Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The paper deals with the case of a 49 years old man having been exposed to cadmium in the production of alkaline Ni-Cd accumulators for a long period. It presents and compares the results of some years lasting biological monitoring of the exposition in vivo (beta 2 microglobulin in urine and serum, Cd in urine, blood, serum and hair, Zn in urine, serum and hair, Ni in urine and hair, alpha 1 antitrypsin in serum, dehydratase activity of delta-aminolevulinic acid in blood, cholinesterase activity in blood, etc., with the Cd concentrations found out in the tissues post mortem (nail 12 micrograms/g, cerebrum 0.4 microgram/g, lungs 19 micrograms/g, liver 165 micrograms/g, kidneys 245 micrograms/g). The Cd contents in the tissue were significantly increased compared with the non-exposed population and in fact, they confirmed the data and conclusions from the biological monitoring in vivo signalling the light tubular renal impairment as the most significant symptom of the exposition.
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PMID:[Evaluation of the effect of cadmium exposure in a worker in Ni-Cd storage battery production by biological tests in vivo and the cadmium content of tissues postmortem]. 235 Mar 92

We have studied the effect of renal function on the pharmacodynamics of mivacurium. Sixty patients were allocated to three groups according to creatinine clearance: group C (control), creatinine clearance > 50 ml min-1; group P (preterminal renal failure), creatinine clearance < 50 ml min-1 > 20 ml min-1; group T(terminal renal failure), creatinine clearance < 20 ml min-1. Neuromuscular transmission (train-of-four) was monitored using electromyography from the hypothenar muscle with stimulation of the ulnar nerve. After an initial bolus, mivacurium was administered continuously to maintain a T1 of 5 (4)% of baseline. The dose of mivacurium necessary to maintain 95% neuromuscular block was similar in patients with normal renal function and patients with different levels of renal impairment. Recovery from neuromuscular block after ceasing mivacurium infusion was significantly prolonged in patients with preterminal renal impairment. There was a close correlation between mivacurium pharmacodynamics and pseudocholinesterase activity, but not creatinine clearance.
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PMID:Effect of renal function on neuromuscular block induced by continuous infusion of mivacurium. 773 67

The aim of this study was to assess the influence of renal function on the pharmacokinetics, pharmacodynamics, safety, and tolerability of the acetylcholinesterase inhibitor metrifonate. Four groups of six age- and gender-matched subjects with varying degrees of renal function (creatinine clearances more than 90, 60-90, 30-60, and less than 30 mL/min/ 1.73 m2, respectively) were administered a single 50-mg oral dose of metrifonate. Blood and urine samples were collected for 24 hours and concentrations of metrifonate and its metabolites dichlorvos, dichloroacetic acid, and M3 were determined. Inhibition of acetylcholinesterase activity in erythrocytes and butyrylcholinesterase in plasma were also measured. Metrifonate was well tolerated in all treatment groups. The urinary excretion of metrifonate and dichlorvos decreased with decreasing renal function but accounted for less than 2% of the elimination. There were no statistically significant differences in primary pharmacokinetic parameters--Cmax, t(max), area under the concentration-time curve (AUC), and t1/2--of metrifonate and dichlorvos among the different groups. The excretion of dichloroacetic acid and M3 was not influenced by renal impairment. Acetylcholinesterase was not inhibited, whereas butyrylcholinesterase was inhibited markedly but independently of renal function. No metrifonate dose adjustments are needed when treating subjects with renal impairment.
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PMID:Pharmacokinetics and pharmacodynamics of the acetylcholinesterase inhibitor metrifonate in patients with renal impairment. 1036 43

Tramadol and tapentadol are two atypical synthetic opioid analgesics, with monoamine reuptake inhibition properties. Mainly aimed at the treatment of moderate to severe pain, these drugs are extensively prescribed for multiple clinical applications. Along with the increase in their use, there has been an increment in their abuse, and consequently in the reported number of adverse reactions and intoxications. However, little is known about their mechanisms of toxicity. In this study, we have analyzed the in vivo toxicological effects in liver and kidney resulting from an acute exposure of a rodent animal model to both opioids. Male Wistar rats were intraperitoneally administered with 10, 25 and 50mg/kg tramadol and tapentadol, corresponding to a low, effective analgesic dose, an intermediate dose and the maximum recommended daily dose, respectively, for 24h. Toxicological effects were assessed in terms of oxidative stress, biochemical and metabolic parameters and histopathology, using serum and urine samples, liver and kidney homogenates and tissue specimens. The acute exposure to tapentadol caused a dose-dependent increase in protein oxidation in liver and kidney. Additionally, exposure to both opioids led to hepatic commitment, as shown by increased serum lipid levels, decreased urea concentration, increased alanine aminotransferase and decreased butyrylcholinesterase activities. It also led to renal impairment, as reflected by proteinuria and decreased glomerular filtration rate. Histopathological findings included sinusoidal dilatation, microsteatosis, vacuolization, cell infiltrates and cell degeneration, indicating metabolic changes, inflammation and cell damage. In conclusion, a single effective analgesic dose or the maximum recommended daily dose of both opioids leads to hepatotoxicity and nephrotoxicity, with tapentadol inducing comparatively more toxicity. Whether these effects reflect risks during the therapeutic use or human overdoses requires focused attention by the medical community.
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PMID:Acute administration of tramadol and tapentadol at effective analgesic and maximum tolerated doses causes hepato- and nephrotoxic effects in Wistar rats. 2868 66

We previously verified a physiologically based pharmacokinetic (PBPK) model for mirabegron in healthy subjects using the Simcyp Simulator by incorporating data on the inhibitory effect on cytochrome P450 (CYP) 2D6 and a multi-elimination pathway mediated by CYP3A4, uridine 5'-diphosphate-glucuronosyltransferase (UGT) 2B7 and butyrylcholinesterase (BChE). The aim of this study was to use this PBPK model to assess the magnitude of drug-drug interactions (DDIs) in an elderly population with severe renal impairment (sRI), which has not been evaluated in clinical trials. We first determined the system parameters, and meta-analyses of literature data suggested that the abundance of UGT2B7 and the BChE activity in an elderly population with sRI was almost equivalent to and 20% lower than that in healthy young subjects, respectively. Other parameters, such as the CYP3A4 abundance, for an sRI population were used according to those built into the Simcyp Simulator. Second, we confirmed that the PBPK model reproduced the plasma concentration-time profile for mirabegron in an sRI population (simulated area under the plasma concentration-time curve (AUC) was within 1.5-times that of the observed value). Finally, we applied the PBPK model to simulate DDIs in an sRI population. The PBPK model predicted that the AUC for mirabegron with itraconazole (a CYP3A4 inhibitor) was 4.12-times that in healthy elderly subjects administered mirabegron alone, and predicted that the proportional change in AUC for desipramine (a CYP2D6 substrate) with mirabegron was greater than that in healthy subjects. In conclusion, the PBPK model was verified for the purpose of DDI assessment in an elderly population with sRI.
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PMID:Application of a physiologically based pharmacokinetic model for the prediction of mirabegron plasma concentrations in a population with severe renal impairment. 3098 42