Plasma Pharmacokinetics of Intravenously Administered Atropine in Normal Human Subjects

Adams, Richard G.; Verma, Pankaj; Jackson, André J.; Miller, Russell L.

doi:10.1002/j.1552-4604.1982.tb02638.x

Cited by 55 publications

(28 citation statements)

References 5 publications

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“…The typical doses ingested (from a few up to more than 100 mg) and half-lives of the substances (range ∼1-6 h) are also variable. [24][25][26][27][28][29] In almost all (93%) of the bioanalytically confirmed intoxications with these substances, the results were in accordance with the clinical record, whereas no specific plant material was indicated in the remaining cases. This high self-report rate is in opposite to the generally lower agreement between verbal measures and laboratory findings seen in illegal drug intoxications.…”

Section: Discussionsupporting

confidence: 77%

Bioanalytical and clinical evaluation of 103 suspected cases of intoxications with psychoactive plant materials

Björnstad

Hultén

Beck

et al. 2009

Clinical Toxicology

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Section: Discussionsupporting

confidence: 77%

Bioanalytical and clinical evaluation of 103 suspected cases of intoxications with psychoactive plant materials

Björnstad

Hultén

Beck

et al. 2009

Clinical Toxicology

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“…The site of action of atropine is in the brain since atropine did not appear in the peripheral circulation, as was the case for other compounds and peptides in dogs (Inui et al 1987) and other species ). The long half-life (4T25 h) of atropine in the blood (Adams et al 1982) makes it unlikely that a pulse of atropine reached the pancreas via the blood but was cleared rapidly within the sampling points of the present experiments.…”

Section: Discussionmentioning

confidence: 96%

Central cholinergic regulation of pancreatic polypeptide secretion in conscious dogs

Okita

Inui²,

Baba³

et al. 1997

Journal of Endocrinology

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The secretion of pancreatic polypeptide (PP) is regulated by fluctuations in blood glucose concentrations and food intake, in which vagal-cholinergic mechanisms play an important role, especially for the cephalic phase of PP secretion. In this study, we examined whether central cholinergic mechanisms are also important for PP secretion by relaying information in the brain to the vagus nerve and the muscarinic cholinergic receptors in the pancreas. Atropine sulfate (20-200 micrograms) was administered into the lateral cerebral ventricle and its effects on the basal secretion of PP as well as the secretions stimulated by insulin-induced hypoglycemia (Actrapid MC, 0.25 U/kg) and a mixed meal (243 kcal) were studied in seven dogs. Intralateral cerebroventricular (ILV) atropine (100 and 200 micrograms) abolished the fluctuations in basal PP secretion without appearing in the plasma. Pretreatment with 20, 100, and 200 micrograms ILV atropine significantly decreased the PP response to insulin-induced hypoglycemia, with the integrated PP response to 58, 32, and 26% of that of controls respectively. Atropine (100 micrograms ILV) significantly reduced the postprandial PP secretion in both the cephalic and the gastrointestinal phases, whereas increased insulin and glucose levels were unaffected. Centrally administered atropine was able to suppress the basal secretion of PP as well as the secretions stimulated by hypoglycemia and food intake. These findings suggest that (1) the spontaneous release of PP is governed by an oscillating, central cholinergic tone, and (2) the stimulating PP secretion is, at least in part, regulated by the central cholinergic system.

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“…Atropine and 2-PAM have short half-lives in humans (Adams et al 1982;Kanto and Klotz 1988;Jovanovic´1989;Sidell et al 1972;Willems et al 1992) and their continuous infusion is recommended in severe OP poisoning. As this was the case in our patient, it should be noted that, whereas 2-PAM was given at the highest doses, atropine was given at far below usual doses for cases of severe poisoning, suggesting that 2-PAM contributed more than atropine to the control of cholinergic toxicity.…”

Section: Median (Range)mentioning

confidence: 97%

The relationship between isofenphos cholinergic toxicity and the development of polyneuropathy in hens and humans

Moretto

Lotti

2002

Archives of Toxicology

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Species differences have been observed between hen and human clinical manifestations of isofenphos toxicities. Hens treated with the insecticide isofenphos (90 mg/kg p.o.) developed severe cholinergic toxicity followed by mild organophosphate-induced delayed polyneuropathy (OPIDP). However, a patient developed severe OPIDP, which was preceded by very mild cholinergic signs, after an attempted suicide with a commercial formulation containing isofenphos and phoxim, an insecticide not causing OPIDP (estimated doses were 500 and 125 mg/kg, respectively). To explain this difference the following hypotheses were tested: (1) phoxim is a promoter of isofenphos-induced OPIDP; (2) whereas neuropathy target esterase (NTE) is thought to be the target of OPIDP, activation of isofenphos by liver microsomes causes the formation of more potent NTE inhibitor(s) in humans than in hens; (3) in contrast to hen NTE, the sensitivity of the human enzyme to such inhibitor(s) is higher than that of acetylcholinesterase (AChE), the target of cholinergic toxicity. Results showed that phoxim (22.5 mg/kg p.o.) was not a promoter of OPIDP in hens and that the ratio AChE inhibition:NTE inhibition by microsome-activated isofenphos was similar for both hen and human enzymes. The schedule of antidotal treatment in hens is the likely explanation for the observed difference from the patient. Peak AChE inhibition was maintained in hen brain up to 6 days after a single dose of isofenphos, suggesting prolonged pharmacokinetics. However, the AChE reactivator pyridine-2-aldoxime (2-PAM) was given to hens before isofenphos and then every 8 h, whereas continuous 2-PAM infusion was provided to the patient. When 2-PAM was given to hens every hour after isofenphos (90 mg/kg p.o.), the birds remained asymptomatic. Since other organophosphates may have a prolonged pharmacokinetics, testing procedures for the potential of these insecticides to cause OPIDP may underestimate the risk for humans.

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Plasma Pharmacokinetics of Intravenously Administered Atropine in Normal Human Subjects

Cited by 55 publications

References 5 publications

Bioanalytical and clinical evaluation of 103 suspected cases of intoxications with psychoactive plant materials

Bioanalytical and clinical evaluation of 103 suspected cases of intoxications with psychoactive plant materials

Central cholinergic regulation of pancreatic polypeptide secretion in conscious dogs

The relationship between isofenphos cholinergic toxicity and the development of polyneuropathy in hens and humans

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