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Percutaneous exposure to ethyl parathion in a feral Griffon vulture (Gyps fulvus).

A feral Griffon vulture (Gyps fulvus) was found with tremors, weakness, digit and wing flexion, and an inability to fly. A zero blood cholinesterase activity and a favorable response to treatment with pralidoxime hydrochloride indicated exposure to an anticholinergic pesticide. The bird died after 7 d, and traces of the organophosphate insecticide ethyl parathion were found in the liver and from a blue discolored skin area of the neck. Continuous exposure to ethyl parathion through dermal absorption was presumed the cause of death of the vulture.

Administration, Cutaneous↗

Carbamate poisoning and oxime treatment in children: a clinical and laboratory study.

OBJECTIVE: (1) Retrospective evaluation of the clinical course of carbamate poisoning and the effect of oxime therapy in children. (2) In vitro study of the effect of oximes on the reactivation of carbamylated cholinesterase. DESIGN: (1) Clinical survey: The records of 26 children intoxicated with carbamates were examined retrospectively. The poisoning agents in all cases were positively identified as methomyl or aldicarb by gas chromatography-mass spectrometry. (2) Laboratory study: The direct effect of obidoxime and of pralidoxime on acetylcholinesterase activity in vitro was investigated in normal human packed red blood cells pretreated with an organophosphate (paraoxon) or a carbamate (aldicarb or methomyl). CLINICAL SETTING: Pediatric intensive care unit of a teaching hospital. PATIENTS: Twenty-six infants and young children (aged 1 to 8 years) admitted to the pediatric intensive care unit with severe carbamate intoxication. INTERVENTIONS: All cases had been treated with repeated doses of atropine sulfate (0.05 mg/kg) administered every 5 to 10 minutes until muscarinic symptoms disappeared. Obidoxime chloride (Toxogonin, 6 mg/kg) was administered on admission, and again after 4 to 5 hours. RESULTS: Predominant symptoms were related to central nervous system and nicotinic effects. All the patients showed marked improvement within several hours and recovered completely within 24 hours. None of the children deteriorated and none showed exacerbation of cholinergic symptoms after obidoxime treatment. In vitro, oximes reactivated acetylcholinesterase inhibited with paraoxon, whereas no significant effect of oximes on carbamylated enzyme activity was observed. CONCLUSIONS: Based on the recovery of all cases, as compared with other reports of carbamate poisoning treated with atropine alone, it is concluded that, in the case of aldicarb or methomyl poisoning, oxime therapy apparently does not contribute to the recovery of poisoned patients. In cases of poisoning by an unknown pesticide or of mixed poisoning, oxime therapy can prove beneficial because no negative effects of the therapy can be discerned.

Aldicarb↗

Sarin induced lung pathology and protection by standard therapy regime.

The effects of atropine, diazepam and pralidoxime were studied for their ability to block the pathological lesions induced by sarin. Rats were exposed to an aerosol of sarin at a concentration of 51.2mg.m-3 for 15 min following the pretreatment with one of the following combinations: atropine (10 mg/kg, i.m.) and diazepam (0.5 mg/kg, i.m.); atropine and pralidoxime (25 mg/kg, i.m.); diazepam and pralidoxime; atropine, diazepam and pralidoxime. Lung exposed to sarin aerosols revealed an increased cellular proliferation with progressive diffused interstitial thickening on the 4th day following exposure. On the 16th day, loss of alveolar space and consolidation of large areas of all lobes were observed. Sarin also caused damage to the respiratory bronchioles. All the therapy regime blocked the development of lung lesions in the descending orders: atropine, diazepam and pralidoxime, atropine and diazepam > diazepam and pralidoxime > atropine and pralidoxime. The result suggests that diazepam in combination with atropine and pralidoxime could be an effective drug combination regime for the lung lesions.

Animals↗

Acute fenitrothion poisoning.

A technician was accidentally exposed to the organophosphorus insecticide fenitrothion and subsequently treated with pralidoxime for the autonomic, somatic and psychiatric manifestations of intoxication. Although long-term therapy with pralidoxime is not recommended, this patient required and obtained symptomatic benefit from its prolonged use. Erythrocytic and plasma cholinesterase activities had been monitored prior to exposure and were monitored throughout treatment and following recovery. Continual monitoring of cholinesterase activities of individuals occupationally exposed to organophosphorus ester insecticides and early diagnosis are essential.

Adult↗

Cholinesterase-inhibiting insecticide toxicity.

Organophosphate toxicity can be fatal. It accounts for almost 40 percent of all insecticide- and pesticide-related illnesses reported by the American Association of Poison Control Centers. Skin contamination is the most important route of occupational exposure. Carbamate insecticides exhibit a similar mechanism of acute toxicity. Organophosphate pesticides act as irreversible acetylcholinesterase inhibitors, while carbamate pesticides produce reversible effects. The inhibition of acetylcholinesterase causes accumulation of acetylcholine at nerve endings, resulting in a cholinergic or hypersecretory syndrome. Persons who are exposed to organophosphates must be admitted to the hospital for careful observation. Symptoms should be treated with atropine, and most patients should also receive pralidoxime, a cholinesterase-regenerating drug.

Antidotes↗

Insufficient stocking of poisoning antidotes in hospital pharmacies.

OBJECTIVE: To determine whether antidotes for poisoning and overdose are available in hospitals that provide emergency department care. DESIGN: Written survey of hospital pharmacy directors, each of whom reported the amount currently in stock of 8 different antidotes: antivenin (Crotalidae) polyvalent, cyanide kit, deferoxamine mesylate, digoxin immune Fab, ethanol, naloxone hydrochloride, pralidoxime chloride, and pyridoxine hydrochloride. PARTICIPANTS: Pharmacy directors of all hospitals with emergency departments in Colorado, Montana, and Nevada. MAIN OUTCOME MEASURES: Proportions of hospitals with insufficient stocking of each antidote, defined as complete lack of the antidote or an amount inadequate to initiate treatment of 1 seriously poisoned 70-kg patient. RESULTS: Questionnaires were mailed to 137 hospital pharmacy directors and 108 (79%) responded. Only 1 (0.9%) of the 108 hospitals stocked all 8 antidotes in adequate amounts. The rate of insufficient stocking for individual antidotes ranged from 2% (for naloxone) to 98% (for digoxin immune Fab). In a multiple regression analysis, smaller hospital size and lack of a formal review of antidote stocking were independent predictors of the number of antidotes stocked insufficiently. CONCLUSIONS: Insufficient stocking of antidotes is a widespread problem in Colorado, Montana, and Nevada. Although these states are served by a certified regional poison center, potentially lifesaving antidotes are frequently not available when and where they might be needed to treat a single poisoned patient.

Analysis of Variance↗

Poisonings associated with illegal use of aldicarb as a rodenticide -- New York City, 1994-1997.

Although rodenticides historically have been among the most toxic substances available to the public and have been implicated as agents in both unintentional and suicidal exposures, the anticoagulant agents currently in use, such as coumadin and their long-acting derivatives (e.g., brodifacoum), are relatively safe. In 1995, most persons who reported exposure to anticoagulant rodenticides did not develop symptoms or require specific therapy. However, during 1994-1997, the New York City Poison Control Center (NYCPCC) was consulted about 25 patients, primarily persons who had emigrated from the Dominican Republic, who had manifestations consistent with the cholinergic toxidrome, which is not characteristic of poisoning by the anticoagulant rodenticides, after ingesting a rodenticide known as Tres Pasitos ("Three Little Steps"). In each case, the product had been purchased at a neighborhood store for use as a household rodenticide. The Environmental Investigation Unit of the New York State Department of Environmental Conservation (NYDEC) investigated the poisoning incidents. Laboratory analysis indicated that the product contained the carbamate pesticide aldicarb (2-methyl-2-(methylthio)-propionaldehyde O-(methylcarbamoyl) oxime), which is not registered for use as a rodenticide in the United States. This report presents a detailed description of two of these cases and a summary of the remaining cases.

Adult↗

New treatment regimens in organophosphate (diazinon) and carbamate (methomyl) insecticide-induced toxicosis in fowl.

The objective of this work was to determine optimal treatment regimens for organophosphate (OP) or carbamate insecticide toxicoses in fowl using the antidotes atropine sulfate and pralidoxime chloride (2-PAM). Broiler chicks in treatment groups, each comprising 3 replicates of 6-7 birds/replicate, were gavaged on a body weight (BW) basis with the OP and carbamate insecticides, diazinon and methomyl, respectively, at lethal dosages. Treatment groups were injected with either or both of the antidotes at various dosages as soon as clinical signs appeared. Birds appearing healthy 24 h thereafter were regarded as having been treated successfully. At a dosage of 100 mg/kg BW, atropine was mildly toxic and at 200 mg/kg 2-PAM was severely toxic (but not lethal), whereas at dosages of 50 and 100 mg/kg BW, respectively, the antidotes were at their most effective. With diazinon, atropine alone was only partially effective (12/20 survivors), whereas 2-PAM was extremely efficacious. (20/20 survivors); the combination of the 2 antidotes at 2 dosages was slightly less effective (19/20 survivors) than 2-PAM alone. For methomyl toxicity, atropine was largely successful (18/20 survivors), whereas 2-PAM was mostly unsuccessful (10/20 survivors); the combination at high dosage was less effective (15/20 survivors) than atropine alone, but at a low dosage the combination was the most successful (20/20 survivors). The results indicate that anticholinesterase insecticide toxicoses in fowl should not be treated according to textbook recommendations, and antidotal dosage with atropine should be up to 100 times greater than is commonly recommended. The specific cause of the toxicoses should ideally be determined before treatment is given, but as this is often unknown, a combination of antidotes may be the optimal treatment protocol.

Animals↗

Intermediate syndrome with delayed distal polyneuropathy from ethyl parathion poisoning.

An acute poisoning in a 44-y-old female who ingested 50 ml of ethyl parathion concentrate (25 g) is described. She was treated by gastric lavage, administration of pralidoxime and atropine, and mechanical ventilation. As signs of intoxication disappeared at day 3, treatment was discontinued. The patient had a relapse of acute cholinergic crisis at day 4, and the same treatment was applied again. The acute poisoning phase was followed by an intermediate syndrome and delayed distal polyneuropathy. The clinical course of this severe ethyl parathion poisoning was favorable after 40 d.

Acute Disease↗

The effects of some cholinesterase reactivators on contractility of the isolated guinea-pig heart atria.

The effect of eight monoquaternary and bisquaternary pyridine aldoxime cholinesterase reactivators was tested on isolated guinea-pig heart atria. 2. Acetylcholine and methylfurthretonium in concentrations ranging from 10(-7) M to 10(-5) M have negative inotropic effects in the electrically stimulated atria and negative chronotropic effects in the spontaneously beating atria. 3. In the presence of higher concentration of cholinesterase reactivators alone, the parameters of heart muscle contractility are significantly altered. 4. Cumulative dose-response curves of methylfurthretonium in the presence of reactivators in the range of concentrations from 10(-5) M to 10(-3) M are shifted parallelly to higher concentrations of the agonist.

Acetylcholine↗

Inhibitory effect of 2,3-butanedione monoxime (BDM) on Na(+)/Ca(2+) exchange current in guinea-pig cardiac ventricular myocytes.

1. The effect of 2,3-butanedione monoxime (BDM), a 'chemical phosphatase', on Na(+)/Ca(2+) exchange current (I(NCX)) was investigated using the whole-cell voltage-clamp technique in single guinea-pig cardiac ventricular myocytes and in CCL39 fibroblast cells expressing canine NCX1. 2. I(NCX) was identified as a current sensitive to KB-R7943, a relatively selective NCX inhibitor, at 140 mM Na(+) and 2 mM Ca(2+) in the external solution and 20 mM Na(+) and 433 nM free Ca(2+) in the pipette solution. 3. In guinea-pig ventricular cells, BDM inhibited I(NCX) in a concentration-dependent manner. The IC(50) value was 2.4 mM with a Hill coefficients of 1. The average time for 50% inhibition by 10 mM BDM was 124+/-31 s (n=5). 4. The effect of BDM was not affected by 1 microM okadaic acid in the pipette solution, indicating that the inhibition was not via activation of okadaic acid-sensitive protein phosphatases. 5. Intracellular trypsin treatment via the pipette solution significantly suppressed the inhibitory effect of BDM, implicating an intracellular site of action of BDM. 6. PAM (pralidoxime), another oxime compound, also inhibited I(NCX) in a manner similar to BDM. 7. Isoprenaline at 50 microM and phorbol 12-myristate 13-acetate (PMA) at 8 microM did not reverse the inhibition of I(NCX) by BDM. 8. BDM inhibited I(NCX) in CCL39 cells expressing NCX1 and in its mutant in which its three major phosphorylatable serine residues were replaced with alanines. 9. We conclude that BDM inhibits I(NCX) but the mechanism of inhibition is not by dephosphorylation of the Na(+)/Ca(2+) exchanger as a 'chemical phosphatase'.

Adenosine Triphosphate↗

Biochemical and clinical profile after organophosphorus poisoning--a placebo-controlled trial using pralidoxime.

BACKGROUND: Organophosphorus (OP) compounds are the most common suicidal poison in developing countries and mortality continues to be high. METHODS: A study was done to see butyryl cholinesterase (BuChE) profile after OP poisoning in pralidoxime (P2AM) and placebo treated cases. Highest recommended dose of P2AM was used to study the reactivation of cholinesterase. Clinical outcomes like, correlation of BuChE and severity of poisoning, mortality and complications like Type I and II paralysis, need for ventilation and ICU stay were also studied. RESULTS: Twenty one cases of moderate and severe poisoning with OP compounds were included in the study. Mean BuChE levels came up gradually over 6-7 days, some taking up to two weeks. There was no. difference between the treatment and placebo groups. BuChE levels did not correlate with severity of poisoning nor did it correlate with Type I or II paralysis, need for ventilation, ICU stay or mortality. CONCLUSIONS: Treatment with P2AM does not make any difference in BuChE reactivation or complications of moderate and severe OP poisoning. We have not been using P2AM for OP poisoning in our medical ICU with good patient outcomes.

Antidotes↗