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Acute yellow oleander (Thevetia peruviana) poisoning: cardiac arrhythmias, electrolyte disturbances, and serum cardiac glycoside concentrations on presentation to hospital.

OBJECTIVE: To describe the cardiac arrhythmias, electrolyte disturbances, and serum cardiac glycoside levels seen in patients presenting to hospital with acute yellow oleander (Thevetia peruviana) poisoning and to compare these with published reports of digitalis poisoning. DESIGN: Case series. SETTING: Medical wards of Anuradhapura District General Hospital, Sri Lanka, and coronary care unit of the Institute of Cardiology, National Hospital of Sri Lanka, Colombo, the national tertiary referral centre for cardiology. PATIENTS: 351 patients with a history of oleander ingestion. MEASUREMENTS: ECG and blood sample analysis on admission. RESULTS: Most symptomatic patients had conduction defects affecting the sinus node, the atrioventricular (AV) node, or both. Patients showing cardiac arrhythmias that required transfer for specialised management had significantly higher mean serum cardiac glycoside and potassium but not magnesium concentrations. Although there was considerable overlap between groups, those with conduction defects affecting both sinus and AV nodes had significantly higher mean serum cardiac glycoside levels. CONCLUSIONS: Most of these young previously healthy patients had conduction defects affecting the sinus or AV nodes. Relatively few had the atrial or ventricular tachyarrhythmias or ventricular ectopic beats that are typical of digoxin poisoning. Serious yellow oleander induced arrhythmias were associated with higher serum cardiac glycoside concentrations and hyperkalaemia but not with disturbances of magnesium.

Adolescent↗

Toxicity of Nerium oleander and Rhazya stricta in Najdi sheep: hematologic and clinicopathologic alterations.

The toxic effects of oral administration of 0.25 g/kg Nerium oleander leaves, 0.25 g/kg Rhazya stricta leaves or their mixture at 0.25 g/kg N. oleander leaves plus 0.25 g/kg R. stricta leaves on Najdi sheep were investigated. Daily oral dosing of R. stricta leaves for 42 days was not fatal to sheep while single oral doses of either N. oleander leaves or the mixture with R. stricta leaves proved fatal to animals within 24 hours with dyspnea, grunting, salivation, grinding of the teeth, ruminal bloat, frequent urination, ataxia and recumbency prior to death. The main lesions were widespread congestion or hemorrhage, pulmonary cyanosis, emphysema, bronchotracheal froths, and hepatonephropathy. The clinical and pathological changes were correlated with alterations in serum LDH and AST activities and concentrations of cholesterol, bilirubin, urea, total protein, albumin, and globulin and hematological values.

Administration, Oral↗

[Poisoning with oleander leaves].

After ingestion of seven leaves of oleander (Nerium oleander) in a suicide attempt, a 37-year-old woman was admitted to hospital with symptoms of digitalis intoxication. The serum digoxin level on arrival was 5.69 nmol/l. The course was uneventful. The usefulness of digoxin radioimmunoassay to demonstrate poisoning with oleander (but not to predict the degree of toxicity) and the potential use of digoxin-specific Fab-antibody fragments in this situation are discussed.

Adult↗

Successful treatment of oleander intoxication (cardiac glycosides) with digoxin-specific Fab antibody fragments in a 7-year-old child: case report and review of literature.

UNLABELLED: A 7-year-old girl presented six hours after ingestion of a yellow oleander seed (Thevetia peruviana) with severe emesis, change in colour vision and complete heart block. Initial treatment with phenytoin and isoprenalin infusion led to intermittent supraventricular and ventricular tachycardia. The patient was then treated with two intravenous doses of 190 mg of digoxin-specific Fab antibody fragments (Digibind). Subsequently the patient's rhythm reverted to sinus rhythm and the symptoms resolved within 2 hours. CONCLUSION: administration of digoxin-specific Fab antibody fragments in an otherwise healthy child after oleander intoxication is safe and without adverse reactions.

Cardiac Glycosides↗

Oleander poisoning: treatment with digoxin-specific Fab antibody fragments.

A 37-year-old man presented two hours after the ingestion of "a handful" of oleander leaves (probably Nerium oleander) in a suicide attempt. Cardiotoxicity was evidenced by the presence of bradycardia (rate, 30 to 45) with sinoatrial nodal arrest and junctional escape consistent with a cardiac glycoside effect. The patient was treated empirically with a single dose of five vials (200 mg) of digoxin-specific Fab antibody fragments (Digibind). The pretreatment digoxin level was 1.5 ng/mL. After treatment, the patient's rhythm stabilized with residual sinus bradycardia (rate, 56). The patient recovered uneventfully and was discharged on the fifth hospital day to inpatient psychiatric care.

Adult↗

Response of Najdi sheep to oral administration of Citrullus colocynthis fruits, Nerium oleander leaves or their mixture.

Susceptibility of sheep to oral administration of Citrullus colocynthis fruits, Nerium oleander leaves or their mixture is described in 12 sheep assigned as untreated controls, C. colocynthis-treated at 0.25g/kg/day, N. oleander-treated at 0.25g/kg and plant mixture-treated at 0.25g of C. colocynthis/kg plus 0.25g of N. oleander/kg. The daily use of 0.25g of C. colocynthis/kg for 42 days was not fatal to sheep and caused slight diarrhoea, catarrhal enteritis, centrilobular hepatocellular fatty change and degeneration of the renal tubular cells. Single oral doses of 0.25g of N. oleander/kg were lethal to sheep within 18-24h and caused uneasiness, grinding of the teeth, dyspnoea, anorexia, frequent urination, ruminal bloat, ataxia and recumbency before death. The main lesions were widespread congestion and haemorrhage, pulmonary cyanosis and emphysema and severe hepatonephropathy. Rapid death was also observed in sheep receiving single doses of the mixture of the two plants. Effects were correlated with changes in the activities of serum lactic dehydrogenase (LDH) and aspartate transaminase (AST) and concentrations of cholesterol, bilirubin, total protein, albumin, globulin and urea and haematological parameters.

Journal Article↗

The effects of anthropogenic particulate emissions on roadway dust and Nerium oleander leaves in Messina (Sicily, Italy).

Complementary studies on the inorganic chemical composition of Nerium oleander leaves collected in the town of Messina (Sicily, Italy) and seven grain-size fractions of local roadway dust have been carried out. Data and maps are presented to show that the particulate matter present in the air of Messina contains trace elements significantly in excess with respect to the average continental earth crust. The anomalies follow the outline of the urban area, the highest concentrations of trace elements being observed where traffic density is highest. Chemical and isotopic analyses of both road dust and Nerium oleander leaves indicate that Pb contamination still characterizes roads with heavy traffic. In addition to Pb, other metals such as Pt, Pd, Sb, Au, Br, Zn, Cu, Mo, and Cd are significantly enriched in roadway dust, indicating their common anthropogenic origin, especially from traffic. SEM/EDS study of some roadway dust particles has shown the presence of gypsum probably of secondary origin, mixed particles formed by coagulation or gas-to-particle conversion, and porous spherical particles apparently emanating from combustion processes.

Air Pollutants↗

Murine pharmacokinetics and metabolism of oleandrin, a cytotoxic component of Nerium oleander.

Pharmacokinetic studies of [3H]oleandrin, a cardiac glycoside component of Anvirzel, were conducted in mice after either an i.v. dose (40 micrograms/kg) or a p.o. dose (80 micrograms/kg). Oleandrin was rapidly absorbed after oral dosing (Cmax at 20 min) although the elimination half-life was longer (2.3 +/- 0.5 h) than that after i.v. dosing (0.4 +/- 0.1 h). The AUC0-infinity values obtained after i.v. and p.o. dosing were 24.6 +/- 11.1 and 14.4 +/- 4.3 (ng.h/ml), respectively, resulting in an oral bioavailability of approximately 30%. After i.v. administration, oleandrin concentration in liver was approximately twice that measured in heart or kidney tissue. Oleandrigenin, the aglycone of oleandrin, was also found in these tissues. At 5 min, > 60% of the total radioactivity in liver was due to oleandrin while 28% of the given dose was present as oleandrigenin. Twenty-four hours following injection, 8% of total radioactivity was excreted in urine and contained both oleandrigenin (4.4% of the injected dose) and oleandrin (1.9%). Sixty-six percent of injected radioactivity was found in feces and consisted of oleandrin and oleandrigenin in equal amounts. Uptake of oleandrin in brain after i.p. injection of oleandrin (3 mg/kg) or oleander extract (700 mg/kg) was examined. Measured by LC/MS/MS, oleandrin content in brain was higher following injection of extract than it was with an equivalent dose of oleandrin. The data suggest that components within oleander extract may enhance transport of oleandrin across the blood brain barrier.

Animals↗

Epidemic of self-poisoning with seeds of the yellow oleander tree (Thevetia peruviana) in northern Sri Lanka.

Deliberate self-harm is an important problem in the developing world. Ingestion of yellow oleander seeds (Thevetia peruviana) has recently become a popular method of self-harm in northern Sri Lanka -- there are now thousands of cases each year. These seeds contain cardiac glycosides that cause vomiting, dizziness, and cardiac dysrhythmias such as conduction block affecting the sinus and AV nodes. This paper reports a study of the condition's mortality and morbidity conducted in 1995 in Anuradhapura General Hospital, a secondary referral centre serving 750 000 people in Sri Lanka's north central province. 415 cases were admitted to the hospital during 11 months; 61% were women and 46% were less than 21 years old. A prospective study of 79 patients showed that 6% died soon after admission. 43% presented with marked cardiac dysrhythmias which necessitated ther transfer to the coronary care unit in Colombo for prophylactic temporary cardiac pacing. The reasons for the acts of self-harm were often relatively trivial, particularly in children; most denied that they wished to die. Unfortunately, the case fatality rate for oleander poisoning in Sri Lanka is at least 10%. This epidemic is not only causing many unnecessary deaths, it is also putting immense stress on the already stretched Sri Lankan health services. There is an urgent need for an intervention which could be used in rural hospitals, thus preventing the hazardous and expensive emergency transfer of patients to the capital.

Adolescent↗

Anvirzel, an extract of Nerium oleander, induces cell death in human but not murine cancer cells.

The purpose of this study was to examine the mechanism(s) and differential cell-killing effects of Anvirzel, an extract of oleander (Nerium oleander; family-Apocynaceae), and its derivative compound Oleandrin on human, canine and murine tumor cells. Cells received different concentrations of Anvirzel (1.0 ng/ml to 500 microg/ml) or Oleandrin (0.01 ng/ml to 50 microg/ml) in both continuously treated and pulse-treated/recovery cultures. The cytotoxicity of these compounds was then determined. Both Anvirzel and Oleandrin were able to induce cell killing in human cancer cells, but not in murine cancer cells; the cell-killing potency of Oleandrin was greater than that of Anvirzel. Canine oral cancer cells treated with Anvirzel showed intermediate levels of response, with some abnormal metaphases and cell death resulting from the treatment. From these results we conclude that Anvirzel and Oleandrin act in a species-specific manner, and while testing the effectiveness of a new compound for cancer treatment, one must use not only murine but a variety of cancer cells, including those of human origin.

Animals↗

Pharmacokinetics of digoxin cross-reacting substances in patients with acute yellow Oleander (Thevetia peruviana) poisoning, including the effect of activated charcoal.

Intentional self-poisonings with seeds from the yellow oleander tree (Thevetia peruviana) are widely reported. Activated charcoal has been suggested to benefit patients with yellow oleander poisoning by reducing absorption and/or facilitating elimination. Two recent randomized controlled trials (RCTs) assessing the efficacy of activated charcoal yielded conflicting outcomes in terms of mortality. The effect of activated charcoal on the pharmacokinetics of Thevetia cardenolides has not been assessed. This information may be useful for determining whether further studies are necessary. Serial blood samples were obtained from patients enrolled in an RCT assessing the relative efficacy of single-dose and multiple-dose activated charcoal (SDAC and MDAC, respectively) compared with no activated charcoal (NoAC). The concentration of Thevetia cardenolides was estimated with a digoxin immunoassay. The effect of activated charcoal on cardenolide pharmacokinetics was compared between treatment groups by determining the area under the curve for each patient in the 24 hours following admission, the 24-hour mean residence time, and regression lines obtained from serial concentration points, adjusted for exposure. Erratic and prolonged absorption patterns were noted in each patient group. The apparent terminal half-life was highly variable, with a median time of 42.9 hours. There was a reduction in 24-hour mean residence time and in the apparent terminal half-life estimated from linear regression in patients administered activated charcoal, versus the control group (NoAC). This effect was approximately equal in patients administered MDAC or SDAC. Activated charcoal appears to favorably influence the pharmacokinetic profile of Thevetia cardenolides in patients with acute self-poisoning and may have clinical benefits. Given the conflicting clinical outcomes noted in previous RCTs, these mechanistic data support the need for further studies to determine whether a particular subgroup of patients (eg, those presenting soon after poisoning) will benefit from activated charcoal.

Absorption↗

Compositional and Thermal Properties of Thylakoid Polar Lipids of Nerium oleander L. in Relation to Chilling Sensitivity.

The polar lipid classes from thylakoids of Nerium oleander L. were studied with the aim of relating changes in their composition and thermal behavior with reported changes in the transition temperature of their polar lipids and chilling sensitivity of their leaves. With an increase in growth temperature, the transition temperature of phosphatidylglycerol increased from 16 degrees C to 26 degrees C, and for sulfoquinovosyldiacylglycerol from 19 degrees C to 24 degrees C. Transitions in the other lipid classes were below -10 degrees C for plants grown at both growth temperature. The major changes in the molecular species of phosphatidylglycerol, with increasing growth temperature, were an increase in 1-oleoyl-2-palmitoyl phosphatidylglycerol from 21 to 39% and a decrease in 1-oleoyl-2-trans-3-hexadecanoic phosphatidylglycerol from 51 to 25%. Although the disaturated species increased from 8 to 23%, the maximum was less than that reported for chilling-sensitive plants. There was no change in the sum of the palmitic, hexadeca-trans-3-enoic and stearic acids. Dipalmitoyl sulfoquinovosyldiacylglycerol increased from 12 to 20% and 1-linolenoyl-2-palmitoyl sulfoquinovosyldiacylglycerol decreased from 40 to 30%. It is concluded that the increase in the transition temperature of the polar lipids and the sensitivity of acclimated oleander plants to chilling could not be predicted by the absolute sum of the saturated fatty acids or disaturated molecular species in phosphatidylglycerol. The polar lipid transition appears to be a product of mixing of both high and low melting-point lipids.

Journal Article↗

Zeaxanthin and the Heat Dissipation of Excess Light Energy in Nerium oleander Exposed to a Combination of High Light and Water Stress.

Upon termination of watering of plants of Nerium oleander exposed to high light, photochemical efficiency became reduced as leaf water content decreased. Evidence is presented that this type of photoinhibition reflects to a substantial degree radiationless dissipation of excitation energy, probably mediated by the carotenoid zeaxanthin. During the imposition of water stress, the zeaxanthin content of leaves increased at the expense of violaxanthin and beta-carotene as a water deficit developed over a period of several days. The increase in zeaxanthin content was linearly related to an increase in the rate of radiationless energy dissipation in the antenna chlorophyll as calculated from the characteristics of chlorophyll a fluorescence measured with a pulse amplitude modulated fluorometer at room temperature. The increase in the rate of radiationless dissipation was also linearly related to a decrease in PSII photochemical efficiency as indicated by the ratio of variable to maximum fluorescence. Leaves of well-watered shade plants of N. oleander exposed to strong light showed a similar increase in zeaxanthin content as sun leaves of the same species subjected to drought in strong light. Shade leaves possessed the same capacity as sun leaves to form zeaxanthin at the expense of both violaxanthin and beta-carotene. The resistance of this species to the destructive effects of excess light appears to be related to interconversions between beta-carotene and the three carotenoids of the xanthophyll cycle.

Journal Article↗

Toxicological interactions of Cassia senna and Nerium oleander in the diet of rats.

The toxic effects of diet containing 10% of C. senna L. fruits or 10% of N. oleander L. leaves or their 1:1 mixture (5% + 5%) on male Wistar rats treated for 6 weeks were investigated. Diarrhea was a prominent sign of C. senna L. toxicosis. In both phytotoxicities, there were decreases in body weight gains, inefficiency of feed utilization, dullness and enterohepatonephropathy. These findings accompanied by leukopenia and anemia were correlated with alterations of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities and concentrations of total protein, albumin, urea and other serum constituents. In both phytotoxicities, the ability of the liver to excrete bilirubin remained unchanged. Feeding the mixture of C. senna L. fruits and N. oleander L. leaves caused more serious effects and death of rats. The implications of these findings are discussed.

Animals↗

Yellow oleander poisoning in Sri Lanka: outcome in a secondary care hospital.

Cardiac toxicity after self-poisoning from ingestion of yellow oleander seeds is common in Sri Lanka. We studied all patients with yellow oleander poisoning (YOP) admitted to a secondary care hospital in north central Sri Lanka from May to August 1999, with the objective of determining the outcome of management using currently available treatment. Patients with bradyarrhythmias were treated with intravenous boluses of atropine and intravenous infusions of isoprenaline. Temporary cardiac pacing was done for those not responding to drug therapy. During the study period 168 patients with YOP were admitted to the hospital (male:female = 55:113). There were six deaths (2.4%), four had third-degree heart block and two died of undetermined causes. They died soon after delayed admission to the hospital before any definitive treatment could be instituted. Of the remaining 162 patients, 90 (55.6%) patients required treatment, and 80 were treated with only atropine and/or isoprenaline while 10 required cardiac pacing in addition. Twenty-five (14.8%) patients had arrhythmias that were considered life threatening (second-degree heart block type II, third-degree heart block and nodal bradycardia). All patients who were treated made a complete recovery. Only a small proportion of patients (17%) admitted with YOP developed life-threatening cardiac arrhythmias. Treatment with atropine and isoprenaline was safe and adequate in most cases.

Adolescent↗

Fatal oleander poisoning.

A case of fatal poisoning due to the presumed ingestion of leaves and/or fruit of the yellow oleander (Thevetia peruviana) is described. The diagnosis was confirmed by radioimmunoassay using antibodies of differential specificity towards cardiac glycosides. Attention is drawn to the potential usefulness of digoxin assay in suspected cases of oleander poisoning.

Child, Preschool↗

Yellow oleander (cerbera thevetia) poisoning with jaundice and renal failure.

Jaundice and renal failure in yellow oleander poisoning have not been reported previously. Similarly no post-mortem report has shown renal tabular necrosis and glomerular pathology, liver and brain changes in this poisoning. Four cases of yellow oleander poisoning with jaundice and renal failure and the postmortem findings in another three cases are reported.

Acute Kidney Injury↗

A case report of Nerium oleander poisoning in cattle.

Nerium oleander leaves caused the death within 36 hours of 7 of 17 cattle which had access to boughs of the plant. Arrhythmia and auriculo-ventricular block at ECG were found in three cattle surviving on day 4. In one animal which died on day 4, postmortem examination revealed subendocardial and abomasal hemorrhages. Epidermic tissues of the leaves of N oleander were found in the rumen content. Recovery occurred in the three animals with marked cardiac signs.

Animals↗