Revisión de medicamentos sin receta con aspartamo: Indicación Farmacéutica segura en fenilcetonuria / Review of non-prescription medicines with aspartame: safe pharmaceutical indication in phenylketonuria

Introducción: La fenilcetonuria es el trastorno hereditario más frecuente del metabolismo de los aminoácidos y su abordaje suele centrarse en die-tas restringidas en fenilalanina, un aminoácido presente en el edulcorante aspartamo habitualmente usado como excipiente en tecnología farmacéutica. Objetivo: El objetivo principal es la revisión de los medicamentos sin receta comercializados en España hasta marzo de 2023 y que contienen aspartamo en su composición. Método: Se realizó una revisión en la base de datos BOT plus de todos los medicamentos comercializados en España que contienen aspartamo. Se seleccionaron solo los MSR. Se consultaron las fichas técnicas en el Centro de información online de medicamentos de la AEMPS (CIMA), y los datos obtenidos se registraron en una tabla. Resultados: Se obtuvieron 570 medicamentos; 58 eran MSR. Cuando exista petición de MSR con aspartamo en pacientes con fenilcetonuria, en el SIF, tras su evaluación, en el 100% de los casos, el farmacéutico aplicando el Servicio de Indicación Farmacéutica podría indicar un MSR alternativo, con el mismo principio activo pero sin aspartamo como excipiente. Conclusiones: La actuación del farmacéutico comunitario para aplicar el SIF es muy importante en pacientes con fenilcetonuria. Existen medicamentos que no requieren prescripción y se pueden indicar en estos pacientes. El farmacéutico debe tener a su disposición las herramientas necesarias que le faciliten el SIF con este tipo de enfermos. (AU)

Introduction: Phenylketonuria is the most common inherited disorder of amino acid metabolism and its management usually focuses on diets restricted in phenylalanine, an amino acid present in the sweet-ener aspartame commonly used as an excipient in pharmaceutical technology. Objective: The main objective is the review of non-prescription medicines marketed in Spain until March 2023 and that contain aspartame in their composition.Methods: A review of all medicines marketed in Spain containing aspartame was carried out in the BOT plus database. Only MSRs were selected. The data sheets were consulted at the AEMPS online medicines information centre (CIMA), and the data obtained were recorded in a table.Results: 570 medicines were obtained; 58 were MSRs. When there is a request for MSRs with aspartame in patients with phenylketonuria, in the SIF, after evaluation, in 100% of the cases, the pharmacist applying the Pharmaceutical Indication Service could indicate an alternative MSR, with the same active ingredient but without aspartame as an excipient.Conclusions: The action of the community phar-macist to apply the SIF is very important in patients with phenylketonuria. There are medicines that do not require a prescription and can be prescribed for these patients. Pharmacists should have the necessary tools at their disposal to facilitate the SIF with this type of patient. (AU)

Protective effect of ZYMT, a traditional Chinese patent medicine in a mouse model of retinitis pigmentosa.

Retinitis pigmentosa (RP) is the most common genetic disorder that causes blindness. At present, there exists no remedy for the disease. The aim of the current research was to investigate the protective effect of Zhangyanming Tablets (ZYMT) in a mouse model of RP, and explore the underlying mechanism. Eighty RP mice were randomly divided into two groups. The mice in ZYMT group were administered with ZYMT suspension(0.0378 g/mL), while the mice in model group were given the same volume of distilled water. At day 7 and day 14 after intervention, electroretinogram (ERG), fundus photography, and histological examination were used to assess the retinal function and structure. TUNEL, immunofluorescence and qPCR were used to evaluate cell apoptosis and expressions of Sirt1, Iba1, Bcl-2, Bax and Caspase-3. A significantly shortened latency of ERG waves was observed in ZYMT-treated mice, in comparison to those in the model group (P < 0.05). Histologically, ultrastructure of the retina was better preserved, and the outer nuclear layer (ONL) exhibited marked increase in thickness and cell count in ZYMP group (P < 0.05). The apoptosis rate was decreased markedly in ZYMT group. Immunofluorescence analysis showed that the expressions of Iba1 and Bcl-2 in the retina were increased, Bax and Caspase-3 were decreased after ZYMT intervention, while the qPCR revealed that the expressions of Iba1 and Sirt1 were significantly increased (P < 0.05). This study indicated that ZYMT has protective effect on retinal function and morphology of inherited RP mice in the early stage, possibly mediated via the regulation of antioxidant and anti-/pro-apoptotic factors expressions.

Chinese patent medicine for osteoporosis: a systematic review and meta-analysis.

Chinese patent medicine (CPM) has been widely used in China for patients with osteoporosis (OP) but a comprehensive literature review is still important. Therefore, we performed meta-analysis using six electronic databases prior to 30 April 2021 only randomized controlled trials (RCTs) using CPM as the first-line treatment in adults with OP were included. Thirty RCTs met the inclusion criteria with a total of 2723 patients, and seven types of CPM were included. Compared with the control group, 23 studies showed significantly improved bone mineral density (BMD) (lumbar spine) (mean difference [MD] = 0.08; confidence interval [CI], 0.03 to 0.13), 15 studies showed significantly improved BMD (femoral) (MD = 0.05; 95% CI, 0.02 to 0.07), 6 studies showed significantly improved BMD (radius) (MD = 0.06; 95% CI, 0.03 to 0.09), 2 trials showed significantly improvement of BMD (ulna) (MD = 0.02; 95% CI, 0.01 to 0.03), and 4 trials showed significantly improved BMD (MD = 0.09; 95% CI, 0.09 to 0.10). The meta-analysis also showed that CPM had superior pain improvement, a higher total effectiveness rate, and a lower risk of adverse events compared with standard western treatment. The findings of this study suggest that CPM therapy may be a safe and effective alternative treatment modality for OP, it has potential benefits in relieving symptoms and improving BMD compared to western medications or placebos.

[Review of taste masking techniques in Chinese patent medicine].

Single herbs and Chinese patent medicine preparations often have bad taste, such as bitterness and astringency, which is one of the key factors affecting patients' medication compliance, and would affect the therapeutic effect and restrict the extensive application in clinical practice. Therefore, how to make use of taste masking techniques to improve the bad taste of traditional Chinese medicines has become an important project. Through the collection and summarization of Chinese and foreign journals and papers in recent years, this paper discussed the generation mechanism of bitter taste, the new methods of masking bitter taste and the evaluation me-thods of bitter taste, in order to provide references for the taste masking of Chinese patent medicines preparations.

Interactions between highly active antiretroviral therapy and over-the-counter agents: a cautionary note.

Highly active antiretroviral therapy (HAART) has dramatically lowered rates of mother-to-child HIV transmission among patients with access to treatment. Barriers to complete viral suppression increase rates of transmission, even with only low levels of viral replication. Here, we present the case of a pregnant patient who developed a detectable viral load in pregnancy, thought to be related to calcium supplement consumption or emesis while using a dolutegravir-based HAART regimen. Ultimately, with adjustments, the patient again reached an undetectable viral load and had an uncomplicated perinatal and neonatal outcome. We discuss new data on the use of dolutegravir in pregnancy and precautions for maintaining viral suppression while on antiretroviral therapy in pregnancy.

Review of taste masking techniques in Chinese patent medicine / 中国中药杂志

Single herbs and Chinese patent medicine preparations often have bad taste, such as bitterness and astringency, which is one of the key factors affecting patients' medication compliance, and would affect the therapeutic effect and restrict the extensive application in clinical practice. Therefore, how to make use of taste masking techniques to improve the bad taste of traditional Chinese medicines has become an important project. Through the collection and summarization of Chinese and foreign journals and papers in recent years, this paper discussed the generation mechanism of bitter taste, the new methods of masking bitter taste and the evaluation me-thods of bitter taste, in order to provide references for the taste masking of Chinese patent medicines preparations.

The Chinese patent medicine, Jin-tang-ning, ameliorates hyperglycemia through improving ß cell function in pre-diabetic KKAy mice.

Jin-tang-ning (JTN), a Chinese patent medicine, mainly comprised of Bombyx moriL., has been proved to show α-glucosidase inhibitory efficacy and clinically effective for the treatment of type 2 diabetes (T2DM). Recently, we have reported that JTN could ameliorate postprandial hyperglycemia and improved ß cell function in monosodium glutamate (MSG)-induced obese mice, suggesting that JTN might play a potential role in preventing the conversion of impaired glucose tolerance (IGT) to T2DM. In this study, we evaluated the effect of JTN on the progression of T2DM in the pre-diabetic KKAy mice. During the 10 weeks of treatment, blood biochemical analysis and oral glucose tolerance tests were performed to evaluate glucose and lipid profiles. The ß cell function was quantified using hyperglycemic clamp at the end of the study. JTN-treated groups exhibited slowly raised fasting and postprandial blood glucose levels, and also ameliorated lipid profile. JTN improved glucose intolerance after 8 weeks of treatment. Meanwhile, JTN restored glucose-stimulated first-phase of insulin secretion and induced higher maximum insulin levels in the hyperglycemic clamp. Thus, to investigate the underlying mechanisms of JTN in protecting ß cell function, the morphologic changes of the pancreatic islets were observed by optical microscope and immunofluorescence of hormones (insulin and glucagon). Pancreatic protein expression levels of key factors involving in insulin secretion-related pathway and ER stress were also detected by Western blot. Pre-diabetic KKAy mice exhibited a compensatory augment in ß cell mass and abnormal α cell distribution. Long-term treatment of JTN recovered islet morphology accompanied by reducing α cell area in KKAy mice. JTN upregulated expression levels of glucokinase (GCK), pyruvate carboxylase (PCB) and pancreas duodenum homeobox-1 (PDX-1), while down-regulating C/EBP homologous protein (Chop) expression in pancreas of the hyperglycemic clamp, which indicated the improvement of mitochondrial metabolism and relief of endoplasmic reticulum (ER) stress of ß cells after JTN treatment. These results will provide a new insight into exploring a novel strategy of JTN for protecting ß cell function and preventing the onset of pre-diabetes to T2DM.

Kojic Acid for Melasma: Popular Ingredient in Skincare Products.

Melasma is a common skin condition that affects many patients with hyperpigmented patches on sun-exposed facial skin. It disproportionately affects people of Asian, African, and Hispanic descents. Unfortunately, there are not many lasting and effective treatment options available, which has led many practitioners and skincare companies to trial various topical ingredients. In the past several years, kojic acid has gained popularity as a skincare ingredient to treat hyperpigmentation and melasma. Kojic acid has more recently become popular in over-the-counter skincare products. We discuss the background of kojic acid, its suggested mechanism, and the available studies evaluating its utility in treating melasma.

ARTICLE: Colloidal Oatmeal Part I: History, Basic Science, Mechanism of Action, and Clinical Efficacy in the Treatment of Atopic Dermatitis.

Colloidal oatmeal has a long-standing history in the treatment of dermatologic disease. It is composed of various phytochemicals, which contribute to its wide-ranging function and clinical use. It has various mechanisms of action including direct anti-inflammatory, anti-pruritic, anti-oxidant, anti-fungal, pre-biotic, barrier repair properties, and beneficial effects on skin pH. These have been shown to be of particular benefit in the treatment of atopic dermatitis. In Part 1 of this two-part series, we will explore the history of colloidal oatmeal, basic science, mechanism of action, and clinical efficacy in the treatment of atopic dermatitis. J Drugs Dermatol. 2020;19:10(Suppl):s4-7.

What is the Role of Over 100 Excipients in Over the Counter (OTC) Cough Medicines?

Most medicines are white bitter powders that are formulated as tablets and capsules but cough medicines are an exception where the taste and appearance of the medicine are more important to the patient than the pharmacology of the active ingredient. Excipients are generally defined as any ingredient in a medicine other than the active ingredient. In most medicines excipients play a supportive role in delivering the medicine, but in the case of cough medicines, excipients have more important and complex roles and they can also be the main active ingredient of the cough medicine as menthol, glycerol, and sugars, which are declared as active ingredients. This review searched the United Kingdom electronic medicines compendium (emc) and found over 100 excipients in 60 different liquid formulations of over the counter cough medicines. The excipients were divided into functional groups: sweeteners, thickeners, flavors, colors, antimicrobials, and buffers, and the incidence and function of the different excipients is discussed. When considering the efficacy of a cough medicine, clinicians and pharmacists tend to think of the pharmacology of antitussives such as dextromethorphan or expectorants such as guaifenesin, and they rarely consider the role of excipients in the efficacy of the medicine. This review discusses the functions and importance of excipients in cough medicines and provides some new information for clinicians, pharmacists, and all interested in the treatment of cough when considering the composition and efficacy of a cough medicine.

Pharmacological Aspects of Over-the-Counter Opioid Drugs Misuse.

Several over-the-counter (OTC) drugs are known to be misused. Among them are opioids such as codeine, dihydrocodeine, and loperamide. This work elucidates their pharmacology, interactions, safety profiles, and how pharmacology is being manipulated to misuse these common medications, with the aim to expand on the subject outlined by the authors focusing on abuse prevention and prevalence rates. The reviewed literature was identified in several online databases through searches conducted with phrases created by combining the international non-proprietary names of the drugs with terms related to drug misuse. The results show that OTC opioids are misused as an alternative for illicit narcotics, or prescription-only opioids. The potency of codeine and loperamide is strongly dependent on the individual enzymatic activity of CYP2D6 and CYP3A4, as well as P-glycoprotein function. Codeine can also be utilized as a substrate for clandestine syntheses of more potent drugs of abuse, namely desomorphine ("Krokodil"), and morphine. The dangerous methods used to prepare these substances can result in poisoning from toxic chemicals and impurities originating from the synthesis procedure. OTC opioids are generally safe when consumed in accordance with medical guidelines. However, the intake of supratherapeutic amounts of these substances may reveal surprising traits of common medications.

Assessment of Pharmacologic Ingredients in Common Over-the-Counter Sinonasal Medications.

Importance: Sinonasal remedies are the most frequently purchased category of over-the-counter (OTC) drugs in the United States. A variety of options for relief are available under proprietary names, although the actual number of available options may not be readily appreciated by the consumer or the clinician. Objective: To determine the prevalence of specific ingredients in OTC sinonasal products. Design, Setting, and Participants: This cross-sectional study took physical inventory of brand-name and generic OTC drugs marketed as sinus, cold, allergy, or nasal remedies. Retail pharmacies in New Orleans, Louisiana, commercial websites, and the Drugs, Herbs and Supplements section of MedlinePlus and drugs.com were searched. Data were collected and analyzed from July 1 to 31, 2018. Main Outcomes and Measures: Frequency of active ingredients in OTC formulations. Results: Five pharmacies were visited to identify 18 brands, for which the commercial websites were then searched. The 14 most common brands represented 211 unique products. Only 8 unique nonanalgesic ingredients were identified among these products, with many products sold under the same brand name and with the same active ingredient. Phenylephrine hydrochloride, dextromethorphan hydrobromide, pseudoephedrine hydrochloride, guaifenesin, chlorpheniramine maleate, brompheniramine maleate, diphenhydramine hydrochloride, and doxylamine succinate were the common active ingredients, with all available OTC sinonasal remedies consisting of 1 or more of these ingredients. The frequency of occurrence of each ingredient ranged from 10 to 261 different products. Combinations of 2, 3, or 4 active ingredients occurred frequently in OTC sinonasal products. Conclusions and Relevance: These findings suggest that proliferation of brand extension products under a common name is pervasive. Clinicians should be aware of the large array of redundant OTC formulations and lack of specificity when discussing brand-name sinonasal remedies with their patients.

Understanding the risk of emerging bacterial resistance to over the counter antibiotics in topical sore throat medicines.

AIMS: The aims of this study were to explore the development of bacterial resistance and cross-resistance in four common human pathogens following realistic exposure to antibiotics found in over-the-counter (OTC) sore throat medicines: gramicidin, neomycin, bacitracin and tyrothricin. METHODS AND RESULTS: Bacterial exposure to in-use (concentration in the product before use) and diluted concentration (i.e. during use) of antibiotic where conducted in broth for 24 h or until growth was visible. The changes in bacterial susceptibility profile before and after exposure was determined using standardized ISO microdilution broth. Antibiotic testing was performed according to EUCAST guidelines. We demonstrated that test bacteria were able to survive exposure to the in-use concentrations of some antibiotics used in OTC medicines. Exposure to during use concentrations of bacitracin resulted in stable increase in minimal inhibitory concentration (MIC) (>8-fold) in Staphylococcus aureus and Acinetobacter baumannii. Exposure to tyrothricin resulted in a stable increase in MIC (2·4-fold) in Klebsiella pneumoniae, and exposure to neomycin resulted in a stable increase MIC (5000-fold higher than the baseline) in Streptococcus pyogenes. Clinical cross-resistance to other antibiotics (ciprofloxacin, fusidic acid, gentamicin, cefpodoxime, amoxicillin/clavulanic acid and cefotaxime) was also demonstrated following exposure to bacitracin or tyrothricin. Bacitracin exposure lead to a stable bacterial resistance after 10 passages. CONCLUSIONS: Our results indicate that OTC antibiotic medicines have the potential to drive resistance and cross-resistance in vitro. SIGNIFICANCE AND IMPACT OF THE STUDY: Tackling antibiotic resistance is a high worldwide priority. It is widely accepted that the overuse and misuse of antibiotics increase the risk of the development and spread of antibiotic resistance within communities. A number of OTC sore throat products, widely available across the world for topical use in respiratory indications, contain locally delivered antibiotics. Our findings showed that these antibiotics in OTC medicines present a risk for emerging cross-resistance in a number of bacterial respiratory pathogens.

RapidAIM: a culture- and metaproteomics-based Rapid Assay of Individual Microbiome responses to drugs.

BACKGROUND: Human-targeted drugs may exert off-target effects or can be repurposed to modulate the gut microbiota. However, our understanding of such effects is limited due to a lack of rapid and scalable assay to comprehensively assess microbiome responses to drugs. Drugs and other compounds can drastically change the overall abundance, taxonomic composition, and functions of a gut microbiome. RESULTS: Here, we developed an approach to screen compounds against individual microbiomes in vitro, using metaproteomics to both measure absolute bacterial abundances and to functionally profile the microbiome. Our approach was evaluated by testing 43 compounds (including 4 antibiotics) against 5 individual microbiomes. The method generated technically highly reproducible readouts, including changes of overall microbiome abundance, microbiome composition, and functional pathways. Results show that besides the antibiotics, the compounds berberine and ibuprofen inhibited the accumulation of biomass during in vitro growth of the microbiota. By comparing genus and species level-biomass contributions, selective antibacterial-like activities were found with 35 of the 39 non-antibiotic compounds. Seven of the compounds led to a global alteration of the metaproteome, with apparent compound-specific patterns of functional responses. The taxonomic distributions of altered proteins varied among drugs, i.e., different drugs affect functions of different members of the microbiome. We also showed that bacterial function can shift in response to drugs without a change in the abundance of the bacteria. CONCLUSIONS: Current drug-microbiome interaction studies largely focus on relative microbiome composition and microbial drug metabolism. In contrast, our workflow enables multiple insights into microbiome absolute abundance and functional responses to drugs. The workflow is robust, reproducible, and quantitative and is scalable for personalized high-throughput drug screening applications.

Factors influencing pharmacists' over-the-counter drug recommendations.

BACKGROUND: Self-care is a growing trend all over the world, and pharmacists have a major role in it since they are the most easily accessible medical experts. OBJECTIVES: Our aim was to investigate factors influencing pharmacists' over-the-counter (OTC) drugs recommendations in Croatia. SETTING: A random sample of 565 (50%) of all pharmacies in Croatia. METHODS: A cross-sectional study with a five-point Likert scale online questionnaire covering medical and non-medical factors influencing OTC drug recommendation was distributed in October 2017 to a random sample of pharmacies. RESULTS: 206/565 (response rate 36.5%) responses were collected. The most important factors influencing pharmacists' recommendation were: composition of the OTC product and its active component (4.76±0.47), scientific evidence of effectiveness (4.54±0.60), feedback from the patients (4.32±0.61) and information from professional journals (4.22±0.67). On average, medical factors had greater importance (4.5±0.58) for pharmacists' OTC recommendation than marketing (3.18±0.84) and social factors (3.15±0.79). Female pharmacists appeared less inclined to recommend an OTC product based on advice of other pharmacists (OR=0.61, CI=0.43 to 0.86, p=0.005) and pharmacists working directly in a pharmacy attached more importance to active components of OTC products during their OTC product counselling (OR=2.28, CI=0.92 to 5.65, p=0.03). CONCLUSION: It is vital to know that pharmacists' OTC recommendations are mainly influenced by medical factors and to a lesser degree by marketing and social factors.

Lista básica de medicamentos / Basic Drug List

El objetivo de este catálogo es contar con una Lista Básica de Medicamentos actualizada, que facilite la disponibilidad de medicamentos eficaces, seguros y accesibles en el sistema público de salud. La idea de este catálogo nace con el fin de fortalecer el acceso y uso racional de medicamentos de calidad, eficaces, seguros y costo-efectivos en los diferentes niveles de atención. Sirve como marco de referencia para la utilización y gestión del medicamento. Incluye un excelente glosario de términos farmacéuticos

Epidemiology and susceptibility profile to classic antifungals and over-the-counter products of Malassezia clinical isolates from a Portuguese University Hospital: a prospective study.

PURPOSE: Clinical epidemiological data about the distinct Malassezia species remain scarce. The recurrence of Malassezia-related skin diseases, despite long-term use of antifungals, raises concern about the hypothetical emergence of antifungal resistance. We aimed to assess the distribution of Malassezia species among patients from a University Hospital with pityriasis versicolor, seborrheic dermatitis and healthy volunteers, and to evaluate the susceptibility profile to classic antifungals and over-the-counter compounds, searching for clinical associations. METHODOLOGY: The enrollment of volunteers was conducted at the Dermatology Department of a University Hospital over a 3 year period. Malassezia culture isolates were identified to the species-level by sequencing. The drug susceptibility profile was assessed according to a broth microdilution assay, as recommended by the Clinical Laboratory Standards Institute. RESULTS: A total of 86 Malassezia isolates were recovered from 182 volunteers. Malassezia sympodialis was the most frequent isolated species. We found high MIC values and a wide MIC range in the case of tested azoles, and very low terbinafine MIC values against most isolates. Previous topical corticosteroid therapy was associated with a significant increase of MIC values of fluconazole and of terbinafine. CONCLUSION: Conversely to other European studies, M. sympodialis was the most common isolated species, which might be related to geographic reasons. The impact of previous topical corticotherapy upon the antifungal susceptibility profile was hereby demonstrated. In vitro susceptibility test results suggest that terbinafine might be a valid alternative for Malassezia-related skin diseases nonresponsive to azoles.