Cholinergic antagonists

Profound bradycardia during eye surgery is potentially serious event. In clinical practice this Oculocardiac Reflex (OCR) is most often encountered during squint surgery. The objective of this study was to assess the occurrence of OCR and prove the effect of anticholinergic premedication (atropine) to prevent OCR. This study comprises of sixty patients (age 2-30 years) operated for squint surgery under general anaesthesia. Cases were divided into two groups of thirty each. Group 1 was premedicated with intravenous injection of atropine and Group 2 did not receive any premedication. Patients were monitored during operation for any bradycardia or dysrhythmias. The observed data showed occurrence of 70% OCR in Group 2 as compared to only 10% in Group 1. Severe bradycardia in 40% cases of Group 2 needed intervention by IV injection of atropine. Our study showed that atropine premedication in the patients of squint surgery under general anaesthesia definitely obtunds OCR and prevents any...

The reason for our search was various investigations about urinary tract dysfunctions in enuretic children. The aim of our study was estimation of lover urinary tract function in children with monosymptomatic primary nocturnal enuresis without positive reaction for a long non pharmacological therapy. 54 children after 9-12 months behavioral therapy and short pharmacological treatment (desmopresin) was undergoing urodynamic investigation (uroflowmetry and cystometry). Urodynamic disorders was found in 44/54 of estimated children. In 34 of children it was overactive bladder, in 6 patients we found detrusor-sphincter discoordination. Five children had decreased bladder capacity. Next to non pharmacological treatment we used anticholinergic or Baclofen depending on the results of urodynamic tests. The response to the treatment (non bedwetting at all) we observed in 34 children (in 9 of them after 3 months of therapy, in 16 after 6 months of therapy and in 12 after 12 months of therapy)....

To estimate the association between the duration and level of exposure to different classes of anticholinergic drugs and subsequent incident dementia. Case-control study. General practices in the UK contributing to the Clinical Practice Research Datalink. 40 770 patients aged 65-99 with a diagnosis of dementia between April 2006 and July 2015, and 283 933 controls without dementia. Daily defined doses of anticholinergic drugs coded using the Anticholinergic Cognitive Burden (ACB) scale, in total and grouped by subclass, prescribed 4-20 years before a diagnosis of dementia. Odds ratios for incident dementia, adjusted for a range of demographic and health related covariates. 14 453 (35%) cases and 86 403 (30%) controls were prescribed at least one anticholinergic drug with an ACB score of 3 (definite anticholinergic activity) during the exposure period. The adjusted odds ratio for any anticholinergic drug with an ACB score of 3 was 1.11 (95% confidence interval 1.08 to 1.14). Dementia...

Zero-G parabolic flight reproduces the weightlessness of space for short periods. However, motion sickness may affect some fliers. The aim was to assess the extent of this problem and to find possible predictors and modifying factors. Airbus zero-G flights consist of 31 parabolas performed in blocks. Each parabola consisted of 20 s of 0 g sandwiched by 20 s of hypergravity of 1.5-1.8 g. The survey covered N = 246 person-flights (193 men, 53 women), ages (M ± SD) 36.0 ± 11.3 yr. An anonymous questionnaire included motion sickness rating (1 = OK to 6 = vomiting), Motion Sickness Susceptibility Questionnaire (MSSQ), antimotion sickness medication, prior zero-G experience, anxiety level, and other characteristics. Participants had lower MSSQ percentile scores (27.4 ± 28.0) than the population norm of 50. Motion sickness was experienced by 33% and 12% vomited. Less motion sickness was predicted by older age, greater prior zero-G flight experience, medication with scopolamine, lower MSSQ ...

Bronchoscopy is a procedure that is likely to provoke anxiety as the patient is surrounded by monitoring and bronchoscopy equipment, and care is administered by strangers who perform intimate, invasive, and sometimes, painful procedures. Sedation is needed, therefore, to allay anxiety and reduce stress, improve patient comfort and co-operation, provide amnesia and facilitate the bronchoscopic procedure. In this review we try to summarize the current knowledge on currently used sedation protocols with special reference to the commonly used pharmacological agents. We believe sedation should be used routinely in fiberoptic bronchoscopy in order to achieve a safe and pleasant procedure for both the patient and the pulmonologist.

Zebrafish embryos have small and slow miniature end-plate currents (mEPCs), whereas only a few days later larval mEPCs are an order of magnitude larger and faster, being among the fastest of all neuromuscular synapses. To identify the bases for these changes we compared, in embryos and larvae, the properties and distributions of acetylcholine (ACh) receptors (AChRs) and acetylcholinesterase (AChE) as well as the ultrastructure of the developing neuromuscular junctions (NMJs). To mimic synaptic release, patches of muscle membrane were exposed briefly (for 1 ms) to a saturating concentration (10 mM) of ACh. The AChR deactivation kinetics were twice as slow in embryos compared with larvae. In both embryos and larvae, AChRs demonstrated open channel block by millimolar ACh, and this was detected during mEPCs, indicating that a high concentration of ACh is released at immature and mature NMJs. AChR and AChE distributions were compared using the selective fluorescently conjugated labels a...

We describe a case of acute poisoning in a 51-year-old female patient who presented to the Emergency Depart-ment with weakness, anxiety, dry mouth, bilateral mydriasis and lid drop. In differential diagnosis, botulism, Guillain– Barre ́ syndrome and myasthenia gravis were considered, as well as cerebral haematoma because of a cranial injury a week before. Symptoms, which resolved within 12h without any therapy, were instead related to the ingestion of lupin seeds. European Journal of Emergency Medicine

The influence of albumin, 4.5 and 45 g/l, on the effects of Cu2+, 10(-9)-10(-3) M, on the neuromuscular transmission of the isolated guinea-pig ileum and vas deferens was investigated. Low concentrations of Cu2+, 10(-9)-10(-6) M, caused a slight and transient increase of the contractile response to direct muscle stimulation of the vas deferens. Albumin at 4.5 g/l inhibited this effect. The basal tone of the ileum increased transiently when Cu2+ was added in the presence of albumin, 4.5 g/l. A stimulant action of Cu2+, 10(-9)-10(-6) M, was seen on both organs, when contractions were induced by nerve stimulation. All these effects were inhibited by albumin, 45 g/l. Higher concentrations of Cu2+, 10(-5)-10(-4) M, increased the basal tone of the ileum and the vas deferens. In the presence of albumin, 45 g/l, this stimulating effect of Cu2+ appeared in higher concentrations. The results suggest that Cu2+ is more likely to influence the function of neuronal tissues when the concentration of protein is low.

The aim of the study was to investigate an action of 2-aminopyridine and its new sulfonylcarbamide derivatives 2-AP21, 2-AP22, 2-AP26, and 2-AP27 (10(-5)-10(-3) M) on carbachol-induced shortening of action potential duration and reduction of contraction force in guinea pig atrial muscles. Experiments were carried out using a standard method of myocardium electromechanical activity registration. Under control conditions (perfusion of atrial strips with Tyrode solution), an average of action potential duration, measured at 90% (AP90) and 50% (AP50) of repolarization, were 112.32+/-6.07 ms and 50.21+/-3.25 ms, (n=19), respectively, and contraction force was of 1.42+/-0.28 mN (n=20). Carbachol (10(-6)M), an agonist of muscarinic acetylcholine receptor and activator of K(Ach) channels, markedly decreased AP90 to 35.31+/-4.21%, AP50--to 26.42+/-2.66% (n=19) (P<0.001), and contraction force--to 24.23+/-2.0% (n=20) (P<0.001) vs. control. Modification of 2-aminopyridine structure by re...

The mechanism responsible for the blocking action of mecamylamine on neuronal nicotinic acetylcholine receptors (nAChRs) was studied on rat isolated chromaffin cells recorded under whole-cell patch clamp. Mecamylamine strongly depressed (IC 50 = 0.34 μM) inward currents elicited by ...

Asthma exacerbations can be classified as mild, moderate, severe, or life threatening. Criteria for exacerbation severity are based on symptoms and physical examination parameters, as well as lung function and oxygen saturation. In patients with a peak expiratory flow of 50 to 79 percent of their personal best, up to two treatments of two to six inhalations of short-acting beta2 agonists 20 minutes apart followed by a reassessment of peak expiratory flow and symptoms may be safely employed at home. Administration using a hand-held metered-dose inhaler with a spacer device is at least equivalent to nebulized beta2 agonist therapy in children and adults. In the ambulatory and emergency department settings, the goals of treatment are correction of severe hypoxemia, rapid reversal of airflow obstruction, and reduction of the risk of relapse. Multiple doses of inhaled anticholinergic medication combined with beta2 agonists improve lung function and decrease hospitalization in school-age ...

The nature and extent of adverse cognitive effects due to the prescription of anticholinergic drugs in older people with and without dementia is unclear. We calculated the anticholinergic load (ACL) of medications taken by participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing, a cohort of 211 Alzheimer's disease (AD) patients, 133 mild cognitive impairment (MCI) patients and 768 healthy controls (HC) all aged over 60 years. The association between ACL and cognitive function was examined for each diagnostic group (HC, MCI, AD). A high ACL within the HC group was associated with significantly slower response speeds for the Stroop color and incongruent trials. No other significant relationships between ACL and cognition were noted. In this large cohort, prescribed anticholinergic drugs appeared to have modest effects upon psychomotor speed and executive function, but not on other areas of cognition in healthy older adults.

Alzheimer's disease (AD), a progressive neurodegenerative disorder with many cognitive and neuropsychiatric symptoms is biochemically characterized by a significant decrease in the brain neurotransmitter acetylcholine (ACh). Plant-derived metabolites, including alkaloids have been reported to possess neuroprotective properties and are considered to be safe, thus have potential for developing effective therapeutic molecules for neurological disorders, such as AD. Therefore, in the present study, thirteen plant-derived alkaloids, namely pleiocarpine, kopsinine, pleiocarpamine (from Pleiocarpa mutica, family: Annonaceae), oliveroline, noroliveroline, liridonine, isooncodine, polyfothine, darienine (from Polyalthia longifolia, family: Apocynaceae) and eburnamine, eburnamonine, eburnamenine and geissoschizol (from Hunteria zeylanica, family: Apocynaceae) were analyzed for their anti-cholinergic action through docking with acetylcholinesterase (AChE) as target. Among the alkaloids, pl...

Asthma exacerbations can be classified as mild, moderate, severe, or life threatening. Criteria for exacerbation severity are based on symptoms and physical examination parameters, as well as lung function and oxygen saturation. In patients with a peak expiratory flow of 50 to 79 percent of their personal best, up to two treatments of two to six inhalations of short-acting beta2 agonists 20 minutes apart followed by a reassessment of peak expiratory flow and symptoms may be safely employed at home. Administration using a hand-held metered-dose inhaler with a spacer device is at least equivalent to nebulized beta2 agonist therapy in children and adults. In the ambulatory and emergency department settings, the goals of treatment are correction of severe hypoxemia, rapid reversal of airflow obstruction, and reduction of the risk of relapse. Multiple doses of inhaled anticholinergic medication combined with beta2 agonists improve lung function and decrease hospitalization in school-age ...

Patients with asthma have exaggerated bronchoconstriction of their airways in response to certain indirect (e.g. cold air, allergens, dust, exercise) or direct (e.g. inhaled methacholine) stimuli. This 'hyper-reactivity' usually co-exists with airway inflammation, although the pathophysiological mechanisms underlying these changes are not fully understood. It is likely that this hyper-reactivity is associated with abnormal autonomic nervous system (ANS) control. In particular, the parasympathetic (vagal) component of the ANS appears to be implicated in the pathogenesis of asthma. In addition, several studies have suggested the existence of differential alteration in ANS function following exercise in asthmatics compared with non-asthmatic individuals. Several early studies suggested that the altered autonomic control of airway calibre in asthma might be reflected by a parallel change in heart rate. Cardiac vagal reactivity does indeed appear to be increased in asthma, as dem...

To compare the efficacy of onabotulinumtoxinA, mirabegron, and anticholinergics in adults with idiopathic overactive bladder (OAB) using network meta-analysis (NMA). Information sources were searched for randomized blinded controlled trials, of at least 2 weeks duration, comparing any dose of onabotulinumtoxinA, eligible oral/transdermal anticholinergics, or mirabegron, with each other or placebo, in adults with OAB. Bayesian random-effects models were used to synthesize the results at week 12: NMA for responder analyses and network meta-regression (NMR) for change from baseline analyses. The NMR was used to adjust for differences in baseline severity between studies. Sensitivity analysis, excluding studies considered to be at a high risk of methodological bias, was conducted. 56 randomized trials were included in the networks. For each outcome, results are reported for all licensed treatment doses. For each NMR, results are based on patients with an average number of episodes of th...