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PubMed1990

Toxic mechanisms of the heart: a review.

Toxic injury is one of the many ways by which the functional integrity of the heart may become compromised. Any of the subcellular elements may be the target of toxic injury, including all of the various membranes and organelles. Understanding the mechanisms underlying cardiotoxicity may lead to treatment of the toxicity or to its prevention. Doxorubicin and its analogs are very important cancer chemotherapeutic agents that can cause cardiotoxicity. Other agents which are cardiotoxic and which have profound public health implications include the alkaloid emetine in ipecac syrup, cocaine, and ethyl alcohol. The most important cardiotoxic mechanisms proposed for doxorubicin include oxidative stress with its resultant damage to myocardial elements, changes in calcium homeostasis, decreased ability to produce ATP, and systemic release of cardiotoxic humoral mediators from tissue mast cells. Each of the first 3 mechanisms can lead to each of the other 2, and the causal relationships between all of these mechanisms are not clear. New evidence suggests that doxorubicinol, one of the metabolites of doxorubicin may be the moiety responsible for cardiotoxicity. Several other potential mechanisms also have been proposed for doxorubicin. Emetine in ipecac syrup is the first aid treatment of choice for many acute toxic oral ingestions and the alkaloid, itself, is used to treat amebiasis. Cardiotoxicity occurs following chronic exposure, such as occurs therapeutically in amebiasis and with ipecac abuse by bulemics. A number of mechanisms are proposed for emetine cardiotoxicity, but the current mechanistic literature is quite scarce. Cocaine abuse recently has caught the public interest, in particular because of the drug-related sudden deaths of certain athletes. Cocaine can cause hypertension, arrhythmias, and reduced coronary blood flow, each of which can contribute to its lethality. However, it may be possible that cocaine sudden death episodes are more related to hyperthermia and convulsive seizures, rather than to cardiovascular toxicity. Chronic alcohol use leads to dilated cardiomyopathy and failure as part of the general physical degeneration that occurs with alcoholism. Several mechanisms are proposed for the cardiomyopathy, but only 2 things seem clear. The cardiotoxicity is due to an intrinsic effect of alcohol, rather than to malnutrition or co-toxicity, and abstinence is the only effective treatment for the cardiomyopathy. Recent articles indicate that very moderate use of alcohol may be beneficial and protect against cardiovascular-related morbidity. One explanation for these findings seems to be that the non-drinking groups, against whom the moderate drinking comparisons were made, were enriched in former drinkers with significant alcohol-related cardiovascular pathology.

Animals↗
PubMed1984

The environment away from home as a source of potential poisoning.

A prospective study investigated poisonings that occur away from home. During the study period, 13% of all poisonings involving children aged 5 years or younger occurred away from home. Drugs accounted for most of these poisonings in both study and control (cases randomly selected from poisoning that occurred at home) groups. The potential toxicity of products involved in the study group was significantly greater than that in controls. Prescription drug poisonings, which occurred with similar frequency in study and control groups, were more potentially toxic in the former. The availability of ipecac syrup was significantly less in the study group. Grandparents' homes, the most common location in the study group, also had the lowest availability of ipecac. Poisonings away from home are frequent, potentially dangerous, and these environments are less adequately prepared to handle such exposures.

Age Factors↗
PubMed1977

Structure and fragmentation mechanisms of some ions in the mass spectrum of ephedrine.

This paper describes the use of gas chromatography mass spectrometry for the confirmation of ephedrine in adulterated powdered ipecac and ipecac fluid extract. Deuteration studies of ephedrine hydrochloride and some related compounds were also performed in an attempt to postulate structures for some of the fragment ions appearing in the spectrum of ephedrine.

Chemical Phenomena↗
PubMed1993

Pediatric gastrointestinal decontamination in acute toxin ingestion.

The appropriate implementation of the various modalities of gastrointestinal (GI) decontamination is critical in the management of the pediatric patient who is examined in the emergency department or private office after an acute ingestion. Gastrointestinal decontamination includes gastric lavage, syrup of ipecac, activated charcoal, and whole bowel irrigation. Clinical studies have delineated the role and efficacy of these procedures. Trends in GI decontamination place less emphasis on ipecac and gastric lavage and more emphasis on activated charcoal alone in the patient with a mild overdose. Gastric lavage is indicated in serious ingestion and is most effective if done soon after the exposure. Whole bowel irrigation is the newest addition and has important clinical use in the treatment of serious iron ingestions as well as in older adolescent cocaine body suffers and packers. Indications and contraindications of the various forms of GI decontamination are discussed and relevant clinical studies are reviewed.

Charcoal↗
PubMed1996

Broad spectrum antiemetic effects of CP-122,721, a tachykinin NK1 receptor antagonist, in ferrets.

The potent, selective, tachykinin NK1 receptor antagonist, CP-122,721 ([(+)-(2S,3S)-3-(2-methoxy-5-trifluoromethoxybenzyl)amino-2- phenylpiperidine]), at 0.01-1 mg/kg, s.c. reduced retching and vomiting elicited by loperamide, copper sulfate, ipecac syrup and cisplatin in a dose-dependent manner. ID50 values after subcutaneous administration ranged from 0.02 mg/kg (loperamide) to 0.08 mg/kg (ipecac). Oral CP-122,721 reduced cisplatin-induced emesis with an ID50 of approximately 0.08 mg/kg. The less active (2R, 3R)-enantiomer, CP-132.687, did not significantly suppress retching or vomiting induced by any of the emetogens. These data support the hypothesis that CP-122,721 blocks emesis by a specific action at tachykinin NK1 receptors. Its broad spectrum of antiemetic activity suggests a central site of action.

Animals↗
PubMed1985

Management of acutely poisoned patients without gastric emptying.

During an 18-month period, 592 acute oral drug overdose patients were studied prospectively in a controlled, randomized fashion to determine the efficacy of gastric emptying procedures in altering clinical outcome. Patients presenting on even-numbered days had no gastric emptying procedures performed, and they were compared to patients presenting on odd-numbered days who received either syrup of ipecac or gastric lavage. Patients were carefully followed for evidence of subsequent clinical improvement or deterioration after initial management. Syrup of ipecac did not significantly alter the clinical outcome of patients who were awake and alert on presentation to the emergency department (ED). Gastric lavage in obtunded patients led to a more satisfactory clinical outcome (P less than .05) only if performed within one hour of ingestion. Gastric emptying procedures in the ED for initial treatment of drug overdose are generally not of benefit unless gastric lavage is performed within one hour of ingestion in obtunded patients.

Adolescent↗
PubMed2004

Sildenafil citrate ingestion in a pediatric patient.

BACKGROUND: Sildenafil citrate is the first FDA-approved oral agent for male erectile dysfunction. Common adverse effects include flushing, headache, and dyspepsia, although more serious side effects have been reported. Because of its specific therapeutic indication, sildenafil toxicity has been limited almost exclusively to adults. We report a symptomatic case of pediatric sildenafil ingestion. CASE: A 2-year-old male ingested 75 mg of sildenafil citrate (Viagra) 2 hours prior to arrival at an emergency room. Ipecac syrup had been given at home with one episode of vomiting. Activated charcoal was considered but withheld due to the delayed presentation to the hospital. The patient was observed in the hospital for 17.5 hours. Observed clinical effects included facial flushing, transient penile engorgement, bilateral rhonchi, and diarrhea. No significant cardiovascular effects were seen. A bronchodilator was given with resolution of rhonchi. No other specific interventions were required. One day after discharge, the patient had one additional bout of diarrhea and complained of pain in the penile region for one day. Two weeks after the exposure, the patient's mother denied any unusual symptoms. CONCLUSION: Pediatric ingestion of sildenafil may result in mild symptoms including persistent flushing and penile engorgement with associated pain. Penile pain may persist even after resolution of the erection. It is questionable whether the respiratory symptoms and diarrhea were related since neither has been described following sildenafil exposure. Significant cardiovascular symptoms were not seen. Early administration of ipecac syrup did not prevent symptoms from developing.

Bronchodilator Agents↗
PubMed1999

Gastric decontamination--a view for the millennium.

The management of acute poisoning remains an important part of accident and emergency (A&E) care. Three gastric decontamination procedures have been widely used: gastric lavage, ipecac, and activated charcoal. Their role has recently been reviewed and position statements developed by working groups of the American Academy of Clinical Toxicology and the European Association of Poisons Centres and Clinical Toxicologists. These have important implications for A&E, as they indicate that activated charcoal is now the agent of choice for most poisons, but than in most situations it is probably only effective if given within an hour of overdose. Ipecac is effectively obsolete and gastric lavage has a narrow range of indications, principally for potentially serious amounts of agents not adsorbed by charcoal. Protocols for care of overdose patients should be modified accordingly.

Acute Disease↗
PubMed1991

A review of the management of oral drug overdose in the Accident and Emergency Department of the Royal Brisbane Hospital.

Two-hundred and eighty-nine patients who made a total of 323 presentations to the Royal Brisbane Hospital Accident and Emergency Department with a known or suspected oral drug overdose were reviewed. The majority of patients (76%) could be managed in a 24 h Accident and Emergency observation unit. Activated charcoal given orally or via a nasogastric tube was the recommended method of preventing further absorption of an ingested drug. The use of syrup of ipecac was not encouraged and orogastric lavage was used in only specific situations. The morbidity and mortality of these patients when compared with other studies, was not adversely affected by this protocol which dramatically reduced the indications for the use of orogastric lavage and syrup of ipecac.

Administration, Oral↗
PubMed1989

Angiotensin converting enzyme inhibitor ingestion in children.

The effect of angiotensin converting enzyme inhibitors on children is not well documented. A recent increase in popularity of the angiotensin converting enzyme inhibitors has resulted in an increased availability in the home with resulting heightened probability of accidental ingestion of angiotensin converting enzyme inhibitors by children. In response to this we did a retrospective study of angiotensin converting enzyme inhibitor ingestions in children (ages 1-5 years) from two regional poison centers certified by the American Association of Poison Control Centers. The records of the Delaware Valley Regional Poison Control Center and the New Jersey Poison Information Education Systems were reviewed for 1986 and 1987. Forty-eight angiotensin converting enzyme inhibitor exposures in children 1-5 were identified. Twenty exposures (12.5-300mg captopril, 5-15mg enalapril) were managed with syrup of ipecac in a hospital emergency room. All 20 remained asymptomatic for their stay. None required admission to the hospital. Seven exposures (12.5-75mg captopril, 5-10mg enalapril) were managed at home with syrup of ipecac and 1-, 4-, 24-hour follow up by telephone. All 7 remained asymptomatic. 16 exposures (12.5-100mg captopril, 5-30mg enalapril) were managed by phone at home with observation alone and 4-6 hour follow up. All 16 remained asymptomatic. Five exposures were lost to follow up. A larger series is needed to determine risk, but home monitoring seems adequate for children ingesting no more than the therapeutic dose for adults (12.5-100 mg captopril, 5-30 mg enalapril).

Administration, Oral↗
PubMed2002

Gastrointestinal decontamination in paediatric exploratory ingestions.

AIM: To review the effect of treatment changes in paediatric exploratory ingestion at Christchurch Hospital. METHODS: We carried out a retrospective review of paediatric patients presenting with potentially toxic ingestion during six month periods of 1994, 1996 and 1999. RESULTS: All three groups were comparable in respect to age and gender. There were minor changes in the range and proportion of substances ingested - with those in the 1999 group more likely to have taken paracetamol. In 1994, 36% of children were treated with syrup of ipecac. By 1996, only 9% were given ipecac, with 49% treated with activated charcoal. By 1999, 12% were treated with activated charcoal, while 88% received no decontamination. There was a lower admission rate in the 1999 group with no overall change in outcome. CONCLUSIONS: It is rare for paediatric exploratory ingestions to result in significant toxicity. Gastrointestinal decontamination should not be routinely used in these patients as the risk of the procedure may outweigh the risk of the poison exposure.

Acetaminophen↗
PubMed1985

Ask your pharmacist?

Retail pharmacists should recognize their inadequate knowledge of Ipecac instructions. When confronted with an acute poisoning, these patients should be referred to their physician or nearest regional poison control center (3). Providing improper instructions creates the risks of: Vomiting a substance with which emesis is contraindicated; Unnecessary emesis; and Use of ineffective and unsafe methods of inducing emesis. Only 2 (6.25%) pharmacists gave complete and accurate instructions for the use of Ipecac--with the exception of mentioning the contraindications to emesis. However, both pharmacists referred the caller to their regional poison control center.

Community Pharmacy Services↗
PubMed1984

Gastrointestinal decontamination in the management of the poisoned patient.

Ipecac syrup is the agent of choice to promote emesis in awake, alert, and cooperative patients who have ingested poison. Lavage is a reasonable alternative when ipecac fails or emesis is contraindicated. Activated charcoal is effective in minimizing absorption of ingested toxins, and saline cathartics may be useful to hasten the elimination of activated charcoal and possibly of enteric-coated or sustained release medications.

Animals↗
PubMed1976

Antinauseant and antiemetic properties of bismuth subsalicylate in dogs and humans.

Laboratory and clinical investigations were carried out to determine the effectiveness of bismuth subsalicylate in allaying nausea by preventing the physical symptom of emesis. In normal conscious dogs, a bismuth subsalicylate formulation caused a dose-related reduction in the incidence of vomiting in response to an emetic dose of ipecac syrup. In normal human subjects, a bismuth subsalicylate suspension, unlike the placebo formulation, successfully subdued nausea and vomiting in 66.7 and 80% of the subjects, respectively, in response to ipecac syrup. Both findings demonstrate that bismuth subsalicylate can provide antiemetic action and that the decreases in the occurrence of emesis in humans and dogs parallels the decrease in nausea found in humans and the nausea suspected to occur prior to emesis in dogs.

Adult↗
PubMed1989

Reversible emetine-induced myopathy with ECG abnormalities: a toxic myopathy.

A young anorexic woman is described with a history of progressive muscle weakness following chronic ingestion of syrup of ipecac that was used in an attempt at weight control. Electrocardiogram (ECG) showed T-wave inversion in all leads and prolongation of the Q-T interval. Electromyography was abnormal. Muscle biopsy revealed a randomized, generalized, predominantly type-2 fibre atrophy and structural alterations in oxidative enzyme stains, such as targetoid and moth-eaten fibres. A few necrotic cells were actively phagocytosed. Electron microscopy revealed severe sarcomeric abnormalities with Z-line streaming, myofibrillar disorganization and increased lysosomal activity. After discontinuation of ipecac syrup, the patient noted a gradual improvement in her condition. The ECG became normal. Emetine and related drug-induced myopathies are uncommon but are of experimental interest because of their effects on mitochondria and the light they shed on autophagic mechanisms in muscle.

Adult↗
PubMed1988

Ultrastructural pathology in emetine-induced myopathy.

Progressive myopathy developed in two women who consumed ipecac syrup containing emetine hydrochloride to induce vomiting as part of their anorexia nervosa. Muscle biopsy specimens were characterized by severe disruption of the sarcomeres. The ultrastructural spectrum extended from "Z-band streaming" to the formation of cytoplasmic bodies and also comprised abnormalities of the sarcotubular system, thus suggesting that muscle weakness may be related to both sarcomeric and sarcotubular lesions in this self-inflicted myopathy. It is tempting to suggest that muscle weakness may be correlated with or based on the pathology in sarcomeres and the sarcotubular system. As the myopathy is clinically reversible upon discontinuation of ipecac consumption the morphological findings should also be potentially reversible. Experimentally induced emetine myopathy may, thus, serve as a useful model to study morphological dynamics of sarcomeric lesions, which may be observed separately or simultaneously in a variety of spontaneously occurring human neuromuscular disorders.

Adult↗
PubMed1995

Comparison of the antiemetic effects of a 5-HT1A agonist, LY228729, and 5-HT3 antagonists in the pigeon.

Vomiting may be induced by a variety of agents such as drugs, oncolytics, and provocative motion, as well as being conditioned to occur to environmental stimuli. Such emesis has recently been shown to be blocked by agonists at the 5-HT1A subtype of serotonin receptor. The antiemetic effects of LY228729 [(-)-4-(dipropylamine)-1,3,4,5-tetrahydrobenz-(c,d)indole-6- carboxamide], a 5-HT1A receptor agonist, were tested and compared to the antiemetic effects of the 5-HT3 receptor antagonists ondansetron, tropisetron, and MDL 72222 (3-tropanyl-3,5-dichlorobenzoate). The emetic stimuli tested are known to be blocked by 5-HT3 antagonists in species other than the pigeon. In the pigeon, LY228729 totally abolished vomiting induced by fully emetic doses of cisplatin (10 mg/kg), ipecac (3 ml/kg), emetine (10 mg/kg), and a 5-HT3 agonist, m-(chlorophenyl)-biguanide (1.25 mg/kg). MDL 72222 blocked ipecac-induced vomiting in a dose-related manner and was partially effective in attenuating cisplatin-induced emesis. Ondansetron and tropisetron were partially effective in blocking emetine- and mCPBG-induced vomiting. Ondansetron exhibited an intrinsic emetic response that could not be blocked by MDL 7222, but which was eliminated by LY228729. It was concluded that 5-HT1A agonists are more effective in the pigeon than are 5-HT3 antagonists against these types of emetic stimuli. These results broaden the range of emetic stimuli that are blocked by 5-HT1A agonists in the pigeon.

Animals↗
PubMed1992

Acute poisoning emergencies. Resolving the gastric decontamination controversy.

As in all medical emergencies, in acute poisoning the cornerstone of management is good supportive care. Aggressive support of the cardiovascular, respiratory, and central nervous systems, along with appropriate gastric decontamination, greatly reduces morbidity and mortality and improves patient outcome. Ipecac is generally reserved for home use, where it can be given to induce emesis immediately after ingestion of toxins, and it is given only in cases of mild or moderate toxicity. Activated charcoal should replace ipecac in the emergency department for cases of mild or moderate toxicity. Gastric lavage and administration of activated charcoal should be considered in cases with life-threatening potential. A cathartic should be considered after activated charcoal has been administered, but only in cases where it will not have a detrimental effect.

Acute Disease↗