Glycopyrrolate vs. atropine during anaesthesia for laryngoscopy and bronchoscopy

As glycopyrrolate has been reported superior to atropine with respect to reduction of salivation, stability of cardiac rate and rhythm, and recovery, a comparison of these properties of the two drugs and placebo was made in 45 patients undergoing direct laryngoscopy and 45 patients undergoing bronchoscopy, in most cases followed by mediastinoscopy. When given i.m. 30 min before anaesthesia (midazolam, alfentanil, thiopentone, and suxamethonium), the two test drugs were found to be equally potent regarding the antisialogogic effect. The same increase in heart rate after the test drugs was seen before induction, and during anaesthesia heart rate rose to the same level in the placebo group as the test groups. During anaesthesia, blood pressure was lowest in the atropine group. No differences could be demonstrated with respect to cardiac arrhythmias, possibly due to the small size of the material. The present study gives no reason for preferring either drug, and only the efficacy of both test drugs in controlling airway secretions provides an argument for using any anticholinergic drug when laryngoscopy or bronchoscopy is performed under the conditions of the present study.     

DIFFERENTIAL SENSITIVITY OF TWO PALMAR SWEAT MEASURES

Two techniques for measuring palmar sweating were tested for their sensitivity to a standard anticholinergic agent. The finger sweat-print and palmar sweatweight methods were compared in a double-blind, crossover study by determining their relative sensitivity in detecting the antisweating effects of 0.5 mg of atropine sulfate. The sweat-print method was significantly superior in detecting drug-induced sweat reduction and hypothesized sex differences.     

Interaction of class III antiarrhythmic drugs with muscarinic M2 and M3 receptors: radioligand binding and functional studies

We have recently reported that class III antiarrhythmic drugs inhibit the muscarinic acetylcholine (ACh) receptor-operated K⁺ current (I _K, ACh) in guinea-pig atrial cells by different molecular mechanisms. The data obtained from the patch-clamp study suggest that d,l-sotalol inhibits I _{K, ACh} by blocking the muscarinic receptors, whereas MS-551 inhibits the K⁺ current by blocking the muscarinic receptors and depressing the function of the K⁺ channel itself and/or the guanine nucleotide-binding protein (G protein). This study was undertaken to determine whether the class III antiarrhythmic drugs d,l-sotalol and MS-551 interact with the muscarinic receptors of cardiac and peripheral tissues. Both drugs inhibited concentration dependently the specific [³H]N-methylscopolamine ([³H]-NMS) binding to membrane preparations obtained from guinea-pig atria and submandibular glands. The competition curves of these drugs for [³H]-NMS binding to glandular membranes were monophasic, suggesting competition with [³H]-NMS at a single site. Although the competition curve of d,l-sotalol for [³H]-NMS binding to atrial membranes was monophasic, that of MS-551 was biphasic and showed high- and low-affinity states of binding. d,l-Sotalol showed slightly, but significantly, higher affinity for cardiac-type muscarinic receptors (M₂) than for glandular-type muscarinic receptors (M₃). The inhibition constant (K _i) for MS-551 in glandular membranes was also slightly greater than the high-affinity K _i value for the drug in atrial membranes. In guinea-pig left atria and ilea, d,l-sotalol shifted the concentration-response curves for the negative inotropic effect and the contracting effect of carbachol in a parallel manner. The slopes of Schild plot were not significantly different from unity, suggesting competitive antagonism, and the pA₂ for d,l-sotalol in left atria was slightly greater than that in ilea. MS-551 also shifted the concentration response curve for the negative inotropic effect of carbachol in atrial preparations to a greater extent than that for the contracting effect in ileal preparations, although MS-551 failed to show a pure competitive antagonism. These results suggest that both d,l-sotalol and MS-551 interact with cardiac M₂ and peripheral M₃ receptors, and that at high concentrations they exert anticholinergic activity in cardiac and peripheral tissues.     

Effect of acute and chronic treatment of tandamine,a new heterocyclic antidepressant,on biogenic amine metabolism and related activities

Summary The effects of tandamine, a clinically effective heterocyclic antidepressant, administered either acutely (10 mg/kg i.p) or chronically (10 mg/kg i.p. daily for 21 days) on biogenic amine uptake and metabolism in the rat were determined and a comparison with desipramine was made. Tandamine, similarly to desipramine, blocked norepinephrine (NE) uptake in rat brain and heart following both acute and chronic administration. No effect of tandamine on dopamine (DA) or serotonin (5-HT) uptake was observed. Both drugs lowered endogenous brain NE when given chronically but not acutely. In contrast, no such effect on brain DA and 5-HT or heart NE was observed. Tandamine, like desipramine, administered chronically prior to an intraventricular injection of ³H-NE, produced increases in the decline of ³H-NE as indicated by decreased ³H-NE with increased levels of ³H-normetanephrine in brain stem of rats, suggesting an increased turnover of NE. No such effect was observed following acute treatment. Both drugs increased the behavioural effects of L-Dopa following an acute oral administration, with tandamine appearing superior to desipramine at the lower dose examined (10 mg/kg). Tandamine was 57–833 times less effective in binding to rat brain muscarinic receptors than desipramine, imipramine, butriptyline and amitriptyline, respectively. Thus, tandamine affects biogenic amine mechanism following either acute or chronic administration in a fashion similar to desipramine, but unlike desipramine, it exhibits relatively little anticholinergic properties, a further indication of the potential use of tandamine in the treatment of human depression, particularly where an increase in drive is desired.     

Drug Burden Index associated with function in community-dwelling older people in Finland: A cross-sectional study

Abstract

Background. This cross-sectional study aimed to investigate the relationship between exposure to anticholinergic and sedative medications, measured with the Drug Burden Index (DBI), and functional outcomes in community-dwelling older people living in Finland.

Methods. The study population consisted of community-dwelling older people (n = 700) enrolled in the Geriatric Multidisciplinary Strategy for the Good Care of the Elderly (GeMS) study. Outcomes included walking speed, chair stands test, grip strength, timed up and go (TUG) test, instrumental activities of daily living (IADL), and Barthel Index.

Results. Exposure to DBI drugs was identified in 37% of participants: 24% had a DBI range between >0 <1, and 13% DBI ≥1. After adjusting for confounders, exposure to DBI drugs was associated with slower walking speed (P < 0.0001), poorer performance on chair stands (P = 0.0001) and TUG (P < 0.0001), difficulties in IADL (P < 0.0001), and Barthel Index (P < 0.0001). The mean adjusted walking speed, time to complete chair stands and TUG, IADL, and Barthel scores were significantly poorer among participants with higher DBI ranges.

Conclusion. In older adults living in Finland, DBI was associated with impaired function on previously tested and new outcomes. This finding supports the use of the DBI as tool, in combination with other assessments, to identify older people at risk of functional impairment. The findings highlight the need for revision of current guidelines to improve the quality of drug use in older people.     

Bad trip due to anticholinergic effect of cannabis

Cannabis in its various forms has been known since time immemorial, the use of which has been rising steadily in India. ‘Bad trips’ have been documented after cannabis use, manifestations ranging from vague anxiety and fear to profoundly disturbing states of terror and psychosis. Cannabis is known to affect various neurotransmitters, but ‘bad trip’ due to its anticholinergic effect has never been described in literature to the best of author's knowledge. Hereby, the author describes a case of a young adult male experiencing profound anticholinergic effects after being exposed for the first time in his life to bhang, a local oral preparation of cannabis.     

Anticonvulsant efficacy of antihistamine cyproheptadine in rats exposed to the chemical warfare nerve agent soman

Organophosphate compounds, such as soman and sarin, are highly toxic chemical warfare nerve agents that cause a build-up of acetylcholine in synapses and neuromuscular junctions. Current therapies aim to prevent seizures and protect against brain injury following exposure. The present study was designed to evaluate the effectiveness of the antihistamine cyproheptadine in improving survival and controlling seizures in rats exposed to soman. Rats were pretreated with the oxime reactivator HI-6 (125 mg/kg, ip) 30 min prior to soman exposure (225 μg/kg, sc) and then treated with atropine methylnitrate (AMN, 2.0 mg/kg, im) 1 min after soman. Cyproheptadine (10, 13, 16 or 20 mg/kg, ip) was given at one of three time points: 1 min after soman intoxication, at the onset of soman-induced seizures or 5 min after seizure onset. Control animals were exposed to soman and given an equivalent volume of sterile water instead of cyproheptadine. The incidence of seizures, mortality, neuron counts, neuropathology and apoptosis in specific regions of the brain were evaluated. In animals given HI-6 and AMN the incidence of soman-induced seizure and mortality rate within the first 24 h were 100%. When cyproheptadine was given at a dose of 13 or 20 mg/kg 1 min after soman exposure, the incidence of seizures was reduced from 100% to 13% and 30%, respectively. In addition, cyproheptadine given at 1 min after soman exposure increased the survival rate to 100% regardless of dose. When cyproheptadine was administered at seizure onset, seizures were terminated in 100% of the animals at doses above 10 mg/kg. The survival rate with cyproheptadine treatment at the onset of seizure was ≥83%. Seizures terminated in ≥75% of the animals that received cyproheptadine 5 min after soman-induced seizure onset. When given at 5 min after seizure onset the survival rate was 100% at all tested doses of cyproheptadine. The neuropathology scores and the number of TUNEL positive cells in the brain regions examined decreased at all time points and cyproheptadine doses tested. These observations indicate that cyproheptadine treatment can effectively control seizures, improve survival, reduce seizure duration and reduce the number of dying cells in the brain following soman exposure.     

噻托溴铵治疗慢性阻塞性肺疾病作用机制研究进展

噻托溴铵是一种新型长效抗胆碱类药物,是目前第一个能每日用药1次的吸人性药物,能高度选择性作用于胆碱M1和M3受体,表现出强大的支气管扩张作用,吸入一次疗效持续24 h以上.临床实验结果表明该药对中、重度慢性阻塞性肺疾病具有良好疗效,与其他常用抗胆碱能药物和β2受体激动剂相比较,噻托溴铵可显著改善肺功能、减少急性发作和改善生命质量,耐受性和安全性较好,主要不良反应为口干.     

肺部吸入给药制剂及临床应用

目的:分析和综述肺吸入制剂的分类、现状及其临床用药。方法:收集国内外发表出版的相关论文及专著,对肺部吸入给药的特点及临床药物制剂进行了分析总结。结果与结论:肺部吸入给药是防治哮喘、慢性阻塞性肺病等呼吸道疾病的首选给药方式。常见的吸入给药制剂包括定量吸入气雾剂、干粉吸入剂和雾化吸入剂,所用药物主要为β2受体激动剂、抗胆碱药物、吸入性糖皮质激素及复方药物等。