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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The development of the antiprogestin RU-486, and its current use in France and the UK, potential other application, politics in the US, and future are presented. Ru-486, as commonly known by its company code name, rather than its generic name mifepristone, is an analogue of a progestin used in oral contraceptives, with an added chemical group that allows it to link up with the progesterone receptor, but prevents progesterone's effects. It was approved in France in 1988, and has been used for early abortion up to 7 weeks LMP on 80,000 women. French women, after an initial diagnostic appointment, take 3 200 mg tablets of RU-486, then 36-48 hr later return for a Sulprostone (prostaglandin) injection, and are checked up 4-6 weeks later. About 96% abort completely. Some have nausea, vomiting, or pain. Bleeding averages 9 days, and 1% require treatment for bleeding. 2 cardiovascular events and 1 heart attack have been associated with the prostaglandin, now contraindicated in smokers or women 35. In England, RU-486 abortions began in late 1991, for pregnancies up to 9 weeks, using a gentler prostaglandin, Gemeprost, in a vaginal suppository. Only company-trained doctors may order the drug. Research continues on lower doses of RU-486, other prostaglandins, and effects on the fetus if abortion fails. While there is no known basis for a teratogenic effect of the antiprogestin, strong uterine contractions brought on by prostaglandins, such as misoprostol, as abused for illegal abortion in Latin America, may cause birth defects. RU-486 is expected to be useful for inducing labor, dilating the cervix, emergency contraception, pre-surgical management of Cushing's syndrome, brain cancers with profesterone receptors, among other conditions. Several of the 400 or so antiprogestins known are being tested clinically, notably HRP 2000 by WHO. Political controversy is so intense in the US that Roussel, the maker of RU-486, has no intention of marketing it, and even research supplies are unreliable. Meanwhile, pro-choice groups are innovating ways to test and market antiprogestins legally, perhaps inside state lines. It is expected that a suitable prostaglandin, misoprostol, licensed for peptic ulcer, will be available soon, and even RU-486 will become generic by 1998 when its patent expires.
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PMID:Antiprogestins and the abortion controversy: a progress report. 178 9

Molar pregnancy, which results from an anomaly in the development of the trophoblastic tissue, is now easy to diagnose based on clinical evidence, beta hCG level, and sonography, although it must be histologically confirmed. Treatment remains difficult because of the danger of hemorrhage or trauma during uterine evacuation. Hydatidiform mole was diagnosed in the 1st pregnancy of a 27-year-old woman on the basis of a routine 1st trimester sonogram. Clinical examination revealed a voluminous uterus and a long, closed, very tonic cervix. Sulprostone was administered to aid cervical dilatation. An initial intramuscular injection of sulprostone caused uterine contractions without cervical modifications. 5 hours later an intravenous perfusion of sulprostone was started, during which significant contractions and cervical modifications were observed. An aspiration curettage was performed, in which numerous vesicles typical of the hydatidiform mole were evacuated. There was no need for further cervical dilatation and the curettage was rapid and nonhemorrhagic. The postoperative course was uneventful, and a test of beta hCG levels 6 weeks later was negative. The patient complained of pain during uterine contractions despite use of high doses of pethidine. The frequency of hydatidiform mole varies in different countries. It has been estimated at 1/85 in Indonesia and 1/2000 in the US. The clinical picture of hydatidiform mole includes vomiting often nonresponsive to treatment and metrorrhagia of varying volume, a large uterus for the gestational age, and often bilateral ovarian cysts. A vasculorenal syndrome may also begin at 13-16 weeks of amenorrhea. Beta hCG levels are high for the gestational age. Sonography reveals no embryonic structures. Biopsy shows a complete absence of embryo and amniotic sac. The karyotype is diploid and almost always XX. The mechanism is fertilization of an ovocyte whose nucleus is absent or inactive. The 2 chromosome sets are contributed by the father, a circumstance incompatible with embryonic development. Trophoblastic proliferation occurs without embryonic development. Hydatidiform moles may be transformed to invasive moles or chorioepithelioma. Treatment includes uterine evacuation by aspiration under sonographic control if possible. Many authors recommend oxytocin and antibiotic cover. The use of prostaglandin analogs to facilitate uterine evacuation is controversial, with some authors citing the increased risk of trophoblastic embolism. The mole should be histopathologically and cytogenetically studied, and postmolar follow-up is essential.
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PMID:[Use of sulprostone in the evacuation of molar pregnancies]. 206 88

In a prospective, randomised study 40 primigravidae were treated intracervically with 0.05 mg or 0.1 mg Sulprostone-Tylose gel in order to soften the cervix prior to first trimester termination of pregnancy. Curettage was performed on the average 7.5 hours after prostaglandin administration. For objective demonstration of the priming effect, the force required for dilatation of the cervical canal was measured in Newtons by a special tonometer before prostaglandin application and before operation. The maximal dilatability with a force of 10 N, the increase in dilatability after local PG application, and the patency of the cervix were measured. The occurrence of PG-induced lower abdominal pain associated with contractions was analysed with regard to the number of episodes at pain, their timing and the required amount of analgesics. A modified visual analogue scale was used to evaluate the subjective pain experience. The abortive effect of 0.1 mg Sulprostone was found to be more efficient than the 0.05 mg dose. There was no statistical significant difference between the two doses, however, for the priming effect detectable with the tonometer. The subjective experience of pain, use of analgesics and the frequency of gastrointestinal side effects were significantly higher with 0.1 mg than with 0.05 mg Sulprostone. The visual analogue scale allows the patient to quantify, at least to some extent, her experience of pain, and enables a differentiated analgetic therapy. Because of its effectiveness and low rate of side effects, the intracervical application of 0.05 mg Sulprostone gel promises to be an advantageous alternative to other methods of cervical priming.
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PMID:[Cervix priming in induced abortion in the 1st trimester using intracervical administration of sulprostone gel]. 384 28

In a randomized, double-blind study, 30 healthy, nulliparous women of similar gestational age were given intracervical applications of 0.5 mg prostaglandin E2 (PGE2), 0.05 mg Suplrostone, or 0.1 mg Sulprostone gel in order to soften the cervix prior to curettage for 1st trimester termination of pregnancy. Preparations were administered 8 hours before curettage. The number of complete and incomplete abortions, ease of passage through the cervical canal, as measured by a tonometer before and 8 hours after the administration of PG, the degree of pain experienced, and the quantity of analgesics required, plus the frequency of systemic side effects were all assessed by 1 trialist. With regard to the rate of abortion and cervical softening, the administration of 0.1 mg Sulprostone gel proved the most effective method. However, in comparison with the others, it also caused the greatest degree of pain and necessitated the greatest use of analgesics. The softening effect of the PGE2 gel was significantly less and in this group, there were 2 cases of cervical lesion due to tenaculum laceration. The intracervical application of 0.05 mg Sulprostone gel is to be recommended for preoperative ripening of the cervix before termination of pregnancy in the 1st trimester, as it effectively dilates the cervix and does not cause systemic side effects or pain in the lower abdomen, enough to make treatment necessary.
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PMID:Comparative study of various intracervically administered PG gel preparations for termination of first trimester pregnancies. 635 31

1. Intrathecal (i.t.) administration of prostaglandin E2 (PGE2) to conscious mice induced allodynia, a state of discomfort and pain evoked by innocuous tactile stimuli, and hyperalgesia as assessed by the hot plate test. We characterized prostaglandin E receptor subtypes (EP1-3) involved in these sensory disorders by use of 7 synthetic prostanoid analogues. 2. Sulprostone (EP1 < EP3) induced allodynia over a wide range of dosages from 50 pg to 5 micrograms kg-1. The maximal allodynic effect was observed at 5 min after i.t. injection, and the response gradually decreased over the experimental period of 50 min. This sulprostone-induced allodynia showed a time course similar to that induced by PGE2. 3. 17-Phenyl-omega-trinor PGE2 (EP1 > EP3) and 16,16-dimethyl PGE2 (EP1 = EP2 = EP3) were as potent as PGE2 in inducing allodynia, and more potent than sulprostone. Butaprost (EP2), 11-deoxy PGE1 (EP2 = EP3), MB 28767 (EP3), and cicaprost (prostaglandin I2 (IP-) receptor) induced allodynia, but with much lower scores. 13,14-Dihydro-15-keto PGE2, a metabolite of PGE2, did not induce allodynia. 4. 16,16-Dimethyl PGE2 as well as PGE2 induced hyperalgesia over a wide range of dosages (16,16-dimethyl PGE2: 5 pg-0.5 micrograms kg-1 PGE2: 50 pg-0.5 micrograms kg-1) with two apparent peaks at 0.5 ng kg-1 and 0.5 micrograms kg-1. Sulprostone (EP1 < EP3) and 17-phenyl-omega-trinor PGE2 (EP1 > EP3) showed a bell-shaped hyperalgesia at lower doses of 5 pg-5 ng kg-1 and 50 pg-50 ng kg-1, respectively. MB28767 (EP3)showed a monophasic hyperalgesic action over a wide range of dosages at 50 pg-S5 Microg kg-1. Butaprost(EP2) induced hyperalgesia at doses higher than 50 ng kg-1.5. These results demonstrate that PGE2 may exert allodynia through the EP1-receptor and hyperalgesia through EP2- and EP3-receptors in the mouse spinal cord.
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PMID:Characterization of EP-receptor subtypes involved in allodynia and hyperalgesia induced by intrathecal administration of prostaglandin E2 to mice. 792 97

In a prospective, randomised study, 40 primi- and plurigravida were treated either intracervically with 50 micrograms Sulprostone gel or vaginally with a pessary containing 1 mg Gemeprost in order to soften the cervix prior to first trimester termination of pregnancy. Curettage was performed on average 6.0 and 3.2 hours, respectively, after prostaglandin administration. For objective demonstration of the priming effect, the force required for dilatation of the cervical canal was measured in Newton by a special tonometer before prostaglandin treatment and before operation. The free passability of the cervical canal, the maximal dilatability with a force of 10 N and the increase in dilatability after local prostaglandin application were measured. A modified visual analogue scale was used to evaluate the subjective pain experience. During the time between administration and curettage, no abortion occurred in any of the patients. There were no statistically significant differences between both groups regarding the free passability and the maximal dilatability, however, the increase in dilatability was significantly greater in the Gemeprost group. The visual analogue scale allows the patient to quantify, at least to some extent, her experience of pain, but there were no differences in the rate of uterine cramps between both groups; gastrointestinal symptoms did not occur. Both methods were found to be equally efficient; the advantages of Gemeprost are the ease of administration and the short application-curettage interval; however, the cost for one Gemeprost application is nearly 6-fold higher than that of one Sulprostone gel application.
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PMID:[Gemeprost vaginal suppositories versus intracervical sulprostone gel administration for cervic priming in the 1st trimester. A tonometric controlled comparative study]. 818 18

We describe the case of a 39-year-old woman, heavy smoker, who received 500 micrograms i.m. of Sulprostone, a synthetic PGE2-derivative, to induce pregnancy termination. Sulprostone is usually administered either to cause abortion in preparation of an instrumental operation or to induce delivery after the intrauterine death of the fetus. This drug has a dilating effect on the cervix uteri and stimulates the uterus muscles. After about fifteen minutes the patient experienced a constrictive chest pain which progressively worsened and spread to the upper limbs. The pain disappeared for a short period and then recurred with greater intensity, accompanied by bradycardia and hypotension. The ECG showed sinus bradycardia, second- and third-degree atrioventricular block, S-T segment elevation in the inferior leads and reciprocal depression in the anterior leads. Intravenous nitroglycerin therapy induced a rapid reduction of the clinical symptoms and changes in the ECG. There was no increase in cardiac enzymes. The exercise test, the cold pressor test and the ECO-dipyridamole test were negative. The patient refused to undergo the ergonovine test and coronary angiography. We hypothesize that the Sulprostone either had a dipyridamole-like effect or that it induced a paradoxal coronary spasm.
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PMID:[Prolonged angina after the administration of a synthetic PGE2 derivative]. 840 38

354 women seeking abortions were treated at a hospital in Paris between February-September 1988 with 600 mg of RU 486 taken orally in 1 dose and an injection of 500 mg sulprostone 48 hours later. The women all had amenorrhea of less than 49 days. 1/3 were 18-25 years old, 1/2 were 25-35, and 16% were over 35. 206 were nulliparas. 110 were married and the rest were separated, widowed, divorced, or single. Sulprostone was injected early in the morning in the hospital and the women were discharged after expulsion of the products of conception, which occurred usually 2 1/2 to 3 1/2 hours later. If expulsion did not occur, the woman returned in 3 days for a sonogram to confirm uterine vacuity. 13 of the 354 women had RU 486 only. 2 refused the sulprostone and underwent aspiration and 11 experienced spontaneous expulsions in the 48 hours following RU 486 administration. 338 of the women had spontaneous expulsions. 2 pregnancies were terminated but not expelled and aspiration was required. 285 of the women expelled in the hospital within 4 hours of sulprostone administration and the other 55 did so at home 6 or more hours later. RU 486 was very well tolerated. Secondary effects were more common with sulprostone but generally subsided within 3 hours. 70 patients required treatment for uterine pain after sulprostone administration. 150 complained of nausea but only 6 required treatment. 5 women required aspiration of curettage for hemorrhage but none required transfusion. In 3 cases the hemorrhages were due to histologically proven retention. 1 patient developed endometritis 3 days after expulsion and another, who had a history of extrauterine pregnancy, developed salpingitis 15 days after expulsion. Both patients were treated with antibiotics. The method appears to be safe and effective. Its major disadvantages are that it prolongs the amount of time required for abortion and it frequently causes pelvic pain. The responsibility of the patient is also increased.
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PMID:[Clinical trial of pregnancy terminations in 353 patients where amenorrhea was present for less than 49 days by 600 mg of RU 486 (administered orally) and 500 mg of sulprostone (Nalador) administered intramuscularly]. 1228 75

Prostaglandins are small pro-inflammatory molecules derived from arachidonic acid that play roles in a multitude of biological processes including, but not limited to, inflammation, pain modulation, allergies, and bone formation. Prostaglandin analogues are the front-line medications for the treatment of glaucoma, a condition resulting in blindness due to the death of retinal ganglion cells. These drugs act by lowering intraocular pressure (IOP), a major risk factor for glaucoma. The currently used prostaglandin analogues (latanoprost, bimatoprost, tafluprost, and travoprost) mimic PGF2 and target one of the prostaglandin receptors (FP), though research into harnessing the other receptors using compounds like Sulprostone (EP3 receptor), or Iloprost (IP receptor) are currently ongoing. In this review, we summarize the research into each of the prostaglandin molecules (PGD2, PGE2, PGF2, PGI2, TXA2) and their respective receptors (DP, EP1, 2, 3, 4, FP, IP). We examine the modes of action of each of these receptors, their expression, their role in aqueous humour production and outflow within the eye, as well as their roles as medications for the treatment of glaucoma.
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PMID:Prostaglandins in the eye: Function, expression, and roles in glaucoma. 2707 Feb 11