Atropine: Updates on myopia pharmacotherapy.

The prevalence of myopia has rapidly increased over the last 30 years, with the World Health Organization estimating a worldwide incidence of 23%, projected to increase to 50% by 2050. The myopia epidemic has prompted a reincarnation in efforts to overcome this challenge. The exploration of atropine use in myopia was a result due to a lack of treatment in effect. This study aimed at reviewing the role of atropine in the management of myopia worldwide based on currently available findings. A literature search was conducted using PubMed/MEDLINE and Google Scholar for studies published up to April 2022 inclusive. Articles with high or medium clinical relevance were selected for this review. Multiple studies have demonstrated the relevance and efficacy rates of different concentrations of atropine, despite still insufficiently explained the exact site and mechanism of action of atropine in slowing myopia progression. Currently available findings highlight that topical atropine opened a new page in pharmacotherapy of myopia and have shown a high therapeutic effect on myopia progression in Asian and European child population, irrespective of ethnicity. There is potential for myopia control with fewer side effects using lower concentrations but still exists a room for improvement, underscoring the requirement of modified atropine topical preparations with increased bioavailability, potentially with nanoparticle formulations, to enable the effective management of myopia.

Impact of atropine use for myopia control on intraocular pressure in children: A comprehensive review including postpupil dilation intraocular pressure changes.

Topical atropine has been widely used for controlling myopia progression in children, yet its long-term efficacy and safety, including potential intraocular pressure (IOP) elevation, are still being studied. The mydriasis and cyclopegia induced by atropine may reduce traction on the trabecular meshwork, together with pigment released into anterior chamber due to the friction between the iris and lens during pupil dilation, may obstruct and reduce the trabecular outflow. This review first explores postdilation IOP changes across different groups - healthy individuals, glaucoma patients, and children. The response to pupil dilation varies widely, with IOP potentially increasing or decreasing. Glaucoma patients, whether with open or closed-angle glaucoma, may experience more significant IOP rises postdilation. The second section examines IOP effects in children using topical atropine for myopia, where most of the 25 reviewed studies showed nonsignificant IOP changes, although slight increases were observed in a few. In addition, no alterations in the retinal nerve fiber layer thickness were found. However, the research on children's IOP under topical atropine is constrained by small sample sizes, cross-sectional studies, brief follow-ups, and often lacks control groups or pretreatment IOP measurements. Given the extended atropine use for myopia and the significant individual variation in IOP response, we recommend routine IOP monitoring for children receiving topical atropine.

Impact of coronavirus disease 2019 restrictions on the efficacy of atropine 0.01% eyedrops for myopia control - Findings from the Western Australia Atropine for the Treatment of Myopia study.

This study explored the impact of short-term coronavirus disease 2019 (COVID-19) restrictions on the efficacy of atropine 0.01% eyedrops on myopia control in a multiethnic cohort of Australian children. In the Western Australia Atropine for the Treatment of Myopia study, 104 and 49 children were randomized to receive atropine 0.01% eyedrops and a placebo, respectively. We compared the 1-year myopia progression and axial elongation following the 2-month lockdown in 2020 to the same months in 2019 and 2021, i.e., the 1-year myopia progression up to May 2019-October 2019 (non-COVID-19) versus the 1-year progression up to May 2020-October 2020 (COVID-19 period), and the 1-year progression up to May 2021-October 2021 (non-COVID-19) versus the 1-year progression up to the same months in 2020. After excluding participants who withdrew, completed their treatment phase prior May 2020, or those whose study visits did not fall between May 2020 and October 2020, 65 participants (mean age at baseline = 11.8 ± 2.5 years) were included in the final analysis (49 in the treatment group; 16 in the placebo group). After correcting for age, sex, and ethnicity, there was no significant main effect of the short-term lockdown on the rate of spherical equivalent or axial length change. However, there was a lockdown × treatment interaction effect on the rate of axial elongation (P = 0.007). This was such that in the treatment group, the 1-year axial elongation was faster during lockdown by 0.056 mm compared to the nonlockdown periods (P = 0.009), while the rate of axial elongation in those on the placebo eye drops was similar during lockdown and nonlockdown. Our findings suggest that there is a decreased efficacy of low-concentration atropine even with relatively lenient restrictions lasting for a few months.

L-carnitine: A novel approach in management of acute cholinesterase inhibitor insecticide poisoning.

Cholinesterase inhibitors (ChEIs) insecticide poisoning is a serious global health concern that results in hundreds of thousands of fatalities each year. Although inhibition of the cholinesterase enzyme is the main mechanism of ChEI poisoning, oxidative stress is considered the mechanism underlying the related complications. The study aimed to assess the oxidative status of the patients with ChEI insecticide poisoning and the role of L-carnitine as adjuvant therapy in their management. Human studies on the efficacy and safety of L-carnitine in treating insecticide poisoning are limited despite its growing research interest as a safe antioxidant. This prospective study was conducted on eighty patients with acute ChEIs insecticide poisoning admitted to Alexandria Poison Center, Alexandria Main University Hospital, Egypt. Patients were allocated into two equal groups randomly. The L-carnitine (LC) group received the conventional treatment (atropine & toxogonin) and LC and the standard treatment (ST) group received the standard treatment only. Outcome measures were fatality rate, the total administered dose of atropine & toxogonin, length of hospital stay, and the requirement for ICU admission or mechanical ventilation. The study results revealed that malondialdehyde (MDA) significantly decreased in the LC group. Cholinesterase enzyme levels increased significantly after treatment in the LC group than in the ST group. The LC group needed lower dosages of atropine and toxogonin than the ST group. Also, the LC group showed no need for ICU admission or mechanical ventilation. The study concluded that LC can be considered a promising adjuvant antioxidant treatment in acute ChEIs pesticide poisoning.

Oculocardiac Reflex in a Patient With Maxillofacial Trauma: A Case Study and Literature Review.

Oculocardiac reflex (OCR), presenting as bradycardia and asystole, is a potential intraoperative complication that may occur during maxillofacial trauma surgery. Bradycardia is the most common symptom of this phenomenon. Surgeons should be aware of its long-term effects, such as arrhythmias and even cardiac arrest. We report the case of a 40-year-old male patient with a fracture of the floor of the orbit. During a surgical exploration of the orbital floor, the patient exhibited sudden symptoms of OCR. It was managed by withholding the surgery and administering atropine. The article also highlights the mechanism, types, incidence, and management of OCR in patients with maxillofacial trauma.

Impact of salivary flow inhibition on masticatory behaviours in healthy individuals.

BACKGROUND: It remains unclear how the salivary flow and the fat content of food affect bolus formation during mastication. OBJECTIVES: We aimed to clarify: (1) how hyposalivation affects jaw-closing and hyoid-elevating muscle activities in bolus formation, and (2) if the effect of hyposalivation on muscle activity depends on the fat content of food. METHODS: Eighteen healthy male volunteers were instructed to freely ingest four test foods: Plain, Fat without seasoning, Fat with seasoning, and Soft rice crackers. Masseter and suprahyoid electromyographic activities were recorded before and 30 min after the administration of atropine sulfate, a muscarinic receptor antagonist that induces hyposalivation. RESULTS: Hyposalivation extended the masticatory duration significantly in all the test foods except Fat with seasoning. Masticatory cycle time was significantly longer with vs without hyposalivation for the Soft (p = .011). Suprahyoid activity/cycle was significantly greater with vs without hyposalivation (p = .013). Masticatory cycle time was significantly longer at the late stage with vs without hyposalivation for the Soft (p < .001). Suprahyoid activity/cycle was significantly greater at the middle (p = .045) and late stages (p = .002) with vs without hyposalivation for the Soft and greater at the late stage with vs without hyposalivation for the Plain (p = .043). Changes in masticatory cycle time and suprahyoid activity/cycle for these foods had significantly positive relationship (p < .001). CONCLUSION: Hyposalivation-induced changes in masticatory behaviours resulted from the middle and late stage suprahyoid activity. Fat content and seasoning compensate for salivary flow inhibition.

Effect of pH and temperature on tropane alkaloids within a processing strategy to provide safe infant cereal-based food.

Tropane alkaloids (TAs) are secondary metabolites from weeds that can contaminate cereals and vegetables during harvest. Due to their toxicity, the Regulation (EC) 2023/915 sets maximum levels for atropine and scopolamine in cereal-based foods for infants containing millet, sorghum, buckwheat or their derived products. The aim of this study was to evaluate the effect of pH and temperature on the stability of TAs, as possible parameters in thermal processing to mitigate this chemical hazard in cereal-based infant food. The effect of pH (4 and 7) and temperature (80 °C and 100 °C) was assessed in buffer solutions. Also, treatment at 180 °C was performed in spiked and naturally incurred millet flour to assess the effect of high temperature, simulating cooking or drying, on the stability of TAs in the cereal matrix. The fate of 24 TAs was assessed by UHPLC-MS/MS. TAs showed high thermostability, although it was variable depending on the specific compound, pH, temperature and treatment time. In buffer solutions, higher degradation was found at 100 °C and pH 7. In spiked millet flour at 180 °C for 10 min, scopolamine and atropine contents decreased by 25 % and 22 %, similarly to other TAs which also showed a slow thermal degradation. Atropine, scopolamine, anisodamine, norscopolamine, scopine and scopoline were found in naturally contaminated millet flour. Interestingly, naturally incurred atropine was more thermostable than when spiked, showing a protective effect of the cereal matrix on TAs degradation. The present results highlight the need for an accurate monitorization of TAs in raw materials, as this chemical hazard may remain in infant cereal-based food even after intense thermal processing.

Absorption and attachment of atropine to etafilcon A contact lenses.

PURPOSE: Myopia (short-sightedness) is a growing vision problem worldwide. Currently atropine eye drops are used to control the progression of myopia but these suffer from potential lack of bioavailability and low ocular residence time. Commercially available myopia control contact lenses are also used to limit myopia progression, but neither atropine nor contact lenses individually completely stop progression. Development of myopia control contact lenses which could deliver therapeutic doses of atropine is thus desirable and may provide increased efficacy. This study was designed to explore the feasibility of attaching atropine to etafilcon A contact lenses through an esterification reaction. METHODS: Carboxylic acid groups on etafilcon A contact lenses were quantified using Toluidine Blue O. The carboxylic acid groups in etafilcon A contact lenses were activated using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC-HCl) and N-hydroxysuccinimide (NHS) crosslinkers after which atropine was added to undergo potential binding via esterification. Atropine was released from lenses by alkaline hydrolysis. Reverse phase high performance liquid chromatography (HPLC) was used to detect and quantify the released atropine and its degradation products in solution. Contact lenses that had not been activated by EDC-NHS (controls) were also examined to determine the amount of atropine that could be absorbed rather than chemically bound to lenses. RESULTS: Each etafilcon A contact lens contained 741.1 ± 5.5 µg carboxylic acid groups which may be available for esterification. HPLC had a limit of detection for atropine of 0.38 µg/mL and for tropic acid, an atropine degradation product, of 0.80 µg/mL. The limits of quantification were 1.16 µg/mL for atropine and 2.41 µg/mL for tropic acid in NH4HCO3. The etafilcon A lenses adsorbed up to 7.69 µg atropine when incubated in a 5 mg/mL atropine solution for 24 h. However, there was no evidence that atropine could be chemically linked to the lenses, as washing in a high concentration of NaCl removed all the atropine from the contact lenses with no atropine being subsequently released from the lenses after incubating in 0.01 N NH4HCO3. CONCLUSIONS: Etafilcon A contact lenses contain free carboxylic acids which may be an appropriate option for attaching drugs such as atropine. Etafilcon A lenses adsorbed up to 7.69 µg atropine, which would be more than enough to deliver atropine to eyes to control myopia. However, atropine could not be chemically bound to the carboxylic acids of the etafilcon A lenses using this methodology.

Under-Recognized Life-Threatening Vasovagal Reflex During Chest Tube Insertion.

Chest tube insertion is a common and relatively safe procedure in an emergency setting. However, a potentially fatal complication, vasovagal reflex, may be under-recognized due to its generally mild severity. We present a case of pulseless electrical activity (PEA) requiring chest compression due to vasovagal reflex during chest tube insertion for spontaneous pneumothorax. A 23-year-old male who had a history of spontaneous pneumothorax presented with left chest pain to our emergency department. Based on point-of-care ultrasonography and chest radiography, we made a diagnosis of recurrent pneumothorax. Although he had stable vital signs and received adequate pain control, during chest tube insertion, he developed severe sinus bradycardia with a six-second pause, leading to PEA requiring chest compressions. After a few compressions, his heart rate increased and he regained consciousness. He underwent video-assisted thoracoscopic surgery for pneumothorax and was discharged without complications. Vasovagal reflex during chest tube insertion in young patients with spontaneous pneumothorax may cause severe bradycardia and cardiac arrest. Physicians should be aware of this rare but potentially fatal complication and be prepared with appropriate measures, such as pre-administration of atropine, before chest tube insertion.

Stability of Multicomponent Antidote Parenteral Formulations for Autoinjectors against Chemical War Agents (Neurotoxics).

Combinations of different drugs are formulated in autoinjectors for parenteral administration against neurotoxic war agents. In this work, the effects on the chemical stability of the following three variables were studied: (i) type of drug combination (pralidoxime, atropine, and midazolam versus obidoxime, atropine, and midazolam); (ii) pH (3 versus 4); and (iii) type of elastomeric sealing material (PH 701/50 C BLACK versus 4023/50 GRAY). Syringes were stored at three different temperatures: 4, 25, and 40 °C. Samples were assayed at different time points to study the physical appearance, drug sorption on the sealing elastomeric materials, and drug content in solution. Midazolam was unstable in all tested experimental conditions. Drug adsorption was observed in both types of sealing elastomeric materials and was significantly (p < 0.01) dependent on the lipophilicity of the drug. The most stable formulation was the combination of pralidoxime and atropine at pH 4 with the elastomeric sealing material 4023/50 GRAY.

Enhanced ophthalmic bioavailability and stability of atropine sulfate via sustained release particles using polystyrene sulfonate resin.

Atropine sulfate (ATS) eye drops at low concentrations constitute a limited selection for myopia treatment, with challenges such as low ophthalmic bioavailability and inadequate stability. This study proposes a novel strategy by synthesizing ophthalmic sodium polystyrene sulfonate resin (SPSR) characterized by a spherical shape and uniform size for cationic exchange with ATS. The formulation of ATS@SPSR suspension eye drops incorporates xanthan gum and hydroxypropyl methylcellulose (HPMC) as suspending agents. In vitro studies demonstrated that ATS@SPSR suspension eye drops exhibited sustained release characteristics, and tropic acid, its degradation product, remained undetected for 30 days at 40 °C. The ATS levels in the tear fluids and aqueous humor of New Zealand rabbits indicated a significant increase in mean residence time (MRT) and area under the drug concentration-time curve (AUC0-12h) for ATS@SPSR suspension eye drops compared to conventional ATS eye drops. Moreover, safety assessment confirmed the non-irritating nature of ATS@SPSR suspension eye drops in rabbit eyes. In conclusion, the cation-responsive sustained-release ATS@SPSR suspension eye drops enhanced the bioavailability and stability of ATS, offering a promising avenue for myopia treatment.

Characterization of Humanized Mouse Model of Organophosphate Poisoning and Detection of Countermeasures via MALDI-MSI.

Organophosphoate (OP) chemicals are known to inhibit the enzyme acetylcholinesterase (AChE). Studying OP poisoning is difficult because common small animal research models have serum carboxylesterase, which contributes to animals' resistance to OP poisoning. Historically, guinea pigs have been used for this research; however, a novel genetically modified mouse strain (KIKO) was developed with nonfunctional serum carboxylase (Es1 KO) and an altered acetylcholinesterase (AChE) gene, which expresses the amino acid sequence of the human form of the same protein (AChE KI). KIKO mice were injected with 1xLD50 of an OP nerve agent or vehicle control with or without atropine. After one to three minutes, animals were injected with 35 mg/kg of the currently fielded Reactivator countermeasure for OP poisoning. Postmortem brains were imaged on a Bruker RapifleX ToF/ToF instrument. Data confirmed the presence of increased acetylcholine in OP-exposed animals, regardless of treatment or atropine status. More interestingly, we detected a small amount of Reactivator within the brain of both exposed and unexposed animals; it is currently debated if reactivators can cross the blood-brain barrier. Further, we were able to simultaneously image acetylcholine, the primary affected neurotransmitter, as well as determine the location of both Reactivator and acetylcholine in the brain. This study, which utilized sensitive MALDI-MSI methods, characterized KIKO mice as a functional model for OP countermeasure development.

Efficacy and Safety of 0.03% Atropine Eye Drops in Controlling Myopia Progression: A One-Year Prospective Clinical Study.

Objective: To investigate the efficacy and safety of one-year treatment with 0.03% atropine eye drops for slowing myopia progression among children aged 6-12 years. Methods: Healthy Caucasian children aged 6-12 years with cycloplegic spherical equivalent (SE) from -1.0 D to -5.0 D and astigmatism and anisometropia ≤1.5 D were included. Changes in mean axial length (AL) and objective SE as well as changes in intraocular pressure (IOP), central corneal thickness (CCT), anterior chamber depth (ACD) and lens thickness (LT) were assessed in the 0.03% atropine eye drops group and the control group from baseline through the 1-year follow-up. The proportion of participants showing myopia progression of <0.5 D from baseline in each group and any potential side effects in 0.03% atropine group were evaluated. Results: The study involved 31 patients in the 0.03% atropine eye drops group and 41 in the control group. Administration of 0.03% atropine for 1 year resulted in a mean change in SE of -0.34 (0.44) D/year, significantly lower than the -0.60 (0.50) D/year observed in the control group (p = 0.024). The change in AL was 0.19 (0.17) mm in the 0.03% atropine group, compared to 0.31 (0.20) mm in the control group (p = 0.015). There were no significant differences in changes of IOP, CCT and LT between the groups (all p ≥ 0.05). The 0.03% atropine group had a significantly greater increase in ACD compared to the control group (p = 0.015). In total, 64.5% of patients in the 0.03% atropine group showed progression <0.5 D/year, in contrast to 39.0% in the control group (p = 0.032). Adverse events were reported in 13 (35.0%) out of 37 patients in the treatment group, leading to discontinuation of the eye drops in six (16.0%) cases. None of the adverse events were severe. Conclusions: Despite a higher incidence of adverse events, 0.03% atropine eye drops effectively slowed the progression of myopia over 1-year.

Congenital Complete Heart Block-To Stimulate (When?) or Not to Stimulate?

This article presents the case of a 27-year-old female patient with idiopathic congenital complete heart block who does not consent to the implantation of a cardiac pacemaker but was referred by her primary care physician for cardiological evaluation. The conduction disturbance was recognized at the age of 6 and was asymptomatic. The professional disqualification from pacemaker implantation included a detailed history of a patient's symptoms, an echocardiographic assessment of the heart, exercise testing and ECG Holter monitoring. The aid of salbutamol administered orally was also useful.

Can Google Help Your Nearsightedness? A Google Trend Analysis of Public Interest in Myopic Progression.

Purpose: To explore public interest in myopia progression and management and to correlate these trends to available treatments. Methods: Keywords were chosen for interest in myopia overall and those signifying interest in myopia treatments. Treatment options were separated into four main categories: atropine, glasses, contact lenses, and orthokeratology. Search terms were queried across ten years of Google Trends data and the relative search volume was analyzed to quantify the change in search volume over time. Results: A positive linear trend over time was present for all myopia interest keywords except "nearsighted" (p = 0.074) and "near work myopia" (p = 0.086). Interest in the four myopia treatment categories included in this study also displayed a significant positive trend over time. There is also a statistically significant positive correlation between all four treatment options and four of the seven categories of population interest, "myopia control", "myopia", "myopia progression", and "screen time myopia". Conclusion: This study demonstrates the utility of GT to correlate public interest in myopia treatments over time. All treatment terms had statistically significant linear search volume growth over a ten-year period. The positive correlation between interest in myopia as a health problem and available treatments supports existing evidence that GT can track rising public health concerns and corresponding treatment-seeking behaviors.

The optimal atropine concentration for myopia control in Chinese children: a systematic review and network Meta-analysis.

AIM: To figure out whether various atropine dosages may slow the progression of myopia in Chinese kids and teenagers and to determine the optimal atropine concentration for effectively slowing the progression of myopia. METHODS: A systematic search was conducted across the Cochrane Library, PubMed, Web of Science, EMBASE, CNKI, CBM, VIP, and Wanfang database, encompassing literature on slowing progression of myopia with varying atropine concentrations from database inception to January 17, 2024. Data extraction and quality assessment were performed, and a network Meta-analysis was executed using Stata version 14.0 Software. Results were visually represented through graphs. RESULTS: Fourteen papers comprising 2475 cases were included; five different concentrations of atropine solution were used. The network Meta-analysis, along with the surface under the cumulative ranking curve (SUCRA), showed that 1% atropine (100%)>0.05% atropine (74.9%) >0.025% atropine (51.6%)>0.02% atropine (47.9%)>0.01% atropine (25.6%)>control in refraction change and 1% atropine (98.7%)>0.05% atropine (70.4%)>0.02% atropine (61.4%)>0.025% atropine (42%)>0.01% atropine (27.4%)>control in axial length (AL) change. CONCLUSION: In Chinese children and teenagers, the five various concentrations of atropine can reduce the progression of myopia. Although the network Meta-analysis showed that 1% atropine is the best one for controlling refraction and AL change, there is a high incidence of adverse effects with the use of 1% atropine. Therefore, we suggest that 0.05% atropine is optimal for Chinese children to slow myopia progression.

The efficacy of the use of atropine in children with reflex anoxic syncope during pallid breath-holding spells: can cardiac pacemaker implantation be avoided?

OBJECTIVES: Reflex anoxic syncope is the result of an overreaction of the vagal system, resulting in hypotension and bradycardia or brief cardiac arrest. Because of the benign character and the absence of complications in short or long term, treatment is only necessary in case of frequent or severe clinical presentation. Treatment options are anticholinergic drugs or cardiac pacemaker placement. We investigated atropine treatment and aimed to examine if pacemaker placement can be avoided. METHODS: We retrospectively reviewed patients treated with atropine for severe reflex anoxic syncope in our centre from January 2017 until May 2023, and compared our results to those in the literature. RESULTS: The study population consisted of 10 children, 70% female, with an age ranging from 5 months to 3 years (mean 14.5 months) when atropine treatment was started (dose 17-50 microg/kg/day). All patient's parents reported adequate symptom management during atropine treatment, with complete resolution in 10%. Minor side effects were reported in 60% (dry mucosa in 40%, obstipation in 20%, and nausea or blurry vision in 10%). DISCUSSION: We consider atropine a safe and effective treatment to manage reflex anoxic syncope with similar success rate to pacemaker implantation. However, pacemaker implantation entails substantial risk for complications (up to 25%) such as infection or technical problems and morbidity such as scar formation. This might be considered redundant for a benign and temporary condition, certainly given the possibility of other efficient treatment options. Consequently, we recommend atropine treatment over implantation of a cardiac pacemaker in children with severe reflex anoxic syncope.

Effect of 0.01% atropine combined with orthokeratology lens on axial elongation: a 2-year randomized, double-masked, placebo-controlled, cross-over trial.

Purpose: To evaluate the effect of 0.01% atropine combined with orthokeratology (OK) lens on axial elongation in schoolchildren with myopia. Methods: Sixty children aged 8-12 years with spherical equivalent refraction (SER) from -1.00D to -4.00D in both eyes were enrolled in this randomized, double-masked, placebo-controlled, cross-over trial. Children who had been wearing OK lenses for 2 months were randomly assigned into combination group (combination of OK lens and 0.01% atropine) for 1 year followed by control group (combination of OK lens and placebo) for another 1 year or vice versa. This trial was registered in the Chinese Clinical Trial Registry (Number: ChiCTR2000033904, 16/06/2020). The primary outcome was changes in axial length (AL). Data of right eyes were analyzed. Results: There were statistically significant differences in the changes in AL between combination and control groups after generalized estimating equation model adjusting for age and baseline SER (p = 0.001). The mean axial elongation difference between combination and control groups was 0.10 mm in the first year (0.10 ± 0.13 mm vs. 0.20 ±0.15 mm; p = 0.01), and 0.09 mm in the second year (0.22 ± 0.10 mm vs. 0.13 ± 0.14 mm; p = 0.01), respectively. The mean axial elongation difference of two groups in the first year was similar to that in the second year during the cross-over treatment. Conclusion: In central Mainland China in myopic children, the treatment of combination therapy is more effective than single OK lens in controlling axial elongation.

Human Plasma Butyrylcholinesterase Hydrolyzes Atropine: Kinetic and Molecular Modeling Studies.

The participation of butyrylcholinesterase (BChE) in the degradation of atropine has been recurrently addressed for more than 70 years. However, no conclusive answer has been provided for the human enzyme so far. In the present work, a steady-state kinetic analysis performed by spectrophotometry showed that highly purified human plasma BChE tetramer slowly hydrolyzes atropine at pH 7.0 and 25 °C. The affinity of atropine for the enzyme is weak, and the observed kinetic rates versus the atropine concentration was of the first order: the maximum atropine concentration in essays was much less than Km. Thus, the bimolecular rate constant was found to be kcat/Km = 7.7 × 104 M-1 min-1. Rough estimates of catalytic parameters provided slow kcat < 40 min-1 and high Km = 0.3-3.3 mM. Then, using a specific organophosphoryl agent, echothiophate, the time-dependent irreversible inhibition profiles of BChE for hydrolysis of atropine and the standard substrate butyrylthiocholine (BTC) were investigated. This established that both substrates are hydrolyzed at the same site, i.e., S198, as for all substrates of this enzyme. Lastly, molecular docking provided evidence that both atropine isomers bind to the active center of BChE. However, free energy perturbations yielded by the Bennett Acceptance Ratio method suggest that the L-atropine isomer is the most reactive enantiomer. In conclusion, the results provided evidence that plasma BChE slowly hydrolyzes atropine but should have no significant role in its metabolism under current conditions of medical use and even under administration of the highest possible doses of this antimuscarinic drug.

Atropine sulfate as a continuous intravenous infusion for the treatment of organophosphate toxicity in a cat.

Case summary: A 1-year-old male neutered domestic shorthair cat presented on an emergency basis with clinical signs suspected to be secondary to organophosphate (OP) toxicity. The control of clinical abnormalities (bradycardia, obtundation, tachypnea, anorexia) was achieved using high-dose continuous rate intravenous infusion (CRI) of atropine sulfate (maximum rate 0.1 mg/kg/h). After 5 days of hospitalization, the patient made a full clinical recovery without the development of atropine toxicity, intermediate syndrome or delayed polyneuropathy at 4 weeks after discharge. Relevance and novel information: Treatment of OP toxicity in cats is sparsely reported in veterinary literature. Current standards of treatment and published protocols recommend the use of atropine sulfate as intermittent boluses for the treatment of muscarinic signs of toxicity; however, there is a paucity of information regarding the safety and efficacy of atropine sulfate as a CRI for severe toxicosis as described in humans. This report includes the first published case using such a treatment protocol in a cat.