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Biotransformation of the ipecac alkaloids cephaeline and emetine from ipecac syrup in rats.

The metabolism of cephaeline and emetine, which are the primary active components of ipecac syrup, were investigated in rats. Cephaeline-6'-O-glucuronide was found to be a biliary metabolite of cephaeline. Cephaeline (6'-O-demethylemetine) and 9-O-demethylemetine were observed to be enzyme-hydrolyzed biliary metabolites of emetine. Cephaeline was conjugated to glucuronide, while emetine was demethylated to cephaeline and 9-0-demethylemetine, and may be conjugated to glucuronides afterwards. Urine, feces and bile were collected from rats within 48 hours following the administration of ipecac syrup containing tritium (3H)--labeled cephaeline or emetine. Metabolites were separated and quantified by thin layer chromatography (TLC) or high-performance liquid chromatography (HPLC). Biliary and urinary excretion rates of 3H-cephaeline were 57.5% and 16.5% of the dose, respectively. Cephaeline-6'-O-glucuronide was comprised 79.5% of biliary radioactivity and 84.3% of urinary radioactivity. Unchanged cephaeline was detected in 42.4% of the dose in feces. Biliary excretion rate of 3H-emetine was 6.9% of the dose. Emetine, cephaeline and 9-0-demethylemetine comprised 5.8%, 43.2% and 13.6% in hydrolyzed bile, respectively. There were no emetine-derived metabolites in urine or feces. The occurrence of unchanged emetine was 6.8% and 19.7% of the dose in urine and feces, respectively.

Animals↗
PubMed2003

Evaluation of the time frame for home ipecac syrup use when not kept in the home.

INTRODUCTION: The home administration of ipecac syrup remains a recommendation in some guidelines for the management of specific pediatric poisonings. A common challenge for poison specialists is how to approach the situation when ipecac syrup is indicated but not kept in the home. This study examines whether or not ipecac syrup can be administered and produce timely emesis in this situation. METHODS: Over a 6-month period, a prospective observational study was undertaken to determine if ipecac syrup can be administered in a timely manner when it is indicated but not available in the home. Cases where ipecac syrup was indicated but not kept in the home were included if parents stated that they could obtain ipecac within 15 minutes. Timely administration and the onset of emesis were defined as < 30 min and < 60 min, respectively. RESULTS: During our study 14,603 human exposures were evaluated; ipecac syrup was recommended by a poison specialist in 75 cases, and 25 of these were included in our study. Ages ranged from 1 to 6 years. The mean time to administration of ipecac from exposure time was 40 min (SD +/- 14 min). Administration of ipecac syrup occurred in < 30 min in 20% of the cases. The mean time to first emesis from exposure was 58 min (SD +/- 13). Initial emesis occurred in < 60 min in 36% of the cases. CONCLUSIONS: Ipecac syrup was rarely recommended by our center and was frequently unavailable when it was recommended. Ipecac syrup often could not be administered in a timely manner because it was not kept in the home. Parents of pediatric patients who have a significant ingestion should not be referred to purchase ipecac syrup.

Child↗
PubMed1994

Effect of zatosetron on ipecac-induced emesis in dogs and healthy men.

Serotonin receptor (5-HT3) antagonists provide effective antiemetic therapy in cancer patients receiving emetogenic chemotherapy, such as cisplatin. Animal studies have shown that 5-HT3 receptor antagonists also have antiemetic activity in ipecac-induced emesis. The authors investigated the antiemetic activity of zatosetron maleate, a 5-HT3 receptor antagonist, on ipecac-induced emesis in dogs and healthy men. They also evaluated the effect of ipecac administration on serotonin release and metabolism by measuring urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion in healthy men. In separate randomized, placebo-controlled trials, 20 dogs received zatosetron intravenously and eight healthy men received zatosetron (50 mg) orally, followed by ipecac syrup. In both trials, emetic response to ipecac was recorded, including the number and time of vomits and retches. Zatosetron treatment inhibited and delayed ipecac-induced emesis in both groups. In dogs, zatosetron inhibited ipecac-induced emesis in a dose-dependent manner with a 100-micrograms/kg dose producing complete inhibition. In men, zatosetron administration resulted in fewer emetic episodes after ipecac than had occurred with placebo administration (P = .03); vomiting was completely inhibited by zatosetron. In men, ipecac administration did not affect the urinary 5-HIAA/creatinine ratio (mg/g) or 5-HIAA excretion rate (microgram/hour). Our study demonstrates that zatosetron has similar efficacy on ipecac-induced emesis in healthy men, as has been shown previously with other 5-HT3 receptor antagonists in chemotherapy-induced emesis in cancer patients. We did not observe the increase of urinary 5-HIAA in our study with ipecac-induced emesis, however, as has been described previously in cisplatin-induced emesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

The effect of providing ipecac to families seeking poison-related services.

Although home availability of ipecac is recommended for families with young children in case of unintentional toxic ingestion, fewer than half actually have it. We designed a study to evaluate the efficacy of providing ipecac to families requiring poison-related services. Families (n = 100) contacting the Children's Memorial Hospital (CMH) emergency department (ED)/poison center were enrolled. Baseline general poison knowledge and self-report of ipecac availability were obtained. Ipecac was discussed, and families were mailed general safety and poison information, the ED telephone number, and a coded package of ipecac, with instructions. Approximately three months later a follow-up call was made to determine change in knowledge, access to our ED (or any poison center) phone number, and availability of ipecac. Initially 71% had heard of ipecac, 51% knew what it did, and 47% said they had it. Ninety families were contacted in follow-up, 82 by phone and eight by mail. Eighty-three of 90 (92%) knew what ipecac did (vs 51/100 initially; P < 0.0001). Sixty-eight of 90 (76%) knew the ED or a poison control phone number (vs 39/100 initially; P < 0.0001). Seventy-seven of 82 (94%) reached by phone read the ipecac code number (vs 47/100 initial self-reports of possession; P < 0.0001). The data indicate that providing ipecac to poison service users increases availability in the home for at least three months. Poison service users may be particularly amenable to anticipatory guidance and interventions related to poisoning prevention and preparedness.

Adult↗
PubMed1985

Risk assessment of ipecac in the home.

To determine how frequently parents give ipecac syrup without medical consultation and what complications result from this practice, 8 months of telephone calls to a regional poison center for poisonings of children less than age 6 years (23,790 calls) and 3 years of medical records for children's poisonings from 21 hospitals (516 cases) were studied. The practice of using ipecac syrup without consultation ranged from 0.4% of poison center callers to 6.0% of hospital patients. Of the 137 parents who gave ipecac without consultation, only 4% gave ipecac syrup for a poisoning exposure for which its use was contraindicated. In one of these cases did medical complications such as aspiration, seizures, or gastrointestinal burns result. Hence, the practice of giving children ipecac syrup without medical advice was found to be relatively infrequent and rarely produced complications. The study pointed out the importance of educating parents about products for which ipecac syrup is contraindicated and about occasions when ipecac is unnecessary. In 61% of cases of poisonings, the parent gives ipecac before calling the poison center and learning that the child did not need the Ipecac. The study also suggested that improvements are needed in warning labels of particular products, and revisions and standardization of the labels found on different brands of ipecac syrup are essential for appropriate emergency care.

Accidents, Home↗
PubMed1985

Nonemetic effects of ipecac syrup.

The aftereffects of home-induced emesis with ipecac syrup were determined by telephone interviews of callers to a poison center. During the 12-week study, the presence of any symptoms at follow-up in 146 patients was compared with findings in 99 callers to the poison center who did not receive ipecac. Within four hours after ipecac-induced emesis, 33.6% had no symptoms and 17.1% experienced protracted emesis. In the ipecac-treated group the incidences of one formed stool (4.1%) and lethargy during a typical sleeping time (42.5%) were not significantly different from the incidences in patients not receiving ipecac syrup. The incidences of diarrhea (13.0%) and atypical lethargy (11.6%) were higher (P less than .025 and P less than .05, respectively) after ipecac-induced emesis than in patients not receiving ipecac syrup. There was no significant statistical association between the propensity of the ingested toxin to produce diarrhea or lethargy and the occurrence of diarrhea or atypical lethargy. Because ipecac-induced emesis can produce diarrhea and lethargy, these side effects should be noted and differentiated from normal conditions when ipecac syrup is administered.

Adolescent↗
PubMed1987

Effectiveness of 15-mL versus 30-mL doses of syrup of ipecac in children.

The rates at which 15- and 30-mL doses of syrup of ipecac induced emesis within 30 minutes were evaluated in pediatric patients treated for accidental poisoning. A two-year prospective study was conducted to collect data on 4306 pediatric patients (aged one to six years) who received syrup of ipecac to treat accidental poisoning. Patients received either 15-mL (during 1983) or 30-mL (during 1984) doses of syrup of ipecac and 120-240 mL of water or clear liquid. Time of administration and time of the first episode of emesis were reported by the person administering the syrup of ipecac; the difference between these times was recorded as the time to emesis. Successful emesis was defined as emesis within 30 minutes after ipecac administration, while failure was defined as emesis occurring more than 30 minutes after administration. Success and failure rates were compared using chi-square analysis. Syrup of ipecac 15 mL was administered to 1905 patients, resulting in a failure-to-produce-emesis rate of 8.82% (168 patients). Syrup of ipecac 30 mL was administered to 2401 patients, resulting in a 0.08% failure rate (two patients). A repeat dose of ipecac syrup in the 15-mL group yielded a 99.74% success rate, which was not significantly different from the 99.96% success rate after a single dose of 30 mL. Although syrup of ipecac dosing in pediatric patients is controversial, our data suggest that increasing the standard pediatric dose from 15 to 30 mL significantly reduces the emesis failure rate.

Child, Preschool↗
PubMed1981

Ipecac syrup for poisonings at home: availability, compliance, and response monitored by telephone.

Ipecac syrup administration at home, following advice by a poison center, was evaluated with respect to the availability of ipecac syrup, length of storage time, compliance with recommended procedures for administration, and time for emetic response. In a three-month period, staff pharmacists of the center completed a survey from when they advised 60 callers to administer ipecac syrup at home. Two follow-up phone calls were made to collect additional data. Fifty-five callers provided adequate data for analysis. Ipecac syrup was available at home for 36%, from a pharmacy for 53%, and from a neighbor for 11% of the callers. Compliances with the recommended doses of ipecac syrup and fluids (+/- S.D.) were 92 +/- 20% and 71 +/- 29%, respectively. Following one dose of ipecac syrup, 86% vomited in 19 +/- 8 minutes; after a second dose, 13% responded in 34 +/- 21 minutes after the first dose. By comparison with those who had ipecac syrup at home, there was an insignificant delay in administration when it was obtained from a neighbor; a significant delay (p less than 0.005) occurred when it was obtained by a pharmacy. The onset of emesis did not correlate with the length of time the ipecac syrup had been stored at home. The findings support the use of ipecac syrup at home based on ready availability, adequate compliance, and rapid emetic response.

Child↗
PubMed1985

Ipecac administration in children younger than 1 year of age.

The efficacy of ipecac syrup in the induction of emesis and safety of its administration was studied in 105 poison-exposed infants 6 through 11 months of age (study subjects) and compared prospectively with 302 poison-exposed infants and children 12 through 35 months of age who served as age controls. Of the 105 study subjects 101 (96.2%) vomited. The failure of ipecac to induce emesis in six patients (four of 105 study subjects two of 302 age control subjects) is comparable with ipecac failure rates reported elsewhere. The frequency of side effects caused by ipecac syrup did not differ between study and control subjects. There were no serious medical complications resulting from the administration of ipecac syrup. When not readily available at home, ipecac administration was delayed an additional 21.8 minutes if obtained from a pharmacy and 38.4 minutes if obtained from an emergency department. Because of the time delay and the increased health care cost, home rather than emergency department administration of ipecac should be advised. These data demonstrate that ipecac syrup effectively induces emesis and is safe for home administration to poisoned infants 6 to 11 months old.

Age Factors↗
PubMed1986

Syrup of ipecac availability: before and after a poisoning.

A retrospective review was conducted of 1,230 human poison exposures in which syrup of ipecac was administered to determine the availability of this emetic. Ipecac was available in 41.1% of the homes, while 42.5% obtained it from the pharmacy. Eight and two tenths percent were referred to a health care facility, 2.9% obtained ipecac from a neighbor, 2.3% went to an emergency room prior to calling the poison center, and 3% obtained ipecac from other sources. A randomly selected sample of 150 of these 1,230 cases were contacted 6 months after their initial call to the poison center to determine any changes in the availability of syrup of ipecac in the home. Although almost 30% more homes had syrup of ipecac than previously, 22.2% of homes still did not have ipecac available, despite the previous poisoning experience. Greater effort should be made during follow-up to educate the public regarding ipecac and its use.

Drug Utilization↗
PubMed1983

Comparison of activated charcoal and ipecac syrup in prevention of drug absorption.

The efficacy of activated charcoal and ipecac syrup in the prevention of drug absorption was studied in 6 healthy adult volunteers, using a randomized, cross-over design. Paracetamol 1000 mg, tetracycline 500 mg and aminophylline 350 mg were ingested on an empty stomach with 100 ml water. Then, after 5 or 30 min, the subjects ingested, either activated charcoal suspension (50 g charcoal), syrup of ipecac, or, only after 5 min, water 300 ml. Activated charcoal, given either after 5 or 30 min, significantly (p less than 0.01 or less 0.05) reduced the absorption of these 3 drugs measured, for example as AUC0-24 h. Syrup of ipecac caused emesis on each occasion, with a mean delay of 15 min. When ipecac was given 5 min after the drugs, its effect on absorption was significant, but when it was given after 30 min only the absorption of tetracycline was reduced. Activated charcoal was significantly (p less than 0.05) more effective than ipecac in reducing drug absorption when given at the same time points. In cases of acute intoxication, depending on the quality and quantity of the drugs ingested, the relative efficacy of charcoal and ipecac may be somewhat different from that observed in the present study. Despite its emetic action, however, ipecac syrup is not very effective in preventing drug absorption and, in general, activated charcoal should also be given after induced emesis or gastric lavage.

Acetaminophen↗
PubMed1993

Evaluation of gastric emptying using radionuclides: gastric lavage versus ipecac-induced emesis.

STUDY OBJECTIVES: To compare the efficacy of gastric lavage and ipecac-induced emesis by using a radionuclide marker in a simulated overdose and to determine the amount of material recoverable after lavage fluid appears clear. DESIGN: Case-control, prospective cross-over study. SETTING: Nuclear medicine department of Valley Medical Center, Fresno, California. TYPE OF PARTICIPANTS: Fourteen male and five nonpregnant female adult volunteers with no pre-existing gastrointestinal disease and no medication use. INTERVENTIONS AND MEASUREMENTS: In phase 1, each volunteer ingested 30 capsules labeled with a measured amount of Tc99m with 75 mL H2O followed in five minutes by ipecac-induced emesis. In phase 2, two to four weeks later, each subject was lavaged after ingesting 30 labeled capsules. After lavage appeared clear, a 1,000-mL supplemental lavage was done and analyzed separately. All emesis or gastric lavage fluid was collected and measured for tracer activity. RESULTS: All subjects in the ipecac group vomited with an average time from ipecac to emesis of 19 minutes. Two subjects withdrew from the study, refusing to complete lavage due to discomfort. Based on retrieved material, ipecac-induced emesis returned significantly more tracer (mean +/- SD, 54.1 +/- 21.3%) than lavage until clear (mean +/- SD, 30.3 +/- 17.4%) (P = .0021). Supplemental lavage returned 12.9% of the total recovered marker (SD, 11.6%). The total of initial and supplemental returns from lavage was 35.5% (SD, 21.0%). This return was significantly less than that returned by ipecac-induced emesis (P = .016). CONCLUSION: In this study, ipecac-induced emesis was significantly more effective than gastric lavage in emptying the stomach after simulated overdose. Significant amounts of ingested material are recoverable in gastric lavage return after it appears clear.

Adult↗
PubMed1977

Toxicology of ipecac: a review.

The general effectiveness and safety of Ipecac syrup, per se, has not been questioned, but rather an attempt has been made to consolidate pertinent literature dealing with the toxic manifestations of Ipecac fluid extract. Ipecac contains both emetine and cephaeline and the toxicity of Ipecac fluid extract is consistent with reports on the toxicity of both compounds. The majority of the work has involved emetine since it is in higher concentration in Ipecac fluid extract than is cephaeline. Comparison of the clinical picture presented in syrup or fluid extract of Ipecac overdose and emetine toxicity in amebiasis treatment permits us to summarize the general characteristics of Ipecac alkaloid toxicity as involving primarily gastrointestinal, cardiovascular, and neuromuscular foci.

Adult↗
PubMed1993

Ipecac abuse in a sample of eating disordered outpatients.

Eight hundred fifty-one consecutive outpatients presenting at a suburban eating disorder clinic were evaluated for current or past ipecac abuse. A percentage (7.6%) of all subjects reported some use or experimentation with ipecac for purging; 4.7% had experimented with it briefly; 3.1% (8.8% of subjects meeting criteria for bulimia) had chronically abused ipecac; and 1.1% (1.5% of subjects meeting criteria for bulimia) were regularly abusing ipecac at the time of intake. Chronic ipecac abusers were more likely to have been hospitalized. Subjects who experimented briefly with ipecac had a longer duration of illness. Both chronic ipecac abusers and experimenters were more prone to abuse other substances for purging and to report alcohol abuse in an immediate family member.

Adolescent↗
PubMed1999

Trends in ipecac use: a survey of poison center staff.

The steady decline in syrup of ipecac used by poisoned victims from a peak of 15% in 1985 to 2.3% in 1995 is of concern. A survey compared syrup of ipecac use by CSPI, ABAT, and ABMT/ACMT members as the first response decontamination. The survey asked CSPI, ABAT, and ABMT/ACMT members their professional opinion on the use of syrup of ipecac in a potentially toxic ingestion. The scenario was "Your 2-y-old child/grandchild accidentally ingested a potentially lethal dose of poison (i.e. colchicine) 5 min ago and you have syrup of ipecac at home. Would you consider using it?" Of the 171 CSPI's who responded, 34.5% favored the use of syrup of ipecac while 63% were against and 2.3% needed more information. Of the 26 ABAT's who responded, 50% favored it's use, 42.3% would not and 7.6% needed more information. From the 55 ABMT/ACMT members who responded, 81.8% would use ipecac while 18.1% would not. ABMT/ACMT members favored the use of syrup of ipecac in this scenario (P < 0.005), while the CSPI's did not (P < 0.005), and the ABAT's did not have statistical difference. With CSPI's providing the treatment recommendations from poison centers, it is important that ABMT/ACMT members influence the recommended treatment protocols.

Child, Preschool↗
PubMed1998

Rapidly reversible cardiomyopathy associated with chronic ipecac ingestion.

Ipecac, an over-the-counter emetic agent, has been a drug of choice for abuse by patients with eating disorders. Its alkaloid emetine has been associated with serious cardiac toxicity; however, the dose effect has not been well established. We present a patient with anorexia and bulimia nervosa who ingested ipecac chronically and developed the characteristic manifestations of ipecac toxicity. Unexpectedly, her induced left ventricular dysfunction returned to normal after only 10 days of withholding the drug. This finding, in contrast with the findings of other reports, establishes that ipecac cardiomyopathy can be readily reversible. The cumulative experience thus far, nonetheless, provides no discernible pattern of the effect of ipecac on the myocardium. Thus, in the continuum of poisoning, the point at which the myocardium becomes irreversibly damaged is undetermined. With continued abuse, potentially lethal outcome, and limited experience with ipecac cardiotoxicity, further investigation and perhaps heightened restriction of the drug are warranted.

Adult↗
PubMed1989

Systemic effect of ipecac on acute toxicity of phenobarbital and theophylline in rats.

The emetic agent ipecac is widely used for the initial treatment of acute oral drug overdose. Its emetic and gastric evacuative efficacies have been studied extensively but its potential for pharmacologic interactions with various drugs and other possible poisons has not been explored. The purpose of this investigation was to determine if ipecac can alter the acute toxicity of two widely used drugs that act on the central nervous system, phenobarbital and theophylline. Ipecac syrup, 5 ml/kg, was administered by gavage to male Lewis rats either 1 hr before or 15 or 30 min after the start of an iv infusion of phenobarbital or theophylline. Control animals received the syrup vehicle only. Ipecac elicited vomiting-like behavior (frequent, wide opening of the mouth) for more than 1 hr. The drug infusion was stopped immediately after onset of the loss of righting reflex (phenobarbital) or maximal seizures (theophylline). Samples of cerebrospinal fluid, blood (for serum), and the brain were obtained at that time for analysis of drug concentrations. There were no significant differences between control and ipecac-treated animals with respect to the dose requirements and drug concentrations in cerebrospinal fluid, serum, and brain at the respective pharmacologic endpoint. It is concluded that ipecac has no apparent effect on the acute toxicity of phenobarbital and theophylline in rats.

Animals↗
PubMed1993

Potential misuse of ipecac.

STUDY OBJECTIVE: To evaluate the use of ipecac by health care professionals. DESIGN: A descriptive case series based on a one-year review of all calls to a poison center. SETTING: A university hospital-affiliated regional poison center. INTERVENTIONS: The use of ipecac was judged appropriate or inappropriate based on the consensus of three professionals associated with the poison center using predetermined contraindications. MEASUREMENTS AND MAIN RESULTS: In 20% of cases in which ipecac was used, its use was inappropriate. The most common inappropriate situation was that too much time had elapsed from the time of ingestion. Among adults the most common contraindication was the ingestion of a substance known to cause altered mental status. Among children, the most common contraindication was the ingestion of a nontoxic substance or amount of substance. The poison center recommended ipecac inappropriately less often than emergency departments and usually in children ingesting a nontoxic substance. EDs recommended ipecac inappropriately with a broader range of contraindications and more often in adults. CONCLUSION: Ipecac has potentially adverse consequences and should not be used reflexively. Providers of emergency care should be educated about possible contraindications to its use.

Adolescent↗