PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “PRALIDOXIME COMPOUNDS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 505 records · Page 28Linked to original sources

Acute malathion toxicosis and related enzymatic alterations in Bubalus bubalis: antidotal treatment with atropine, 2-PAM, and diazepam.

Oral administration of malathion (MTH) in sublethal (100 mg/kg) or minimal lethal (125 mg/kg) doses in buffalo calves produced toxicity with an onset within 15-20 min and peak effects including severe tremors and convulsions within 40-60 min. Various antidotal drugs were administered alone or in combination at the time of peak malathion toxicity (within 1 h) and were assessed for their ability to alleviate signs of cholinergic toxicity. Blood cholinesterase and aminotransferases activities were monitored at various times. A combination of atropine sulfate (0.5 mg/kg, 1/4 iv and 3/4 im) and pyridine 2-aldoxime methiodide (2-PAM, 20 mg/kg, iv) reversed the clinical evidence of malathion toxicity within 15 min. The combination of atropine sulfate and diazepam (0.75 mg/kg, iv) prevented death and cholinergic signs of toxicity except for weak muscular fasciculations, which persisted for 30-60 min. Atropine sulfate alone was less effective and also did not reverse malathion-induced biochemical changes. In contrast, administration of either 2-PAM (10-30 mg/kg, iv) or diazepam (0.5-1.0 mg/kg, iv) alone accentuated malathion toxicity. Thus, the combination of atropine sulfate and 2-PAM was the most effective antidotal treatment in acute malathion toxicity.

Animals↗

Intermediate syndrome after malathion ingestion despite continuous infusion of pralidoxime.

CASE REPORT: A 33-year-old female ingested an unknown quantity of malathion in a suicide attempt. Cholinergic signs consistent with severe organ, phosphate intoxication developed and were treated within 6 hours of ingestion. Intravenous atropine and a continuous infusion of pralidoxime (400 mg/h) were administered. Prolonged depression of plasma and red blood cell cholinesterases were documented. Despite an initial clinical improvement and the presence of plasma pralidoxime concentrations exceeding 4 microg/mL, the patient developed profound motor paralysis consistent with the diagnosis of Intermediate Syndrome. In addition to the dose and frequency of pralidoxime administration, other factors including persistence of organophosphate in the body, the chemical structure of the ingested organophosphate, and the time elapsed between ingestion and treatment may limit the effectiveness of pralidoxime as an antidote in organophosphate ingestions. This case study suggests that these factors should be taken into account in assessing the risk of Intermediate Syndrome after intentional organophosphate ingestions.

Adult↗

Permanent paralysis at sites of dermal exposure to chlorpyrifos.

OBJECTIVE: Poisoning with organophosphate pesticides can cause sensory and motor neuropathy with permanent paralysis. Paralysis at the site of dermal exposure has not been reported. CASE REPORT: A 61-year-old carpenter sprayed a nest of termites with an insecticide containing chlorpyrifos without protective equipment and with direct contact of pesticide solution to hands, lower arms, feet, and lower legs, as well as inhalation of vapors from spraying. After 30 min he became ill with nausea, abdominal cramping, arm and leg weakness, bilateral shoulder pain, chest pain, and numbness in the left hand and arm. At a hospital, he was treated with atropine 1 mg IV and pralidoxime Cl 2 g IV There was 0/5 strength in the hands and wrists and 3/5 elsewhere, a left peritoneal palsy, and urinary retention. He was transferred to a tertiary care hospital where paralysis persisted. Electromyogram studies documented widespread peripheral neuropathy. With continued progression of neuropathy, pralidoxime was repeated on the third day. By day 12, motor strength improved except for the hands and left lower leg. Right interosseous muscle strength was 1/5 and left was 0/5. Right-hand grip was 2/5, and left-hand grip was 0/5. He was transferred to a rehabilitation center. He never regained use of his hands and was disabled from employment as a carpenter. There was a disturbed gait, with inability to clear his left foot with walking. Urinary retention persisted and required self-catherization. CONCLUSION: Dermal exposure of the hands and feet to chlorpyrifos was associated with atrophy and permanent paralysis of exposed areas. The importance of protective equipment is emphasized.

Atropine↗

The effects of fresh frozen plasma on cholinesterase levels and outcomes in patients with organophosphate poisoning.

OBJECTIVE: The aim of this study is to determine the effects of fresh frozen plasma, as a source of cholinesterase, on butyrylcholinesterase (BuChE; plasma or pseudo cholinesterase) levels and outcomes in patients with organophosphate poisoning. MATERIALS AND METHODS: This prospective study was performed at the Department of Intensive Care of Erciyes University Medical School. Over 2 yrs, patients admitted to the ICU for OP poisoning were entered into the study. OP poisoning was diagnosed on the basis of history and BuChE levels. All patients received atropine. Fresh frozen plasma was given to 12 patients. The study was approved by the Ethical Committee, and verbal informed consent was obtained. RESULTS: Thirty-three patients were included in the study. BuChE levels measured at admission and the pralidoxime and atropine doses administered were not different between groups (p>0.05). Although intermediate syndrome developed in 28.6% of patients receiving pralidoxime, there were no intermediate syndrome cases in patients receiving plasma prior to developing intermediate syndrome. The mortality rates were 14.3% in the pralidoxime group and 0% in the plasma+atropine+pralidoxime group. Two patients received plasma after developing the intermediate syndrome, and one patient who received only atropine died. BuChE levels of fresh frozen plasma were 4069.5 +/- 565.1 IU/L. Every two bags of plasma provided an increase in BuChE levels of approximately 461.7 +/- 142.1 IU/L. CONCLUSION: Fresh frozen plasma therapy increases BuChE levels in patients with organophosphate poisonings. The administration of plasma may also prevent the development of intermediate syndrome and related mortality. Plasma (fresh frozen or freshly prepared) therapy may be used as an alternative or adjunctive treatment method in patients with organophosphate pesticide poisoning, especially in cases not given pralidoxime. Further randomized controlled and animal studies are required to infer a definitive result.

Atropine↗

Effects of fosphenytoin on nerve agent-induced status epilepticus.

This study evaluated the effectiveness of fosphenytoin as a single or adjunctive anticonvulsant treatment for nerve agent-induced status epilepticus. Guinea pigs, implanted with cortical electroencephalographic (EEG) recording electrodes, were pretreated with pyridostigmine bromide (0.026 mg/kg, intramuscular (i.m.)) 30 min before challenge with 56 micrograms/kg, subcutaneous (s.c.), (2 x LD50) of the nerve agent soman. One min after soman, the animals were treated (i.m.) with 2 mg/kg atropine sulfate admixed with 25 mg/kg of the oxime 2-pralidoxime chloride, and the EEG was observed for seizure onset. When administered (intraperitoneal, i.p.) therapeutically 5 min after seizure onset, only the highest fosphenytoin dose (180 mg/kg) was capable of terminating seizure activity in 50% of the animals tested (3 of 6). When fosphenytoin (18-180 mg/kg) was administered as a pretreatment, i.p., 30 min before soman challenge, seizures were blocked or terminated in a dose-dependent fashion (ED50 = 61.8 mg/kg; 40.5-94.7 mg/kg = 95% confidence limits). Combinations of diazepam and fosphenytoin were also tested for effectiveness. No dose of fosphenytoin (18-56 mg/kg), given in conjunction with a fixed dose of diazepam (4.8 mg/kg, i.m.) 5 min after seizure onset, enhanced the anticonvulsant effect of diazepam. When fosphenytoin (18 or 32 mg/kg, i.p.) was given as a pretreatment and diazepam was given 5 min after seizure onset, the 32 mg/kg dose of fosphenytoin significantly reduced the time for seizure control. These studies show that fosphenytoin, either alone or in combination with diazepam, has little or no therapeutic anticonvulsant effectiveness for nerve agent-induced status epilepticus.

Animals↗

Quantitative studies on enzymes in structures in striated muscles by labeled inhibitor methods. I. The number of acetylcholinesterase molecules and of other DFP-reactive sites at motor endplates, measured by radioautography.

Di-isopropylfluorophosphate (DFP) labeled with phosphorus-32 was applied to fragments of the diaphragm and sternomastoid muscles of the mouse, in conditions in which it saturated all available sites at the motor endplates. After adequate washing and exchange with unlabeled DFP, single endplates were obtained by microdissection and their radioactivity was found by beta track radioautography. The number of sites phosphorylated by DFP-(32)P per endplate was relatively constant for each muscle: in the sternomastoid, about 9 x 10(7) sites per endplate, in the diaphragm, about 3 x 10(7). Reaction with DFP-(32)P was abolished by prior treatment with unlabeled DFP. Labeling was unaffected by prior fixation in formaldehyde, but was inversely proportional to the time of incubation in the Koelle staining medium, when this preceded labeling. The contribution of acetylcholinesterase (AChase) to this total number of DFP-reactive sites was determined by three methods. The first involved reactivation of the phosphorylated AChase by pyridine-2-aldoxime methiodide (2-PAM), in conditions in which the reactivation of other enzymes would be insignificant. The other two methods involved protection of the active centers of AChase from phosphorylation by labeled DFP by use of 284C51, an inhibitor highly specific for this enzyme, or by use of eserine. Each of these methods indicated that about 35% of the DFP-reactive sites at endplates of the sternomastoid and diaphragm are AChase. The mean number of AChase molecules was thus found to be 3.1 x 10(7) and 1.1 x 10(7)per endplate in sternomastoid and diaphragm, respectively. No significant reaction of labeled DFP with muscle and nerve was observed. Mast cells in the muscle had a concentration of DFP-reactive sites far higher than the endplates.

Acetylcholinesterase↗

Quantitative studies on enzymes in structures in striated muscles by labeled inhibitor methods. II. Confirmation of radioautographic measurement by liquid-scintillation counting.

Fragments of mouse diaphragm and sternomastoid muscles were incubated in diisopropyl-fluorophosphate (DFP)-(3)H in conditions known to saturate all the available DFP-sensitive reaction sites. After being extensively washed, the enzyme acetylcholinesterase (AChase) was specifically reactivated by treatment with pyridine-2-aldoxime methiodide (2-PAM). The radioactive DP-groups released into solution by 2-PAM were measured by liquid scintillation counting, and related to the known number of motor endplates present. Considerable difficulty was encountered in reducing the excess, adsorbed radioactivity to acceptable levels: long washing routines, extraction with organic solvents, and removing excess muscle fiber by microdissection were necessary. Six experiments gave a mean value of 2.4 x 10(7)molecules AChase per sternomastoid endplate, in reasonable agreement with the previously reported measurements by radioautography.

Acetylcholinesterase↗

Effect of PAM-2 Cl, HI-6, and HGG-12 in poisoning by tabun and its thiocholine-like analog in the rat.

It has been shown that HI-6 was the most potent oxime so far known in poisoning by sarin, VX , and soman, but its protective effect in tabun poisoning, allegedly due to poor reactivation of inhibited ChE, was much less pronounced. We have found that the thiocholine-like analog of tabun , O-ethyl, N-N- dimethyamino -S-(2-diethylaminoethyl)- thiophosphatemethylsul fomethylate (Ta-S-N+), was very useful in resolving this problem and established the relationship between reactivating and protective effects of PAM-2 Cl, HI-6, and HGG-12 in rats. PAM-2 Cl (protective ratio (PR) = 22.1) and HI-6 (PR = 24.8), combined with atropine, were very effective against Ta-S-N+ poisoning and reactivating inhibited RBC AChE in vitro and rat blood ChE in vivo. The inefficiency of PAM-2 Cl (PR = 1.6) and HI-6 (PR = 2) in tabun poisoning was due to their inadequacy to reactive tabun -inhibited ChEs . The protective effects of HGG-12 in tabun (PR = 2.8) and Ta-S-N+ poisoning (PR = 2.6) were low, and in the absence of any reactivation of inhibited ChEs , have been attributed to its direct pharmacological effects, which were much more potent in the comparison with PAM-2 Cl or HI-6. It is concluded that the reactivation of inhibited ChE is of decisive importance in the efficient protection in poisoning by tabun and other known chemical warfare nerve agents, whereas their direct pharmacological effects are of limited value, allowing survival of animals only against a few LD50s .

Animals↗

Comparing therapeutic and prophylactic protection against the lethal effect of paraoxon.

Prophylactic and therapeutic efficacy against organophosphorus (OP) intoxication by pralidoxime (2-PAM) and atropine were studied and compared with sterically stabilized long-circulating liposomes encapsulating recombinant organophosphorus hydrolase (OPH), either alone or in various specific combinations, in paraoxon poisoning. Prophylactic and therapeutic properties of atropine and 2-PAM are diminished when they are used alone. However, their prophylactic effects are enhanced when they are used in combination. Present studies indicate that sterically stabilized liposomes (SL) encapsulating recombinant OPH (SL-OPH) alone can provide much better therapeutic and prophylactic protection than the classic 2-PAM + atropine combination. This protection was even more dramatic when SL-OPH was employed in combination with 2-PAM and/or atropine: the magnitude of prophylactic antidotal protection was an astounding 1022 LD(50) [920 mg/kg (LD(50) of paraoxon with antagonists)/ 0.95 mg/kg (LD(50) of control paraoxon)], and the therapeutic antidotal protection was 156 LD(50) [140 mg/kg (LD(50) of paraoxon with antagonists)/0.9 mg/kg (LD(50) of control paraoxon)]. The current study firmly establishes the value of using liposome encapsulating OPH.

Animals↗

Percutaneous organophosphate poisoning.

After cutaneous application of the organophosphate insecticide Diazinon for pubic lice, our patient had symptoms of cholinergic excess, lost consciousness, and had a seizure. Because of the high index of clinical suspicion for potentially lethal organophosphate poisoning, the patient received empiric therapy with pralidoxime and atropine and completely recovered.

Atropine↗

Survey of the stocking of poison antidotes in Alabama hospitals.

BACKGROUND: We wanted to estimate the current antidote supply in Alabama hospitals, establish if certain antidotes were stocked more than others, and identify certain parameters (eg, treatment level of care, licensed bed size, or county population) as predictors for the current antidote supply. METHODS: We faxed surveys to treatment level I/II hospitals and a random sample of treatment level III hospitals. Antidote supply was reported for digoxin immune Fab, pyridoxine, ethanol, pralidoxime, antivenin (Crotalidae), deferoxamine, cyanide, naloxone, and fomepizole. RESULTS: Of treatment level I/II and level III hospitals surveyed, 28 (100%) and 20 (71.4%) responded, respectively. None (0%) of the hospitals surveyed had adequate stocking for all nine antidotes. The results illustrate the common practice of understocking poison antidotes. CONCLUSIONS: Hospitals must reevaluate their current antidote inventories for meeting the needs of acutely poisoned patients. Policy containing specific guidelines must be developed and uniformly adopted as standard of practice.

Alabama↗

Oxime therapy and outcomes in human organophosphate poisoning: an evaluation using meta-analytic techniques.

OBJECTIVE: The status of oximes in human organophosphate poisoning is controversial. This analysis compares the outcomes of therapy with or without oximes. DESIGN: Quantitative analysis using meta-analytic techniques. METHODS: Controlled trials of oximes in human organophosphate poisoning were identified by search of MEDLINE and TOXLINE (1966 to May 2005) and review of published articles. MEASUREMENTS AND MAIN RESULTS: Of the 3,122 articles on organophosphate poisoning identified by electronic search, 116 related to oxime use in human organophosphate poisoning. Seven trials, including two randomized controlled trials, compared oximes with standard medical care. Varying dosage schedules of pralidoxime or obidoxime were used. The effects of oxime therapy on mortality rate, mechanical ventilation, incidence of intermediate syndrome, and need for intensive care therapy were analyzed and expressed as risk difference (positive values indicating oxime harm). The random effects estimator was reported because of underlying heterogeneity of treatment effects between study types. No statistically significant association of oxime therapy was demonstrated for either mortality (risk difference 0.09, 95% confidence interval -0.08 to 0.27), ventilatory requirements (risk difference 0.16, 95% confidence interval -0.07 to 0.38), or the incidence of intermediate syndrome (risk difference 0.16, 95% confidence interval -0.12 to 0.45), although point estimates of effect suggested harm. An increased need for intensive care therapy (risk difference 0.19, 95% confidence interval 0.01 to 0.36) was apparent with oxime therapy. CONCLUSIONS: Based on the current available data on human organophosphate poisoning, oxime was associated with either a null effect or possible harm. The lack of current prospective randomized controlled trials, with appropriate patient stratification, mandates ongoing assessment of the role of oximes in organophosphate poisoning.

Adult↗

Pediatric nerve agent poisoning: medical and operational considerations for emergency medical services in a large American city.

Most published recommendations for treatment of pediatric nerve agent poisoning are based on standard resuscitation doses for these agents. However, certain medical and operational concerns suggest that an alternative approach may be warranted for treatment of children by emergency medical personnel after mass chemical events. (1) There is evidence both that suprapharmacological doses may be warranted and that side effects from antidote overdosage can be tolerated. (2) There is concern that many emergency medical personnel will have difficulty determining both the age of the child and the severity of the symptoms. Therefore, the Regional Emergency Medical Advisory Committee of New York City and the Fire Department, City of New York, Bureau of Emergency Medical Services, in collaboration with the Center for Pediatric Emergency Medicine of the New York University School of Medicine and the Bellevue Hospital Center, have developed a pediatric nerve agent antidote dosing schedule that addresses these considerations. These doses are comparable to those being administered to adults with severe symptoms and within limits deemed tolerable after inadvertent nerve agent overdose in children. We conclude that the above approach is likely a safe and effective alternative to weight-based dosing of children, which will be nearly impossible to attain under field conditions.

Antidotes↗

A case of acute poisoning due to organophosphate insecticide.

A case of acute severe organophosphate poisoning by deliberate self administration is reported. The patient required intensive therapy for 30 days. Unusual features of the case were the avoidance of atropine, because of the high risk of ventricular fibrillation, and the ineffectiveness of pralidoxime.

Acute Disease↗

Pralidoxime mesylate absorption and heart rate response to atropine sulphate following intramuscular administration of solution mixtures.

1. The oxime pralidoxime mesylate (P2S) and atropine sulphate, alone and mixed, have been administered intramuscularly to forty-four human subjects. Doses of 750 mg and 500 mg P2S and 2.0 mg atropine sulphate were used. 2. The presence of P2S had no significant influence, as judged by effect on heart rate, on the absorption of atropine although there was a tendency for atropine to exert its effects more rapidly when administered mixed with P2S. 3. No significant difference in the rate of uptake of P2S as judged by plasma levels following injection, between a combined (plus atropines) and single (P2S alone) intramuscular injection was found.

Absorption↗