RESUMO
A dose-finding study was carried out with two different doses of RU 486 (200mg or 600mg) each in combination with two doses of 9-methylene-PGE2 gel (3mg or 5mg) for termination of pregnancy between 7 to 28 days after missed menstrual period. It was observed that the success rates with 200mg RU 486 followed by 5mg 9-methylene-PGE2 gel were 94.5% and 89.6% in women with 7-14 days and 15-28 days of missed menstrual period, respectively. These rates were similar to those observed with 600mg RU 486 given along with 3mg or 5mg 9- methylene-PGE2 gel and were significantly higher than those observed with 200mg RU 486 given along with 3mg 9-methylene-PGE2 gel. All subjects except four started bleeding following the treatment. The average duration of bleeding in subjects with successful outcome (complete abortion) ranged between 7.0 to 11.8 days in the four different treatment schedules. There were no serious side effects with any of the treatment schedules; only one subject required transfusion of one unit of blood for heavy bleeding. The immediate and delayed complication rates were similar with the four treatment schedules.
Assuntos
16,16-Dimetilprostaglandina E2/análogos & derivados , Abortivos/administração & dosagem , Aborto Induzido , Mifepristona/administração & dosagem , Vagina , 16,16-Dimetilprostaglandina E2/administração & dosagem , 16,16-Dimetilprostaglandina E2/efeitos adversos , Abortivos/efeitos adversos , Adulto , Feminino , Géis , Humanos , Mifepristona/efeitos adversos , GravidezRESUMO
This study was performed to determine the effect of 16,16-dimethyl prostaglandin E2 (dmPGE2) on mucous glycoprotein secretion by the guinea pig gallbladder. The prostaglandin was given intraperitoneally for 4 weeks at daily doses of 0 (controls), 10, 20, or 30 micrograms/kg body weight (n = 18 at each dose). These 72 animals were fed normal chow. A 5th group of 18 animals received chow containing 1% cholesterol and 0.5% cholic acid, and no dmPGE2. There were statistically significant increases in the concentrations in gallbladder bile of mucous glycoprotein in the animals fed cholesterol and those treated with dmPGE2, as compared with the controls. Moreover, the animals treated with dmPGE2 formed black-pigmented gallstones, the incidence being dose-dependent, whereas all animals fed a cholesterol-rich diet formed amorphous yellow-brown gallstones. Even though these two types of gallstones appeared different on macroscopic examination, both consisted primarily of calcium phosphate and calcium bilirubinate. These results suggest that exogenous prostaglandin E2 increases concentrations of mucous glycoprotein in the gallbladder bile, resulting in gallstone formation by a mechanism in part similar to the one whereby cholesterol loading promotes gallstone formation in this model.
Assuntos
16,16-Dimetilprostaglandina E2/farmacologia , Bile/efeitos dos fármacos , Colelitíase/induzido quimicamente , Vesícula Biliar/metabolismo , Glicoproteínas/efeitos dos fármacos , 16,16-Dimetilprostaglandina E2/efeitos adversos , Animais , Bile/química , Colelitíase/química , Colesterol na Dieta/administração & dosagem , Vesícula Biliar/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Glicoproteínas/metabolismo , Cobaias , MasculinoRESUMO
Pretreatment with laminaria tent is often used in prostaglandin-induced second-trimester abortion to increase efficacy and shorten induction-to-abortion time. In the present study, two alternatives to soften the cervix and dilate the cervical canal, the antiprogestin RU 486 and intra-cervical application of PGE2, were studied. The study included 71 women requesting legal abortion in the 15th to 23rd week of pregnancy who were treated with repeated vaginal applications of 9-methylene PGE2 in a hydrophilic gel (5 mg every 4th hour) following pretreatment with 200 mg of RU 486 and/or intracervical administration of 0.5 mg of PGE2 gel. The mean interval from start of vaginal prostaglandin treatment to abortion was 13.2 h after intracervical PG-treatment, 10.0 h after antiprogestin and 6.6 h after the combined pretreatment. Patients who received pretreatment with RU 486 alone or in combination with intracervical PGE2 experienced the lowest frequency of episodes of vomiting. Of these two pretreatment alternatives, RU 486 alone has the advantage of a shorter hospital stay. It can be concluded that vaginal administration of 9-methylene PGE2 after pretreatment with RU 486 was a highly effective, safe and rapid procedure for termination of mid-trimester pregnancy, was well tolerated by the patients and was associated with few side effects.
Assuntos
Aborto Induzido , Mifepristona , Segundo Trimestre da Gravidez , 16,16-Dimetilprostaglandina E2/administração & dosagem , 16,16-Dimetilprostaglandina E2/efeitos adversos , 16,16-Dimetilprostaglandina E2/análogos & derivados , Abortivos não Esteroides/administração & dosagem , Abortivos não Esteroides/efeitos adversos , Dinoprostona/administração & dosagem , Dinoprostona/efeitos adversos , Feminino , Humanos , Mifepristona/administração & dosagem , Mifepristona/efeitos adversos , GravidezRESUMO
Termination of early pregnancy (less than 49 days of amenorrhea) was induced in 75 patients with the combination of the antigestagen mifepristone and a prostaglandin analogue, meteneprost. After 48 h a single oral dose of 600 mg of mifepristone was followed by a 10 mg meteneprost vaginal pessary. Pregnancy was confirmed by clinical and ultrasound examinations and plasma HCG assessment. Complete abortion occurred in 72 patients (96%) and the three others required a surgical uterine aspiration. Bleeding continued for 4 to 12 days (mean = 8). Uterine pain and side effects occurred during the 3 h following the use of prostaglandin. Only minor analgesic were required in 30 patients. The combination of mifepristone and meteneprost is a safe and effective method to terminate an early pregnancy.
PIP: Termination of early pregnancy (49 days of amenorrhea) was induced in 75 patients with the combination of the antigestagen mifepristone and a prostaglandin (PG) analogue, meteneprost. After 48 hours, a single oral dose of 600 mg mifepristone was followed by a 10 mg meteneprost vaginal pessary. Pregnancy was confirmed by clinical and ultrasound examinations and plasma hCG assessment. Complete abortion occurred in 72 patients (96%) and the 3 others required a surgical uterine aspiration. Bleeding continued for 4-12 days (mean=8). Uterine pain and side effects occurred during the 3 hours following the use of PG; only minor analgesics were required in 30 patients. The combination of mifepristone and meteneprost is a safe and effective method of terminating and early pregnancy.
Assuntos
16,16-Dimetilprostaglandina E2/administração & dosagem , Abortivos não Esteroides/administração & dosagem , Abortivos/administração & dosagem , Aborto Induzido/métodos , Mifepristona/administração & dosagem , Prostaglandinas E Sintéticas/administração & dosagem , 16,16-Dimetilprostaglandina E2/efeitos adversos , 16,16-Dimetilprostaglandina E2/análogos & derivados , Abortivos não Esteroides/efeitos adversos , Aborto Legal , Administração Intravaginal , Administração Oral , Adolescente , Adulto , Feminino , França , Humanos , Mifepristona/efeitos adversos , Gravidez , Primeiro Trimestre da GravidezRESUMO
It has been shown that the antiprogestin RU 486 increases the sensitivity of the early pregnant human uterus to the stimulatory action of prostaglandin E analogues administered vaginally or intramuscularly. To examine if RU 486 also increases uterine sensitivity to a PGE analogue given orally, two investigative approaches were used in the present study: 1) direct registration of uterine contractions before and after administration of 9-methylene PGE2 in untreated and RU-486-treated early pregnant women; and 2) an efficacy trial involving treatment of pregnant women (amenorrhea of 49 days or less) with 25 mg RU 486 twice daily for three or four days followed by 2.5, 5.0 or 10 mg 9-methylene PGE2, or 600 mg RU486 followed by 10 mg 9-methylene PGE2 administered on day 3 and 4. The results showed that oral 9-methylene PGE2 had a clear stimulatory effect on uterine contractility which was further increased by pretreatment with RU 486. Following 2.5, 5.0 or 10.0 mg 9-methylene PGE2, the frequency of complete abortion was the same, or approximately 80%. The success rate is higher than that generally reported for RU 486 treatment alone. If 600 mg RU 486 was complemented with 10 mg 9-methylene PGE2 administered on both days 3 and 4, the frequency of complete abortion increased to 95%. Side effects were of a mild nature and generally occurred following administration of 9-methylene PGE2. The results of the present study indicate that a combined treatment based on oral administration of both the antiprogestin and the prostaglandin analogue can be developed into a highly effective and simple method to terminate early pregnancy.
Assuntos
16,16-Dimetilprostaglandina E2/administração & dosagem , Abortivos , Aborto Induzido/métodos , Mifepristona/administração & dosagem , Progestinas/antagonistas & inibidores , Prostaglandinas E Sintéticas/administração & dosagem , 16,16-Dimetilprostaglandina E2/efeitos adversos , 16,16-Dimetilprostaglandina E2/análogos & derivados , 16,16-Dimetilprostaglandina E2/sangue , Administração Oral , Gonadotropina Coriônica/sangue , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Hemoglobinas/análise , Humanos , Mifepristona/efeitos adversos , Gravidez , Primeiro Trimestre da Gravidez , Contração Uterina/efeitos dos fármacosRESUMO
A randomized doubleblind investigation of prostaglandin vaginal suppositories prior to hysteroscopy was undertaken in 30 non-pregnant women. PGE2 in 14 of 15 treated patients we found a softening and a dilatation of the cervical canal, but with a relatively high frequency of side effects-nausea, vomiting and diarrhea. No serious bleeding or side effects were observed.
Assuntos
16,16-Dimetilprostaglandina E2/administração & dosagem , Colo do Útero/efeitos dos fármacos , Dilatação/métodos , Prostaglandinas E Sintéticas/administração & dosagem , 16,16-Dimetilprostaglandina E2/efeitos adversos , 16,16-Dimetilprostaglandina E2/análogos & derivados , Ensaios Clínicos como Assunto , Método Duplo-Cego , Endoscopia , Feminino , Humanos , Distribuição Aleatória , Supositórios , Útero , VaginaRESUMO
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.
Assuntos
Dilatação e Curetagem , Dinoprostona/análogos & derivados , Laminaria , Prostaglandinas , Alga Marinha , Curetagem a Vácuo , 16,16-Dimetilprostaglandina E2/efeitos adversos , 16,16-Dimetilprostaglandina E2/análogos & derivados , Abortivos , Adolescente , Adulto , Alprostadil/efeitos adversos , Alprostadil/análogos & derivados , Carboprosta/efeitos adversos , Ensaios Clínicos como Assunto , Feminino , Humanos , Prostaglandinas/administração & dosagem , Prostaglandinas/efeitos adversos , Prostaglandinas E Sintéticas/efeitos adversos , Distribuição AleatóriaRESUMO
The effects of 0, 0.3, 1.0, and 3.0 mg of 16,16-dimethyl prostaglandin E2 methyl ester (Di-M-PGE2) per kilogram per day administered subcutaneously for 21 days to fluorescent-labeled weanling rats were studied, by single-photon absorptiometric and static and dynamic histomorphometric techniques, to determine possible alterations in growth and mineralized tissue mass and their mechanisms of response. Specimens of femurs, proximal tibia, and tibial shaft were analyzed. Di-M-PGE2 caused a reduction in bone elongation and a dramatic accumulation in metaphyseal trabecular hard tissue mass. At high doses, the growth cartilage exhibited reduced thickness and degenerative cell size and cell production rate. The increased metaphyseal trabecular hard tissue mass was restricted to the secondary spongiosa region and was observed at all dose levels. The metaphysis was further characterized by an increase in bone and calcified cartilage cores, a marked elevation in osteoblast and osteoclast numbers, in osteoblast-to-osteoclast ratios, and in ratios of differentiated cells to osteoprogenitor cells. These findings were consistent with the interpretations that Di-M-PGE2 depressed bone elongation by delaying the division and maturation of growth plate chondrocytes; stimulated the differentiation of osteoblasts and osteoclasts, thus generating more differentiated bone cells but suppressing their activities; and increased metaphyseal trabecular hard tissue by creating an imbalance in osteoblasts over osteoclasts and suppressing hard tissue resorption.
Assuntos
16,16-Dimetilprostaglandina E2/farmacologia , Desenvolvimento Ósseo/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Prostaglandinas E Sintéticas/farmacologia , 16,16-Dimetilprostaglandina E2/administração & dosagem , 16,16-Dimetilprostaglandina E2/efeitos adversos , Animais , Animais Lactentes , Osso e Ossos/análise , Osso e Ossos/anatomia & histologia , Esquema de Medicação , Injeções Subcutâneas , Masculino , Osteoclastos/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Tíbia/efeitos dos fármacosRESUMO
Forty nulliparous women were treated with vaginal suppositories containing Meteneprost (9-deoxo-16, 16-dimethyl-9-methylene PGE2) (Upjohn Co.) 10 mg or placebo prior to termination of first trimester pregnancy in a double-blind study. The suppository was inserted three hours before vacuum aspiration. The cervical diameter as measured by the size of the largest Hegar dilatator inserted without resistance was significantly larger in women treated with Meteneprost. The operative blood loss was also reduced in the Meteneprost group.
Assuntos
16,16-Dimetilprostaglandina E2/farmacologia , Abortivos não Esteroides/farmacologia , Abortivos/farmacologia , Aborto Induzido/métodos , Colo do Útero/efeitos dos fármacos , Prostaglandinas E Sintéticas/farmacologia , 16,16-Dimetilprostaglandina E2/efeitos adversos , 16,16-Dimetilprostaglandina E2/análogos & derivados , Abortivos não Esteroides/efeitos adversos , Adulto , Método Duplo-Cego , Feminino , Humanos , Gravidez , Primeiro Trimestre da Gravidez , Distribuição Aleatória , Supositórios , Hemorragia Uterina/prevenção & controle , Curetagem a Vácuo/efeitos adversos , Vômito/induzido quimicamenteRESUMO
PIP: 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.^ieng
Assuntos
Aborto Induzido , 16,16-Dimetilprostaglandina E2/administração & dosagem , 16,16-Dimetilprostaglandina E2/efeitos adversos , 16,16-Dimetilprostaglandina E2/análogos & derivados , Abortivos , Aborto Induzido/efeitos adversos , Aborto Induzido/métodos , Aborto Induzido/psicologia , Alprostadil/administração & dosagem , Alprostadil/efeitos adversos , Alprostadil/análogos & derivados , Âmnio , Anestesia/efeitos adversos , Animais , Arbaprostilo/administração & dosagem , Arbaprostilo/efeitos adversos , Infecções Bacterianas/etiologia , Carboprosta/administração & dosagem , Carboprosta/efeitos adversos , Colo do Útero/lesões , Dilatação e Curetagem/efeitos adversos , Dinoprosta , Dinoprostona , Feminino , Humanos , Soluções Hipertônicas , Ocitocina , Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Progestinas/antagonistas & inibidores , Prostaglandinas E/administração & dosagem , Prostaglandinas E/efeitos adversos , Prostaglandinas E Sintéticas/administração & dosagem , Prostaglandinas E Sintéticas/efeitos adversos , Prostaglandinas F/administração & dosagem , Prostaglandinas F/efeitos adversos , Embolia Pulmonar/etiologia , Risco , Solução Salina Hipertônica , Fatores de Tempo , Ureia , Hemorragia Uterina/etiologia , Perfuração Uterina/etiologiaRESUMO
Single vaginal application of a suppository containing 10 mg of 9-deoxo-16-PGE2 3 hours prior to suction curettage in nulliparous women with gestational ages from 8 to 12 weeks resulted in significant cervical softening (p less than 0.0001), and facilitated additional instrumental dilatation when required. Moderate side effects occurred in the majority of treated patients, disappeared however with appropriate medication. This procedure may thus be considered as effective, safe and reliable.
Assuntos
16,16-Dimetilprostaglandina E2/farmacologia , Aborto Induzido/métodos , Colo do Útero/efeitos dos fármacos , Dilatação e Curetagem/métodos , Prostaglandinas E Sintéticas/farmacologia , 16,16-Dimetilprostaglandina E2/efeitos adversos , 16,16-Dimetilprostaglandina E2/análogos & derivados , Adulto , Ensaios Clínicos como Assunto , Método Duplo-Cego , Feminino , Humanos , Gravidez , Primeiro Trimestre da Gravidez , Cuidados Pré-Operatórios , SupositóriosRESUMO
In the double-blind study reported here the authors were able to confirm the time- and dose-related effect of dilatation of the cervix by means of the new prostaglandin-E2 derivative (9-deoxo-16, 16-dimethyl-9-methylene-PG-E2-potassium salt) as compared to placebo. In spite of the short preoperative duration of action of three hours it was observed that half of the patients treated with the prostaglandin derivative vomited once or several times. The authors therefore consider that administration of the prostaglandin vaginal suppository is only justified in cases with a high risk of cervical injury, and in primiparae undergoing termination under local anesthesia. In 38 patients termination was performed by means of direct cervicomyometrial analgesia. With one exception they approved of chemical dilatation of the cervix in spite of the side-effects, assuming that it would result in less intraoperative pain.
Assuntos
16,16-Dimetilprostaglandina E2/farmacologia , Abortivos não Esteroides/farmacologia , Abortivos/farmacologia , Aborto Induzido , Colo do Útero/efeitos dos fármacos , Prostaglandinas E Sintéticas/farmacologia , 16,16-Dimetilprostaglandina E2/efeitos adversos , 16,16-Dimetilprostaglandina E2/análogos & derivados , Adulto , Dilatação e Curetagem , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Gravidez , Distribuição Aleatória , Fatores de Tempo , Vômito/induzido quimicamenteRESUMO
The trauma of mechanical cervical dilatation preceding abortion is directly related to the degree of cervical resistance. Prostaglandins may reduce cervical rigidity but are accompanied by undesirable side effects. Our aims were to ascertain if a low-dose (10 mg) analogue (9-deoxo-16, 16 dimethyl-9-methylene PGE2) is effective and well tolerated and, if so, to try to determine the possible mechanism by which it works. To this end, we studied 39 women with gestational ages ranging from 7 to 19 weeks who were given a single vaginal suppository 1 to 4 hours before suction curettage. In addition to demographic data on age, gravidity, parity, and previous abortions, we determined progesterone, human chorionic gonadotropin and prostaglandin plasma levels. This low-dose prostaglandin E2 analogue was found to be effective in achieving cervical dilatation and softening with minimal side effects (mild nausea in one patient only). Mean cervical dilatation achieved was 7.8 +/- 2.3 mm. Softening was apparent and facilitated additional instrumental dilatation when required. No correlation was found between drug effectiveness and gravidity, gestational age, or duration of action. There was no detectable trend with regard to baseline progesterone or human chorionic gonadotropin levels. This suggested a specific sensitivity to the local effect by the drug, apparently unrelated to dosage.
PIP: The trauma of mechanical cervical dilatation preceding abortion is directly related to the degree of cervical resistance. Prostaglandins (PGs) may reduce cervical regidity but are accompanied by undesirable side effects. The aims of this study were to ascertain if a low dose (10 mg) analogue (9-deoxo-16,16 dimethyl-9-methylene PGE2) is effective and well tolerated and, if so, to try to determine the possible mechanism by which it works. To this end, there were 39 women studied withgestational ages ranging from 7-19 weeks who were given a single vaginal suppository 1-4 hours before suction curettage. In addition to demographic data on age, gravidity, parity, and previous abortion, the authors determined progesterone, human chorionic gonadotropin (hCG) and PG plasma levels. This low dose PGE2 analogue was found to be effective in achieving cervical dilatation and softening with minimal side effects (mild nausea in only 1 patient). Mean cervical dilatation was achieved 7.8 +or- 2.3 mm. Softening was apparent and facilitated additional instrumental dilatation when required. No correlation was found between drug effectiveness and gravidity, gestational age, or duration of action. There was no detectable trend with regard to baseline progesterone or hCG. This suggested a specific sensitivity to the local effect by the drug, apparently unrelated to dosage.
Assuntos
16,16-Dimetilprostaglandina E2/farmacologia , Abortivos , Aborto Induzido , Colo do Útero/efeitos dos fármacos , Prostaglandinas E Sintéticas/farmacologia , 16,16-Dimetilprostaglandina E2/administração & dosagem , 16,16-Dimetilprostaglandina E2/efeitos adversos , 16,16-Dimetilprostaglandina E2/análogos & derivados , Adolescente , Adulto , Gonadotropina Coriônica/sangue , Feminino , Idade Gestacional , Humanos , Gravidez , Progesterona/sangue , Prostaglandinas/sangue , Supositórios , Curetagem a VácuoRESUMO
Both Lamicel and 16,16-dimethyl-trans delta 2 prostaglandin (PG) E1 methyl ester pessaries have recently been shown to be effective for cervical dilatation prior to first-trimester abortion. In the study described, the force required to dilate the cervix prior to vaginal termination of pregnancy was measured in three groups of patients--a control group, a group which received Lamicel , and a group which received 16,16-dimethyl-trans delta 2 PGE1 methyl ester pessaries. The total force required to dilate the cervix to 10 mm was significantly reduced in the treated groups, but there was no significant difference between the two treatment regimens. The use of Lamicel is associated with fewer side effects.
Assuntos
16,16-Dimetilprostaglandina E2/farmacologia , Colo do Útero/efeitos dos fármacos , Sulfato de Magnésio/farmacologia , Álcool de Polivinil/farmacologia , Prostaglandinas E Sintéticas/farmacologia , 16,16-Dimetilprostaglandina E2/efeitos adversos , Aborto Espontâneo , Adolescente , Adulto , Dilatação , Feminino , Humanos , Sulfato de Magnésio/efeitos adversos , Pessários , Álcool de Polivinil/efeitos adversos , Gravidez , Pré-MedicaçãoAssuntos
Aborto Induzido/métodos , Dinoprostona/análogos & derivados , Prostaglandinas E Sintéticas , 16,16-Dimetilprostaglandina E2/efeitos adversos , 16,16-Dimetilprostaglandina E2/análogos & derivados , Abortivos não Esteroides , Avaliação de Medicamentos , Feminino , Humanos , Injeções Intramusculares , Dor , Gravidez , Prostaglandinas E Sintéticas/administração & dosagem , Prostaglandinas E Sintéticas/efeitos adversos , Autoadministração , Supositórios , VaginaRESUMO
In the present study the efficacy of a new stable prostaglandin E analogue, 9-deoxo-16,16-dimethyl-9-methylene-PGE2 (9-methylene-PGE2), administered as a single vaginal suppository for preoperative dilatation of the cervical canal was evaluated in 382 mainly nulliparous patients. Late first trimester patients received either 20 mg 3 hours prior to or 30 mg 12 hours prior to vacuum aspiration. Early second-trimester patients received 40 mg of the analogue and vacuum aspiration was performed 12 hours later. The degree of cervical dilatation was related to the pretreatment time and the dose of 9-methylene-PGE2. However, even with 20 mg of the analogue and 3 hours pretreatment time, cervical dilatation was adequate in almost 40% of the patients and in the remaining women further mechanical dilatation was regularly performed with ease. The frequency of gastro-intestinal side effects was significantly lower than that found for comparable doses of 15-methyl-PGF2 alpha methyl ester administered by the same route. With 20 mg 9-methylene PGE2, side effects were very rare; only 9% of the patients experienced occasional episodes of vomiting. Three hours' pretreatment with 20 mg of the analogue seems suitable for late first trimester pregnant women in whom the abortion is performed on an outpatient basis. For early second trimester patients pretreatment with 40 mg 9-methylene-PGE2 for 12 hours followed by vacuum aspiration seems to be a better alternative than the two-stage procedures in current use.
Assuntos
16,16-Dimetilprostaglandina E2 , Aborto Induzido/métodos , Prostaglandinas E Sintéticas , 16,16-Dimetilprostaglandina E2/administração & dosagem , 16,16-Dimetilprostaglandina E2/efeitos adversos , 16,16-Dimetilprostaglandina E2/análogos & derivados , Adolescente , Adulto , Carboprosta/uso terapêutico , Colo do Útero/efeitos dos fármacos , Dilatação e Curetagem/métodos , Avaliação de Medicamentos , Feminino , Idade Gestacional , Humanos , Pessoa de Meia-Idade , Gravidez , Prostaglandinas E Sintéticas/administração & dosagem , Supositórios , VaginaRESUMO
Termination of abnormal pregnancy has long been a major gynecological problem. Both surgical and non-surgical procedures are associated with a significant risk for both minor and major complications. Treatment with natural prostaglandins and especially prostaglandin analogues administered by non-invasive routes seems to be an attractive alternative to methods in current use. In the present study 68 consecutive patients with a missed abortion or hydatiform mole were treated with vaginal suppositories containing either 15-methyl-PGF2 alpha methyl ester or 9-deoxo-16,16-dimethyl-9-methylene PGE2. When the uterine size at treatment was 13 weeks or less, vacuum aspiration was performed 12 hours after start of prostaglandin therapy (group I: 41 patients). When the uterus was larger, curettage was performed only after abortion (group II: 27 patients). In group I approximately 45% of the patients aborted within 12 hours from the start of prostaglandin treatment. In the remaining patients the cervical canal was sufficiently dilated and the uterus contracted to allow an easy evacuation. In group II all patients aborted within 26 hours from start of therapy. No serious complications were observed. Both prostaglandin analogues seemed equally effective in terminating an abnormal pregnancy. The E analogue has the advantage of causing significantly fewer gastro-intestinal side effects than the F analogue, though temperature elevation is more common with the former. It may be concluded that vaginal administration of prostaglandin analogues is a simple and effective therapy for termination of abnormal pregnancy and seems to offer considerable advantages over methods in current use.
Assuntos
16,16-Dimetilprostaglandina E2/uso terapêutico , Aborto Retido/terapia , Carboprosta/uso terapêutico , Mola Hidatiforme/terapia , Prostaglandinas E Sintéticas/uso terapêutico , Prostaglandinas F Sintéticas/uso terapêutico , Neoplasias Uterinas/terapia , 16,16-Dimetilprostaglandina E2/efeitos adversos , 16,16-Dimetilprostaglandina E2/análogos & derivados , Adulto , Carboprosta/efeitos adversos , Dilatação e Curetagem , Avaliação de Medicamentos , Feminino , Idade Gestacional , Humanos , Pessoa de Meia-Idade , Gravidez , Útero/anatomia & histologiaRESUMO
Vaginal suppositories containing 9-deoxo-16,16-dimethyl-9-methylene prostaglandin E2 were administered to 40 subjects in an attempt to induce an early abortion. All subjects were 49 days or less from their last menstrual period. Ten subjects (Group A) received the 75-mg suppository followed in 6 hours by a 30-mg suppository, ten subjects (Group B) received the 30-mg suppository followed in 2 hours by the 75-mg suppository and twenty subjects (Group C) received a 30-mg suppository followed in 3 hours by a second 30-mg suppository and in three more hours, at the discretion of the principal investigator, they could receive a third 30-mg suppository. Twenty-seven subjects (68%) had a successful termination of their pregnancy using the multiple vaginal prostaglandin suppository regimens. Seven subjects from Group A, 6 subjects from Group B, and 14 subjects from Group C successfully aborted. One subject in Group B and one subject in Group C were lost to follow-up and the remaining 11 subjects (28%) failed to abort. Twenty-six subjects reported side effects which included nausea, emesis, diarrhea, and uterine cramping requiring analgesia. Thirty-four subjects experienced hyperpyrexia of 99.6 degrees or greater and 12 subjects had their body temperature reach 101 degrees or higher. The use of vaginal suppositories containing 9-deoxo-16,16-dimethyl-9-methylene prostaglandin E2 did not significantly increase the overall abortifacient efficacy of this method from the 60% rate we previously observed with (15S)-15-methyl-prostaglandin F2 alpha methyl ester suppositories.
Assuntos
16,16-Dimetilprostaglandina E2/administração & dosagem , Aborto Induzido/métodos , Prostaglandinas E Sintéticas/administração & dosagem , 16,16-Dimetilprostaglandina E2/efeitos adversos , 16,16-Dimetilprostaglandina E2/análogos & derivados , Aborto Induzido/efeitos adversos , Adulto , Gonadotropina Coriônica/sangue , Gonadotropina Coriônica Humana Subunidade beta , Relação Dose-Resposta a Droga , Avaliação de Medicamentos , Feminino , Humanos , Fragmentos de Peptídeos/sangue , Gravidez , Supositórios , VaginaAssuntos
16,16-Dimetilprostaglandina E2/administração & dosagem , Aborto Induzido/métodos , Prostaglandinas E Sintéticas/administração & dosagem , 16,16-Dimetilprostaglandina E2/efeitos adversos , 16,16-Dimetilprostaglandina E2/análogos & derivados , Ensaios Clínicos como Assunto , Feminino , Humanos , Gravidez , Primeiro Trimestre da Gravidez , Autoadministração , Supositórios , VaginaRESUMO
Oral 16,16-dimethyl prostaglandin E2 is a potent inhibitor of meal-stimulated gastric acid secretion and gastrin release in humans. Experiments were performed in 5 patients with inactive duodenal ulcer to determine the effect of graded doses of intravenous 16,16-dimethyl PGE2 on meal-stimulated gastric acid secretion and gastrin release to demonstrate whether it is necessary for 16-16-dimethyl PGE2 to come into direct luminal contact with the oxyntic and antral gland portions of the stomach to produce its inhibitory effects. All doses of 16,16-dimethyl PGE2, between 0.01 and 0.1 microgram/kg i.v. and between 0.01 and 1.0 microgram/kg orally produced significant postprandial inhibitory effects on both gastric acid secretion and gastrin release as compared with saline control. 0.1 microgram/kg of intravenous of 1 microgram/kg of oral 16,16-dimethyl PGE2 inhibited meal-stimulated acid secretion and gastrin by 80-90%. In 6 unoperated Zollinger-Ellison syndrome patients, 1 microgram/kg of oral 16,16-dimethyl PGE2 significantly inhibited fasting gastric acid hypersecretion by approximately 85% without significantly altering serum gastrin. Each of the oral doses of 16,16-dimethyl PGE2 (0.01-1 microgram/kg) were without untoward effect, as were intravenous doses of 0.01-01 microgram/kg. Maximal inhibition of acid secretion was found with 0.1 microgram/kg 16,16-dimethyl PGE2 i.v. as compared with 1.0 microgram/kg orally. Since 16,16-dimethyl PGE2, whether given orally or intravenously, is a potent inhibitor of both gastric acid secretion and meal-stimulated gastrin release, without apparent untoward side effects, clinical trials with 16,16-dimethyl PGE2 are indicated in patients with acid peptic disease.