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Background: Sialorrhea is a common concern in patients with swallowing disorders after stroke. Atropine sulfate blocks the muscarinic receptors in the salivary glands and leads to reduced saliva production., Objective: The present study aimed to assess the safety, efficacy, and tolerability of sublingual administration of atropine eye drops for treating sialorrhea after stroke., Design: This was a prospective cohort study., Setting: This study was conducted at Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Hubei Province, China., Population: Stroke patients with sialorrhea were analyzed., Methods: One hundred stroke patients with sialorrhea were randomly assigned to the control group and the test group (n = 50 per group). The control group received routine swallowing rehabilitation training and neuromuscular electrical stimulation. The test group received therapy with 1% atropine eye drops, wherein one drop was administered sublingually 3 times per day. The Sialorrhea Scoring Scale and the incidence of adverse events were used to compare the severity of sialorrhea in the two groups., Results: The mean (standard deviation) sialorrhea score improved from 5.12 for the control group with routine rehabilitation training to 3.94 for the test group with atropine eye drop administration (P < 0.01). No significant differences in the incidence of adverse events were observed between the two groups., Conclusions: The sublingual administration of 1% atropine eye drops three times per day can reduce the degree of sialorrhea to an extent more than that achieved with routine rehabilitation training; thus, this approach is effective, safe, and minimally invasive for treating sialorrhea after stroke., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background/aims: We examined the involvement of cholecystokinin (CCK) in the exacerbation of indomethacin (IND)-induced gastric antral ulcers by gastroparesis caused by atropine or dopamine in mice., Methods: Male mice were fed for 2 h (re-feeding) following a 22-h fast. Indomethacin (IND; 10 mg/kg, s.c.) was administered after re-feeding; gastric lesions were examined 24 h after IND treatment. In another experiment, mice were fed for 2 h after a 22-h fast, after which the stomachs were removed 1.5 h after the end of the feeding period. Antral lesions, the amount of gastric contents, and the gastric luminal bile acids concentration were measured with or without the administration of the pro- and antimotility drugs CCK-octapeptide (CCK-8), atropine, dopamine, SR57227 (5-HT 3 receptor agonist), apomorphine, lorglumide (CCK 1 receptor antagonist), ondansetron, and haloperidol alone and in combination., Results: IND produced severe lesions only in the gastric antrum in re-fed mice. CCK-8, atropine, dopamine, SR57227 and apomorphine administered just after re-feeding increased bile reflux and worsened IND-induced antral lesions. These effects were significantly prevented by pretreatment with lorglumide. Although atropine and dopamine also increased the amount of gastric content, lorglumide had no effect on the delayed gastric emptying provoked by atropine and dopamine. Both ondansetron and haloperidol significantly inhibited the increase of bile reflux and the exacerbation of antral lesions induced by atropine and dopamine, respectively, but did not affect the effects of CCK-8., Conclusions: These results suggest that CCK-CCK 1 receptor signal increases bile reflux during gastroparesis induced by atropine and dopamine, exacerbating IND-induced antral ulcers., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A large number of studies have evaluated the efficacy of low-dose atropine in preventing or slowing myopic progression. However, it is challenging to evaluate the ocular safety from these studies. We aimed to evaluate the incidence of adverse events induced by atropine in children with myopia. We performed a systematic literature search in several databases for studies published until November 2022. The incidence of adverse events induced by atropine was pooled by a common-effect (fixed-effect) or random-effects model. Subgroup analyses were conducted according to drug doses, types of adverse events, and ethnicity. A total of 31 articles were ultimately included in the study. The overall incidence of adverse events for atropine was 5.9%, and the incidence of severe adverse events was 0.0%. The most commonly reported adverse events were photophobia (9.1%) and blurred near vision (2.9%). Other adverse events including eye irritation/discomfort, allergic reactions, headache, stye/chalazion, glare, and dizziness occurred in less than 1% of the patients. The incidence of atropine-induced adverse events varied depending on the drug doses. A lower dose of atropine was associated with a lower incidence of adverse events. There was no significant difference in the incidence of adverse events for low-dose atropine between Asian and White children. Our study suggests photophobia and blurred near vision are the most frequently reported adverse events induced by atropine. Low-dose atropine is safer than moderate- and high-dose atropine. Our study could provide a safe reference for ophthalmologists to prescribe atropine for myopic children., (© 2023, The American College of Clinical Pharmacology.)

Purpose: To evaluate the safety and efficacy of atropine for childhood myopia and further explore the optimal concentration of atropine, so as to provide more reference for clinical application., Methods: PubMed, Embase, Cochrane Library and ClinicalTrials.gov were comprehensively searched for randomized controlled trials (RCTs) up to October 14, 2021. The efficacy outcomes were progression of spherical equivalent (SE) and axial length (AL). The safety outcomes included accommodation amplitude, pupil size and adverse effects. The meta-analysis was performed using Review Manager 5.3., Results: Eighteen RCTs involving 3002 eyes were included. The results showed that at 6-36 months of treatment, atropine was effective in slowing the progression of myopia in children. At 12 months, the WMD of SE and AL of low-dose atropine was 0.25 diopters (D) and 0.1 millimeter (mm), moderate-dose atropine was 0.44 D and 0.16mm, high-dose atropine was 1.21 D and 0.82mm, respectively, compared with the control group. Similarly, at 24 months, low-dose atropine was 0.22 D and 0.14mm, moderate-dose atropine was 0.60 D, high-dose atropine was 0.66 D and 0.24mm, respectively. Interestingly, we also found that there was no significant difference in the effects of low-dose atropine on accommodation amplitude and photopic pupil size compared with the control group, and the rate of photophobia, allergy, blurred vision and other side effects was similar between the low-dose atropine group and the control group. In addition, atropine appears to be more effective in myopic children in China than in other countries., Conclusions: Atropine in various concentrations can effectively slow myopia progression in children, and its effect is dose-dependent, while low-dose atropine (0.01% atropine) appears to be safer., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background/aims: We examined the contributions of gastric emptying and duodenogastric bile reflux in the formation of gastric antral ulcers induced by NSAIDs in mice., Methods: We used the murine re-fed indomethacin (IND) experimental ulcer model. Outcome measures included the appearance of gastric lesions 24 h after IND treatment and the assessment of gastric contents and the concentration of bile acids 1.5 h after re-feeding. The effects of atropine, dopamine, SR57227 (5-HT 3 receptor agonist), apomorphine, ondansetron, haloperidol, and dietary taurocholate and cholestyramine were also examined., Results: IND (10 mg/kg, s.c.) induced severe lesions only in the gastric antrum in the re-fed model. The antral lesion index and the amount of food intake during the 2-h refeeding period were positively correlated. Atropine and dopamine delayed gastric emptying, increased bile reflux, and worsened IND-induced antral lesions. SR57227 and apomorphine worsened antral lesions with increased bile reflux. These effects were prevented by the anti-emetic drugs ondansetron and haloperidol, respectively. The anti-emetic drugs markedly decreased the severity of antral lesions and the increase of bile reflux induced by atropine or dopamine without affecting delayed gastric emptying. Antral lesions induced by IND were increased by dietary taurocholate but decreased by the addition of the bile acid sequestrant cholestyramine., Conclusions: These results suggest that gastroparesis induced by atropine or dopamine worsens NSAID-induced gastric antral ulcers by increasing duodenogastric bile reflux via activation of 5-HT 3 and dopamine D 2 receptors., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

To evaluate the age-related efficacy and safety of atropine 0.01% eye drops over 2 years for myopia control in a multicentric pediatric Spanish cohort. A non-controlled, interventional, prospective multicenter study was conducted as an extension of the Spanish Group of Atropine Treatment for Myopia Control Study (GTAM 1). Children aged 6-14 years with myopia from - 2.00 to - 6.00 D, astigmatism < 1.50 D and documented annual myopic progression of at least - 0.50 D under cycloplegic examination were recruited. From the original cohort of 105 participants, 92 children who had been receiving atropine 0.01% eye drops once nightly in each eye for 1 year continued their participation in this extended study (GTAM 2). All the patients underwent a standardized quarterly follow-up protocol, which included measurements of best-corrected visual acuity (BCVA), cycloplegic autorefraction, axial length (AL), anterior chamber depth (ACD), and pupil diameter. The study sample was divided into three age groups: 6-8, 9-11, and 12-14 years old. The mean change in cycloplegic spherical equivalent (SE) and axial length (AL) during the 24 months of follow-up was analyzed. Correlations between SE and AL, as well as the distribution of annual progression, were evaluated. Adverse effects were recorded using a specific questionnaire. Finally, 81 children completed the follow-up and were included in the analysis. Over the 2-year period, the mean changes in SE and AL were - 0.88 ± 0.60 D and 0.49 ± 0.25 mm, respectively. Additionally, 51 patients (63%) experienced SE annual progression lower than - 0.50 D. The correlation between the progression of SE and AL during the total period of treatment was mild (r = - 0.36; p < 0.001). There were no differences between the first and the second year of treatment in the progression of SE (- 0.42 ± 0.41 D versus - 0.45 ± 0.39 D; p = 0.69) or AL (0.25 ± 0.16 mm versus 0.23 ± 0.14 mm; p = 0.43). Older patients (12-14 years old) showed less AL progression than younger children (6-8 years old): 0.36 ± 0.18 mm versus 0.59 ± 0.30 mm; p = 0.01. Adverse effects were mild, infrequent, and decreased over time. On average, the myopia progression in control groups from other published biannual studies exceeded that observed in our study. Over 2 years, atropine 0.01% demonstrated a safe treatment for controlling myopia progression in a multicentric cohort of Spanish children. The effect remained stable during this period. Older patients exhibited a more favorable response in terms of AL enlargement. However, further studies are needed to investigate the age-related effect of low-dose atropine in the Caucasian population., (© 2023. Springer Nature Limited.)

Importance: Early onset of myopia is associated with high myopia later in life, and myopia is irreversible once developed., Objective: To evaluate the efficacy of low-concentration atropine eyedrops at 0.05% and 0.01% concentration for delaying the onset of myopia., Design, Setting, and Participants: This randomized, placebo-controlled, double-masked trial conducted at the Chinese University of Hong Kong Eye Centre enrolled 474 nonmyopic children aged 4 through 9 years with cycloplegic spherical equivalent between +1.00 D to 0.00 D and astigmatism less than -1.00 D. The first recruited participant started treatment on July 11, 2017, and the last participant was enrolled on June 4, 2020; the date of the final follow-up session was June 4, 2022., Interventions: Participants were assigned at random to the 0.05% atropine (n = 160), 0.01% atropine (n = 159), and placebo (n = 155) groups and had eyedrops applied once nightly in both eyes over 2 years., Main Outcomes and Measures: The primary outcomes were the 2-year cumulative incidence rate of myopia (cycloplegic spherical equivalent of at least -0.50 D in either eye) and the percentage of participants with fast myopic shift (spherical equivalent myopic shift of at least 1.00 D)., Results: Of the 474 randomized patients (mean age, 6.8 years; 50% female), 353 (74.5%) completed the trial. The 2-year cumulative incidence of myopia in the 0.05% atropine, 0.01% atropine, and placebo groups were 28.4% (33/116), 45.9% (56/122), and 53.0% (61/115), respectively, and the percentages of participants with fast myopic shift at 2 years were 25.0%, 45.1%, and 53.9%. Compared with the placebo group, the 0.05% atropine group had significantly lower 2-year cumulative myopia incidence (difference, 24.6% [95% CI, 12.0%-36.4%]) and percentage of patients with fast myopic shift (difference, 28.9% [95% CI, 16.5%-40.5%]). Compared with the 0.01% atropine group, the 0.05% atropine group had significantly lower 2-year cumulative myopia incidence (difference, 17.5% [95% CI, 5.2%-29.2%]) and percentage of patients with fast myopic shift (difference, 20.1% [95% CI, 8.0%-31.6%]). The 0.01% atropine and placebo groups were not significantly different in 2-year cumulative myopia incidence or percentage of patients with fast myopic shift. Photophobia was the most common adverse event and was reported by 12.9% of participants in the 0.05% atropine group, 18.9% in the 0.01% atropine group, and 12.2% in the placebo group in the second year., Conclusions and Relevance: Among children aged 4 to 9 years without myopia, nightly use of 0.05% atropine eyedrops compared with placebo resulted in a significantly lower incidence of myopia and lower percentage of participants with fast myopic shift at 2 years. There was no significant difference between 0.01% atropine and placebo. Further research is needed to replicate the findings, to understand whether this represents a delay or prevention of myopia, and to assess longer-term safety., Trial Registration: Chinese Clinical Trial Registry: ChiCTR-IPR-15006883.

Myopia, short-sightedness, is the most frequent cause of vision difficulty and its prevalence is expected to rise. Nowadays, the usage of atropine drops is effective for myopia progression control. Studies on the Asian population showed that atropine 0.01% is more efficient and safer than solutions that have a higher concentration. In this study, we report findings from a multicenter Spanish study that showed that atropine 0.01% decreases the progression of myopia in a pediatric population, with relatively few adverse effects. The results of this study may be relevant to doctors who treat children who have myopia, as well as to the children treated and their parents.

We aimed to evaluate the efficacy and safety of low-dose atropine compared to placebo in the Indian population and also to study the impact of various modifiable and non-modifiable factors on myopia progression (MP) and drug efficacy (DE). It was a single-centre prospective placebo-controlled interventional study. 43 participants aged 6-16 years with progressive myopia received 0.01% atropine in the right eyes (treatment) and placebo in the left eyes (control) for 1-year. The main outcome measures were annual MP and axial length elongation (ALE) in treatment and control eyes and their percentage difference between two eyes (drug efficacy). Secondary outcome measures were the occurrence of any adverse events and the correlation of MP, ALE, and DE with various factors. 40 participants (80 eyes) completed the follow-up. After 1-year, MP was 0.25 D (IQR 0.13-0.44) and 0.69 D (IQR 0.50-1.0) (p < 0.001) in treatment and control respectively (63.89% reduction) with respective ALE of 0.14 mm (IQR 0.05-0.35) and 0.32 mm (IQR 0.19-0.46) (p < 0.001) (44.44% reduction). No adverse events were noted. Reduction in MP and ALE was statistically significant in all children irrespective of age-group, baseline MP, family history, screen-time, near and outdoor-time. The strongest determinants of annual MP were age (Treatment: r = - 0.418, p = 0.007; Control: r = - 0.452, p = 0.003) and baseline MP (Treatment: r = 0.64, p = 0.000; Control: r = 0.79, p = 0.000). Screen-time in control eyes was associated with greater ALE (r = 0.620, p = 0.042). DE was higher when outdoor time exceeded 2 h/day (p = 0.035) while the efficacy was lower with prolonged near activities (p = 0.03), baseline fast-progressors (p < 0.05) and history of parental myopia (p < 0.05). 0.01% atropine is effective and safe in retarding MP and ALE in Indian eyes., (© 2022. The Author(s).)

Background: Pediatric sedation is a clinical activity with potential for serious but rare airway adverse events, particularly laryngospasm. Anticholinergic drugs, atropine and glycopyrrolate, are frequently used with the intention to improve sedation safety by virtue of their antisialagogue effects., Aims: The objective of this study is to describe the current practice of anticholinergic use in pediatric sedation and to compare the frequency of serious sedation-related adverse events in patients who received anticholinergics to those who did not., Methods: We examined prospectively collected data from the Pediatric Sedation Research Consortium database. Patient characteristics, procedure type, sedation provider, sedatives, location of sedation, anticholinergic administered, adverse events, and airway interventions were reported. Propensity score matching and multivariable logistic regression were used to test whether any association exists between anticholinergic use and serious sedation-related adverse events., Results: Anticholinergics were administered in 7.1% (n = 18 707) of all cases (n = 263 883) reported between November 2011 and October 2017. When anticholinergics were used, atropine was used in 22% (n = 4111) and glycopyrrolate in 78.1% (n = 14 601) of sedations. Use of anticholinergics was more common in patients with well-described risk factors for airway adverse events: active/history of upper respiratory infection, history of reactive airway disease/asthma, and exposure to smoke. However, infants and ASA 3 patients were not associated with higher rate of anticholinergic use. Anticholinergic use was independently associated with an increase in the odds of serious adverse events, OR 1.8 (95% CI 1.6-2.1), especially airway adverse events., Conclusions: In this large Pediatric Sedation Research Consortium study, we found the use of anticholinergic adjuvants independently associated with greater odds of serious adverse events, especially airway adverse events, after adjusting for well-known sedation risk factors using propensity score matching and multivariate analysis., (© 2022 John Wiley & Sons Ltd.)

Four hundred myopic children randomly received atropine 0.02% (n = 138) or 0.01% (n = 142) in both eyes once-nightly or only wore single-vision spectacles (control group) (n = 120) for 2 years. Spherical equivalent refractive error (SER), axial length (AL), pupil diameter (PD), and amplitude of accommodation (AMP) were measured every 4 months. After 2 years, the SER changes were - 0.80 (0.52) D, - 0.93 (0.59) D and - 1.33 (0.72) D and the AL changes were 0.62 (0.29) mm, 0.72 (0.31) mm and 0.88 (0.35) mm in the 0.02% and 0.01% atropine groups and control group, respectively. There were significant differences between changes in SER and AL in the three groups (all P < 0.001). The changes in SER and AL in the 2nd year were similar to the changes in the 1st year in the three groups (all P > 0.05). From baseline to 2 years, the overall decrease in AMP and increase in PD were not significantly different in the two atropine groups, whereas the AMP and PD in the control group remained stable (all P > 0.05). 0.02% atropine had a better effect on myopia control than 0.01% atropine, and its effects on PD and AMP were similar to 0.01% atropine. 0.02% or 0.01% atropine controlled myopia progression and AL elongation synchronously and had similar effects on myopia control each year., (© 2021. The Author(s).)

Background: To date, guidelines on the impact and value of atropine combined with omeprazole in the treatment of acute gastritis have not been well established or well defined. This study aimed to clarify the efficacy and safety of combined atropine and omeprazole therapy for the management of patients with acute gastritis., Methods: Through searching the electronic database, the related literature of the combination of atropine with omeprazole in the treatment of acute gastritis were reviewed. A meta-analysis was performed after literature selection according to inclusion criteria. The treatment efficiency and the incidence of adverse reactions were used as the main outcome indicators. The odds ratios (ORs), standardized mean differences (SMDs), and 95% confidence intervals (CIs) of the two treatment regimens were analyzed., Results: This study analyzed 11 articles from the literature with a total of 1,053 subjects. The combination of atropine and omeprazole significantly improved the clinical outcomes of patients with acute gastritis compared to patients treated with combined anisodamine and omeprazole (control group). The effective rate of combined atropine and omeprazole treatment was 1.21 times higher than that observed with the control group, and the incidence of adverse reactions was 0.41 times that of the control group. Atropine combined with omeprazole significantly alleviated the clinical symptoms of the patients. The total treatment time was shortened by 0.57 days, duration of abdominal pain was shortened by 2.82 days, duration of diarrhea was reduced by 1.99 days, and the duration of nausea and vomiting was shortened by 2.68 days compared to the control group., Discussion: The combination of atropine with omeprazole in the treatment of acute gastritis demonstrated a high effective rate with few adverse reactions than. It was effective at alleviating the clinical symptoms associated with acute gastritis. The results of this study provide support for the clinical implementation of combined atropine and omeprazole in the treatment of patients with acute gastritis.

Sialorrhea is a troublesome and disabling symptom defined by the unintentional loss of saliva from the mouth, usually associated with swallowing disorders. Today there is no consensus about the management of sialorrhoea, but off-label use of ophthalmic atropine eyedrop administered sublingually may offer benefits, despite limited safety data. We report 2 cases of atropine overdose after sublingual administration illustrating that atropine can expose to severe adverse effects when administered sublingually. The noncompartmental pharmacokinetic study of atropine performed in 1 patient highlighted that systemic absorption of sublingual atropine was effective (C max [1 h] = 2.2 ng mL -1 ; approximately) after a single dose of 1 mg., (© 2021 British Pharmacological Society.)

Three hundred and twenty-eight myopic children, randomized to use either 0.01% (N = 166) or 0.02% (N = 162) atropine were enrolled in this study. Gender, age, body mass index(BMI), parental myopia status, atropine concentration used, pupil diameter, amplitude of accommodation, spherical equivalent refractive error (SER), anterior chamber depth (ACD) and axial length (AL) were collected at baseline and 1 year after using atropine. Rapid AL elongation was defined as > 0.36 mm growth per year. Univariate analyses showed that children with rapid AL elongation tend to be younger, have a smaller BMI, use of 0.01% atropine, narrow ACD, lower SER, shorter AL, smaller change in pupil diameter between 1 year and baseline (all P < 0.05). Multivariate logistic regression analyses confirmed that rapid AL elongation was associated with children that were younger at baseline (P < 0.0001), use of 0.01% atropine (P = 0.04), a shorter baseline AL (P = 0.03) and a smaller change in pupil diameter between 1 year and baseline (P = 0.04). Younger children with shorter AL at baseline, less change in their pupil diameter with atropine treatment and using the lower of the two atropine concentrations may undergo rapid AL elongation over a 12 months myopia control treatment period.

Atropine is a classical drug with a wide use in clinical practice. In ophthalmology, atropine can be used for cycloplegia before optometry, and the treatment of amblyopia, iridocyclitis, malignant glaucoma, etc. In recent years, the "old drugs with new application " research and application of atropine for myopia prevention and control has become a hotspot and the efficacy of atropine has been preliminarily recognized. However, before the widely used in clinical, the safety of atropine draws attention. Researches concerning side effects of atropine were searched. The most common problem is photophobia due to dilated pupils, followed by poor near visual acuity, allergy and inflammation, local irritation. Other side effects include withdraw rebound, dry eyes, elevation of intraocular pressure, system reactions, photic damage and toxicity. Among them, some side effects are theoretical yet, and the long-term effects of some side reactions are not clear. Further research and exploration is needed to serve clinical evidence. At present, investigational usage for myopia prevention and control in clinical trials of atropine can be beneficial. Safety observation and efficacy evaluation are equally important in the course of application. ( Chin J Ophthalmol, 2021, 57: 299-304) .

Organophosphorus (OP) pesticides and nerve agents still pose a threat to the population. Treatment of OP poisoning is an ongoing challenge and burden for medical services. Standard drug treatment consists of atropine and an oxime as reactivator of OP-inhibited acetylcholinesterase and is virtually unchanged since more than six decades. Established oximes, i.e. pralidoxime, obidoxime, TMB-4, HI-6 and MMB-4, are of insufficient effectiveness in some poisonings and often cover only a limited spectrum of the different nerve agents and pesticides. Moreover, the value of oximes in human OP pesticide poisoning is still disputed. Long-lasting research efforts resulted in the preparation of countless experimental oximes, and more recently non-oxime reactivators, intended to replace or supplement the established and licensed oximes. The progress of this development is slow and none of the novel compounds appears to be suitable for transfer into advanced development or into clinical use. This situation calls for a critical analysis of the value of oximes as mainstay of treatment as well as the potential and limitations of established and novel reactivators. Requirements for a straightforward identification of superior reactivators and their development to licensed drugs need to be addressed as well as options for interim solutions as a chance to improve the therapy of OP poisoning in a foreseeable time frame.

Background/aims: To report the protocol of a trial designed to evaluate the efficacy, safety and mechanism of action of low-dose atropine (0.01%) eye-drops for reducing progression of myopia in UK children., Methods: Multicentre, double-masked, superiority, placebo-controlled, randomised trial. We will enrol children aged 6-12 years with myopia of -0.50 dioptres or worse in both eyes.We will recruit 289 participants with an allocation ratio of 2:1 (193 atropine; 96 placebo) from five centres. Participants will instil one drop in each eye every day for 2 years and attend a research centre every 6 months. The vehicle and preservative will be the same in both study arms.The primary outcome is SER of both eyes measured by autorefractor under cycloplegia at 2 years (adjusted for baseline). Secondary outcomes include axial length, best corrected distance visual acuity, near visual acuity, reading speed, pupil diameter, accommodation, adverse event rates and allergic reactions, quality of life (EQ-5D-Y) and tolerability at 2 years. Mechanistic evaluations will include: peripheral axial length, peripheral retinal defocus, anterior chamber depth, iris colour, height and weight, activities questionnaire, ciliary body biometry and chorioretinal thickness. Endpoints from both eyes will be pooled in combined analysis using generalised estimating equations to allow for the correlation between eyes within participant. Three years after cessation of treatment, we will also evaluate refractive error and adverse events., Conclusions: The Childhood Atropine for Myopia Progression in the UK study will be the first randomised trial reporting outcomes of low-dose atropine eye-drops for children with myopia in a UK population., Trial Registration Number: ISRCTN99883695, NCT03690089., Competing Interests: Competing interests: NL: research funding from CooperVision, Essilor and Zeiss., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

This is a first case report of atropine eye drops used inappropriately to treat diplopia that followed botulinum A toxin injections for a cosmetic indication. Also presented is a review of precautions on use of atropine eye drops by non-ophthalmic physicians., (Copyright 2020 by the Missouri State Medical Association.)

Background: To evaluate the long-term efficacy and safety of topical 1% atropine for retarding moderate myopia. Methods: A randomized, controlled study evaluating atropine and placebo in 660 Chinese children. Patients received drops q1month for 24 months, then q2month for 12 months, followed by no drops for 12 months. Spherical equivalent, axial length, intraocular pressure and atropine-related side effects were examined at 6, 12, 24, 36 and 48 months for all children. Results: Spherical equivalent, myopic progression, axial length augmentation, and progression rate were significantly reduced in the atropine group than those in the placebo group (all P<0.05), indicating that 1% atropine effectively retarded myopia. Moreover, myopic rebound and adverse effects of 1% atropine were eliminated by gradual withdrawal and elimination of 1% atropine. Furthermore, pupil size, near visual acuity, and amplitude of accommodation returned to pretreatment levels after withdrawal of atropine. Conclusion: Topical 1% atropine periodically and alternatively in phase I with gradual reduction in phase II and final withdrawal in phase III may effectively improve atropine efficacy, retard moderate myopia, reduce atropine side effects, minimize myopic rebound, and increase compliance of children simultaneously., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

In recent years, some studies indicates that atropine eye drops is one of the most effective interventions for myopia. Due to large demand, the use of low-concentration atropine eye drops to reduce myopia progression is popular in China. Considering that the underlying mechanism of atropine eye drops in controlling the progression of myopia is still unclear, it is reasonable to pay enough attention to whether the long-term use of atropine eye drops in children will increase the risk of dry eye., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Anticholinergic drugs based on tropane alkaloids, including atropine, scopolamine, and hyoscyamine, have been used for various medicinal and toxic purposes for millennia. These drugs are competitive antagonists of acetylcholine muscarinic (M-) receptors that potently modulate the central nervous system (CNS). Currently used clinically to treat vomiting, nausea, and bradycardia, as well as alongside other anesthetics to avoid vagal inhibition, these drugs also evoke potent psychotropic effects, including characteristic delirium-like states with hallucinations, altered mood, and cognitive deficits. Given the growing clinical importance of anti-M deliriant hallucinogens, here we discuss their use and abuse, clinical importance, and the growing value in preclinical (experimental) animal models relevant to modeling CNS functions and dysfunctions.

Purpose: To report clinical manifestations of ocular allergy to atropine eye drops used for retardation of progressive myopia in children., Methods: Myopic children, who developed bothersome itching that subsided promptly after cessation of atropine eye drops, were included. History of systemic or ocular allergy, preexisting ocular conditions, and clinical features of allergy were noted., Results: Six children, age 5-15 years, were included. Four developed allergy to 1% atropine sulfate eye drops and two to 0.01% concentration of atropine sulfate. The onset of allergy was within a month to as late as 4 years after using atropine eye drops. The severity of allergy was higher with 1% concentration. The most common symptoms of atropine allergy were itching and burning. The most common signs were lid swelling and hyperemia. The allergic manifestations promptly reversed with the stoppage of eye drops. Reintroduction was possible in three patients, either by reducing the concentration of atropine or using benzalkonium free formulation., Conclusion: Allergy to atropine eye drops in children may develop within a few weeks or after many years of usage. Prompt cessation followed by a reintroduction and continuation of therapy may be possible in few patients., Competing Interests: There are no conflicts of interest

1. (S)-MP3950 is the (S)-enantiomer of active metabolite of mosapride, which exhibits higher 5-HT 4 receptor agonistic effect than mosapride. It shows promise to become a novel drug candidate for the treatment of gastrointestinal motility disorders (GMDs). However, the pharmacokinetic behavior of (S)-MP3950 in the pathological state of GMDs remains unclear. Herein, we investigated the comparative pharmacokinetics of (S)-MP3950 in normal and GMDs rats. 2. The comparative pharmacokinetics of (S)-MP3950 in normal and atropine-induced GMD rats were studied by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The validated UPLC-MS/MS method was successfully applied to investigate the pharmacokinetic profiles of (S)-MP3950 in normal and atropine-induced GMDs rats. Results showed that comparing to normal rats, C max reduced by 73.8%, AUC 0-t decreased by 57.6% and AUC 0-∞ declined by 56.8% in model rats. Additionally, the elimination half-life (t 1/2 ) and T max were prolonged slightly. 3. The pharmacokinetic results demonstrated that the atropine-induced GMDs reduced the absorption of (S)-MP3950. The pharmacokinetics research in the pathological state might provide more useful information for further study of novel gastric motility candidates.

Background: Sublingual atropine, dosed at 0.4-0.8 mg, is used by dentists as an antisialogogue to facilitate and increase the speed of procedures. Concentrated ophthalmic atropine drops (10 mg/mL) are commonly used off-label for this purpose. These highly concentrated drops may result in medication errors, atropine toxicity, and the antimuscarinic toxidrome. We report a case of a man who suffered acute delirium and dysarthria (from dry mouth) after an iatrogenic overdose from a dental procedure. His symptoms were initially interpreted as a stroke, but they completely resolved with physostigmine., Case Report: A 57-year-old man presented with acute dysarthria and delirium after a dental procedure; 4 hours earlier he was fitted for a temporary replacement of some premolar/molar teeth. He received sublingual atropine to assist in gingival drying for molding of his prosthesis, but a calculation error resulted in the administration of approximately 113 mg. A stroke evaluation was initially planned; however, 2.5 mg of intravenous physostigmine completely reversed his symptoms. His symptoms reoccurred and were successfully treated twice more with physostigmine; the patient was observed overnight with no additional symptoms and safely discharged the next morning. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Ophthalmic atropine drops are highly concentrated and may cause an overdose after ingestion of small amounts. This novel case highlights the importance of considering antimuscarinic poisoning in cases of acute delirium or dysarthria after dental procedures and stands as a reminder to inquire about the use of atropine drops in such cases. Timely recognition of the antimuscarinic toxidrome and appropriate use of physostigmine may prevent unnecessary testing while providing an effective therapy. This case also highlights the need for observation after resolution of delirium treated with physostigmine., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Multiple eccrine hidrocystoma (EH) has been treated with topical atropine with variable results. However, in rare cases, anticholinergic side effects have been seen after the use of the topical form of this drug. We presented a 50-year-old woman who developed recent onset of visual disturbance and photophobia from 2 weeks prior. The diagnosis of topical atropine-induced bilateral mydriasis was made. We reported a recognized but often overlooked case of bilateral mydriasis caused by application of topical 1% atropine for treatment of multiple EH., (© 2017 Wiley Periodicals, Inc.)

The prevalence of myopia has increased worldwide in recent decades. In East Asia's metropolises ≥ 80% of young adults are affected. This dramatic increase is mainly caused by changes in lifestyle and behaviour. Atropine has been used for more than 100 years to arrest myopia progression. It has become an evidence-based treatment regimen in the last decade, although the exact mechanism of the effect of treatment is still unknown. Atropine eye drops can slow myopia progression by an average of - 0.54 dioptres (D)/year in Asian children and - 0.35 D/year in Caucasian children. However, a non-response rate of about 10% has been found. Treatment should be established in schoolchildren only (age ≥ 6 years) with myopia ≤ - 2 D (spherical equivalent, cycoplegic refraction) and with documented myopic progression of - 0.5 D in the preceding year. 0.01% eyedrops should be instilled into the lower fornix at bedtime. Atropine 0.01% therapy is well tolerated. Atropine is usually administered for 2 years since efficacy is somewhat better in the second year. During treatment, a 6-month follow-up with cycoplegic refraction and axial length measurement is recommended. After the 2-year period, atropine withdrawal is justified if progression is less than - 0.25 D/year in the second year. Even after atropine has been stopped, follow-up examinations are needed to detect any rebound. Atropine-therapy is resumed if progression is again higher than - 0.5 D/year. Topical atropine is used off-label., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Patent ductus arteriosus (PDA) is one of the most common cardiac conditions in preterm infants. Closure of the PDA in symptomatic patients can be achieved medically or surgically. Atropine is commonly administered in general anesthesia as a premedication in this age group but with limited evidence addressing the effect of its use. Our study examined the association of the use of atropine as a premedication in PDA ligation and the risk of post-operative respiratory complications., Methods: This retrospective cohort study included 150 newborns who have failed medical treatment for PDA and received PDA ligation during 2008-2012 in a single tertiary medical center. Ninety-two of them (61.3%) received atropine as premedication for general anesthesia while 58 (38.7%) did not. Post-operative respiratory condition, the need of cardiopulmonary resuscitation and the presence of bradycardia were measured., Results: Patients with atropine use were associated with increased odds of respiratory acidosis in both univariate analysis (22.9% vs 7.3%; OR = 3.785, 95% CI = 1.211-11.826, p = 0.022) and multivariate analysis (OR = 4.030, 95% CI = 1.230-13.202, p = 0.021), with an even higher odds of respiratory acidosis in patients receiving both atropine and ketamine., Conclusion: The use of atropine as premedication in general anesthesia for neonatal PDA ligation is associated with higher risk of respiratory acidosis, which worsens with the combined use of ketamine., (Copyright © 2017. Published by Elsevier B.V.)

Objective: To confirm the clinical security and effectiveness of the daily application of 0.01% superdiluted atropine eyedrops in the progression of myopia in children., Material and Methods: A total of 200 children 9-12 years of age were randomised into a treated group and a control without treatment. Refraction under cycloplegia was performed., Results: Myopia progression of the treated group was -0.14±0.35 versus -0.65±0.54 in the control group without treatment. Only 2% of patients were forced to stop treatment due to side effects., Conclusion: Atropine superdiluted atropine 0.01% eyedrops is effective and well tolerated, and reduced myopia progression by 25%., (Copyright © 2018 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.)

OBJECTIVE To determine the safety of topical administration of 1% atropine ophthalmic solution in healthy horses by objectively measuring gastrointestinal transit time. DESIGN Randomized, masked, controlled crossover study. ANIMALS 6 adult geldings. PROCEDURES Horses were randomly assigned (3/group) to first receive topical treatment of the left eye with 1% atropine or artificial tears solution; the right eye was left untreated. After 24 hours of treatment every 6 hours, 200 nontoxic beads were administered to each horse via nasogastric intubation and treatment frequency was decreased to every 12 hours for 4 more days. Pupillary light reflexes (PLRs), mydriasis, heart rate, fecal bead passage, abdominal girth measurements, auscultable gut sounds, fecal weight, and clinical signs of abdominal pain were monitored. Following a 4-week washout period, horses received the opposite treatment in the left eye and measurements were repeated. Serum atropine concentration (reflecting systemic absorption) was measured with an ELISA at various points after initial atropine administration. RESULTS No horse had subjective or objective evidence of colic or ileus at any monitoring point. Complete mydriasis of the left eye with absence of the PLR was identified in 5 horses within 6 hours and in all 6 horses within 12 hours after initial atropine administration. One horse had mydriasis with an absent PLR in the untreated eye by day 5 of atropine treatment. At no point was atropine detected in serum samples of any horse. CONCLUSIONS AND CLINICAL RELEVANCE Topical atropine application at clinically appropriate doses induced no evidence of ileus in healthy horses.

The main therapeutic basis for a case of organophosphate poisoning is a combination therapy which includes atropine as an anticholinergic drug and pralidoxime. If the poisoning is severe, a high dose of this combination of medicines may be needed, but this may cause serious side effects: paralytic ileus or even megacolon; however, these gastrointestinal events are very rare. Here, we report a case of organophosphate poisoning where atropine therapy was given and led to drug-associated toxic megacolon.

Purpose: Describe an unusual case of bilateral pigment dispersion syndrome (PDS) following years of uninterrupted treatment with atropine 1% for bilateral congenital cataracts, speculate on potential mechanisms leading to this condition., Design: This is a case report., Case: A 45-year-old white patient on long-term treatment with atropine 1% ointment since his infancy for bilateral congenital cataracts developed PDS with secondary ocular hypertension., Results: The patient showed all the hallmarks of PDS with secondary ocular hypertension. An anterior segment Swept-Source optical coherence tomography was obtained to review the iris profile. The patient showed good pressure response to topical prostaglandin therapy., Conclusions: This is the second case report of PDS in a patient with chronic use of topical atropine. The proposed mechanisms for pigment dispersion are discussed and the possibility raised of dispersion being a potential side effect of the drug.

Background: This study aimed to assess the efficacy and safety of atropine 0.5% eyedrops (ATE) for the treatment of children with low myopia (LM)., Methods: In this study, a total of 126 children with LM were randomly divided into an intervention group (administered 0.5% ATE) and a control group (administered a placebo), with 63 children in each group. The outcome measurements were changes in the spherical equivalent (SE), and axial length (AL), as well as adverse events (AEs)., Results: Compared with placebo, administration of 0.5% ATE led to less progression in LM, as measured by SE, and less increase in AL (P < .01). In addition, no serious AEs occurred in both the groups., Conclusion: About 0.5% ATE was efficacious and safe for controlling myopia in children with LM.

Background: It remains unknown how single-shot anesthesia influences physical parameters, especially respiratory function and blood oxygen level of common marmosets (Callithrix jacchus) which came to be used for laboratory research., Methods: We measured blood oxygen levels, both before and after oxygenation, in 13 common marmosets under two single-shot anesthesia conditions: ketamine/xylazine/atropine and alphaxalone., Results and Conclusions: We found that SpO 2 values decreased to about 80% in the ketamine/xylazine/atropine protocol and fell just below 90% in the alphaxalone protocol. We observed a clear decrease in PaO 2 values under the anesthetized condition compared to the awake condition. Our data indicate that single-shot anesthesia may cause hypoxemia in marmosets. Previous studies on other non-human primate have reported no SpO 2 decrease and hypoxemia; thus, our experiment suggests that marmosets may have a more fragile respiratory system and require intensive veterinary care during anesthesia., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In randomized controlled trials, medication side effects may lead to beliefs that one is receiving the active intervention and enhance active treatment responses, thereby increasing drug-placebo differences. We tested these hypotheses with an experimental double-blind randomized controlled trial of a nonsteroidal anti-inflammatory drug with and without the addition of atropine to induce side effects. One hundred healthy volunteers were told they would be randomized to either combined analgesics that might produce dry mouth or inert placebos. In reality, they were randomized double blind, double-dummy to 1 of the 4 conditions: (1) 100 mg diclofenac + 1.2 mg atropine, (2) placebo + 1.2 mg atropine, (3) 100 mg diclofenac + placebo, or (4) placebo + placebo, and tested with heat-induced pain. Groups did not differ significantly in demographics, temperature producing moderate pain, state anxiety, or depression. Analgesia was observed in all groups; there was a significant interaction between diclofenac and atropine, without main effects. Diclofenac alone was not better than double-placebo. The addition of atropine increased pain relief more than 3-fold among participants given diclofenac (d = 0.77), but did not enhance the response to placebo (d = 0.09). A chain of mediation analysis demonstrated that the addition of atropine increased dry mouth symptoms, which increased beliefs that one had received the active medication, which, in turn, increased analgesia. In addition to this indirect effect of atropine on analgesia (via dry mouth and beliefs), analyses suggest that among those who received diclofenac, atropine directly increased analgesia. This possible synergistic effect between diclofenac and atropine might warrant future research.

Objective: To report the effect of sublingual atropine sulfate to treat drooling in children with cerebral palsy by comparing the results of the Drooling Impact Scale in a non-controlled open clinical trial., Results: Twenty-five children were assessed. The difference in the mean scores of the pre- and post-treatment scales reached statistical significance. There was a low frequency of side effects compared to studies with other anticholinergics., Conclusion: The use of sublingual atropine sulfate seems to be safe and there is a reduction in the Drooling Impact Scale score, which suggests efficacy in the treatment of drooling in children and adolescents with cerebral palsy. Our results should be replicated in randomized, placebo-controlled studies with larger numbers of participants.

Background: Despite good manufacturing practice and quality control, consumer products can become contaminated. In some cases, this can result in severe and life-threatening intoxication with potentially fatal consequences., Case Description: A 27-year-old man and a 28-year-old pregnant woman presented to the Emergency Department with severe anticholinergic syndrome after using a marshmallow root (Althaea officinalis) herbal remedy, mixed into hot chocolate drink, to reduce symptoms of common cold. After a short stay in Intensive Care, the symptoms diminished and the patients could be released from hospital. The herbs were found to be contaminated with atropine, most probably derived from deadly nightshade (Atropa belladonna). Analyses of the contaminated product indicated that the patients were exposed to 20-200 mg atropine, while a dose of 2 mg is already considered mildly toxic., Conclusion: Consultation of the Dutch National Poisons Information Center resulted in rapid detection of the contamination; close collaboration with the Netherlands Food and Consumer Product Safety Authority and the manufacturer of the product allowed rapid identification of the source of contamination and facilitated the prevention of an epidemic.

Myopia is the most common childhood refractive disorder. Atropine inhibits myopia progression, but its mechanism is unknown. Here, we show that myopia-prevention by atropine requires production of nitric oxide (NO). Form-deprivation myopia (FDM) was induced in week-old chicks by diffusers over the right eye (OD); the left eye (OS) remained ungoggled. On post-goggling days 1, 3, and 5, OD received intravitreally 20 µL of phosphate-buffered saline (vehicle), or vehicle plus: NO source: L-arginine (L-Arg, 60-6,000 nmol) or sodium nitroprusside (SNP, 10-1,000 nmol); atropine (240 nmol); NO inhibitors: L-NIO or L-NMMA (6 nmol); negative controls: D-Arg (10 µmol) or D-NMMA (6 nmol); or atropine plus L-NIO, L-NMMA, or D-NMMA; OS received vehicle. On day 6 post-goggling, refractive error, axial length, equatorial diameter, and wet weight were measured. Vehicle-injected goggled eyes developed significant FDM. This was inhibited by L-Arg (ED50 = 400 nmol) or SNP (ED50 = 20 nmol), but not D-Arg. Higher-dose SNP, but not L-Arg, was toxic to retina/RPE. Atropine inhibited FDM as expected; adding NOS-inhibitors (L-NIO, L-NMMA) to atropine inhibited this effect dose-dependently, but adding D-NMMA did not. Equatorial diameter, wet weight, and metrics of control eyes were not affected by any treatment. In summary, intraocular NO inhibits myopia dose-dependently and is obligatory for inhibition of myopia by atropine.

Efforts to reduce myopia progression in childhood are driven by the increasing incidence of high myopia and its attendant health risks. Interventional approaches to reduce myopia progression in childhood have included the use of spectacles, contact lens, and pharmacological methods, of which the latter appear to be most promising. We review the use of topical atropine eye drops in the retardation of myopia progression in children and discuss the efficacy and safety profiles when used at different concentrations (1.0%, 0.5%, 0.1%, and 0.01%). Topical atropine reduces myopia progression and axial elongation in children in a dose-related manner, but a rebound phenomenon occurs with higher doses. Its use has been shown to be safe, but higher doses cause pupil dilation, loss of accommodation and near vision. Atropine 0.01% has the best therapeutic index, with clinically insignificant amounts of pupil dilation, near vision, and accommodation loss but remains as effective as higher doses.

Atropine, a widely used topical anticholinergic drug, might have adverse effects on human corneas in vivo. However, its cytotoxic effect on human corneal endothelium (HCE) and its possible mechanisms are unclear. Here, we investigated the cytotoxicity of atropine and its underlying cellular and molecular mechanisms using an in vitro model of HCE cells and verified the cytotoxicity using cat corneal endothelium (CCE) in vivo. Our results showed that atropine at concentrations above 0.3125 g/L could induce abnormal morphology and viability decline in a dose- and time-dependent manner in vitro. The cytotoxicity of atropine was proven by the induced density decrease and abnormality of morphology and ultrastructure of CCE cells in vivo. Meanwhile, atropine could also induce dose- and time-dependent elevation of plasma membrane permeability, G1 phase arrest, phosphatidylserine externalization, DNA fragmentation, and apoptotic body formation of HCE cells. Moreover, 2.5 g/L atropine could also induce caspase-2/-3/-9 activation, mitochondrial transmembrane potential disruption, downregulation of anti-apoptotic Bcl-2 and Bcl-xL, upregulation of pro-apoptotic Bax and Bad, and upregulation of cytoplasmic cytochrome c and apoptosis-inducing factor. In conclusion, atropine above 1/128 of its clinical therapeutic dosage has a dose- and time-dependent cytotoxicity to HCE cells in vitro which is confirmed by CCE cells in vivo, and its cytotoxicity is achieved by inducing HCE cell apoptosis via a death receptor-mediated mitochondrion-dependent signaling pathway. Our findings provide new insights into the cytotoxicity and apoptosis-inducing effect of atropine which should be used with great caution in eye clinic., (© 2016 by the Society for Experimental Biology and Medicine.)

PurposeRandomized controlled trials have shown the efficacy of atropine for progressive myopia, and this treatment has become the preferred pattern for this condition in Taiwan. This study explores the effectiveness of atropine 0.5% treatment for progressive high myopia and adherence to therapy in a non-Asian country.MethodsAn effectiveness study was performed in Rotterdam, the Netherlands. Overall 77 children (mean age 10.3 years±2.3), of European (n=53), Asian (n=18), and African (n=6) descent with progressive myopia were prescribed atropine 0.5% eye drops daily. Both parents and children filled in a questionnaire regarding adverse events and adherence to therapy. A standardized eye examination including cycloplegic refraction and axial length was performed at baseline and 1, 4, and 12 months after initiation of therapy.ResultsMean spherical equivalent at baseline was -6.6D (±3.3). The majority (60/77, 78%) of children adhered to atropine treatment for 12 months; 11 of the 17 children who discontinued therapy did so within 1 month after the start of therapy. The most prominent reported adverse events were photophobia (72%), followed by reading problems (38%), and headaches (22%). The progression rate of spherical equivalent before treatment (-1.0D/year±0.7) diminished substantially during treatment (-0.1D/year±0.7) compared to those who ceased therapy (-0.5D/year±0.6; P=0.03).ConclusionsDespite the relatively high occurrence of adverse events, our study shows that atropine can be an effective and sustainable treatment for progressive high myopia in Europeans.

A 58-year-old male was scheduled to undergo radical gastrectomy for cancer under general anesthesia. The patient developed agitation and irregular breathing after receiving a single dose of atropine (0.5 mg) to treat bradycardia immediately prior to induction of anesthesia. Within 5 min after the atropine injection, the patient became unresponsive with facial flushing and diaphoresis. When a drop in oxygen saturation was observed, a laryngeal mask airway was inserted after administering a small bolus dose of propofol (80 mg) and the patient was ventilated with 100% oxygen. Physostigmine was not administered because of the relatively low dose of atropine and the fact that his symptoms were not totally consistent with central anticholinergic syndrome (CAS). The differential diagnosis at the time also included an acute cardiovascular event and an idiosyncratic reaction to atropine. The patient fully recovered within 80 min from this highly unusual reaction to a single 0.5 mg IV dose of atropine., (© 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)