Further exploration of the collision-induced dissociation of select beta blockers: Acebutolol, atenolol, bisoprolol, carteolol, and labetalol.

Beta blockers are a class of drugs commonly used to treat heart-related diseases; they are also regulated under the World Anti-Doping Agency. Tandem mass spectrometry is often used in the pharmaceutical industry, clinical analysis laboratory, and antidoping laboratory for detection and characterization of drugs and their metabolites. A deeper chemical understanding of dissociation pathways may eventually lead to an improved ability to predict tandem mass spectra of compounds based strictly on their chemical structure (or vice versa), which is especially important for characterization of unknowns such as emerging designer drugs or novel metabolites. In addition to providing insights into dissociation pathways, the use of energy-resolved breakdown curves can produce improved selectivity and lend insights into optimal fragmentation conditions for liquid chromatography-tandem mass spectrometry LC-MS/MS workflows. Here, we perform energy-resolved collision cell and multistage ion trap collision-induced dissociation-mass spectrometry (CID-MS) experiments, along with complementary density functional theory calculations, on five beta blockers (acebutolol, atenolol, bisoprolol, carteolol, and labetalol), to better understand the details of the pathways giving rise to the observed MS/MS patterns. Results from this work are contextualized within previously reported literature on these compounds. New insights into the formation of the characteristic product ion m/z 116 and the pathway leading to characteristic loss of 77 u are highlighted. We also present comparisons of breakdown curves obtained via qToF, quadrupole ion trap, and in-source CID, allowing for differences between the data to be noted and providing a step toward allowing for improved selectivity of breakdown curves to be realized on simple instruments such as single quadrupoles or ion traps.

Persistence of the carteolol hydrochloride/latanoprost fixed-combination ophthalmic solution, compared with the other ß-blocker/prostanoid FP receptor agonist fixed-combination ophthalmic solutions.

PURPOSE: To investigate the treatment persistence of carteolol hydrochloride/latanoprost fixed-combination ophthalmic solution (CAR/LAT) and other ß-blocker/prostanoid FP receptor agonist fixed-combination ophthalmic solutions (BB/FP) in the treatment of glaucoma. STUDY DESIGN: Retrospective observational cohort study. METHODS: A retrospective observational cohort study using JMDC Claims Database. Patients aged 20 years or older diagnosed with glaucoma between February 1, 2017, and March 31, 2020, and prescribed CAR/LAT or another BB/FP were included. RESULTS: A total of 16,612 patients (7423 in the CAR/LAT group and 9189 in the other BB/FP group) were included. The cumulative treatment persistence rate at the end of follow-up was 42.0% (64.9% at 1 year, 53.4% at 2 years, 45.0% at 3 years, and 42.0% at 4 years) in the CAR/LAT group and 34.7% (54.8% at 1 year, 43.6% at 2 years, 37.1% at 3 years, and 34.7% at 4 years) in the other BB/FP group. Treatment persistence was significantly longer in the CAR/LAT group compared to that in the other BB/FP group (hazard ratio 0.747, p < 0.0001). Over the treatment period, the number of patients who discontinued treatment was 3281 (44.2%) in the CAR/LAT group and 4926 (53.6%) in the other BB/FP group; the median duration of treatment was 135 days and 97 days, respectively. CONCLUSION: The study results suggest that persistence rates vary depending on the BB/FP and CAR/LAT appears to be more persistent than other BB/FP.

Carteolol triggers senescence via activation of ß-arrestin-ERK-NOX4-ROS pathway in human corneal endothelial cells in vitro.

Carteolol is a commonly-used topical medication for primary open-angle glaucoma. However, long-term and frequent ocular application of carteolol entails its residuals at low concentration in the aqueous humor for a long duration and may exert latent toxicity in the human corneal endothelial cells (HCEnCs). Here, we treated the HCEnCs in vitro with 0.0117% carteolol for 10 days. Thereafter, we removed the cartelolol and normally cultured the cells for 25 days to investigate the chronical toxicity of carteolol and the underlying mechanism. The results exhibited that 0.0117% carteolol induces senescent features in the HCEnCs, such as increased senescence-associated ß-galactosidase positive rates, enlarged relative cell area and upregulated p16INK4A and senescence-associated secretory phenotypes, including IL-1α, TGF-ß1, IL-10, TNF-α, CCL-27, IL-6 and IL-8, as well as decreased Lamin B1 expression and cell viability and proliferation. Thereby, further exploration demonstrated that the carteolol activates ß-arrestin-ERK-NOX4 pathway to increase reactive oxygen species (ROS) production that imposes oxidative stress on energetic metabolism causing a vicious cycle between declining ATP and increasing ROS production and downregulation of NAD+ resulting in metabolic disturbance-mediated senescence of the HCEnCs. The excess ROS also impair DNA to activate the DNA damage response (DDR) pathway of ATM-p53-p21WAF1/CIP1 with diminished poly(ADP-Ribose) polymerase (PARP) 1, a NAD+-dependent enzyme for DNA damage repair, resulting in cell cycle arrest and subsequent DDR-mediated senescence. Taken together, carteolol induces excess ROS to trigger HCEnC senescence via metabolic disturbance and DDR pathway.

Urinary excretion patterns and potential risks of beta-blocker ophthalmic drops in sports.

Beta-blockers have been prohibited by the World Anti-Doping Agency (WADA) in certain sports, but insufficient research data make it difficult to distinguish between therapeutic uses or misuses. This study aimed at investigating the urinary excretion pattern following beta-blocker ophthalmic drops and the potential risk of constituting an adverse analytical finding (AAF) in sports. Prescribed timolol and carteolol ophthalmic drops were used in healthy participants and glaucoma patients. The urine samples were then collected to investigate the urinary excretion pattern following acute and chronic administration of the above beta-blocker ophthalmic drops. The liquid chromatograph-tandem mass spectrometry method was applied for measuring urinary beta-blockers. Our results demonstrated that the levels of both urinary timolol and carteolol exceeded the minimum reporting levels (MRL) following acute and chronic administration. The highest levels of urinary timolol and carteolol observed in the present study were 255.7 and 923.8 ng/ml, respectively. Regarding the acute administration of timolol ophthalmic drop, 26.19 (11/42) of urine samples were detected with timolol higher than the MRL in timed and random sampling. In contrast, the acute administration of carteolol ophthalmic drops made the carteolol levels higher than the MRL among most urine samples. On the other hand, 36.36% (4/11) of urine samples were detected with beta-blockers higher than the MRL during the chronic administration of timolol and carteolol ophthalmic drops. In the context of receiving ophthalmic beta-blocker medications, the present study has highlighted the potential risk of constituting an AAF in specific sports and suggests strengthening athletes' awareness of therapeutic use exemptions.

Beta-blocker carteolol and oxprenolol produce cutaneous analgesia in response to needle pinpricks in the rat.

BACKGROUND: This present study was undertaken to determine whether beta-blockers produce the cutaneous analgesic effect, comparing them with the long-acting local anesthetic bupivacaine. METHODS: Using a rat model of infiltrative cutaneous analgesia, the effect of 5 beta-blockers (oxprenolol, carteolol, butaxamine, metoprolol, and acebutolol) and bupivacaine was compared and eventually combined with epinephrine. RESULTS: Among 5 beta-blockers, oxprenolol exhibited the most potent and the longest duration of cutaneous analgesia. In dose-response studies, the rank order of efficacy (ED50 [50% effective dose]) was bupivacaine (0.40 [0.35-0.47] µmol) > oxprenolol (2.33 [2.06-2.64] µmol) > carteolol (4.86 [4.27-5.53] µmol) (p< 0.01). Carteolol provoked a longer duration of analgesia (p< 0.01) than oxprenolol or bupivacaine on an equipotent basis (ED25, ED50, and ED75). Adding epinephrine 1:200,000 to drug preparations (carteolol, oxprenolol, and bupivacaine) at ED95 had a peripheral action in prolonging the duration of action. CONCLUSIONS: Oxprenolol and carteolol had greater potencies and longer durations of cutaneous analgesia than butaxamine, metoprolol, and acebutolol. Oxprenolol produced a similar duration of action when compared to bupivacaine, while carteolol had a greater duration of action than bupivacaine. Cutaneous analgesia of oxprenolol (or carteolol) plus adrenaline was greater than that of bupivacaine plus adrenaline.

Life-threatening Vasospastic Angina Induced by Carteolol Eye Drops.

Vasospastic angina (VSA) can be worsened by oral nonselective beta-blockers. Ophthalmic carteolol eye drops are nonselective beta-blockers and effective against glaucoma and ocular hypertension. Systemic effects of ophthalmic beta-blockers on VSA have not yet been reported. We herein report a case of VSA that developed after a patient started carteolol eye drops for ocular hypertension. Even though benidipine, a calcium channel blocker, was started, a VSA attack with incessant non-sustained ventricular tachycardia occurred. Once the carteolol eyedrops were discontinued, the VSA resolved. This case demonstrates that carteolol eye drops can induce life-threatening VSA.

Topical ophthalmic beta-blockers are associated with ocular pseudopemphigoid: A pharmacovigilance study of antiglaucoma medications utilising the FDA adverse event reporting system.

BACKGROUND/OBJECTIVE: The association between antiglaucoma medications and the development of ocular pseudopemphigoid (OPP) has been described; however, the independent risk of each medication has not been quantified. METHODS: Case/non-case analyses were performed in the FDA Adverse Events Reporting System (FAERS) using data from 2010-2020 to examine the reporting odds ratio (ROR) signal for OPP for all classes of antiglaucoma medications under multiple conditions: (i) comparison to all other drugs in FAERs, (ii) comparison to other antiglaucoma medications, (iii) comparison to vehicle/hydrating eye drops with cases of OPP and (iv) comparison to vehicle/hydrating eyedrops with and without cases of OPP to control for topical irritant and preservative effects. RESULTS: A statistically significant ROR for OPP was found for aggregate antiglaucoma medications under the first condition but not the third or fourth (i.96.97 (95% CI 52.54-178.98). The largest signal for OPP when compared to other glaucoma drugs and eye drops was seen with unoprostone (ii.68.96 (95% CI 8.35-569.50, iii.39.85 (95% CI 4.14-383.33), iv.581.67 (95% CI 49.38-6851.57) followed by carteolol (ii.32.51(95% CI 9.02-117.67), iii.10.67 (95% CI 1.77-64.13), iv.77.84 (95% CI 12.95-467.78) and betaxolol (ii.23.38 (95% CI 7.28-74.46), iii.6.94 (95% CI 1.27-38.01), iv.50.67 (95% CI 9.26-277.25). A statistically significant ROR was noted only for the beta-blockers class aggregate under conditions ii and iv. CONCLUSIONS: Our findings support an association between OPP and antiglaucoma medications; under the most stringent control for topical irritant/preservative effect by of comparison to topical eye drops, unoprostone, carteolol, betaxolol and timolol all had a significant ROR for OPP.

Short-term efficacy of latanoprostene bunod for the treatment of open-angle glaucoma and ocular hypertension: a systematic literature review and a network meta-analysis.

BACKGROUND/AIMS: To assess the comparative efficacy of latanoprostene bunod (LBN), a novel prostaglandin analogue (PGA), to other medications for open-angle glaucoma and ocular hypertension on lowering intraocular pressure (IOP). METHODS: A systematic literature review adapted from the Li et al (Ophthalmology, 2016) study was conducted. Medline, Embase and PubMed were searched for randomised controlled trials published between 1 January 2014 and 19 March 2020. Studies had to report IOP reduction after 3 months for at least two different treatments among placebo, PGAs (bimatoprost 0.01%, bimatoprost 0.03%, latanoprost, LBN, tafluprost, unoprostone) or apraclonidine, betaxolol, brimonidine, brinzolamide, carteolol, dorzolamide, levobunolol, timolol, travoprost. A Bayesian network meta-analysis was performed to provide the relative effect in terms of mean difference (95% credible interval) of IOP reduction and ranking probabilities. Surface under the cumulative ranking curve (SUCRA) was generated. RESULTS: A total of 106 trials were included with data for 18 523 participants. LBN was significantly more effective than unoprostone (-3.45 (-4.77 to -2.12)). Although relative effect was not significative, compared with other PGAs, LBN numerically outperformed latanoprost (-0.70 (-1.83 to 0.43)) and tafluoprost (-0.41 (-1.87 to 1.07)), was similar to bimatoprost 0.01% (-0.02(-1.59 to 1.55)) and was slightly disadvantaged by bimatoprost 0.03% (-0.17 (-1.42 to 1.07)). LBN was significantly more efficient than the beta-blockers apraclonidine, betaxolol, brimonidine, brinzolamide, carteolol, dorzolamide and timolol. According to SUCRA, LBN was ranked second after bimatoprost 0.03%, followed by bimatoprost 0.01%. CONCLUSION: LBN was significantly more effective than the PGA unoprostone and most of the beta-blockers. Compared with the most widely used PGAs, LBN numerically outperformed latanoprost and travoprost and was similar to bimatoprost 0.01%.

Formulation of carteolol chitosomes for ocular delivery: formulation optimization, ex-vivo permeation, and ocular toxicity examination.

Background:Conventional delivery systems like solution and suspension are commonly used for the treatment of ocular diseases but have low corneal residence time and hence the duration of effect is limited. These drawbacks of conventional systems can be reduced by preparing bioadhesive chitosan (CH) coated noisome.Methods: Niosomes (NIM) of carteolol (CT) were developed by the thin-film hydration method and optimised by the Box-Behnken statistical design. Further, the optimised CT-NIM was coated with CH to enhance the ocular residence time . The optimised formulation was evaluated for vesicle size, entrapment efficiency, and in-vitro drug release and transcorneal permeation, histopathology, etc.Results: CT-NIM-opt showed the vesicle size and entrapment efficiency of 235 ± 3.54 nm, and 70.45 ± 0.87%, respectively. DSC spectra exhibited that CT was completely encapsulated into the CH-CT-NIM matrix. Drug release from CH-CT-NIM-opt was more sustained (68.28 ± 4.2%) than CT-NIM (75.69 ± 4.5% in 12 h) and CT solution (99.89 ± 2.8% in 4 h). The CH-CT-NIM-opt represented a strong bio-adhesion (89.76 ± 3.6%) than CT-NIM-opt (15.65 ± 3.4%). The permeation flux exhibited 1.13-fold higher permeation than CT-NIM and 3.23 fold than CT solution. The corneal hydration was found to be within the limit value. The histopathology study exhibited no structural damage to the cornea . HET-CAM results showed zero scores indicating no bleeding or haemorrhage. CH-CT-NIM-opt was found to be isotonic and exhibited good stability when stored at 4 °C for the stated duration of time.Conclusion: The above findings suggested that NIM can be a potential carrier for the delivery of CT with better ocular residence time.

Comparison of the 24-h efficacy and safety of fixed combination carteolol/latanoprost and timolol/latanoprost in patients with primary open-angle glaucoma and ocular hypertension: a prospective crossover study.

PURPOSE: To evaluate the 24-h efficacy and safety of fixed combination carteolol/latanoprost (LCFC) and timolol/latanoprost (LTFC) in patients with primary open-angle glaucoma and ocular hypertension. STUDY DESIGN: Prospective, randomized, crossover study METHODS: Twenty-two patients pretreated with a prostaglandin analog at baseline were randomly assigned at a 1:1 ratio to either LCFC or LTFC treatment. The patients received the assigned study drug in both eyes daily in the evening (20:00). Each treatment group crossed over after a 2-month treatment period. The 24-h curves of intraocular pressure (IOP), pulse rate, and blood pressure were evaluated. Safety was also assessed. RESULTS: The changes in mean daytime IOP from baseline at the end of the 2-month treatment period in the LCFC and LTFC groups were - 0.93 and - 1.15 mmHg, respectively. The changes in peak IOP in the 2 groups were - 0.91 and - 0.68 mmHg, respectively. The nighttime pulse rate in the LCFC group increased; that in the LTFC group was lower at all time points. The changes in pulse rate from baseline at 22:00, 2:00, 4:00, and 6:00 differed statistically between the 2 groups. No differences in changes from baseline in systolic and diastolic blood pressures were found between the groups. CONCLUSION: The 24-h IOP curve of patients in the LCFC group was similar to that of the LTFC group, but on the basis of the pulse rate findings, the effect of LCFC on the cardiovascular system over 24 h was less than that of LTFC.

Research and correlation analysis on the dripper contamination of carteolol hydrochloride eye drops.

BACKGROUND: Multi-dose eye drops are easily contaminated by microorganisms, and reportedly, the highest contamination rate can reach 96.46%. The use of contaminated eye drops can cause serious eye infections. METHODS: Carteolol hydrochloride eye drops provided by glaucoma patients who visited the ophthalmic clinic of the First Affiliated Hospital of Soochow University from May 2018 to December 2019 were collected. Microbial culture was carried out on the eye drops, and the microbial species were identified by standard procedures. At the same time, the unsealing time, storage method, hand cleaning before dripping, and contact with the eyelid or the surrounding environment during infusion were recorded. Univariate and multivariate logistic regression analyses were used to analyze the risk factors associated with the contamination of carteolol hydrochloride eye drops. RESULTS: A total of 244 bottles of carteolol hydrochloride eye drops were collected, and the positive rate of flora culture was 6.6%. A total of 18 strains of bacteria were isolated. The most common bacteria were Staphylococcus epidermidis and Corynebacterium. Univariate analysis showed that the risk factors associated with contamination were the unsealing time, the frequency of daily use, contact with the eyelid or the surrounding environment during the infusion process, and the use of more than 2 kinds of eye drops at the same time. Multivariate analysis showed that the unsealing time, the frequency of daily use, and contact with the eyelid or the surrounding environment were independent risk factors associated with contamination. CONCLUSIONS: A long unsealing time, frequent use, and non-standard operation can increase the risk of eye drop contamination, which cannot be ignored.

Optical Coherence Tomography Angiography Vessel Density Changes in Normal-tension Glaucoma Treated With Carteolol, Brimonidine, or Dorzolamide.

PRECIS: In patients with normal-tension glaucoma (NTG), topical dorzolamide might enhance the vessel density (VD), topical carteolol decreased the VD in the inferior-temporal peripapillary retina, whereas topical brimonidine did not change the VD. PURPOSE: Topical antiglaucoma medications may improve ocular perfusion pressure or microcirculation in the optic nerve head. The study evaluated responses of retinal VD to topical carteolol, brimonidine, and dorzolamide in NTG using optical coherence tomography angiography. PATIENTS AND METHODS: This is a retrospective, nonrandomized, comparative study. The study included 131 individuals (77 men, 54 women) diagnosed with NTG, without systemic medication use, who visited the glaucoma clinic of Chang Gung Memorial Hospital, Taiwan, between January 2019 and May 2020. If both eyes were diagnosed with NTG, only the right eye was included. Of these, there were 80 carteolol-treated eyes, 27 brimonidine-treated eyes, and 24 dorzolamide-treated eyes. We studied the response of optical coherence tomography angiography parameters and retinal nerve fiber layer (RNFL) thickness to drugs, 6 months after treatment. RESULTS: In dorzolamide-treated eyes, increases in the peripapillary superficial retinal VD, especially in the superior-nasal area, were significant; however, no RNFL thickness changes were observed. In contrast, the superficial retinal VD decreased at the inferior-temporal peripapillary area, and RNFL thickness decreased in the inferior-nasal peripapillary area of carteolol-treated eyes. Finally, in brimonidine-treated eyes, changes in either VD parameters or RNFL thickness were not significant. CONCLUSIONS: Topical dorzolamide possibly enhanced the VD of the peripapillary retina in NTG eyes. On the contrary, topical carteolol possibly decreased VD in the inferior-temporal peripapillary retina. Finally, in cases treated with topical brimonidine, peripapillary microcirculation remained unchanged. The study shows preliminary results and future large-scale studies are needed to confirm findings.

Bradycardia Shock Caused by the Combined Use of Carteolol Eye Drops and Verapamil in an Elderly Patient with Atrial Fibrillation and Chronic Kidney Disease.

Ophthalmic carteolol is often used to treat glaucoma. Elderly patients with atrial fibrillation (AF) and chronic kidney disease (CKD) are common among the super-elderly in Japan. Because these patients are exposed to polypharmacy, they are at a high-risk of adverse drug interactions. We herein report an elderly patient with CKD who suffered bradycardia shock after the combined use of carteolol eye drops and verapamil for glaucoma and paroxysmal AF. This case highlights the fact that eye drops have a similar systemic effect to oral drugs, and especially in elderly patients with polypharmacy, drug interactions can unwittingly lead to serious events.

Betaxolol, Brimonidin and Carteolol in the Therapy of Normal-Tension Glaucoma.

PURPOSE: The purpose of the study was to evaluate influence of betaxolol, brimonidine and carteolol in the progression of the visual field defects during time at patients with normotensive glaucoma (NTG). MATERIALS AND METHODS: This study included (60 eyes of) 30 patients with NTG. First group consisted of 20 eyes of 10 patients of the average age of 58.5 years, who were treated by betaxolol. Second group also consisted of 20 eyes of 10 patients of the average age of 62.6 years and they were treated by brimonidine. Third group had the same count of the eyes and patients, the average age was 61.1 years and these patients were treated by carteolol. Diagnose of NTG was based on the comprehensive ophthalmological examination including electroretinography and visual evoked potentials. Visual fields were examined by fast threshold glaucoma test using Medmont M700 device. We compared pattern defect (PD) in the visual field for 3 years. The including criteria were: similar visual field findings at the beginning of the study, stable eye therapy (treatment was not changed during the study), uncorrected or best corrected (up to +-3 D) visual acuity of 1,0 of ETDRS, intraocular pressure between 10-15 mm Hg, if present, then compensated cardiovascular disease, no other internal or neurological disorders. RESULTS: We didnt notice any statistically important difference of PD. The study revealed that brimonidin (p=0,99) and betaxolol (p = 0,81) had the best effect. CONCLUSION: Local therapy of betaxolol, brimonidine and carteolol has an essential clinical value in normotensive glaucoma. All the mentioned treatments had a protective effect on the visual field. However, local side-effects of brimonidinu are a question.

Phosphorus dendrimers as powerful nanoplatforms for drug delivery, as fluorescent probes and for liposome interaction studies: A concise overview.

Gene therapy is a new and promising tool to treat many severe diseases and the silencing of proteins is the safest and the most efficient tool to treat diseases because it does not induce changes in human genome and avoids a huge problem encompassing insertional mutagenesis. Using small RNAs to switch on/off target proteins is limited due to existence of some barriers for them in the human body (blood RNAses, serum albumins, cell walls, etc). For therapeutic applications they need the efficient and non-toxic carrier which will deliver them into cell cytoplasm. Within the huge range of carriers available, dendrimers can be underlined as new promising efficient carriers. This review summarizes several findings in phosphorus dendrimers based on in vitro and in vivo studies. As a result, we can conclude that advantages of phosphorus dendrimers are strong interaction with siRNA/DNA and formation of small and compact positively charged complexes of high and fast penetration into cells; efficient release of siRNA/pDNA in endosomes due to "proton sponge" effect; possibility of their modification including addition of fluorescent probes - in this case fluorescent dendrimer can be used both as a gene carrier and a tracer of delivery into cells. Additional benefit of using fluorescent phosphorus dendrimers is their ability to monitor the macrophage physiological status in vitro and in vivo.

[Type IV hypersensitivity to timolol]. / Hipersensibilidad tipo IV por timolol.

BACKGROUND: In recent years, there have been reports of contact dermatitis due to the beta-blockers that are used in the treatment of glaucoma, such as timolol, levubonolol, carteolol, or betaxolol. CASE REPORT: A 37-year-old male patient, who was diagnosed with bilateral primary open-angle glaucoma two years ago, was in therapy with dorzolamide and a topical ß-adrenergic blocker (timolol) in drops twice a day. Months later, he reported conjunctival hyperemia, stinging, and inflammation of both eyelids, followed by erythematous dermatitis, which improved upon treatment discontinuation. The patch test came back negative, but the conjunctival provocation test came back positive 48 hours later. CONCLUSION: Sensitization to the ophthalmic drops that are used to control glaucoma proved to be the mechanism that was causing the clinical picture of the patient. Performing a tolerance test for active anti-glaucoma agents may be helpful in improving tolerance to the medical treatment of some patients, thus, avoiding laser procedures and/or precipitated antiglaucomatous surgeries.

Antecedentes: En los últimos años se han comunicado casos de dermatitis de contacto debido a betabloqueadores utilizados en el tratamiento del glaucoma como el timolol, levubonol, carteolol o betaxolol. Caso clínico: Hombre de 37 años de edad con diagnóstico dos años atrás de glaucoma primario de ángulo abierto bilateral, en terapia con dorzolamida y un agente betabloqueador adrenérgico tópico (timolol) en gotas, dos veces al día. Meses después consultó por hiperemia conjuntival, escozor e inflamación de párpados de ambos ojos seguida de dermatitis eritematosa, que mejoraban al suspender el tratamiento. La prueba del parche resultó negativa, pero la prueba de provocación conjuntival resultó positiva a las 48 horas. Conclusión: La sensibilización a las gotas oftálmicas que se emplean para controlar el glaucoma resultó ser el mecanismo responsable del cuadro clínico de la paciente. La prueba de tolerancia a los principios activos antiglaucomatosos puede resultar de ayuda para mejorar la tolerancia al tratamiento médico de algunos pacientes, con lo que podría evitarse procedimientos con láser o cirugías antiglaucomatosas precipitadas.

Efficacy and safety of the fixed combinations of tafluprost/timolol and latanoprost/carteolol.

In this study, we made a comparative efficacy and safety assessment of two different fixed combinations of drugs, viz., tafluprost/timolol (TAF/TIM) and latanoprost/carteolol (LAT/CAR), by determining their effects on intraocular pressure (IOP) in ocular normotensive monkeys and examining their toxic effects on ocular surface using human corneal epithelial cells. TAF/TIM was found to be more effective in lowering IOP for a longer duration compared to LAT/CAR. We found that the difference in the intensity of IOP-lowering effect was because of the differences in the strength of timolol compared with that of carteolol as a beta-adrenergic antagonist and strength of tafluprost compared with that of latanoprost as a prostaglandin analogue. In addition, TAF/TIM showed much less cytotoxic effects compared to LAT/CAR on the human corneal epithelial cells. Our findings showed that TAF/TIM is better than LAT/CAR with regard to the IOP-lowering effect in monkeys and toxicity on ocular surface.

Insidious-onset, non-wheezing carteolol-induced asthma in an atopic patient without asthma history.

Carteolol, a non-selective beta-antagonist with a potential risk of severe bronchial constriction in patients with asthma, is one of the most commonly prescribed medication for managing ocular pressure in glaucoma. We present a case of a 24-year-old woman with a history of atopy but no known asthma who presented an insidious onset of clinical manifestations compatible with drug-induced asthma after the initiation of carteolol for ocular hypertension control. The patient developed progressive chest tightness and dyspnoea for 2 months before the pulmonary function test revealed a positive bronchoprovocation response. She reported significant improvement of respiratory symptoms within 2 weeks after the discontinuation of carteolol, and a negative provocation response was later confirmed by repeat pulmonary function test. In conclusion, eye drops with non-selective beta-antagonising effect can induce asthmatic symptoms in patients without a previous diagnosis of asthma and should be administered with caution in patients with associated risk factors.

Enantioseparation of chiral ß-blockers using polynorepinephrine-coated nanoparticles and chiral capillary electrophoresis.

A method of combining magnetic solid-phase separation (MSPE) and chiral capillary electrophoresis (CE) is developed for enantioseparation of trace amounts of ß-blockers. Polynorepinephrine-functionalized magnetic nanoparticles (polyNE-MNPs) are synthesized and applied to simultaneously extract three ß-blockers (carteolol, metoprolol, and betaxolol). The prepared polyNE-MNPs are spherical with a diameter of 198 ± 17 nm and the thickness of the polyNE coating is about 14 nm. PolyNE possesses abundant catechol hydroxyl and secondary amine groups, endowing the MNPs with excellent hydrophilicity. Under the optimum conditions, the extraction efficiencies of polyNE-MNPs for ß-blockers are in the range of 89.6 to 100%, with relative standard deviations (RSDs) below 3.5%. The extraction process can be finished in 4 min. Field-enhanced sample injection (FESI) in chiral CE is constructed to further enhance the sensitivities of ß-blocker enantiomers. The limits of detection for ß-blocker enantiomers by the FESI-CE with polyNE-MNPs are in the range of 0.401 to 1.59 ng mL-1. The practicability of this method in real samples is evaluated by analysis of human urine samples. The recoveries for each enantiomer of ß-blockers in the real samples range from 89.5 to 92.8%, with RSDs ranging from 0.37 to 5.9%. The whole detection process can be finished in less than 0.5 h. The method demonstrates its great potential in the pharmacokinetic and pharmacodynamic studies of chiral drugs in humans. Graphical abstract ᅟ.