Anticholinergic and cardiodepressive effects of levomepromazine and two of its metabolites on isolated rat atria

The effects of monodesmethyl levomepromazine on effective rafractory period (ERP) threhold for electrical stimulation and contractile force on isolated rat atria were compared to the effects of levomepromazine and levomepromazine sulfoxide. All agents caused an apparently dose-dependent increase in ERP, and antagonized acetycholine-induced reductions in ERP. Levomepromazine and monodesmethyl levomepromazine decreased excitability and contractile force to a similar extent.     

Assessment of the anticholinergic effects of antidepressants in a single-dose cross-over study of salivation and plasma levels

In order to evaluate the anticholinergic effect of antidepressant drugs, 11 healthy volunteers were given single oral doses of reference drug, test drugs or placebo on a double-blind basis at weekly intervals. The doses corresponded to average daily patient medications. Spontaneous whole mouth and parotid salivation, and plasma levels of drug and possible metabolites were measured 2, 6 and 10h after drug administration.Moderate, statistically significant inhibition of salivation was found when nortriptyline, imipramine-N-oxide and mianserin were given. Less pronounced, but still statistically significant inhibition occurred after ingestion of nomifensine and zimelidine. The zimelidine effect was exclusively due to the metabolite norzimelidine, and the inhibition after imipramine-N-oxide was mainly due to the metabolite imipramine, but imipramine-N-oxide itself also had slight activity. Isocarboxazide and lithium had no effect on salivation.From these results and reported values of pharmacokinetic variables, the average level of anticholinergic activity during long-term treatment may be predicted: for mianserin and (nor-)zimelidine moderate inhibition of salivation, although less pronounced than with nortriptyline; for nomifensine no clinically significant effect; and for imipramine-N-oxide a negligible contribution from the unmetabolized drug.     

Effects of two antidepressants on memory performance in depressed outpatients: a double-blind study

Forty outpatients with primary depression were randomly assigned on a double-blind basis to treatment with amitriptyline (a tricyclic antidepressant) or clovoxamine (a nontricyclic, experimental antidepressant). Memory and depression were assessed during a pretreatment baseline period and at the end of days 4, 7, and 28 of drug treatment. A signal detection recognition memory task and conventional memory measures (including the Benton Visual Retention, Wechsler Logical Memory, and verbal learning tests) were used to assess memory.Although both drugs led to comparable clinical improvement in depression, they affected memory performance differently. The signal detection recognition memory task detected an impairment in memory after chronic amitriptyline administration, as contrasted with an improvement in memory after chronic administration of clovoxamine. The memory impairment in the amitriptyline group and improvement in the clovoxamine group were the result of changes in sensitivity [P(A)]. No changes in response bias (BO were detected. Conventional memory tests failed to detect drug-related differences in memory between the two groups. On the Benton, errors decreased over time within both drug treatment groups, whereas correct reproductions increased within the amitriptyline group only. However, between-group differences on the Benton did not reach significance.Results from the signal detection task suggest an amitriptyline-associated memory impairment. However, this interpretation is tempered by the finding that conventional memory measures failed to detect differences in memory performance between the two groups. We discuss the limitations of traditional memory measures and the utility of a signal detection approach in studies of psychopharmacologic influences on memory.     

Haloperidol-induced disruption of conditioned avoidance responding: Attenuation by prior training or by anticholinergic drugs

Rats injected daily with haloperidol (0.15 mg/kg) failed to acquire a one-way active avoidance response over a 9 day period (10 traisl/day). When these animals were subsequently tested without haloperidol, on the first drug-free day they performed as well as animals given saline throughout the training period and significantly better than naive saline-treated animals on the first day of training. The performance of rats were trained for two days before receiving haloperidol was only partly blocked by the drug, while animals trained for 9 days before drug administration were immune to the disruptive effects. Three anticholinergic (muscarinic) drugs, atropine (10 mg/kg), scopolamine (1 mg/kg) and benztropine (2 mg/kg) significantly reversed the effect of haloperidol on the acquisition of the avoidance response. These results are similar to those observed after bilateral destruction of the dipaminergic nigroneostriatal projection and support the view that this system is critically involved in the acquisition of learned instrumental responses. The nature of the avoidance deficit produced by these treatments is discussed with reference on the possibility that they selectively block the initiation of voluntary motor responses. According to this hypothesis, the failure of these treatments to disrupt escape responding may be due to the fact that the unconditioned stimulus generates reflexive motor responses (flinch, jump, etc.) which are sufficient to begin the motoric sequences that cannot be initiated voluntarily in response to the conditioned stimulus.     

Anticholinergic burden risk and prevalence of medications carrying anticholinergic properties in elderly cancer patients in Jordan

BackgroundGeriatric cancer patients are susceptible to adverse drug events due to the complexity of their chemotherapy regimens and collateral treatments for their comorbid conditions. Prescribing medications with anticholinergic burden characteristics can complicate their condition, leading to negative impacts on their health outcomes and quality of life, including an increase in adverse drug event frequency, physical and cognitive impairments.ObjectiveThis study aims to examine the prevalence of anticholinergic prescribing and identify the cumulative anticholinergic load risk associated with drugs prescribed to elderly cancer patients. Also, to identify the predictors that might lead to raised anticholinergic burden in these patients.MethodologyThis retrospective cross-sectional study included elderly patients (age ≥ 65) diagnosed with cancer and admitted to the adult oncology unit at King Abdullah University Hospital (KAUH) in Jordan during the period between (January 1st, 2019, and January 1st, 2022). The medication charts of 420 patients were evaluated for study outcomes.ResultsOf the total subjects, females represented 49.3%, and the average age was 72.95 (SD = 7.33). A total of 354 (84.3%) patients were prescribed at least one drug carrying anticholinergic burden properties. Median for anticholinergic medications was 3 (IQR = 4). Our study found that 194 (46.2%) patients were at a high risk of adverse events associated with anticholinergic load (cumulative score ≥ 3). Metoclopramide, furosemide, and tramadol were the most frequently prescribed drugs with anticholinergic properties. Alimentary tract drugs with anticholinergic action were the most commonly encountered items in our study population.ConclusionOur study revealed a significantly high prevalence of anticholinergic prescribing among elderly cancer patients. Nearly half of the patients were at high risk of developing serious effects related to anticholinergic activity from the drugs administered. Polypharmacy was strongly associated with increased anticholinergic burden score. Evidence-based recommendations utilizing prescribing strategies for safer alternatives and deprescribing of inappropriate medications could reduce such inappropriate prescribing.     

Novel Use of Dexmedetomidine for the Treatment of Anticholinergic Toxidrome

Introduction

We report the case of an adolescent with anticholinergic toxidrome from diphenhydramine overdose, whose symptoms were treated with a novel application of dexmedetomidine.

Case Report

A 13-year-old female developed an anticholinergic toxidrome after intentionally ingesting 9.5 mg/kg of diphenhydramine. Despite routine supportive therapies, to include appropriate doses of lorazepam, she continued to have significant agitation, psychosis, and hallucinations. A dexmedetomidine infusion was started to aid in the treatment of her agitation and psychosis with marked improvement of her symptoms.

Discussion

Using dexmedetomidine for the treatment of anticholinergic toxidrome has not been previously described in the literature, but there are multiple reports of its use in alcohol withdrawal syndrome. We suggest that adding dexmedetomidine as an adjunctive agent in the therapy of anticholinergic toxidrome may relieve the symptoms of agitation, psychosis, tachycardia, and hypertension, without the attendant risk of respiratory depression associated with high doses of benzodiazepines.     

采用心率变异性分析抗胆碱能药物治疗前后哮喘患者自主神经的变化

目的探讨使用长效抗胆碱能药物噻托溴铵治疗成人哮喘6周前后的自主神经功能改变及临床效果。方法45例非急性发作的中度哮喘患者随机分为A组15例：噻托溴铵粉吸入剂＋丙氟酸氟替卡松气雾剂组;B组15例：吸入沙美特罗替卡松干粉剂组;C组15例：噻托溴铵粉吸入剂＋沙美特罗替卡松干粉剂。观察三组患者治疗前后心率变异性、肺功能指标及症状控制情况。结果①治疗6周后,A组的HF、PNN50降低,与用药前对比差异有统计学意义（P〈0．05）,LF、SDANN增高,差异无统计学意义（P〉0．05）;B组的HF、PNN50降低,LF、SDANN增高,与用药前对比差异均无统计学意义（P〉0．05）;c组的HF、PNN50降低,LF、SDANN增高,与用药前对比差异均有统计学意义（P〈0．05）;②三组的日间、夜间症状评分较用药前有所降低,使用短效β2-受体激动剂的次数减少,肺功能中的FEV1、FEV1％较用药前改善,三组与治疗前对比差异均有统计学意义;③组间对比得出心率变异性的定量分析指标（HF、PNN50、LF、SDANN）A组与B组,B与C组有统计学意义（P〈0．05）,A组与C组差异无统计学意义（P〉0．05）;肺功能中的FEV1、FEV1％显示A组与B组无统计学意义（P〉0．05）,而A组与C组、B组与C组差异均有统计学意义（P〈0．05）;日间、夜间症状评分、使用短效β2-受体激动剂的次数显示A组与B组差异无统计学意义（P〉0．05）,A组与C组,B组与C组差异有统计学意义（P〈0．05）。长效抗胆碱能药物噻托溴铵粉吸人剂联合糖皮质激素可以降低HF、PNN50,使迷走神经兴奋性降低,与长效β2-受体激动剂（LABA）联合糖皮质激素相比在改善肺功能中FEV1、FEV1％值,减少使用短效β2-受体激动剂的次数,降低哮喘症状评分方面,效果相当。结论以上三种药物联合使用在改善肺功能、降低心率变异性、降低哮喘症状评分及使用短效β2-受体激动剂次数等方面均表现出更明显的优势。     

Iatrogenic glaucoma secondary to medications

Glaucoma is a progressive optic neuropathy with primary and secondary forms. Iatrogenic glaucoma secondary to medications is potentially blinding but preventable. Most drug profiles listing glaucoma as a contraindication or an adverse effect are concerned with inducing acute angle-closure glaucoma. Anticholinergic or adrenergic agents are the most common for inducing “pupillary block” angle-closure glaucoma. Patients with a narrow irido-corneal angle are at high risk. Sulfa drugs induce “non-pupillary block” angle-closure glaucoma as an idiosyncratic reaction to the drug in patients with an open or narrow irido-corneal angle. Steroids and a few antineoplastic agents induce open-angle glaucoma. The risk is higher with topical rather than systemic steroids. The first step in the management is discontinuation of the drug, followed by medical, laser, and, if necessary, surgical intervention.     

长托宁抢救重度有机磷农药中毒疗效观察

目的：比较观察阿托品和盐酸戊乙奎醚（商品名：长托宁）分别用于重度有机磷中毒（acute organophosphorus pesticide poisoning,AOPP）抢救的疗效。方法：选择60例重度AOPP患者,随机分成长托宁＋氯解磷定组（P组）及阿托品＋氯解磷定组（A组）,各30例,两组基础治疗相同,P组肌注长托宁4～6mg,氯磷定2．0～3．0g静脉注射;A组给予阿托品首剂10～20mg静脉注射后间断维持,同时氯磷定2．0～3．0g静脉注射,观察记录两组患者毒蕈碱样症状消失时间、烟碱样症状消失时间、中枢神经系统症状消失时间及胆碱酯酶活力恢复60％时间,统计各组治愈率、住院时间及严重并发症发生率,观察药物不良反应发生情况。结果：P组患者蕈碱样症状消失时间、烟碱样症状消失时间、中枢神经系统症状消失时间及胆碱酯酶活力恢复60％时间均低于A组（P〈0．05）,P组胆碱酯酶活力恢复明显较A组快,P组治愈率高于A组（P〈0．05）,P组住院时间较A组缩短,严重并发症发生率及药物不良反应发生率P组均低于A组（P〈0．05）。结论：长托宁能有效缓解重度AOPP症状,促进胆碱酯酶活力恢复,不良反应少,是较阿托品更为理想的重度AOPP治疗药物。     

Reduced Heart Rate Variability in Patients with Chronic Obstructive Pulmonary Disease Independent of Anticholinergic or β-agonist Medications

ABSTRACT

Reduced heart rate variability (HRV) is a predictor of poor outcome in several pathologies and in general population. Whether HRV is altered during normal daily activities or influenced by anticholinergic and β-adrenergic medications in chronic obstructive pulmonary disease (COPD) remains unknown. Forty-one clinically stable COPD patients and 19 healthy controls matched for age, sex and smoking history underwent a 24-hour ambulatory ECG recording during normal daily activities. HRV was assessed by standardized temporal and spectral analysis. COPD patients showed a reduced HRV (LF/HF ratio) compared with healthy controls (median [interquartile range]) during daytime (2.6 [1.5–3.8] vs. 3.5 [2.9–5.6]), nighttime (1.8 [1.1–4.3] vs. 4.2 [2.7–6.9]) as well as during the entire 24-hour (1.9 [1.5–3.4] vs. 3.9 [3.2–5.6]) recordings (all P < 0.005). There was no significant difference between the two groups in the time domain and in the low frequency or high frequency domain for the 24-hour period analysis. In COPD patients, the 24-hour LF/HF ratio positively correlated with forced expiratory volume in 1 second (FEV₁) (r = 0.342, P = 0.028) and negatively correlated with age (r = ?0.317, P = 0.044). In multiple regression analysis, LF/HF ratio was associated with FEV₁ (P = 0.05) but not with age (P = 0.08). There was no difference of HRV between patients using or not anticholinergic or β-agonist medications. These results demonstrate that COPD patients have a reduced sympatho-vagal balance compared with healthy subjects. HRV correlates with disease severity and does not seem to be influenced by anticholinergic or adrenergic medications.