Incidence Of Gastrointestinal Side Effects Research Articles

Amoxicillin-potassium clavulanate: a novel beta-lactamase inhibitor.

Potassium clavulanate is a novel beta-lactamase inhibitor, which, in combination, expands the spectrum of amoxicillin to include many amoxicillin-resistant organisms. Potassium clavulanate is excreted 30-50 percent unchanged renally and its plasma time-course parallels that of amoxicillin. Several studies suggest that an increased incidence of gastrointestinal side effects may occur with this combination. In the current oral formulation, its greatest utility may be in pediatric infections due to beta-lactamase-producing Haemophilus influenzae and B. cattarhalis. In adults, the combination has not been adequately studied against other effective antibiotics.

Randomized trial of intracervical prostaglandin E 2 gel and intraamniotic prostaglandin F 2α for induction of second trimester abortion

For the purpose of reducing the side effects and complication rate when inducing second trimester abortion, intracervically administered PGE 2 gel was tested for the first time and compared with a single intraamniotic instillation of PGF 2α by a randomized allocation of 41 consecutive patients in the 13th to 24th week of gestation. In both groups the treatment was supplemented with oxytocin 5–6 hours after starting the induction. The methods proved of equal value as regards the abortion success rate and the induction-abortion interval, whereas the incidence of gastrointestinal side effects on intracervical application of PGE 2 gel was only half as high and the occurrence of diarrhea significantly lower (p < 0.05) with this non-invasive method than with intraamniotic PGF 2α. Intracervical PGE 2 gel also possessed other advantages, being int. al. more acceptable by the patients and technically easier to administer.

Studies of the Interaction of Betacyclodextrin with Ampicillin, Methicillin and Phenytoin

AbstractThe interaction of betacyclodextrin with ampicillin, methicillin and phenytoin has been investigated. All three drugs, (in the unionized form) interact strongly with betacyclodextrin. It is suggested that the interaction of all three drugs with betacyclodextrin could perhaps be exploited to pharmaceutical advantage. For ampicillin it is possible that the complex may have an improved bioavailability and a reduction in the incidence of gastro-intestinal side effects in comparision with the uncomplexed drug. For methicillin the significant extension of the hydrolytic half life for the complex makes the oral route a possibility for this drug, which is normally given intravenously because of stability problems. The interaction of phenytoin with betacyclodextrin produces a complex with a substantially enhanced solubility likely to give greatly improved bioavailability and a reduction in intra and inter subject blood level variation.

The vaginal administration of 9-Deoxo-16,16-dimethyl-9-methylene PGE2 for second trimester abortion

9-Deoxo-16,16-dimethyl 9-methylene PGE2 was given as a vaginal suppository at 0 and 8 hours to 37 patients. Two different doses were given, a 75-mg and 60-mg dose. The larger dose achieved an 86% abortion rate at 24 hours and for the smaller dose it was 53%. When an intramuscular injection of 15-methyl PGF2 alpha Tham was added at 24 hours, the success rate was 91% and 80% at 36 hours. The incidence of gastrointestinal side effects were significantly reduced when compared to vaginal administration of either PGE2 or 15-methyl PGF2 alpha methyl ester. The incidence of temperature elevation was similar to that achieved with the use of vaginal PGE2 but higher than with the use of vaginal 15-methyl PGF2 alpha methyl ester.

Use of intramuscular prostaglandin for failure of mid-trimester abortion by another method

Eight investigators, using a common protocol, studied the use of intramuscular (15S)-15-methyl prostaglandin F2α to abort midtrimester pregnancies which had failed treatment by other methods in 398 cases. Results of treatment of 3 subgroups, defined by reason for primary treatment failure, are presented. The combined efficacy rate was 96.2% with 79.6% of the abortions being complete. The mean time from starting intramuscular therapy to successful abortion was 7.35 hours. The incidence of gastrointestinal side-effects was lower than that previously reported for systemically administered prostaglandins. Serious complications were not appreciably different from those reported for commonly used methods of second trimester abortion except for a slightly higher incidence of excessive bleeding requiring blood replacement. Advantages of this method over currently used methods of treating failures of primary attempts to induce midtrimester abortion by pharmacologie means are discussed.

Analysis of a study of menses induction using a vaginal suppository containing 3.0 mg 15(S)-15-methyl-PGF2α methyl ester

Peripheral blood levels of 15-methyl-PGF2α, human chorionic gonadotropin (hCG) and progesterone were determined in patients treated for the induction of menses with a single vaginal suppository containing 3.0 mg 15(S)-15-methyl-PGF2α methyl ester. The mean blood levels of 15-methyl-PGF2α were higher in the successful cases than in the failures or in cases that were defined as partial successes. The plasma level of 15-methyl-PGF2α increased faster in the successful cases than in the failure cases, and was maintained at elevated levels longer in the successful cases than in the partially successful cases. Serum concentrations of hCG declined following treatment in both the successful and unsuccessful cases. At the follow-up visit (approximately 2 weeks after treatment), the level of hCG was significantly lower in the successful cases than in the unsuccessful cases. Serum concentrations of progesterone did not change significantly in any of the groups during the first 10 hr after treatment. However, at the follow-up visit the concentration of progesterone in the successful cases was significantly lower than in the failure cases. A larger percentage of the patients in whom menses was successfully induced had gastrointestinal side effects than patients who were considered treatment failures. This analysis has demonstrated a distinct relationship between blood levels of 15-methyl-PGF2α and the efficacy of these vaginal suppositories for menses induction. The successful induction of menses was associated with a more rapid increase in the plasma concentration of 15-methyl-PGF2α and with mean concentrations of drug that were significantly higher than in the cases that were considered failures. The higher blood levels of drug were also associated with a higher incidence of gastrointestinal side effects. The experience accumulated to date indicates that a vaginal delivery system for 15(S)-15-methyl-PGF2α methyl ester that releases the drug faster and in a more predictable fashion than the vaginal suppository is required for the successful induction of menses.

How many oral iron preparations does a prescriber need?

There are at least 40 oral iron preparations available to the prescriber; some contain iron alone, others have in addition haematinics, vitamins or substances claimed to promote iron absorption. For many there are optimistic claims concerning the incidence of gastro-intestinal side effects.

Termination of second trimester pregnancy with intramuscular administration of 16 phenoxy-ω-17,18,19,20 tetranor PGE 2 methylsulfonylamide

A new prostaglandin analogue, 16 phenoxy-ω-17,18,19,20 tetranor PGE 2 methylsulfonylamide was used for the termination of second trimester pregnancy in 60 patients. The drug was injected intramuscularly in doses of 0. 5 mg 4 hourly, 1 mg 8 hourly or 1 mg 6 hourly for a maximum of 36 hours. Fifty five patients aborted. The incidence of gastrointestinal side effects was low and there were no complications.

Midtrimester Abortion With Prostaglandin and Hypertonic Saline—A Comparative Study

This study was conducted in Baroda, India, to evaluate and compare the safety and effectiveness of intraamniotic prostaglandin F2alpha (PGF2alpha) and 20% saline augmented with intravenous oxytocin for terminating 200 pregnancies of 14 to 20 weeks' gestation. While there was no method failure among the group treated with saline, ten method failures were reported for patients treated with the PGF2alpha. The rate of incomplete abortions was significantly lower for the group treated with saline (19.4%) than it was for the group treated with the PGF2alpha (33.7%). The administration of oxytocin after fetal expulsion did not reduce the rate of incomplete abortion. The mean instillation-to-abortion time was significantly lower with saline than with PGF2alpha. The incidence of gastrointestinal side effects and excessive bleeding (less than 200 ml) during the procedure was significantly higher for patients treated with PGF2alpha than for those treated with saline.

Administration of prostaglandins by various routes for induction of abortion merits and demerits

Prostaglandin F 2α and its methyl analogues were used for induction of abortion in 598 patients with gestational age from 9 to 20 weeks. Different routes of administration were studied and varous dosages given. The incidence of gastrointestinal side effects were within acceptable range for all methods. Both intra-amniotic injections of 50 mg PGF 2α and 2.5 mg 15-methyl PGF 2α as well as intramuscular and vaginal administration of 15-methyl PGF 2α or its methyl ester, respectively, were highly effective in termination of pregnancy. The intramuscular route was, however, associated with the highest frequency of gastrointestinal side effects. If both efficacy and side effects were taken into consideration, the intra-amniotic and vaginal routes were superior. The ease of administration as well as the applicability over a wider range of gestation in termination of pregnancy may, however, in many situations speak in favour of the repeated vaginal administration of 15-methyl PGF 2α methyl ester.

The Menstrual Regulation Procedure

Menstrual regulation is the induction of uterine bleeding that has been delayed up to 14 days from its anticipated date of onset. MR can be accomplished mechanically and through the administration of drugs. By far the most common method of performing menstrual regulation is by mini-vacuum aspiration. Induction of delayed menstruation through prostaglandin compounds initially appeared promising but was associated with a high and unacceptable incidence of gastrointestinal side effects. Although the use of estrogens and progesterones to induce delayed menstruation has been a common practice, these drugs not only are ineffective, but they are also potentially dangerous to both the woman and her offspring (Vengadasalam et al., 1976, 1977). New analogs are constantly under investigation, especially those having the potential for self-administration, but at this time they offer no advantages over vacuum aspiration. Menstrual regulation by vacuum aspiration is generally performed as an outpatient procedure, without anesthesia, using relatively simple and inexpensive equipment. It is frequently performed without a positive pregnancy test during the interval before conventional pregnancy testing is reliable (the first two weeks after a missed menstrual period). This technique has achieved international acceptance as an uncomplicated, safe, and effective method of inducing uterine bleeding irrespective of the cause of the delay.

Oral Prostaglandins E2 and F2a in the Induction of Labour

Summary: Oral prostaglandins E2 and F2a were used to augment amniotomy in the induction of labour in 173 patients. The success rate was significantly higher with prostaglandin E2 than with prostaglandin F2a (89% and 75%, respectively). This was achieved despite a significantly lower incidence of gastrointestinal side effects. No serious maternal or fetal complications occurred with either drug. It is concluded that oral prostaglandin E2 is more efficient than oral prostaglandin F2a in the induction of labour.

Development of a vaginal suppository suitable for single administration for interruption of second trimester pregnancy

Extra- and intra-amniotic administration of prostaglandins are accepted methods for interruption of second trimester pregnancy. However, an equally effective nonsurgical method would give important advantages especially for large scale programs. Repeated vaginal administration of suppositories containing either 15-methyl PGF 2α methyl ester or 16,16-dimethyl PGE 2 has been effective in inducing abortion during the first and second trimesters of pregnancy. By using different bases for the suppository and different amounts of 15-methyl PGF 2α methyl ester, a long-acting vaginal suppository has been developed. Recording of uterine contractility and measurement of plasma concentration showed sufficient release of 15-methyl PGF 2α methyl ester for 12 to 24 hours. One suppository containing 3.0 to 3.5 mg 15-methyl PGF 2α methyl ester in 2.2 or 2.5 g of the base Witepsol E-76 was given to 25 second trimester patients. Twenty-three patients (92%) aborted within 24 hours following one suppository. The mean induction-abortion interval was 12.4 hours. The abortion process was completed in the remaining two patients by one to three intramuscular injections of 15-methyl PGF 2α. The incidence of gastrointestinal side effects was low. The mean frequency of vomiting and diarrhea per patient was 1.7 and 0.7, respectively. The results of this single dose vaginal suppository has been encouraging and appears to be an important break-through in the research for an ideal abortifacient.

Induction of Labour Using Oral Prostaglandin E2 Tablets

Labour was induced in 91 patients by means of low amniotomy and an escalating dose of oral prostaglandin E2 tablets* up to a maximum dose of 1.5 mg hourly. This regime led to vaginal delivery in 91.2% of patients. The induction delivery interval was 11.2 ± 4.9 and 7.5 ± 4.5 hours for primiparous and multiparous patients respectively. The incidence of gastrointestinal side-effects was 15.4%, with 6 patients being unable to tolerate the regime. It is suggested that a higher hourly dose is necessary for primiparous patients with a low Bishop score.

Cervical dilatation with prostaglandin analogues prior to vaginal termination of first trimester pregnancy in nulliparous patients

Dilatation of the cervix with prostaglandin analogues prior to vaginal termination of pregnancy was attempted in 125 nulliparous women in the first trimester of pregnancy. The patients were divided into five groups (25 in each group) and given a single extra-amniotic dose of one of the following prostaglandin analogues 14–16 hours prior to the evacuation of the uterus by vacuum aspiration. (Group A) 15 (S) 15 methyl PGE 2 (free acid); (Group B) 15 (S) 15 methyl PGE 2 methyl ester; (Group C) 15 (S) 15 methyl PGF 2α (free acid); (Group D) 15 (S) 15 methyl PGF 2α methyl ester and(Group E) a mixture of 15 (S) 15 methyl PGE 2 methyl ester and 15 (S) 15 methyl PGF 2α methyl ester. Evacuation of the uterus without mechanical dilatation of the cervix was possible in 111 (90%) of the patients. In an additional 10 patients (8%) there was some degree of cervical dilatation and further mechanical dilatation could be performed easily. With the combination of 15 (S) 15 methyl PGE 2 methyl ester and 15 (S) 15 methyl PGF 2α methyl ester the incidence of gastrointestinal side effects and pyrexia were considerably reduced.

Intravenous hyperalimentation as an adjunct to cancer chemotherapy with 5-fluorouracil

In a series of 30 male Sprague-Dawley rats fed orally, the LD-80 dosage of 5-FU was determined to be 15 mg/kg/day for 7 days. When this dosage was given to a series of rats nourished entirely parenterally by intravenous hyperalimentation, there was a lower incidence of gastrointestinal toxicity, and the mean survival rate was twice that obtained in the orally fed group. In a pilot series of 10 cachectic human beings with metastatic adenocarcinoma of the colon, who were treated simultaneously with 5-FU and intravenous hyperalimentation, the incidence of gastrointestinal side effects was significantly reduced, tolerance to 5-FU per unit time was doubled, and response rate (50% reduction in measurable tumor mass) was 40%, which is greater than that usually reported in comparable patients fed by mouth.

The Relative Merits of a Slow-Release and a Standard Iron Preparation during Pregnancy

SummaryA comprehensive study was carried out in 248 pregnant women between a once-daily slow-release preparation of ferrous sulphate/folic acid (105 mg. elemental iron) and a twice-daily standard tablet preparation of ferrous fumarate/folic acid (80 mg. elemental iron per day). The slow-release iron preparation led to significantly higher serum levels at the end of pregnancy and to marginally higher haemoglobin levels. The incidence of gastro-intestinal side-effects caused by this preparation, however, was significantly higher.

Abortifacient action of orally administered 16, 16 dimethyl prostaglandin E 2 and its methyl ester

16, 16 dimethyl Prostaglandin E 2 (Free acid and methyl ester) administered orally have a stimulant effect on the pregnant human uterus. Pregnancy was terminated in twelve out of twenty women by two hourly oral doses of 100μg of these analogues The relatively high incidence of gastrointestinal side effects — nausea, vomitting and diarrhoea — would tend to limit the usefulness of orally administered 16, 16 dimethyl PGE 2 and its methyl ester as abortifacients.

The induction of midtrimester abortion with intra-amniotic prostaglandin F2α: A single-dose technique

30 healthy women between 14-37 and between 14-20 weeks' gestation were administered with a single injection of 40 mg of PGF2 alpha over a 5 minute period to induce abortion. 28 patients aborted within 48 hours; 14 aborted completely and 14 required surgical removal of the placenta; 1 patient required intravenous oxytocin, and 1 failed to abort within 48 hours. The mean instillation to abortion interval for multiparas was 18.6 hours, for nulliparas it was 32.2 hours. Only 1 patient had excessive bleeding, 3 had syncopal episodes, 9 experienced vomiting, 3 diarrhea, and 3 diarrhea, nausea, and vomiting. A single injection of PGF2 alpha seems superior to intraamniotic hypertonic saline solution administration alone, and is effective as administration of hypertonic saline and intravenous oxytocin. The multiple dose technique of PG administration does reduce the mean abortion time, but entails an increased incidence of gastrointestinal side effects and requires repuncture or the use of an indwelling catheter, which may increase the incidence of infection. The mode of administration described can be used in selected patients when hypertonic saline solution is contraindicated.

Response of the midpregnant human uterus to systemic administration of 15(S)-15-methyl-prostaglandin F 2α

The contractile response of the midpregnant human uterus to a new prostaglandin analogue, 15(S)-15-methyl-prostaglandin F 2α (15-me-PGF 2α), was investigated and compared to the effect of natural prostaglandin F 2α (PGF 2α). It was found that the threshold dose of 15-me-PGF 2α was around 10 μg, when given as a single intravenous injection, which is approximately 1/10th of the corresponding dose of PGF 2α. It was also found that higher intravenous doses of 15-me-PGF 2α resulted in a uterine response of longer duration than that following PGF 2α. Intramuscular injection of the analogue at doses of 1.0–1.5 mg induced a marked uterine stimulation sustained for 5–7 hours without causing local reaction. Intravenous infusion of 5μg/min of 15-me-PGF 2α stimulated a level of uterine activity equivalent to that of 75 μg/min of PGF 2α. The incidence of gastro-intestinal side-effects was the same in the two treatment groups. However, there seemed to be a tendency toward a significantly higher abortion rate with the analogue.