SciCombinator

Discover the most talked about and latest scientific content & concepts.

Concept: Anticholinergic

296

To estimate the association between the duration and level of exposure to different classes of anticholinergic drugs and subsequent incident dementia.

Concepts: The Association, Case-control study, Anticholinergic

151

Elderly adults should avoid medications with anticholinergic effects since they may increase the risk of adverse events, including falls, delirium, and cognitive impairment. However, data on anticholinergic burden are limited in subpopulations, such as individuals with Parkinson disease (PD). The objective of this study was to determine whether anticholinergic burden was associated with adverse outcomes in a PD inpatient population.

Concepts: Medicine, Demography, Parkinson's disease, Dementia, Geriatrics, Anticholinergic, Haloperidol, James Parkinson

48

Many medications have anticholinergic effects. In general, anticholinergic-induced cognitive impairment is considered reversible on discontinuation of anticholinergic therapy. However, a few studies suggest that anticholinergics may be associated with an increased risk for dementia.

Concepts: Cohort study, Anticholinergic, Delirium

29

Abstract “Death rattle” is a term used to describe the noisy sound produced by dying patients caused by the oscillatory movements of secretions in the upper airways. Antimuscarinic drugs, including atropine, scopolamine (hyoscine hydrobromide), hyoscine butylbromide, and glycopyrronium, have been used to diminish the noisy sound by reducing airway secretions. We report on the effectiveness of sublingual atropine eyedrops in alleviating death rattle in a terminal cancer patient. We present a 58-year-old man with pancreatic cancer who was admitted to our hospital because of severe dyspnea, cough, and death rattle with excessive bronchial secretion as a result of multiple lung metastases. We administered 1% atropine eyedrops sublingually to obviate the need for subcutaneous infusions and to prevent somnolence. On the basis of our experience, we conclude that atropine eyedrops, administered sublingually for distressing upper respiratory secretions, may be an effective alternative to the injection of antimuscarinic drugs, or as an option when other antimuscarinic formulations are not available.

Concepts: Cancer, Death, Muscarinic antagonists, Respiratory system, Anticholinergic, Hyoscyamine, Scopolamine, Muscarinic antagonist

29

The majority of deaths in COPD are from cardiovascular causes. Several large randomized controlled trials demonstrate that inhaled anticholinergic agents ipratropium and tiotropium increase the risk of serious cardiovascular events, including cardiovascular mortality. Tiotropium Respimat is associated with a statistically significant increased risk of mortality (RR 1.52; 95% CI 1.06 to 2.16) and cardiovascular death (RR 2.05; 95% CI 1.06 to 3.99) compared with placebo in a meta-analysis of clinical trials. In the largest study, the subgroup of patients with COPD in the Respimat group with known rhythm and cardiac disorders at baseline had an especially high risk for cardiac death (RR 8.6; 95% CI 1.1 to 67.2). Although there was no significantly increased risk of mortality (HR 0.89; 95% CI 0.79 to 1.02) or myocardial infarction (MI) (RR 0.73; 95% CI 0.53 to 1.00) with tiotropium handihaler in the Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) trial, the reported excess of angina (RR 1.44; 95% CI 0.91 to 2.26), imbalance in strokes related to ischaemia and rates of supraventricular tachyarrhythmias are consistent with the pro-ischemic and pro-arrhythmic effects. The subjects at greatest risk of cardiovascular death, such as those with a recent history of MI, unstable or life-threatening cardiac arrhythmias or hospitalisation with heart failure, were excluded from the UPLIFT trial. The Prevention of Exacerbations with Tiotropium in COPD trial showed an excess of serious coronary ischaemic events of angina, myocardial ischaemia and MI with the tiotropium Handihaler compared with salmeterol. The authors urge caution in prescribing inhaled anticholinergics for patients with pre-existing arrhythmias or cardiac disorders.

Concepts: Asthma, Myocardial infarction, Angina pectoris, Cardiology, Cardiac arrest, Tiotropium, Anticholinergic, Ischaemic heart disease

27

OBJECTIVE: Recent evidence indicates that antihistamines can affect movement, which is most likely due to altered neurotransmission in cholinergic and histaminergic pathways. The purpose of this study was to determine if antihistamines with varying anticholinergic properties differentially affect voluntary and involuntary movement control. METHODS: Eleven healthy subjects were enlisted into a human double blind, placebo-controlled, five-way crossover study. Drowsiness, reaction time, and physiological tremor were examined 1-, 2-, and 3-hr post-ingestion of antihistamines with known anticholinergic profiles. These were the first-generation promethazine, and second-generation loratadine, desloratadine, and fexofenadine. Hyoscine butylbromide was used in an additional experiment to determine how a peripheral antimuscarinic drug influenced neuromotor function. RESULTS: Promethazine, desloratadine and fexofenadine increased drowsiness. Promethazine increased simple and choice reaction time and reduced tremor. Desloratadine increased choice reaction time and tremor, while loratadine slowed simple and choice reaction time. CONCLUSION: Central anticholinergic and antihistaminergic properties of antihistamines potentially contribute to movement dysfunction. SIGNIFICANCE: Second-generation antihistamines have provided the consumer with a safer alternative to the first-generation sedating antihistamine. However, the results of this study suggest that loratadine and desloratadine have the potential to affect movement control, and further research is warranted to understand the clinical relevance of these findings.

Concepts: Crossover study, Histamine, Anticholinergic, H1 antagonist, Histamine antagonist, Antihistamines, H1 receptor antagonists, Scopolamine

27

OBJECTIVE:To review clinical data on the use of the long-acting anticholinergic agent tiotropium in patients with asthma.DATA SOURCES:A literature search was performed via EMBASE and MEDLINE (1966-November 2012). The search was limited to human data published in the English language. Search terms included asthma, tiotropium, and long-acting anticholinergics.STUDY SELECTION AND DATA EXTRACTION:Relevant information related to the use of tiotropium in patients with asthma was reviewed. Randomized controlled trials and open-label trials were included. The references of published articles identified in the search were also examined for additional studies appropriate to include in the review. Data were prioritized if they originated from human studies, especially if derived from randomized, placebo-controlled trials. Trials and case reports involving the use of long-acting anticholinergic tiotropium in asthma patients were included; conversely, trials involving ipratropium were not.DATA SYNTHESIS:Two large randomized controlled trials support the safety and efficacy of adding tiotropium to the treatment regimen of select patients with poorly controlled asthma already receiving combination high-dose glucocorticosteroid/long-acting β-agonist (LABA) therapy. Pharmacogenomic studies have shown that patients with polymorphisms of the β2-adrenoreceptor (ADRB2; 16 Arg/Arg and 16 Arg/Gly) are particularly responsive to treatment with tiotropium. Smaller studies indicate that the advantages may be most pronounced in patients with a predominance of sputum neutrophils and that tiotropium can assist with decreasing the inhaled corticosteroid (ICS) dose. An increased risk of cardiovascular events was not identified.CONCLUSIONS:Tiotropium should be considered in patients with asthma who remain symptomatic while receiving high-dose ICS and LABA therapy. Specifically, patients with high sputum neutrophil levels or with 16 Arg/Arg or 16 Arg/Gly polymorphism of the ADRB2 gene appear to respond best.

Concepts: Pharmacology, Asthma, Randomized controlled trial, Chronic obstructive pulmonary disease, Corticosteroid, Tiotropium, Anticholinergic, Clinical data acquisition

27

ABSTRACT BACKGROUND: Patients with post-infectious bronchiolitis obliterans(PIBO) usually have severe airflow obstruction and respond poorly to beta-adrenergic drugs. However, the bronchodilator response to an anticholinergic agent such as tiotropium bromide is not known. We studied the acute bronchodilator response to tiotropium for up to 24 hours in children with PIBO using spirometric and plethysmographic criteria. METHODS: A randomized, double blind, placebo-controlled, crossover, prospective study was performed in stable PIBO patients, 6 to 16 years of age. Standard spirometry and plethysmography were performed before and at 30, 60, 120 and 180 minutes and 24 hours after inhalation of 18 mcg of tiotropium or a placebo. After 7-14 days, the drugs were inverted, and the procedures were repeated. The changes in lung function parameters at each time point were compared to the baseline by analysis of variance (ANOVA) and Tukey’s post-test and the differences in all time points assessment versus baseline in tiotropium versus placebo groups were compared using the Friedman test. RESULTS: A total of 30 patients were enrolled in the study (23 male, 7 female; age 10.9±2.8 y) with baseline lung function values (% predicted) of FVC, FEV1, FEV1/FVC, FEF25-75%, TLC, RV, RV/TLC, airway resistance(raw) and conductance(sGaw) of 75±15, 48±14, 59±11, 22±11, 120±19, 281±101, 49±13, 250±65 and 23±9, respectively. Statistically significant differences were observed after tiotropium inhalation in the following parameters compared to baseline: FVCx60/120/180min/24h, FEV1x30/60/120/180min, FEV1/FVCx60/120/180min, FEF25-75%x60/120/180min, RVx30/60/120/180min, TLCx30/120/180min, RV/TLCx30/60/120/180min, rawx30/60/120/180min/24h and sGawx30/60/120/180min/24h. For the placebo group, no significant differences were observed in any lung function parameters at any time. The differences in the main functional measurements between the tiotropium and placebo groups were statistically significant. CONCLUSIONS: Tiotropium acutely decreased airway obstruction and air trapping for up to 24 hours in children with post-infectious bronchiolitis obliterans.

Concepts: Pulmonology, Asthma, Chronic obstructive pulmonary disease, Analysis of variance, Spirometry, Tiotropium, Anticholinergic, Obstructive lung disease

27

Antipsychotics are associated with cardiovascular risk, but the relationship between their anticholinergic properties and cardiac function is not clear. We hypothesize that antipsychotics with a high muscarinic affinity (HMA) may reduce parasympathetic modulation, which should be observable by means of heart rate variability (HRV) measurement. We also assume that anticholinergics, which are commonly used in patients with schizophrenia to treat drug-induced parkinsonism, interact with antipsychotics, and this may also affect HRV. Fifty-five patients with schizophrenia were recruited into this study. Twenty-eight subjects used antipsychotics with an HMA and 27 subjects used antipsychotics with a low muscarinic affinity (LMA). Heart rate variability values between the patients on antipsychotics with HMA and those on antipsychotics with LMA were compared. Correlation and regression analysis were then performed to clarify the relationship between HMA, LMA, and HRV. The influence of anticholinergics was also assessed by correlation analysis. The HMA group showed significantly reduced low-frequency (LF) power, high-frequency (HF) power, total power (TP), and normalized LF (LF%) than the LMA group. Regression analysis supported the hypothesis that muscarinic affinity was related to LF (β = -0.447; P < 0.001), HF (β = -0.390; P = 0.002), and TP (β = -0.399; P = 0.001). The interaction between LMA and anticholinergic use also influenced LF% (β = 0.326; P = 0.006). In the LMA group, the use of anticholinergics was positively correlated with LF% and LF/HF. In the HMA group, after exclusion of the patients using anticholinergics, the equivalent dose of antipsychotics showed a negative correlation with HF. Our results suggest that the muscarinic affinity of antipsychotics affects both sympathetic and parasympathetic modulation and that anticholinergics interact with antipsychotics to influence HRV.

Concepts: Scientific method, Heart, Observation, Acetylcholine, Autonomic nervous system, Sympathetic nervous system, Anticholinergic, Dicycloverine

26

Anticholinergic medication is the mainstay of pharmacotherapy for overactive bladder (OAB). The aim of the study is to investigate the effect of oral solifenacin succinate on intraocular pressure (IOP) in female OAB patients and to discuss the ocular drawbacks during treatment.

Concepts: Intraocular pressure, Glaucoma, Anticholinergic, Overactive bladder, Solifenacin