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Anesthesiology Apr 1987To determine the potencies of neostigmine, pyridostigmine, and edrophonium in reversing pancuronium and d-tubocurarine blockade, dose-response curves were established... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
To determine the potencies of neostigmine, pyridostigmine, and edrophonium in reversing pancuronium and d-tubocurarine blockade, dose-response curves were established for first twitch height recovery and train-of-four ratio. One hundred and twenty ASA physical status I or II patients scheduled for elective surgery received either 0.06 mg/kg pancuronium or 0.36 mg/kg d-tubocurarine during a thiopental-nitrous oxide-enflurane anesthetic. Train-of-four stimulation was applied every 12 s, and the force of contraction of the adductor pollicis muscle was recorded. When first twitch height had recovered spontaneously to 10% of its initial value, neostigmine (0.005, 0.01, 0.02 or 0.05 mg/kg), pyridostigmine (0.02, 0.04, 0.1, or 0.2 mg/kg), or edrophonium (0.1, 0.2, 0.4 or 1 mg/kg) was injected by random allocation. Recovery was measured 10 min after the injection of the antagonist. First twitch ED50's were 0.013, 0.085, and 0.17 mg/kg after pancuronium, and 0.017, 0.11, and 0.27 mg/kg after d-tubocurarine, for neostigmine, pyridostigmine, and edrophonium, respectively. The ED50 for pyridostigmine and edrophonium obtained after d-tubocurarine was significantly larger (P less than 0.05) than that after pancuronium. The train-of-four dose-response curves were significantly flatter for edrophonium than for the other two agents, indicating a greater ability of edrophonium to antagonize fade at low doses. It is concluded that the potency of reversal agents may be different for different relaxants, and that potency ratios might depend upon the end-point chosen as full neuromuscular recovery.
Topics: Adult; Dose-Response Relationship, Drug; Edrophonium; Female; Humans; Male; Middle Aged; Muscle Contraction; Neostigmine; Neuromuscular Junction; Pancuronium; Pyridostigmine Bromide; Tubocurarine
PubMed: 3565812
DOI: 10.1097/00000542-198704000-00004 -
Case Reports in Neurology 2021It remains uncertain to what extent lower urinary tract (LUT) symptom (LUTS) is a comorbidity of myasthenia gravis (MG). We prospectively administered a LUTS...
It remains uncertain to what extent lower urinary tract (LUT) symptom (LUTS) is a comorbidity of myasthenia gravis (MG). We prospectively administered a LUTS questionnaire devised for detecting neurogenic pelvic organ dysfunction (not validated) in an MG group and a healthy control group and compared the results. The MG group comprised 21 patients: 15 women and 6 men, with age range 22-73 (mean 47) years, illness duration range 0.2-8 (mean 3.5) years, median Myasthenia Gravis Foundation of America (MGFA) grade 2, all walking independently. Therapies included thymectomy in 17, predonisolone 5-20 mg/day in 10, and pyridostigmine bromide 60-180 mg/day in 9 patients. The control group, who were undergoing an annual health survey, comprised 235 consecutive subjects: 120 women and 115 men, with age range 30-69 (mean 48) years. The questionnaire had 9 questions. Each question was scored from 0 (none) to 3 (severe) with an additional quality of life (QOL) index scored from 0 (satisfied) to 3 (extremely dissatisfied). Statistical analysis was made using Student's test. Compared with the control subjects, the frequency of LUTSs in the MG patients was significantly higher for daytime frequency (43%; < 0.01), nocturia (24%; < 0.01), and urinary incontinence (43%; < 0.05). The LUTS-related QOL index for the MG patients was significantly higher for MG patients as a whole than that for all control patients (29%) ( < 0.05). In conclusion, our study results showed that MG patients had significantly more LUTSs (overactive bladder) than healthy control subjects and had worse LUTS-related QOL; therefore, amelioration of LUTS in MG is important.
PubMed: 34413752
DOI: 10.1159/000514825 -
Respiratory Physiology & Neurobiology Sep 2017The current work was conducted to verify the contribution of neuromuscular transmission defects at the neuromuscular junction to Duchenne Muscular Dystrophy disease...
The current work was conducted to verify the contribution of neuromuscular transmission defects at the neuromuscular junction to Duchenne Muscular Dystrophy disease progression and respiratory dysfunction. We tested pyridostigmine and pyridostigmine encapsulated in liposomes (liposomal PYR), an acetylcholinesterase inhibitor to improve muscular contraction on respiratory muscle function in mdx mice at different ages. We evaluated in vivo with the whole-body plethysmography, the ventilatory response to hypercapnia, and measured in vitro diaphragm strength in each group. Compared to C57BL10 mice, only 17 and 22 month-old mdx presented blunted ventilatory response, under normocapnia and hypercapnia. Free pyridostigmine (1mg/kg) was toxic to mdx mice, unlike liposomal PYR, which did not show any side effect, confirming that the encapsulation in liposomes is effective in reducing the toxic effects of this drug. Treatment with liposomal PYR, either acute or chronic, did not show any beneficial effect on respiratory function of this DMD experimental model. The encapsulation in liposomes is effective to abolish toxic effects of drugs.
Topics: Age Factors; Animals; Cholinesterase Inhibitors; Disease Models, Animal; Drug Delivery Systems; In Vitro Techniques; Liposomes; Male; Mice; Mice, Inbred C57BL; Mice, Inbred mdx; Muscle Contraction; Muscular Dystrophy, Duchenne; Plethysmography; Pyridostigmine Bromide; Respiration Disorders; Respiratory Muscles; Respiratory Rate; Spectrophotometry, Ultraviolet; Tidal Volume
PubMed: 28624507
DOI: 10.1016/j.resp.2017.06.001 -
Journal of Pharmacy & Pharmaceutical... 2006Pyridostigmine bromide (PB) is a quartenary ammonium compound that inhibits the hydrolysis of acetylcholine by competitive reversible binding to acetylcholinesterase. PB...
Pyridostigmine bromide (PB) is a quartenary ammonium compound that inhibits the hydrolysis of acetylcholine by competitive reversible binding to acetylcholinesterase. PB is used for the symptomatic treatment of myasthenia gravis and has been applied as a prophylaxis against nerve agents. Many studies on PB have involved the reliance on techniques that extract and quantify PB in biological samples. This article presents an overview of the currently applied methodologies for the determination of PB and its metabolites in various biological samples. Articles published from January 1975 to the July 2005 were taken into consideration for the discussion of the metabolism and analytical method of PB. HPLC and GC methods have been used and discussed in most of the references cited in this review. Other methods such as RIA and CE that have been recently reported are also mentioned in this article. Basic information about the type of sample used for analysis, sample preparation, chromatographic column, mobile phase, detection mode and validation data are summarized in a table.
Topics: Animals; Cholinesterase Inhibitors; Chromatography, Gas; Chromatography, High Pressure Liquid; Humans; Myasthenia Gravis; Plasma; Pyridostigmine Bromide; Reproducibility of Results; Urine
PubMed: 16849010
DOI: No ID Found -
Medicina (Kaunas, Lithuania) Dec 2023: The association between myasthenia gravis (MG) and depression is intricate and characterized by bidirectional causality. In this regard, MG can be a contributing...
: The association between myasthenia gravis (MG) and depression is intricate and characterized by bidirectional causality. In this regard, MG can be a contributing factor to depression and, conversely, depression may worsen the symptoms of MG. This study aimed to identify any differences in the progression of the disease among patients with MG who were also diagnosed with depression as compared to those without depression. Our hypothesis focused on the theory that patients with more severe MG symptoms may have a higher likelihood of suffering depression at the same time. : One hundred twenty-two male and female patients (N = 122) aged over 18 with a confirmed diagnosis of autoimmune MG who were admitted to the Neurology II department of Myasthenia Gravis, Clinical Institute Fundeni in Bucharest between January 2019 and December 2020, were included in the study. Patients were assessed at baseline and after six months. The psychiatric assessment of the patients included the Hamilton Depression Rating Scale-17 items (HAM-D), and neurological status was determined with two outcome measures: Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis Activities of Daily Life (MG-ADL). The patients were divided into two distinct groups as follows: group MG w/dep, which comprised 49 MG patients diagnosed with depressive disorder who were also currently receiving antidepressant medication, and group MG w/o dep, which consisted of 73 patients who did not have depression. : In our study, 40.16% of the myasthenia gravis (MG) patients exhibited a comorbid diagnosis of depression. Among the MG patients receiving antidepressant treatment, baseline assessments revealed a mean MG-ADL score of 7.73 (SD = 5.05), an average QMG score of 18.40 (SD = 8.61), and a mean Ham-D score of 21.53 (SD = 7.49). After a six-month period, a statistically significant decrease was observed in the MG-ADL (2.92, SD = 1.82), QMG (7.15, SD = 4.46), and Ham-D scores (11.16, SD = 7.49) ( < 0.0001). These results suggest a significant correlation between MG severity and elevated HAM-D depression scores. Regarding the MG treatment in the group with depression, at baseline, the mean dose of oral corticosteroids was 45.10 mg (SD = 16.60). Regarding the treatment with pyridostigmine, patients with depression and undergoing antidepressant treatment remained with an increased need for pyridostigmine, 144.49 mg (SD = 51.84), compared to those in the group without depression, 107.67 mg (SD = 55.64, < 0.001). : Our investigation confirms that the occurrence of depressive symptoms is significantly widespread among individuals diagnosed with MG. Disease severity, along with younger age and higher doses of cortisone, is a significant factor associated with depression in patients with MG. Substantial reductions in MG-ADL and QMG scores were observed within each group after six months, highlighting the effectiveness of MG management. The findings suggest that addressing depressive symptoms in MG patients, in addition to standard MG management, can lead to improved clinical outcomes.
Topics: Humans; Female; Male; Adolescent; Adult; Pyridostigmine Bromide; Depression; Myasthenia Gravis; Antidepressive Agents; Disease Progression
PubMed: 38256317
DOI: 10.3390/medicina60010056 -
British Journal of Pharmacology Sep 1968
Topics: Cholinesterases; Electromyography; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Maternal-Fetal Exchange; Myasthenia Gravis; Neostigmine; Pregnancy; Pyridostigmine Bromide; Time Factors
PubMed: 5692081
DOI: No ID Found -
Journal of Cellular and Molecular... May 2021Heart failure (HF) is characterized by asymmetrical autonomic balance. Treatments to restore parasympathetic activity in human heart failure trials have shown beneficial...
Heart failure (HF) is characterized by asymmetrical autonomic balance. Treatments to restore parasympathetic activity in human heart failure trials have shown beneficial effects. However, mechanisms of parasympathetic-mediated improvement in cardiac function remain unclear. The present study examined the effects and underpinning mechanisms of chronic treatment with the cholinesterase inhibitor, pyridostigmine (PYR), in pressure overload HF induced by transverse aortic constriction (TAC) in mice. TAC mice exhibited characteristic adverse structural (left ventricular hypertrophy) and functional remodelling (reduced ejection fraction, altered myocyte calcium (Ca) handling, increased arrhythmogenesis) with enhanced predisposition to arrhythmogenic aberrant sarcoplasmic reticulum (SR) Ca release, cardiac ryanodine receptor (RyR2) hyper-phosphorylation and up-regulated store-operated Ca entry (SOCE). PYR treatment resulted in improved cardiac contractile performance and rhythmic activity relative to untreated TAC mice. Chronic PYR treatment inhibited altered intracellular Ca handling by alleviating aberrant Ca release and diminishing pathologically enhanced SOCE in TAC myocytes. At the molecular level, these PYR-induced changes in Ca handling were associated with reductions of pathologically enhanced phosphorylation of RyR2 serine-2814 and STIM1 expression in HF myocytes. These results suggest that chronic cholinergic augmentation alleviates HF via normalization of both canonical RyR2-mediated SR Ca release and non-canonical hypertrophic Ca signaling via STIM1-dependent SOCE.
Topics: Animals; Arrhythmias, Cardiac; Calcium; Cholinesterase Inhibitors; Heart Failure; Male; Mice; Mice, Inbred C57BL; Pyridostigmine Bromide; Ryanodine Receptor Calcium Release Channel; Stromal Interaction Molecule 1
PubMed: 33755308
DOI: 10.1111/jcmm.16356 -
Brain Sciences Nov 2021About 25-35% of United States veterans who fought in the 1990-1991 Gulf War report several moderate or severe chronic systemic symptoms, defined as Gulf War illness...
About 25-35% of United States veterans who fought in the 1990-1991 Gulf War report several moderate or severe chronic systemic symptoms, defined as Gulf War illness (GWI). Thirty years later, there is little consensus on the causes or biological underpinnings of GWI. The Gulf War Era Cohort and Biorepository (GWECB) was designed to investigate genetic and environmental associations with GWI and consists of 1343 veterans. We investigate candidate gene-toxicant interactions that may be associated with GWI based on prior associations found in human and animal model studies, focusing on SNPs in or near , , and genes to replicate results from prior studies. was also considered as a candidate gene. CDC Severe GWI, the primary outcome, was observed in 26% of the 810 deployed veterans included in this study. The interaction between the candidate SNP rs662 and pyridostigmine bromide (PB) pills was found to be associated with CDC Severe GWI. Interactions between PB pill exposure and rs3917545, rs3917550, and rs2299255, all in high linkage disequilibrium in , were also associated with respiratory symptoms. These SNPs could point toward biological pathways through which GWI may develop, which could lead to biomarkers to detect GWI or to better treatment options for veterans with GWI.
PubMed: 34942860
DOI: 10.3390/brainsci11121558 -
Anesthesiology Oct 1992
Review
Topics: Age Factors; Cholinesterase Inhibitors; Drug Interactions; Edrophonium; Humans; Neostigmine; Neuromuscular Blocking Agents; Pyridostigmine Bromide
PubMed: 1416176
DOI: 10.1097/00000542-199210000-00025 -
Neuropharmacology Jul 2020Gulf War Illness (GWI) is a chronic multi-symptom disorder, characterized by symptoms such as fatigue, pain, cognitive and memory impairment, respiratory, skin and... (Review)
Review
Gulf War Illness (GWI) is a chronic multi-symptom disorder, characterized by symptoms such as fatigue, pain, cognitive and memory impairment, respiratory, skin and gastrointestinal problems, that is experienced by approximately one-third of 1991 Gulf War veterans. Over the nearly three decades since the end of the war, investigators have worked to elucidate the initiating factors and underlying causes of GWI. A significant portion of this research has indicated a strong correlation between GWI and exposure to a number of different acetycholinesterase inhibitors (AChEIs) in theater, such as sarin and cyclosarin nerve agents, chlorpyrifos and dichlorvos pesticides, and the anti-nerve agent prophylactic pyridostigmine bromide. Through studying these exposures and their relationship to the symptoms presented by ill veterans, it has become increasingly apparent that GWI is the likely result of an underlying neuroimmune disorder. While evidence indicates that AChEIs are a key exposure in the development of GWI, particularly organophosphate AChEIs, the mechanism(s) by which these chemicals instigate illness appears to be related to "off-target", non-cholinergic effects. In this review, we will discuss the role of AChEI exposure in the development and persistence of GWI; in particular, how these chemicals, combined with other exposures, have led to a chronic neuroimmune disorder. This article is part of the special issue entitled 'Acetylcholinesterase Inhibitors: From Bench to Bedside to Battlefield'.
Topics: Chemical Warfare Agents; Cholinesterase Inhibitors; Encephalitis; Gulf War; Humans; Persian Gulf Syndrome; Veterans
PubMed: 32247728
DOI: 10.1016/j.neuropharm.2020.108073