Gene/Protein Disease Symptom Drug Enzyme Compound
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The purpose of prescribing combined oral contraceptives (OCs) is achievement of good cycle control and effective contraception with the least side effects, using an OC with the lowest possible dose of estrogen. Triphasil, Triquilar, Nordette, Microgynon 30, and Brevinor are good 1st choices because of the low estrogen dose (30-35 mcg). Women who probably cannot tolerate breakthrough bleeding and who need simple packaging should use a monophasic, more progestogenic OC, e.g., Nordette or Microgynon 30. Physicians should suggest a low dose estrogen and low dose antiandrogenic progestogen (OC) (e.g., Diane-35 ED) for women who have acne. They should advise patients that when they take OCs, their menstrual periods usually become shorter, regular, and lighter. Women need not take a break from OC usage. Vitamin C, antibiotics, griseofulvin, rifampicin, and anticonvulsants (except sodium valproate) interact with OCs. Women using warfarin and oral hypoglycemics and wanting to start using OCs need to consult their physician about changing requirements for warfarin and oral hypoglycemics. The effectiveness of OCs can be diminished by diarrhea and vomiting. Absolute contraindications to OCs include pregnancy, use during the first 2 weeks postpartum, history of thromboembolism, undiagnosed abnormal vaginal bleeding, focal migraine, coronary heart disease, steroid-dependent tumors, recent impaired liver function, and cardiovascular accidents. Some relative contraindications are older than 35 years old and smoking, breast feeding, and hypertension. This article provides a section on how to manage common side effects. For example, if the side effect is acne, the physician should prescribe an OC with increased estrogen and reduced progestogen (e.g., Triphasil/Triquilar to Biphasil/Sequilar). This article lists trade names of various OCs and their estrogen and progestogen doses, e.g., Nordette has 30 mcg ethinyl estradiol and 150 mcg levonorgestrel.
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PMID:Combined oral contraception. 147 9

A new form of postcoital contraceptive therapy is described as more effective because of reduced incidence of nausea, vomiting, and breast tenderness. Other forms of emergency contraceptive pills (ECPs) are the "Yuzpe" method or high-dose contraceptives. The new method calls for administration of 3 200-mg tablets of danocrine (Danazol) within 72 hours of unprotected intercourse and a second dose 12 hours later. There are mixed reviews of the efficacy of danocrine and ECPs. In one comparative study of ECP and danocrine use, efficacy of danocrine was greater but not significantly so. Another study found danocrine so ineffective that the study was halted. ECP use would not end unintended pregnancies caused by method failure unless it was condom failure. Estimates of ECP use involve 75% of the 1.7 million women with user or method failure, all 1.9 million women with unintended pregnancies from nonuse of contraceptives, and some of the 1.6 million abortion users. An obstacle to ECP use is lack of knowledge due to lack of Food and Drug Administration approval of Ovral and Danazol and physician concern for legal liability. Another obstacle consists in the logistics of obtaining ECPs and the fear of side effects. Provision of ECP kits with 3-5 regimens in clinic or physician offices is proposed for women without contraindications. Anticipated objections are reported to be encouragement of contraceptive risk taking, the health risks of repeated use, restrictions in Title X programs, and the drug effect on fertilization. Another proposal is to sell ECPs as over the counter drugs or in vending machines and changing US contraceptive prescription laws. Objections to elimination of the physician prescription requirement might be an increase in use among women with contraindications and a decrease in regular checkups and Pap tests. The objections could be overcome with proper package labeling. Paternalism is not a sufficient justification for requiring prescription of contraceptives and medical visits. ECPs, in fact, are already available as low dose contraceptives such as Lo/Ovral, Nordette, Levlen, Triphasil, and Tri-Levlen when 4 pills are used. Instructions for ECP use are given.
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PMID:Emergency contraceptive pills: a simple proposal to reduce unintended pregnancies. 148 31

At this time 3 triphasics are widely used in the US: Ortho-Novum 7/7/7, Tri-Norinyl, and Triphasil. Ethinyl estradiol is the preferred estrogenic agent for the triphasic products. Torethindrone and levonorgestrel were chosen as the progestins for the triphasic products. It is the combined effects of estrogen and progestin in the triphasics that provide their contraceptive action. Triphasil increases both the estrogen and the progestin at midcycle; Tri-Norinyl and Ortho-Novum 7/7/7 elevate the progestin only. The midcycle surges of estrogen and luteinizing hormone are dampened, and ovulation is inhibited. The triphasics represent a 98.7% reduction in total steroid content since oral contraceptives (OCs) were introduced. An estrogen dose of 30-50 mcg will inhibit ovulation, and side effects with such a dose are considered tolerable. The triphasic OCs are in this range. An estrogen dose of 20 mcg has been tested but is slightly less effective and is not recommended. Contraceptive failures have occurred with the triphasic products. In 1486 women studied, 6 pregnancies have occurred. Of these failures, one may have been because of a drug interaction with a barbituate. 1 pregnancy was due to patient failure; 3 consecutive pills were missed. Only 2 pregnancies were certain drug failures. Because of the gentle suppression of ovarian function, it has been observed that the menstrual flow is less affected than by standard OCs. Due to the fact that less total steroid is delivered and more endometrial shedding occurs, it is hoped that the triphasic preparations will have less of a "lingering" effect on the return to functional fertility. Most of the published data on side effects is available from the UK, North America, and Europe on the formulation known in the US as Triphasil. Nausea, vomiting, breakthrough bleeding, weight gain, and breast tenderness appear to be the most common side effects. The major medical reasons for triphasic discontinuation include breast tenderness, weight gain, breakthrough bleeding, nausea and vomiting, headache, and increased bleeding during the 1 week of withdrawal. Rifampin and phenobarbital are examples of drugs found to decrease pill efficiency, including triphasics. Also, a triphasic may interfere with the action of another drug. The new triphasics are appropriate when starting new patients on OCs. Patient counseling is essential. Due to the low margin of error as a consequence of lesser suppression of ovarian function, the patient needs to be well instructed in how to take the pill and advised of the consequences of missed tables.
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PMID:The triphasics: insights for effective clinical use. 382 67

This study was conducted to assess the efficacy of d-Norgestrel associated with Ethinylestradiol (Neogynon 21) as postcoital contraception and to report on the clinical experience obtained with this type of contraception. 323 women were treated during 72 h. period following unprotected intercourse. All subjects received 0,2 mg Ethinylestradiol and 1 mg d-Norgestrel (Levonorgestrel) in 2 equally divided doses 12 hours apart. - 1 mg Levonorgestrel was observed to be as effective as 2 mg of the racemic Norgestrel. PCC given during the first part of the cycle, shortened the latter in 80% of relevant cases. Nausea occurred in 30.3% of all patients; among these 14.2% also mentioned vomiting. Three pregnancies occurred of which only one could be attributed to method failure. The corrected failure rate is thus estimated at 0.3%.
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PMID:[Post-coital contraception using a combination of d-norgestrel and ethinyloestradiol]. 403 32

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

A double-blind, randomized controlled trial conducted at 21 centers in 14 countries compared the effectiveness and side effects of the traditional Yuzpe method of emergency contraception (200 mcg of ethinyl estradiol and 1 mg of levonorgestrel divided into 2 equal doses) and levonorgestrel alone (2 doses of 0.75 mg each). 1955 women (979 in the Yuzpe group and 976 in the levonorgestrel group) completed the study. 42 women had subsequent pregnancies, although at least 4 women were pregnant at the time of treatment. The pregnancy rate was 1.1% (95% confidence interval [CI], 0.6-2.0) for the levonorgestrel group and 3.2% (95% CI, 2.2-3.5) for the Yuzpe regimen. The relative risk of pregnancy was 0.36 (95% CI, 0.18-0.70). Levonorgestrel prevented 85% of expected pregnancies while the Yuzpe method prevented only 57%. Efficacy increased when the regimen was initiated within 24 hours and decreased as the time after unprotected intercourse approached 72 hours. Women in the levonorgestrel group reported less nausea, vomiting, dizziness, and fatigue than their counterparts in the Yuzpe group. Overall, 57% of women started bleeding within 3 days of their expected menses and the mean duration of menses of 4.7 days in both groups. Results of this study support use of levonorgestrel alone as an alternative for emergency contraception.
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PMID:Levonorgestrel versus the "Yuzpe" regimen. New choices in emergency contraception. 1009 1

Outlined is a protocol for the administration of emergency contraceptive pills. The indication for such treatment is unprotected intercourse within the past 72 hours. Absolute contraindications include the possibility of an existing pregnancy and a family history of stroke, heart attack, thrombophlebitis, breast or endometrial cancer, or liver tumor. Possibly excluded, depending on evaluation by a physician, are women with abnormal vaginal bleeding, active hepatitis, active gallbladder disease, high blood pressure, acute focal migraine, breastfeeding women, and those unable to understand instructions. The recommended regimen consists of six tablets of Ovral (two taken immediately, two more in 12 hours) or 12 tablets of Lo/Ovral, Nordette, or Levlen (four taken immediately, repeat dosage in 12 hours). The extra pills are to be used in cases of vomiting within three hours of pill ingestion. Women with a history of oral contraceptive-related nausea and vomiting should be provided with Compazine. Women should be informed that this method is effective in only about 92% of cases. All women who receive emergency contraception should be counseled that this is strictly a back-up method and helped to formulate a long-term birth control strategy.
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PMID:Emergency contraceptive pills (ECP) protocol. 1228 80

Women who do not have contraindications for oral contraceptives (OCs) and have experienced failure of their contraceptive method or used no contraceptive at all an use emergency postcoital contraceptive pills (ECPs). In fact, if used correctly, they could prevent 1.7 million unplanned pregnancies each year which is 50% lower than such pregnancies which already occur each year. They could also reduce the number of annual induced abortions by 50% from (1.6 million to 800,000). Various postcoital treatments in the US are 2 pills of Ovral within 72 hours of intercourse then 2 more pills 12 hours later and 4 pills of either Lo/Ovral, Nordette, Levlen, Triphasil, or Tri-Levlen followed by 4 more pills 12 hours later. Some gynecologists contend that any low-dose combined OC could be used as an ECP, but not study proves this. Besides, providers who do so risk a malpractice suit, because postcoital contraception is not on OC labels. An attorney suggests using OCs only for an emergency and to document all attempts at informed consent. Many children and clinicians have limited or no knowledge about ECPs. Those health providers who are familiar with them tend not to prescribe them because they fear legal actions. ECP side effects include severe nausea or vomiting, headache, breast tenderness,, dizziness, and fluid retention. These effects are not as great as the health risks of unplanned pregnancies, however. Yet, they are unpleasant enough to discourage repeated ECP use. Use of different methods of determining the number of pregnancies has resulted in broad ECP effectiveness rates (0-96% and 56-94%). Another analysis using combined data from the studies yielding the various results shows the effectiveness rate to be 75%. Anti-abortion groups may object to ECP use, just as they do for RU-486 which has fewer side effects, because one of its mechanisms of preventing pregnancy is it prevents implantation.
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PMID:Postcoital pills could cut unplanned pregnancies by half. 1231 83

Emergency contraception may avoid pregnancy after unprotected intercourse or when regular contraceptive measures fail. Levonorgestrel, a synthetic gestagen, is recommended for emergency contraception as a single 1.5-mg dose or, alternatively, two 0.75-mg doses taken 12 h apart. Its efficacy is moderate, preventing about 80% of pregnancies. Efficacy is higher the earlier after unprotected intercourse the drug is taken, but it may be administered up to 5 days post-coitum. Tolerance is similar to, or better than, those of other oral emergency contraceptives. Adverse effects include nausea, vomiting, headache, breast tenderness and transient alteration of menstrual bleeding pattern. It is not known whether levonogestrel increases the risk of ectopic pregnancy when the treatment fails. Its use as an ongoing contraceptive method is discouraged. When given before the preovulatory LH peak, levonorgestrel blocks or delays ovulation. It may also affect sperm migration in the female reproductive tract and have an effect on fertilization. Although it has been often postulated, there is no evidence for an anti-implantatory effect. Acquaintance with the method is quite variable among different societies, but it remains underutilized even where it is well known. Advance provision of the drug has been proposed as a way to promote its use. In clinical trials, advance provision did not adversely modify sexual or regular contraceptive behavior, but it did not reduce pregnancy or abortion rate either. Therefore, emergency contraception with levonorgestrel should be regarded as a backup method which is not a substitute for the continued use of more effective contraceptive methods.
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PMID:[Emergency contraception with levonorgestrel]. 1805 Dec 34