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Query: UMLS:C0042963 (vomiting)
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The methods known to be practical for post-ovulatory contraception, defined as any substance or device used after coitus to prevent establishment of pregnancy up to 14 days after ovulation are reviewed. Most are used only in emergency for a single episode of unprotected intercourse or failed contraception, exceptions being the "visiting pill" of norethindrone used for migrant workers in China, and the IUD when inserted for this purpose as well as ongoing contraception. The physiology of ovulation, fertilization, transport of the ovum, and implantation of the blastocyst are reviewed. Estimates of the odds of becoming pregnant after an isolated unprotected intercourse range from 10-25%. High-dose estrogens, either stilbestrol (no longer used in the U.S.), ethinyl estradiol 5 mg, or conjugated estrogens 30 mg, have been used since early trials in the 1960s. Estrogen must be given for 5 days, started within 72 hours of coitus, and cause several unpleasant side effects, notably nausea, vomiting, mastalgia, and menstrual irregularity. Although no incidents have been reported, they are contraindicated for those at risk of thromboembolism. The failure rate is about 0.7%. Combined estrogen and progestagen, known as the Yuzpe method, consists of 2 dose of 100 mcg ethinyl estradiol and 1 mg norgestrel, repeated in 12 hours. The reported failure rates range from 0.2%-7.4%. Insertion of a copper IUD is effective post-coitally within 66 days, with failure rate less than 0.1%. The antiestrogen Danazol, which actually acts as an antigonadotrophin, can be used as a postcoital agent, in divided doses of 800 or 1200 mg 12 hours apart within 72 hours of exposure. Published failure rates are 2.5 and 0.9% with these doses. Progestagens alone have been studied by WHO, but failure rates were as high as 10.1% in women with frequent intercourse. Regular use was not recommended since cycles became unpredictable. Studies are being conducted on RU-486 and prostaglandins for postcoital use, in comparison with the Yuzpe regimen. A true luteolytic agent for women would seem to be the perfect postcoital agent, yet none exist.
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PMID:Post-ovulatory contraception. 222

The increased risk of thromboembolism in women using estrogen-containing (OCs) oral contraceptives has been related to decreased (AT3) antithrombin 3 levels of about 10%. A dose-dependent effect on AT3 has been suggested. Using an automated chromogenic technique, we have studied the effect on AT3 of a very high dose of ethinyl estradiol (5 mg daily for 5 days), popularly known as the "morning after pill," which in the Netherlands is prescribed to 45,000 women. The mean decrease in AT3 level in 13 patients of average age 23 was 17% of the pretreatment value (p=0.0013). Values in U/ml as mean + or - 50 were 1.03 + or - 0.12 on day 0, 0.86 + or - 0.12 on day 5, and 0.97 + or - 0.15 on day 12. The day 0 samples were taken immediately before the start of therapy and those on day 12 were taken 1 week after discontinuing therapy. The normal range is 0.80-1.40 U/ml. The effect of this dose was also studied in 2 volunteers. The 1st volunteer did not wish to continue after the first dose of 5 mg ethinyl estradiol because of vomiting. On day 2 AT3 had increased by 22% and on day 4 had decreased by 12% of the pretreatment level. The 2nd volunteer also vomited on day 1, but continued the medication. AT3 increased on day 2 and then fell to 18.5% of pretreatment level on day 4. Changes in AT3 ran parallel with changes in hematocrit (seen in figure). High doses of estrogen have been reported to cause an increase in blood volume of 18% and a decrease in hematocrit of 15%. Plasma volume increases by 11% during OC use. Estrogen induced retention of salt and water causing hemodilution rather than increased consumption or decreased synthesis, may explain the reported decreases in AT3 levels. This does not rule out the possibility that subnormal values contribute to a hypercoagulable state. In 1 of our patients on day 5 of treatment AT3 fell to 0.60 U/ml, which is within the range where thromboembolism may occur in certain settings, such as emergency surgery or a history of thrombosis.
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PMID:"Morning after pill" and antithrombin III. 611 73

Progress in new drug developments is discussed in relation to newly registered drugs and drugs in the animal and/or clinical research stage. Of central nervous system drugs new neuroleptics, antidepressants, tranquilizers, psychotropics, antiparkinson and anticonvulsant agents are discussed in terms of chemical structure, pharmacokinetics and toxicity. Likewise for anti-infective drugs such as antibiotics, antifungal, and antiparasitic agents. New synthetic antiinflammatory glucocorticoids are being developed and tested for toxicity and clinical effect. Estrogen and gestagen research continues but few new substances with more effective action than currently-used compounds have been found. Initial clinical testing of Tibolon shows it to prevent postmenopausal osteolysis and hot flashes. ST-1435 is still being tested as an implantable contraceptive. It causes amenorrhea and reduces plasma estradiol and progesterone. No progress is seen in research on nonhormonal substances with contraceptive action, except for prostaglandins although no new derivatives with high tissue selectivity for uterine smooth muscle, nor early applicable abortifacients, have been found. Metenprost is being studied as a self-administered abortifacient: in one study 98% of completed abortions were seen with 30-40% adverse effects (nausea, vomiting, fever). DL204-IT and L-11,204 are triazoloisoindole and triazoloisoquinolone derivatives which have been tested in various dosages and dosage forms on animals in various pregnancy stages. Optimum contraceptive action occurs in the early blastocyst stage. The plant extracts Zoapatanol and Montanol show dose-dependent inhibition of implantation in animal studies but the contraceptive action mechanism is not known. Oxendolone shows an unmistakable antiandrogenic effect. Action mechanism is assumed to be inhibition of the 5 alpha-reduction of testosterone. It has a long plasma half-life in rats (3.6 days). It has been clinically tested in Japan (weekly intramuscular injection of 200-400 mg) in prostatic hypertrophy. Longterm studies are not yet available.
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PMID:[Progress in the area of drug development. 15]. 613 42

The efficacy of oral contraceptives (OCs) is influenced by any factor that affects circulating blood levels of exogenous estrogen or progesterone or that interferes with their action at a cellular level. Inadvertent pregnancies are not uncommon in combined pill users, and are usually due to errors of tablet taking. Estrogen-progestogen combinations work mainly by hypothalamic suppression; basal plasma levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) are usually repressed and their cyclical surges eliminated. Progestogen-only formulations have much less effect on central control and depend more on effects on the cervical mucus, endometrium, and possibly tubal function. Significant increases in FSH and LH levels may occur in the pill-free week among combined pill users. Reduction in dosage of some newer preparations appears to reduce the margin of error and, in low-dose progestogen-only pills, progestogen may reach inadequate levels for contraceptive effect before the expected time of the next pill. Higher failure rates in the 1st rather than in subsequent treatment cycles are mainly due to user failure, but method failures also may be more common, possibly because hypothalamic suppression increases over the 1st few cycles. 3 studies on pituitary and ovarian function in women who deliberately missed pills at specific stages showed an increase in breakthrough ovulation. Other clinical factors which may affect pill efficacy included vomiting, diarrhea, changing to a lower dose formulation, obesity, and drug interaction, especially with the antituberculosis drug rifampicin, some anticonvulsants, and antibiotics. Breakthrough ovulation from drug interaction is more likely to occur when OCs are administered early or late in the cycle. Analogously, the most hazardous times to miss pills are at the beginning or end of a monthly course.
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PMID:Why do inadvertent pregnancies occur in oral contraceptive users? Effectiveness of oral contraceptive regimens and interfering factors. 641 29

Postcoital contraception (PC) has become more effective in recent years and is recommended for women who have had unprotected coitus between the 8th and 17th days of their cycles. Vaginal douche using a spermicide solution is ineffective as it has resulted in a 37% pregnancy rate. Estrogens are far more effective: Diethylstilbestrol (DES), taken in doses of 25-50 mg daily for 5 days, e.g., 10 mg of conjugated estrogens 3 times daily, and 2.5 mg ethinyl estradiol 2 times daily for 5 days 24-72 hours after coitus, has resulted in a .5-1.5% pregnancy rate. Side effects, however, include nausea, vomiting, mastalgia, menorrhagia, extrauterine pregnancy, and adenocarcinoma in daughters of DES-treated women. Gestagens, such as .15-.40 mg of d-norgestrel taken 3 hours after coitus, can be used as a form of planned PC. In an experiment, an estrogen-gestagen preparation consisting of 50 mcg ethinyl estradiol and 500 mcg dl-norgestrel taken 12-72 hours after coitus produced a .9% pregnancy rate in 1300 menstrual cycles with few serious side effects. Copper 7 or copper-T IUDs also prevent the implantation of the fertilized egg, and, when used within 5 days after coitus, produced only 1 pregnancy in 727 cases. The ideal future PC would be a preparation that inhibits either ovulation or nidation and has limited side effects. Among some promising agents are a luteinizing hormone-releasing factor agonist as well as natural and synthetic prostaglandins; however, until their cardiovascular and gastrointestinal side effects have been ameliorated, their routine use is unlikely.
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PMID:[Postcoital contraception]. 661 4

A worsening of migraine headaches has been associated with estrogens, given for birth control and menopausal syndrome. It is suggested in this case history report that the same may be true in the male migrainous patient, in whom estrogens are rarely used. 1 week following surgery for prostatic carcinoma a 75-year-old white man who was started on stilbestrol 5 mg daily began to experience severe bifrontal, throbbing headaches with nausea and occasional vomiting. The headaches lasted 4-6 hours and appeared 3 or 4 times weekly. Fortification spectra in both visual fields and language disturbances occurred during the headache period. Stilbestrol was discontinued 4 months later, and the headaches improved. After 1 week without headaches, stilbestrol was begun again and similar headaches promptly recurred. Stilbestro was again discontinued, and the headaches immediately improved. 1 month later the patient was free from headache and has since remained so. Between the periods of headache, neurological examination was normal. The patient had a history of moderate common migraine, but following estrogen medication his symptoms became those of a severe clsssic migraine. The case raises the possiblity that the relation between estrogens and migraines is not limited to a fall in estrogen blood levels; steady or rising levels of estrogens possibly produce a similar effect.
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PMID:Estrogens and migraine. 721 75

Some form of postcoital contraception for protection against unwanted pregnancy is indispensable today especially in cases of rape, failed mechanical contraception, or 1st sexual contact without contraception. A tabletform of postcoital contraceptive would be acceptable if 100% certainty is assured and it doesn't involve adverse effects. Postcoitally administered high-dose estrogens proved effective in Macaca mulatta. Diethylstilbestrol in variable dosages with or without ethinylestradiol was used in various studies and with variable results. Pregnancy rates depended on time of coitus in cycle, contraceptive dosage, and time of administration after coitus (within 72 hours). Conjugated estrogens and various progestagens or combinations of both have been tried with variable success. Another form of postcoital contraception is IUD insertion within 7 days following unprotected coitus. Advantages of this method are the time factors and absence of adverse effects of hormonal contraceptives. Postcoital hormonal contraceptives cause changes in the endometrium which prevent blastocyst implantation. They alter tubal function affecting zygote movement towards the uterus. They have an antiovulatory effect and may be luteolytic. Estrogens have more severe side effects than progestagens. Nausea, vomiting, mastodynia, fluid retention, and vaginal bleeding can result from estrogens. Progestagens can cause irregular bleeding. Combination of both can cause menstrual irregularity. Postcoital hormonal contraceptives are contraindicated in heart and liver diseases, thrombosis, and pregnancy (teratogenic and carcinogenic effects on offspring). Pregnancy despite postcoital contraception results in extrauterine pregnancy in 10% of patients. The most important reservations in evaluating publications on this subject are: 1) lack of control group; 2) estimation of pregnancy probability is not reliable because of study population used; 3) patient fertility cannot be ascertained; and 4) reliability of information provided by patient. Conclusion from literature studies is that postcoital hormonal contraception is of value but effectiveness is not proven. More research is needed and indications are that other less radical drugs may be found in near future.
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PMID:[Postcoital contraception]. 725 97

Postcoital contraceptives are available for adolescent use in the US. They include combination oral contraceptives (OCs), high dose estrogens, danazol, and IUDs. Mifepristone (RU-486) is currently not available in the US but is used in France, the UK, and Sweden. Postcoital contraception is especially important for adolescents who have a very high pregnancy rate due to poor contraceptive use. Administration of 2-5 mg ethinyl estradiol (EE) for 5 days beginning within 72 hours of unprotected intercourse yields pregnancy rates ranging from 0-0.92%. EE-related side effects include nausea, vomiting, sore breasts, and irregular menstrual bleeding. DES should not be used, since it is associated with reproductive tract anomalies and vaginal cancers in exposed offspring. Conjugated estrogens have not been used in adolescents for postcoital contraception. The Yuzpe regimen consists of 2 tablets of a combined OC with 200 mg EE and 2 mg dl-norgestrel administered within 72 hours of unprotected intercourse followed by the same dose 12 hours later. Common side effects are nausea and vomiting. Its pregnancy rate is 1.8%. Levonorgestrel-containing OCs can also be used. Administration of 800-1200 mg danazol up to 120 hours after unprotected intercourse protects against pregnancy in about 98% of cases. Copper IUDs have a high efficacy rate when used as postcoital contraception (99.9%), but public opinion, medicolegal considerations, financial costs, and potential for infection impede IUD as a postcoital contraceptive in the US. RU-486 is best known as an abortifacient. It is also a potential postcoital contraceptive. Two UK studies find that RU-486 used as a postcoital contraceptive has a very low pregnancy rate and fewer side effects than the Yuzpe regimen and danazol. It is much more costly than currently used postcoital contraceptives (600 mg of RU-486 cost US$ 68, while Ovral costs US$ 0.48-2.24). Nevertheless, RU-486 may replace the higher doses of OCs as a postcoital contraceptive method.
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PMID:Postcoital contraception: present and future options. 774 40

Adverse reactions to radiopharmaceuticals are comparatively few in number. Various estimates quote an incident rate of 1 to 6 reactions per 100,000 injections. Other figures quoted are 1 in 800 for the bone-seeking radiopharmaceutical methylene diphosphonate, and 1 in 400 for the lung visualisation agent macroaggregated albumin. The very low numbers of reported adverse effects probably reflect the tiny amounts of material which are used in the formulation of radiopharmaceuticals. Adverse reactions to radiopharmaceuticals are usually mild and transient and require little or no medical treatment. A few reactions involve respiratory or circulatory collapse or loss of consciousness. Several fatalities have been reported with the liver scanning agent 99mTc (technetium 99m)-albumin colloid. Clinical manifestations may be categorised under the headings of vasomotor effects i.e. faintness, pallor, diaphoresis or hypotension, and anaphylactoid effects such as nausea, dermographism, wheezing, bronchospasm, erythema and pruritus. The most prominent group of radiopharmaceuticals that have been reported to produce adverse events are the diphosphonates, which are used for scanning the skeleton. Typical diphosphonate reactions include erythema (especially over the extremities), nausea, vomiting and malaise. The onset of reaction is usually 2 to 3 hours after injection. The second group of radiopharmaceuticals which give rise to adverse events are the colloids, which are used for liver and spleen scintigraphy. Typical colloid reactions include pallor, nausea, flush and pulse changes. Adverse events may also occur as a result of the patient's medication interfering with the disposition of the radiopharmaceutical. Although not usually hazardous or dangerous, such events may be so pronounced that a marked deviation in the expected pharmacokinetics may occur. Drug interactions can be conveniently categorised under the headings of unusual handling of the radiopharmaceutical because of pharmacological action, genuine in vivo interaction between the medication and radiopharmaceutical, drug-induced disease and interaction between the radiopharmaceutical and catheters or syringes. The most serious drug interactions are those where the patient is taking cortisone or cytotoxic agents prior to tumour scintigraphy. Other important effects occur in patients undergoing bone scanning who are receiving iron preparations. Nifedipine has been reported to produce quite severe problems in scanning, including difficulties in the radiolabelling of red cells (for cardiac scintigraphy), and other effects where the drug appears to prevent the transport of bone-seeking materials into the skeleton. Many drugs alter hormonal status and these effects may produce marked deviations from the expected biodistribution. Diethylstilbestrol (stilboestrol), digitalis, gonadotrophins, phenothiazines and cimetidine all increase estrogen levels in high doses.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Adverse reactions and drug interactions with radiopharmaceuticals. 848 Dec 15

A review of oral contraceptives, their potency, side effects, and factors in the choice of preparation, is presented. The type of oral contraceptive regimen influences the patient's reactions toward the pill. The regimens, unequal in biological properties, efficacy and side effects include: combined pills, sequential pills, and continuous low-dose progestagens or luteal supplementation. If the assumed role of endocrine balance in the genesis of some side-effects is correct, relief should clearly be obtained by changing preparations. Side-effects from estrogen excess decrease with a switch to a less estrogenic preparation and so forth. Regarding initial choice of preparation, an approximation to an individual's steroid balance can be made by carefully examining her genital tract, and by inquiring about symptoms of increased sensitivity to endogenous steroids. Estrogen sensitivity are suggested by symptoms that include nausea, emesis gravidarum premenstrual and/or intermenstrual congestion and abundant discharge of mucous at time of ovulation. Sensitivity to progestagen are seen in excessive anabolic weight gain during previous pregnancies.
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PMID:Choice of oral contraceptives. 1227 80


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