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Australasian Psychiatry : Bulletin of... Feb 2024This study examined the rates and persistence of clozapine-induced tachycardia and heart-rate differences in patients treated with β-blockers in the largest sample of...
OBJECTIVE
This study examined the rates and persistence of clozapine-induced tachycardia and heart-rate differences in patients treated with β-blockers in the largest sample of patients with a psychotic disorder to date.
METHOD
An audit of medical files for 101 patients who attended a clozapine community clinic and analysis of monthly measurements of resting heart rates.
RESULTS
51% met the clinical criteria for tachycardia. Heart rates were stable over time. β-blockers were associated with small but significant reductions in heart rates.
CONCLUSION
The cardiovascular risks of clozapine are often overlooked. β-blockers are useful in lowering heart rates but they may be insufficient to reduce cardiac risk.
Topics: Humans; Clozapine; Tachycardia; Adrenergic beta-Antagonists; Psychotic Disorders
PubMed: 38165132
DOI: 10.1177/10398562231224156 -
Cureus Nov 2023Supraventricular tachycardia (SVT) is the most common tachyarrhythmia of pregnancy. Catecholamine surges, the use of vasoactive agents during delivery, and increased...
Supraventricular tachycardia (SVT) is the most common tachyarrhythmia of pregnancy. Catecholamine surges, the use of vasoactive agents during delivery, and increased cardiac output during pregnancy are the most common contributing factors to developing SVT. SVT is usually benign in presentation but can lead to more serious arrhythmias in patients with a history of mitral stenosis secondary to rheumatic heart disease. When an SVT is detected, organic heart causes should be ruled out first. Symptoms of SVT include shortness of breath, palpitations, syncope, sweating, chest pain, and dizziness. In patients who are refractory to pharmacologic management and hemodynamically unstable, electrical cardioversion has proven to be efficacious and safe in all trimesters. The initial treatment for hemodynamically stable patients is to attempt vagal maneuvers, such as carotid sinus massage or Valsalva maneuver. If the SVT does not convert to normal sinus rhythm, treatment with adenosine or beta-blockers may be initiated. Treatment with atenolol and verapamil should be avoided due to their teratogenic effects.
PubMed: 38143604
DOI: 10.7759/cureus.49256 -
Organic & Biomolecular Chemistry Feb 2024The sustainability of amide bond formation is an ever-present topic in the pharmaceutical industry, as it represents the common motif in many clinically approved drugs....
The sustainability of amide bond formation is an ever-present topic in the pharmaceutical industry, as it represents the common motif in many clinically approved drugs. Despite many procedures for accomplishing eco-friendly amide synthesis having been developed, this transformation still remains a contemporary challenge. Herein, we report a greener approach for amide synthesis by using Reactive Deep Eutectic Solvents (RDESs) acting as both the reaction medium and reactants. The procedure not only avoids the use of hazardous solvents but also provides operationally simple product recovery with high purity and efficiency, without chromatographic purification. This approach was efficiently applied to the synthesis of a key intermediate in the production of an active pharmaceutical ingredient like atenolol. The green metrics of the gram-scale procedure were compared to the conventional industrial strategy showing an advancement in the greening of amide synthesis.
PubMed: 38126479
DOI: 10.1039/d3ob01673k -
Journal of Chromatography. A Jan 2024Here, we report the preparation and application of two new chiral monoliths for the enantioseparation of chiral drugs in nano-LC. Using...
Here, we report the preparation and application of two new chiral monoliths for the enantioseparation of chiral drugs in nano-LC. Using 3‑chloro-2-hydroxypropylmethacrylate (HPMA-Cl, 2) as a precursor monomer, two different chiral monomers namely, N-Boc-Lys-HPMA (3A) and N-Fmoc-Lys-HPMA (3B) were synthesized and used for the preparation of chiral polymer monoliths. The first monolithic column (referred to as monolith I) was prepared by an in-situ polymerization of N-Boc-Lys-HPMA as the chiral monomer and ethylene dimethacrylate while the second monolithic column (referred to as monolith II) was prepared by an in-situ polymerization of N-Fmoc-Lys-HPMA as the chiral monomer and ethylene dimethacrylate as the crosslinker. Methanol and 1-propanol were used as the porogenic solvents. The prepared chiral monoliths were investigated for the enantioseparation of chiral drugs, including β-blockers (e.g., atenolol, propranolol, metoprolol) and anti-inflammatory drugs (e.g., ketoprofen, ibuprofen, flurbiprofen, naproxen, etodolac). The enantioseparation could be achieved via the formation of π-π interactions on the aromate-rich and aromate-poor chiral molecules while enantioseparation mechanism of chiral drugs included mostly π-π interactions and hydrogen bonding. Monolith II showed better enantioselectivity than Monolith I and the resolution values up to 2.12 were successfully achieved.
Topics: Chromatography, Liquid; Polymers; Solvents; Stereoisomerism
PubMed: 38101302
DOI: 10.1016/j.chroma.2023.464573 -
Chemosphere Feb 2024Most research on pharmaceutical presence in the environment to date has focused on smaller scale assessments of freshwater and riverine systems, relying mainly on assays...
Most research on pharmaceutical presence in the environment to date has focused on smaller scale assessments of freshwater and riverine systems, relying mainly on assays of water samples, while studies in marine ecosystems and of exposed biota are sparse. This study investigated the pharmaceutical burden in bonefish (Albula vulpes), an important recreational and artisanal fishery, to quantify pharmaceutical exposure throughout the Caribbean Basin. We sampled 74 bonefish from five regions, and analyzed them for 102 pharmaceuticals. We assessed the influence of sampling region on the number of pharmaceuticals, pharmaceutical assemblage, and risk of pharmacological effects. To evaluate the risk of pharmacological effects at the scale of the individual, we proposed a metric based on the human therapeutic plasma concentration (HPC), comparing measured concentrations to a threshold of 1/3 the HPC for each pharmaceutical. Every bonefish had at least one pharmaceutical, with an average of 4.9 and a maximum of 16 pharmaceuticals in one individual. At least one pharmaceutical was detected in exceedance of the 1/3 HPC threshold in 39% of bonefish, with an average of 0.6 and a maximum of 11 pharmaceuticals exceeding in a Key West individual. The number of pharmaceuticals (49 detected in total) differed across regions, but the risk of pharmacological effects did not (23 pharmaceuticals exceeded the 1/3 HPC threshold). The most common pharmaceuticals were venlafaxine (43 bonefish), atenolol (36), naloxone (27), codeine (27), and trimethoprim (24). Findings suggest that pharmaceutical detections and concentration may be independent, emphasizing the need to monitor risk to biota regardless of exposure diversity, and to focus on risk quantified at the individual level. This study supports the widespread presence of pharmaceuticals in marine systems and shows the utility of applying the HPC to assess the potential for pharmacological effects, and thus quantify impact of exposure at large spatial scales.
Topics: Humans; Animals; Ecosystem; Fishes; Caribbean Region; Biota; Pharmaceutical Preparations; Water Pollutants, Chemical; Environmental Monitoring
PubMed: 38096990
DOI: 10.1016/j.chemosphere.2023.140949 -
Heliyon Dec 2023To determine the concentrations of nine drugs used in the treatment of cardiovascular diseases in human plasma through QuEChERS pre-treatment combined with...
To determine the concentrations of nine drugs used in the treatment of cardiovascular diseases in human plasma through QuEChERS pre-treatment combined with ultra-performance liquid chromatography-tandem mass spectrometry. Plasma samples were extracted with 3 mL of acetonitrile, 400 mg of anhydrous magnesium sulfate as a salting agent, and 20 mg of C18 as a sorbent. An Agilent Poroshell 120 EC-C18 column (4.6 × 100 mm, 2.7 μm) was selected and methanol-0.1 % water was used as the mobile phase, and ESI positive ion detection mode was selected. Results: The plasma concentrations of nisoldipine, metoprolol, and prazosin exhibited good linearity within the range of 0.05-4.0 ng/mL (r > 0.99), while atenolol, bisoprolol, propranolol, rosuvastatin, and atorvastatin showed linearity within the range of 0.5-40 ng/mL (r > 0.99). Fluvastatin showed good linearity within the range of 5.0-400 ng/mL. The accuracy of the method ranged from 94.15 to 110.62 %, while the recovery levels were in the range of 85.23 %-115.13 %. The matrix effects were observed between-6.54 % and 12.43 %. The intra-day and inter-day RSD was <15 % for the three concentrations of low, medium, and high. Conclusion The proposed method is rapid, accurate, specific, simple, reproducible, and suitable for the simultaneous measurement of the concentrations of nine drugs used in the treatment of cardiovascular diseases in human plasma.
PubMed: 38094060
DOI: 10.1016/j.heliyon.2023.e22543 -
American Journal of Obstetrics &... Jan 2024Risk mitigation for most teratogenic medications relies on risk communication via drug label, and prenatal exposures remain common. Information on the types of and risk...
BACKGROUND
Risk mitigation for most teratogenic medications relies on risk communication via drug label, and prenatal exposures remain common. Information on the types of and risk factors for prenatal exposures to medications with teratogenic risk can guide strategies to reduce exposure.
OBJECTIVE
This study aimed to identify medications with known or potential teratogenic risk commonly used during pregnancy among privately insured persons.
STUDY DESIGN
We used the Merative™ MarketScan® Commercial Database to identify pregnancies with live or nonlive (ectopic pregnancies, spontaneous and elective abortions, stillbirths) outcomes among persons aged 12 to 55 years from 2011 to 2018. Start/end dates of medication exposure and pregnancy outcomes were identified via an adapted algorithm based on validation studies. We required continuous health plan enrollment from 90 days before conception until 30 days after the pregnancy end date. Medications with known or potential teratogenic risk were selected from TERIS (Teratogen Information System) and drug monographs based on the level of risk and quality of evidence (138 with known and 60 with potential risk). We defined prenatal exposure on the basis of ≥1 outpatient pharmacy claim or medical encounter for medication administration during target pregnancy periods considering medication risk profiles (eg, risk only in the first trimester or at a certain dose threshold). Sex hormones and hormone analogs, and abortion and postpartum/abortion hemorrhage treatments were not considered as teratogenic medications because of challenges in separating pregnancy-related indications, nor were opioids (because of complex risk-benefit considerations) or antiobesity medications if their only teratogenic mechanism was weight loss.
RESULTS
Among all pregnancies, the 10 medications with known teratogenic risk and the highest prenatal exposures were sulfamethoxazole/trimethoprim (1988 per 100,000 pregnancy-years), high-dose fluconazole (1248), topiramate (351), lisinopril (144), warfarin (57), losartan (56), carbamazepine (50), valproate (49), vedolizumab (28 since 2015), and valsartan (25). Prevalence of exposure to sulfamethoxazole/trimethoprim decreased from 2346 to 1453 per 100,000 pregnancy-years from 2011 to 2018, but prevalence of exposure to vedolizumab increased 6-fold since its approval in 2015. Prenatal exposures in the first trimester were higher among nonlive pregnancies than among live-birth pregnancies, with the largest difference observed for warfarin (nonlive 370 vs live birth 78), followed by valproate (258 vs 86) and topiramate (1728 vs 674). Prenatal exposures to medications with potential teratogenic risk were most prevalent for low-dose fluconazole (6495), metoprolol (1325), and atenolol (448). The largest first-trimester exposure differences between nonlive and live-birth pregnancies were observed for lithium (242 vs 89), gabapentin (1639 vs 653), and duloxetine (1914 vs 860). Steady increases in hydralazine and gabapentin exposures were observed during the study years, whereas atenolol exposure decreased (561 to 280).
CONCLUSION
Several medications with teratogenic risk for which there are potentially safer alternatives continue to be used during pregnancy. The fluctuating rates of prenatal exposure observed for select teratogenic medications suggest that regular reevaluation of risk mitigation strategies is needed. Future research focusing on understanding the clinical context of medication use is necessary to develop effective strategies for reducing exposures to medications with teratogenic risk during pregnancy.
Topics: Pregnancy; Female; Humans; United States; Teratogens; Valproic Acid; Topiramate; Prenatal Exposure Delayed Effects; Gabapentin; Warfarin; Atenolol; Fluconazole; Sulfamethoxazole; Trimethoprim
PubMed: 38061552
DOI: 10.1016/j.ajogmf.2023.101245 -
Medwave Dec 2023Infantile hemangioma is the most frequent benign vascular tumor in childhood, with an incidence of 3 to 10%. When patients require treatment, oral propranolol, a... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Infantile hemangioma is the most frequent benign vascular tumor in childhood, with an incidence of 3 to 10%. When patients require treatment, oral propranolol, a non-selective lipophilic beta-blocker, is usually considered the therapy of choice. However, its use has been associated with several adverse events related to its β-2 action and its ability to cross the blood-brain barrier. Because of this, oral atenolol, a hydrophilic β-1 receptor-selective beta-blocker, may represent a valid treatment alternative. Nonetheless, there is still controversy regarding the efficacy and safety of atenolol when compared with propranolol as monotherapy for this condition.
METHODS
We searched Epistemonikos, the largest database of systematic reviews in health science, which is maintained by screening multiple sources of information, including MEDLINE/PubMed, EMBASE, and Cochrane, among others. Data were extracted from the identified reviews, data from the primary studies were analyzed, a meta-analysis was performed, and a summary table of the results was prepared using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method.
RESULTS
Nine systematic reviews were identified, including 10 primary studies and three randomized trials. The three randomized trials were included in the analysis of this investigation.
CONCLUSION
The use of oral atenolol compared with oral propranolol as monotherapies may result in little or no difference in terms of likelihood of complete remission, decrease in Hemangioma Activity Score, likelihood of post-treatment relapse, and risk of adverse events and severe adverse events, in infantile hemangioma (low certainty of evidence).
Topics: Humans; Propranolol; Atenolol; Treatment Outcome; Neoplasm Recurrence, Local; Systematic Reviews as Topic; Adrenergic beta-Antagonists; Hemangioma, Capillary; Hemangioma
PubMed: 38061014
DOI: 10.5867/medwave.2023.11.2753 -
Environmental Science and Pollution... Jan 2024This study aimed to assess the dynamic simulation models provided by Aspen adsorption (ASPAD) and artificial neural network (ANN) in understanding the adsorption...
This study aimed to assess the dynamic simulation models provided by Aspen adsorption (ASPAD) and artificial neural network (ANN) in understanding the adsorption behavior of atenolol (ATN) on gasified Glyricidia sepium woodchips activated carbon (GGSWAC) within fixed bed columns for wastewater treatment. The findings demonstrated that increasing the bed height from 1 to 3 cm extended breakthrough and exhaustion times while enhancing adsorption capacity. Conversely, higher initial ATN concentrations resulted in shorter breakthrough and exhaustion times but increased adsorption capacity. Elevated influent flow rates reduced breakthrough and exhaustion times while maintaining constant adsorption capacity. The ASPAD software demonstrated competence in accurately modeling the crucial exhaustion points. However, there is room for enhancement in forecasting breakthrough times, as it exhibited deviations ranging from 6.52 to 239.53% when compared to the actual experimental data. ANN models in both MATLAB and Python demonstrated precise predictive abilities, with the Python model (R = 0.985) outperforming the MATLAB model (R = 0.9691). The Python ANN also exhibited superior fitting performance with lower MSE and MAE. The most influential factor was the initial ATN concentration (28.96%), followed by bed height (26.39%), influent flow rate (22.43%), and total effluent time (22.22%). The findings of this study offer an extensive comprehension of breakthrough patterns and enable accurate forecasts of column performance.
Topics: Adsorption; Atenolol; Charcoal; Neural Networks, Computer; Water Purification; Water Pollutants, Chemical
PubMed: 38038911
DOI: 10.1007/s11356-023-31177-1 -
PloS One 2023Co-existence of life style disorders, like, Diabetes or Hypertension, increases risk of, treatment failure, deaths and developing drug-resistant TB. Concomitant...
Co-existence of life style disorders, like, Diabetes or Hypertension, increases risk of, treatment failure, deaths and developing drug-resistant TB. Concomitant administration of drugs to treat dual/multi-morbidities may alter their effectiveness, in additive/synergistic or adverse/antagonistic manner. We evaluated interactive effect of 7 anti-hyperglycaemic (HG) and 6 anti-hypertensive (HT) drugs on the inhibitory (MICs) and bactericidal (% killing of intracellular bacilli) activities of anti-TB drugs, Isoniazid (INH), Rifampicin (RFM), Ethambutol (EMB) and Streptomycin (STR) against M. tuberculosis. Five anti-HG drugs, namely, Acarbose, Acetohexamide, Glyburide, Repaglinide and Sitagliptin imparted either 'additive' or 'no effect' on the activities (inhibition or % killing) of all the four anti-TB drugs, as evident by their lower FICs (Fractional Inhibitory concentrations) and higher bacterial killing in combination. Metformin and Rosiglitazone, however, exerted adverse effect on the Ethambutol (FICs >2.0). All the six anti-HT drugs, namely, Atenolol, Hydrochlorothiazide, Ramipril, Valsartan, Nifedipine and Verapamil exerted either 'additive'/'synergistic' or 'no effect' on the activities of anti-TB drugs. These findings may help clinicians to select safe and helpful anti-HG or anti-HT drugs for TB patients, if, suffering with diabetes or hypertension like co-morbidities and receiving DOTs (a set regimen for the treatment of TB based on the WHO guidelines).
Topics: Humans; Antitubercular Agents; Antihypertensive Agents; Ethambutol; Pharmaceutical Preparations; Mycobacterium tuberculosis; Isoniazid; Microbial Sensitivity Tests; Tuberculosis; Hypertension; Diabetes Mellitus; Hypoglycemic Agents; Tuberculosis, Multidrug-Resistant
PubMed: 38032920
DOI: 10.1371/journal.pone.0292397