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RSC Advances Jun 2019Three sets of functional monomers namely urea-based, 2-ureido-4[1]-primidone (UPy)-based and norbornene based functional monomers were designed and synthesized. These...
Three sets of functional monomers namely urea-based, 2-ureido-4[1]-primidone (UPy)-based and norbornene based functional monomers were designed and synthesized. These functional monomers (FM) were obtained in decent yields using amine and isocyanate/norbornene as starting materials. Methacrylate and styrene isocyanate with 1,4-diaminobutane/tris(2-aminoethyl)amine were chosen for the synthesis of symmetrical, asymmetrical and three-branched urea-functional monomers, respectively. UPy-based FMs were synthesized with isocyanate and 2-amino-4-hydroxy-6-methylpyrimidine. The synthesis of these monomers feature short reaction times, mild reaction conditions and no need for column chromatographic purification. Furthermore, the norbornene based FM was used for preparing molecularly imprinted polymers (MIPs) by Ring-Opening Metathesis Polymerization (ROMP). Results showed that these synthetic routes represent a convenient and useful approach for synthesis of novel functional monomers.
PubMed: 35514692
DOI: 10.1039/c9ra01852b -
Molecules (Basel, Switzerland) May 2019In this work, primidone, a high persistent pharmacological drug typically found in urban wastewaters, was degraded by different ozone combined AOPs using TiO P25 and...
In this work, primidone, a high persistent pharmacological drug typically found in urban wastewaters, was degraded by different ozone combined AOPs using TiO P25 and commercial WO as photocatalyst. The comparison of processes, kinetics, nature of transformation products, and ecotoxicity of treated water samples, as well as the influence of the water matrix (ultrapure water or a secondary effluent), is presented and discussed. In presence of ozone, primidone is rapidly eliminated, with hydroxyl radicals being the main species involved. TiO was the most active catalyst regardless of the water matrix and the type of solar (global or visible) radiation applied. The synergy between ozone and photocatalysis (photocatalytic ozonation) for TOC removal was more evident at low O doses. In spite of having a lower band gap than TiO P25, WO did not bring any beneficial effects compared to TiO P25 regarding PRM and TOC removal. Based on the transformation products identified during ozonation and photocatalytic ozonation of primidone (hydroxyprimidone, phenyl-ethyl-malonamide, and 5-ethyldihydropirimidine-4,6(1H,5H)-dione), a degradation pathway is proposed. The application of the different processes resulted in an environmentally safe effluent for .
Topics: Animals; Catalysis; Daphnia; Hydroxyl Radical; Kinetics; Oxidation-Reduction; Oxides; Ozone; Photochemical Processes; Primidone; Sunlight; Titanium; Tungsten; Ultraviolet Rays; Water; Water Pollutants, Chemical; Water Purification
PubMed: 31058864
DOI: 10.3390/molecules24091728 -
Annals of Neurology Nov 2018A recent study observed a 2-fold greater risk of Parkinson disease (PD) in relation to the β2-adrenoreceptor antagonist propranolol and a markedly lower risk of PD for...
OBJECTIVE
A recent study observed a 2-fold greater risk of Parkinson disease (PD) in relation to the β2-adrenoreceptor antagonist propranolol and a markedly lower risk of PD for the β2-adrenoreceptor agonist salbutamol. We examined whether confounding by clinical indication for these medications, that is, tremor and smoking-related pulmonary conditions, explained these associations.
METHODS
In a large, population-based case-control study of United States Medicare beneficiaries in 2009 with diagnosis codes, procedure codes, and prescription data (48,295 incident PD cases, 52,324 controls), we examined the risk of PD in relation to use of selected β antagonists (propranolol, carvedilol, metoprolol), the β2 agonist salbutamol, and other medications used for the same clinical indications (primidone, inhaled corticosteroids). We adjusted for demographics, smoking, and overall use of medical care. We then examined the effect of also adjusting for clinical indication and applying medication exposure lagging.
RESULTS
Propranolol appeared to increase PD risk (odds ratio [OR] = 3.62, 95% confidence interval [CI] = 3.31-3.96). When we adjusted for tremor or abnormal involuntary movement prior to the PD diagnosis/reference date and lagged propranolol exposure, the association was 0.97 (95% CI = 0.80-1.18). Primidone, also used for tremor, was similarly sensitive to this adjustment and lagging. β Antagonists not indicated for tremor appeared to reduce PD risk (carvedilol: OR = 0.77, 95% CI = 0.73-0.81; metoprolol: OR = 0.94, 95% CI = 0.91-0.97) and were insensitive to adjustment for indications and lagging. Neither salbutamol nor inhaled corticosteroids were consistently associated with PD risk.
INTERPRETATION
β2-adrenoreceptor agonists and antagonists do not appear to alter PD risk. Ann Neurol 2018;84:691-701.
Topics: Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Antagonists; Aged; Case-Control Studies; Female; Humans; Male; Parkinson Disease
PubMed: 30225948
DOI: 10.1002/ana.25341 -
The Turkish Journal of Pediatrics 2018Acar T, Alkan G, Çaksen H, Ertekin B, Ergin M, Koçak S, Cander B. Phenytoin induced dystonia. Turk J Pediatr 2018; 60: 111-112. The abnormalities of dopaminergic...
Acar T, Alkan G, Çaksen H, Ertekin B, Ergin M, Koçak S, Cander B. Phenytoin induced dystonia. Turk J Pediatr 2018; 60: 111-112. The abnormalities of dopaminergic activity in the basal ganglia have been emphasized to be effective in dystonia. We hereby report a case of a 2.5-year-old male patient who presented with tonic-clonic sezures and who developed dystonia after being given phenytoin. Biperidene hydrochloride was administered intramuscularly; primidone was added to the treatment regimen. After a 7-day-follow-up at the hospital, the patient had no dystonia and was discharged.
Topics: Anticonvulsants; Child, Preschool; Dystonia; Epilepsy; Humans; Male; Phenytoin; Primidone
PubMed: 30102491
DOI: 10.24953/turkjped.2018.01.019 -
The Journal of Clinical Psychiatry Jul 2018Major congenital malformation risks in association with gestational exposure to antiepileptic drugs (AEDs) have been extensively studied. Less information is available...
Major congenital malformation risks in association with gestational exposure to antiepileptic drugs (AEDs) have been extensively studied. Less information is available on other adverse outcomes associated with the use of these drugs during pregnancy. This article critically examines the risk of fetal loss, intrauterine growth retardation (IUGR), and preterm birth following gestational exposure to 14 AEDs, based on information obtained from a recent network meta-analysis of mostly nonrandomized, observational studies. The AEDs studied were carbamazepine, clobazam, clonazepam, ethosuximide, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbitone, phenytoin, primidone, topiramate, valproate, and vigabatrin. The results show that very few AEDs are significantly associated with each adverse outcome and that the implicated AEDs are different for different outcomes. Furthermore, when one discounts findings obtained in small sample analyses, almost no significant associations remain. Next, even these associations become questionable when one considers that they could have been due to confounding by indication. Finally, the few significant associations may have been false-positive findings because they were identified after performing a very large number of statistical tests. These caveats notwithstanding, guidance should err on the side of caution. Therefore, a conservative conclusion is that whereas analyses based on exposures in 2,000-4,000 pregnancies suggest that lamotrigine and carbamazepine are not associated with an increased risk of fetal loss, IUGR, and preterm birth, there is insufficient evidence to either firmly indict or firmly exonerate the other AEDs with regard to these outcomes.
Topics: Anticonvulsants; Female; Fetal Death; Fetal Growth Retardation; Humans; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth
PubMed: 30085439
DOI: 10.4088/JCP.18f12467 -
BMJ Case Reports Mar 2018Essential tremor is a common neurological disease. The medical treatment of this affection currently involves the use of propranolol, primidone and other drugs. These...
Essential tremor is a common neurological disease. The medical treatment of this affection currently involves the use of propranolol, primidone and other drugs. These drugs, however, are often not effective in reducing tremor and cause side effects in a large share of the patients treated. The treatment with intramuscular high-dose thiamine has led to a rapid, remarkable and persistent improvement of the symptoms in two patients with essential tremor. This result suggests the possibility that high doses of intramuscular thiamine may be an affordable alternative, highly effective and long-lasting medical treatment that has shown no relevant side effect.
Topics: Aged; Dose-Response Relationship, Drug; Essential Tremor; Humans; Male; Thiamine; Treatment Outcome; Vitamin B Complex
PubMed: 29602891
DOI: 10.1136/bcr-2017-223945 -
Therapeutic Advances in Drug Safety Oct 2017To determine the prevalence and nature of potential drug-drug interactions (DDIs) with direct oral anticoagulants (DOACs) in elderly hospitalized patients.
BACKGROUND
To determine the prevalence and nature of potential drug-drug interactions (DDIs) with direct oral anticoagulants (DOACs) in elderly hospitalized patients.
METHODS
This was a retrospective observational study. Inclusion criteria were: aged over 65 years; taking apixaban, rivaroxaban or dabigatran; and admitted to the Repatriation General Hospital between April 2014 and July 2015. A list of clinically relevant 'perpetrator' drugs was compiled from product information, the Australian Medicines Handbook, the Australian National Prescribing Service resources, and local health network guidelines. The prevalence and nature of potential DDIs with DOACs was determined by comparing inpatient drug charts with the list of perpetrator drugs.
RESULTS
There were 122 patients in the study with a mean age of 82 years. Most patients had nonvalvular atrial fibrillation and were taking DOACs to prevent thrombotic stroke (83%). Overall, 45 patients (37%) had a total of 54 potential DDIs. Thirty-five patients had potential pharmacodynamic DDIs with antidepressants, nonsteroidal anti-inflammatory drugs and antiplatelets (35/122, 29%). Nineteen patients had potential pharmacokinetic DDIs (19/122, 16%). Of these, 68% (13/19) were taking drugs that increase DOAC plasma concentrations (amiodarone, erythromycin, diltiazem or verapamil) and 32% (6/19) were taking drugs that decrease DOAC plasma concentrations (carbamazepine, primidone or phenytoin). There were no cases of patients taking contraindicated interacting drugs.
DISCUSSION
Potential DDIs with DOACs in elderly hospital inpatients are relatively common, particularly interactions that may increase the risk of bleeding. The risk-benefit ratio of DOACs in elderly patients on polypharmacy should always be carefully considered.
PubMed: 29593860
DOI: 10.1177/2042098617719815 -
RSC Advances Mar 2018The rejection behaviors of two different charged composite hollow fiber nanofiltration (NF) membranes for six pharmaceutical molecules, primidone, carbamazepine,...
The rejection behaviors of two different charged composite hollow fiber nanofiltration (NF) membranes for six pharmaceutical molecules, primidone, carbamazepine, sulfamethoxazole, atenolol, sulfadimidine and norfloxacin, were characterized in this study. The saturation adsorption behaviors of the different pharmaceutical molecules on each membrane surface were studied and found to be related to the molecular weight, charge and hydrophilicity of the pharmaceutical molecules. After the pharmaceutical molecules reached adsorption equilibrium, the rejection rates of different NF membranes were characterized. The rejection rates of primidone, carbamazepine, sulfamethoxazole, atenolol, sulfadimidine and norfloxacin by the PEI-NF membrane were 85.6%, 91.8%, 79.9%, 98.1%, 93.3%, and 97.1%, respectively. Meanwhile, the rejection rates of the pharmaceutical molecules by the PIP-NF membrane were 82.2%, 85.4%, 91.5%, 79.1%, 87% and 93.3%, respectively. The influence of feed concentration, operation pressure, temperature, pH and ionic strength on the rejection behaviors of the different charged NF membranes were also studied.
PubMed: 35540449
DOI: 10.1039/c8ra00519b -
British Journal of Clinical Pharmacology Jun 2018Saliva, as a matrix, offers many benefits over blood in therapeutic drug monitoring (TDM), in particular for infantile TDM. However, the accuracy of salivary TDM in...
AIMS
Saliva, as a matrix, offers many benefits over blood in therapeutic drug monitoring (TDM), in particular for infantile TDM. However, the accuracy of salivary TDM in infants remains an area of debate. This review explored the accuracy, applicability and advantages of using saliva TDM in infants and neonates.
METHODS
Databases were searched up to and including September 2016. Studies were included based on PICO as follows: P: infants and neonates being treated with any medication, I: salivary TDM vs. C: traditional methods and O: accuracy, advantages/disadvantages and applicability to practice. Compounds were assessed by their physicochemical and pharmacokinetic properties, as well as published quantitative saliva monitoring data.
RESULTS
Twenty-four studies and their respective 13 compounds were investigated. Four neutral and two acidic compounds, oxcarbazepine, primidone, fluconazole, busulfan, theophylline and phenytoin displayed excellent/very good correlation between blood plasma and saliva. Lamotrigine was the only basic compound to show excellent correlation with morphine exhibiting no correlation between saliva and blood plasma. Any compound with an acid dissociation constant (pKa) within physiological range (pH 6-8) gave a more varied response.
CONCLUSION
There is significant potential for infantile saliva testing and in particular for neutral and weakly acidic compounds. Of the properties investigated, pKa was the most influential with both logP and protein binding having little effect on this correlation. To conclude, any compound with a pKa within physiological range (pH 6-8) should be considered with extra care, with the extraction and analysis method examined and optimized on a case-by-case basis.
Topics: Age Factors; Drug Monitoring; Humans; Infant; Infant, Newborn; Pharmaceutical Preparations; Pharmacokinetics; Predictive Value of Tests; Reproducibility of Results; Saliva
PubMed: 29442362
DOI: 10.1111/bcp.13553 -
Toxins Nov 2017Essential tremor is characterized by persistent, usually bilateral and symmetric, postural or kinetic activation of agonist and antagonist muscles involving either the... (Review)
Review
Essential tremor is characterized by persistent, usually bilateral and symmetric, postural or kinetic activation of agonist and antagonist muscles involving either the distal or proximal upper extremity. Quality of life is often affected and one's ability to perform daily tasks becomes impaired. Oral therapies, including propranolol and primidone, can be effective in the management of essential tremor, although adverse effects can limit their use and about 50% of individuals lack response to oral pharmacotherapy. Locally administered botulinum toxin injection has become increasingly useful in the management of essential tremor. Targeting of select muscles with botulinum toxin is an area of active research, and muscle selection has important implications for toxin dosing and functional outcomes. The use of anatomical landmarks with palpation, EMG guidance, electrical stimulation, and ultrasound has been studied as a technique for muscle localization in toxin injection. Earlier studies implemented a standard protocol for the injection of (predominantly) wrist flexors and extensors using palpation and EMG guidance. Targeting of muscles by selection of specific activators of tremor (tailored to each patient) using kinematic analysis might allow for improvement in efficacy, including functional outcomes. It is this individualized muscle selection and toxin dosing (requiring injection within various sites of a single muscle) that has allowed for success in the management of tremors.
Topics: Botulinum Toxins; Electric Stimulation; Electromyography; Extremities; Humans; Tremor
PubMed: 29125566
DOI: 10.3390/toxins9110365