogs, respectively, within 24 h of prostaglandin treatment. The mean duration of prostaglandin treatment was for Nalodor 10.8 h and for Prostin 15M 11.3 h. The mean total dose given of the two analogs was 1.85 mg and 1.65 mg, respectively. With the E analog, the frequency of gastrointestinal side effects was significantly lower than with the F analog. With the former compound, 83.2% had no episodes of diarrhea and 58.9% no vomiting. The mean number of episodes of vomiting and diarrhea per patient was for the E analog 1.0 and 0.4, respectively. The corresponding figures for the F analog were 2.3 episodes of vomiting and 2.2 episodes of diarrhea per patient. Only in three patients (0.5%) cervical laceration was found. It may be concluded that intramuscular administration of either analog after pretreatment with laminaria would appear to be more effective than other methods presently in use for termination of second trimester pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Abortifacient Agents; Abortifacient Agents, Nonsteroidal; Abortion, Induced; Adult; Carboprost; Clinical Trials as Topic; Dinoprostone; Female; Humans; Injections, Intramuscular; Laminaria; Pregnancy; Pregnancy Trimester, Second; Prostaglandins E, Synthetic; Prostaglandins F, Synthetic; Random Allocation; Seaweed

In an eleven-centre study, 627 nulliparous subjects in the 8th to 12th week of gestation admitted for termination of pregnancy were allocated to one of five treatments to induce pre-operative cervical dilatation. The treatments were: 0.5 mg PGE2 methyl sulphonylamide; 1.0 mg PGE1 methyl ester; 30 mg 9-methylene PGE2 free acid, 0.5 mg 15-methyl PGF2 alpha; a single medium-sized laminaria tent. The results indicate that the three PGE analogues are at least equally effective as one medium sized laminaria tent and more effective than 0.5 mg 15-methyl PGF2 alpha in producing adequate pre-operative cervical dilatation prior to vacuum aspiration. It is concluded that both pre-treatment with prostaglandin analogues and laminaria tent are effective methods for preoperative cervical dilatation and both types of treatment are associated with a low incidence of side effects. Prostaglandin analogue treatment can be administered by paramedical personnel but laminaria tent insertion has to be performed by medical staff.

Topics: 16,16-Dimethylprostaglandin E2; Abortifacient Agents; Adolescent; Adult; Alprostadil; Carboprost; Clinical Trials as Topic; Dilatation and Curettage; Dinoprostone; Female; Humans; Laminaria; Prostaglandins; Prostaglandins E, Synthetic; Random Allocation; Seaweed; Vacuum Curettage

The present study included 120 second-trimester patients admitted to the hospital for termination of pregnancy. In all patients, one medium-size laminaria tent was introduced into the cervical canal. The laminaria was withdrawn 12 hours later and the patients randomly allocated to either i.m. injection of 15-methyl PGF2 alpha, 0.25 mg every second hour, or 16-phenoxy-omega-17,18,19,20-tetranor PGE2 methyl sulfonyl-amide, 0.5 mg every fourth hour. Both treatment schedules were equally effective. All patients but 2 (98.3%), one in each group, aborted within 24 hours of prostaglandin treatment. Both methods seem far more effective than other methods at present in use for termination of second-trimester pregnancy. With the E analogue, the frequency of gastro-intestinal side effects was significantly lower than with the F analogue and not more common than following hypertonic saline. The use of laminaria tent was normally uneventful and seemed to reduce the risk of cervical laceration significantly.

Topics: Abortion, Induced; Carboprost; Clinical Trials as Topic; Dinoprostone; Female; Humans; Laminaria; Pregnancy; Pregnancy Trimester, Second; Prostaglandins E, Synthetic; Prostaglandins F, Synthetic; Random Allocation; Seaweed

To extend observations in 11 weeks pregnant patients the mechanism of prostaglandin (PG) action has been examined in 6 weeks pregnant women (LMP). In 10 gravidas menstrual induction was attempted with a single slow release vaginal suppository containing 3000 microgram (155)-methyl PGF2 alpha methyl ester (U-36,384). In 10 additional gravidas menstruation was provoked by the intramuscular injection of 500 microgram 16-phenoxy-omega-tetranor PGE2 methyl sulfonylamide (Sulproston) at 4 hour intervals, totalling 1250 +/- 154 microgram. The PGF2 alpha and PGE2-analogues provoked similar changes in hormone levels and uterine function, sequentially measured by radioimmunoassays and the recording of intrauterine pressure. However, the effects of the intramuscular regimen developed earlier. Both treatments successfully terminated early pregnancy with clinical symptoms of menstruation if they irreversible compromised the conceptus within 12 hours. However, while both formulations represent advances in postconceptional therapy, only further modifications may closely approximate the "ideal" method of non-surgical menstrual induction.

Topics: Abortion, Induced; Animals; Carboprost; Dinoprostone; Drug Evaluation; Female; Humans; Injections, Intramuscular; Pregnancy; Pregnancy Trimester, First; Prostaglandins E, Synthetic; Prostaglandins F, Synthetic; Sheep; Suppositories; Uterus

A comparative study of a synthetic prostaglandin E2 (PGE2) derivative and 15-methyl prostaglandin F2 alpha (PGF2 alpha) in the termination of midtrimester pregnancy of 13-20 weeks of gestation by intramuscular route, showed 97.5% success rate in both the groups but in comparison to 15-methyl PGF2 alpha which produced severe side-effects eg. diarrhoea and vomiting, synthetic PGE2 derivative had minimal or no side-effects.

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Carboprost; Dinoprostone; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Injections, Intramuscular; Pregnancy; Pregnancy Trimester, Second; Treatment Outcome

Topics: Abortifacient Agents; Abortifacient Agents, Nonsteroidal; Abortion, Induced; Adolescent; Adult; Carboprost; Dinoprostone; Female; Humans; Injections, Intramuscular; Laminaria; Pregnancy; Pregnancy Trimester, Second; Prostaglandins E, Synthetic; Prostaglandins F, Synthetic; Seaweed

Therapeutic abortion in the first trimester of pregnancy have been done in ten primigravidae using PGF2 alpha, 15-methyl-PGF2 alpha, or Sulprostone. Bleeding and recalcification time, platelet count, fibrin, platelet adhesiveness, partial thromboplastin time and thromboplastin time were examined before, during and after treatment. We found a decrease of platelet count and a prolongation of bleeding and recalcification time. There was no intensive-influence on coagulation system by the prostaglandin used. Therefore prostaglandins may be used for therapeutic abortion.. 30 healthy primigravidae aged 16-19 were treated (10 each) with PGF2 alpha, 15-Methyl-PGF2 alpha or Sulproston. Bleeding time, recalcification time, platelet count, fibrin, platelet adhesiveness, partial thromboplastin time and thromboplastin time were examined before, during, and after treatment. A decrease in platelet count and a prolongation of bleeding and recalcification time were observed. In all, none of the coagulation parameters showed any harmful change. PGF2 alpha and 15-Methyl-PGF2 alpha showed a greater tendency toward prolongation of bleeding and recalcification time than did Sulproston. The authors conclude that Sulproston is especially suitable for induction of abortion in the 1st trimester of pregnancy in young primigravidae.

Topics: Abortifacient Agents; Abortifacient Agents, Nonsteroidal; Abortion, Induced; Adolescent; Adult; Blood Coagulation Factors; Blood Coagulation Tests; Carboprost; Dinoprost; Dinoprostone; Female; Humans; Platelet Count; Pregnancy; Prostaglandins E, Synthetic; Prostaglandins F; Prostaglandins F, Synthetic

The abortifacient effect has been compared of 15 me-PGF2 alpha, ONO 802 and 16 phenoxy-w-17,18,19,20-tetranor PGE2 given intra-muscularly, intravaginally and with or without laminaria dilatation of the cervix. Locally administered, 15 me-PGF2 alpha, proved to be more efficient than ONO 802. Laminaria had a beneficial effect on dilatation. Intramuscular administration involved the necessity of frequent injections and gastrointestinal side effects. A total of 143 patients participated in the study.. Synthetic analogues of prostaglandins (PGs) E and F are now being used widely to induce abortion at any point in pregnancy without surgical intervention. This study compared the abortifacient effect of PGE and PGF given intramuscularly, intravaginally, and with and without laminaria dilatation in 72 1st-trimester abortion patients. Pregnancy was terminated in 40 women through use of a single suppository containing 3 mg of 15-me-PGF2 beta: complete abortion occurred in 18 of the 20 pregnancies at 6-7 weeks gestation but in only 5 of the 20 pregnancies 10-12 weeks gestation. An additional 32 pregnancies at 6-7 weeks gestation were aborted through vaginal suppositories containing 1 mg of 16.16 dimethyltrans-delta 2-PGE1 methyl ether (ONO-802); complete abortion occurred in 24 of these women, within an average of 5-10 hours. Although suppositories containing 15-me-PGF2 beta were more effective than those with ONO-802, the number of side effects experienced was considerably lower with PGE2. Abortion, whether complete or incomplete, was associated in both groups with full cervical dilatation--a factor of significance in the prevention of future is thmicocervical insufficiency. Pregnancy was also terminated in 47 2nd-trimester patients given either intramuscular PGE2 methyl sulfonylamide or intramuscular 15-m3-PGF2 alpha. The abortion time was an average of 14.3 hours with PGE2 and 4.3 hours with PGF2 alpha; patients in both groups experienced severe low back pain of 25-30 seconds' duration. Complete abortion occurred in 3/4 of the PGF2 alpha women and 1/2 of the women receiving PGE2. Complete abortion was twice as likely in parous women than in primigravidae. The use of PGF2 was associated with no side effects, while PGE2 caused vomiting and diarrhea.

Topics: Abortifacient Agents; Abortifacient Agents, Nonsteroidal; Administration, Intravaginal; Alprostadil; Carboprost; Dinoprostone; Female; Humans; Infusions, Intravenous; Laminaria; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Prostaglandins E, Synthetic; Prostaglandins F, Synthetic

Since 1977 the number of therapeutic abortions has been decreasing in Norway, a trend which is probably due to improved contraceptive practice. The results with PGs used for cervical dilatation in late first trimester and induction of abortion in the second trimester are reported. Pretreatment overnight or for 3-4 hours simplified the surgical procedure and Sulprostone (Schering AG) caused fewer side effects than 15(S) 15 Me F2 alpha. In the second trimester 15(S) 15 Me F2 alpha was administered by different routes and in different doses. 16,16 diMe trans delta 2E2 was given only as vaginal suppositories. Side effects were fewer by the intraamniotic route than by the other routes. The need for and benefits of PGs for therapeutic abortions are discussed.

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Therapeutic; Age Factors; Carboprost; Dinoprost; Dinoprostone; Female; Gestational Age; Humans; Norway; Pelvic Inflammatory Disease; Pregnancy; Prostaglandins; Prostaglandins E, Synthetic; Prostaglandins F

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Amnion; Carboprost; Cardiovascular Diseases; Cervix Uteri; Dinoprost; Dinoprostone; Female; Humans; Injections; Injections, Intramuscular; Oxytocin; Pregnancy; Pregnancy Trimester, Second; Prostaglandins; Prostaglandins E, Synthetic; Prostaglandins F; Suppositories; Uterus; Vagina

The present study included 550 mainly primiparous women in the 8th to 12th week of pregnancy admitted to the hospital for termination of pregnancy. The patients were treated by different prostaglandin analogues or one medium size laminaria tent followed by vacuum aspiration. The treatment period was three hours, which for some analogues was extended to six and twelve hours. The prostaglandins studied were 15-methyl PGF2 alpha methyl ester (0.5 and 1.0 mg), 16,16-dimethyl-trans-delta 2 PGE1 methyl ester (1.0 mg), 9-deoxo-16,16-dimethyl-9-methylene PGE2 (30 mg), all administered by the vaginal route, and 16-phenoxy-omega-17,18, 19,20-tetranor PGE2 methyl sulfonylamide (0.25 and 0.5 mg) given as i.m. injections. At operation the degree of cervical dilatation, the amount of blood loss and other operative complications were registered. The patients were continuously supervised during treatment and during at least three hours after operation. Side effects, complications and vital signs were recorded. The degree of cervical dilatation was related to the duration of prostaglandin treatment. If the duration of prostaglandin treatment was prolonged, the frequency of gastrointestinal side effects, abortion prior to scheduled time for vacuum aspiration and pain needing analgesic treatment also increased. Both the efficacy and the frequency of side effects were dose dependent. The outcome of therapy after three-hour pretreatment was evaluated. All the prostaglandins were more effective than one medium size laminaria tent in dilating the cervical canal. The three E analogues were most effective. The number of patients with bleeding at operation of 50 ml or more was also higher following laminaria than following prostaglandin pretreatment. Most advantageous in this respect were the three E analogues. Frequency of gastrointestinal side effects and degree of pain following 9-methylene PGE2 and 16,16-dimethyl PGE1 methyl ester was the same as following laminaria treatment.

Topics: 16,16-Dimethylprostaglandin E2; Abortion, Induced; Alprostadil; Carboprost; Dinoprostone; Female; Humans; Laminaria; Pregnancy; Prostaglandins E, Synthetic; Seaweed

Topics: Abortion, Induced; Adolescent; Adult; Carboprost; Dinoprostone; Female; Humans; Injections, Intramuscular; Pregnancy; Pregnancy Trimester, First; Prostaglandins E, Synthetic; Prostaglandins F, Synthetic