Purpose The Essential Medicines List (EML), published by the World Health Organization since 1977, provides global guidance for the selection of effective, safe, and essential medicines. Following the publication of the 24th edition in 2025, this study sought to compare nearly five decades of EML development in order to identify and evaluate “core essential drugs” with long-standing use and efficacy. Methods The 1st (1977) and 24th (2025) edition of the EML were compared in regard to listed drugs. Extracted were explanations for changes and indications to summarize usage fields and generalize patterns. Changes of drug listings were categorized as additions, deletions, or modifications, while drugs retaining were defined as “core essential drugs”. Results The total number of listed drugs increased strongly from 1977 to 2025. Despite this, the proportional distribution of most usage fields remained relatively stable. Anti-infective, antineoplastic, central nervous system, cardiovascular, and immunization-related medicines experienced many changes and represent dynamic categories. In contrast, blood components, nutrition, electrolyte-correcting solutions, and respiratory system demonstrated high preservation rates and can be regarded as comparatively static. 143 medicines were identified as core essential drugs retained in both editions. Conclusions The long-term comparison highlights consistent patterns of both stability and change within the EML. Despite significant therapeutic advancements, a substantial group of core essential drugs has remained central for nearly five decades, reflecting their continued importance in global pharmacotherapy. Identifying which medicines persist and evaluating the reasons for their retention can support evidence-based updates to future EML editions and inform medicine list development.

Medication errors remain a challenge in the pharmacological treatment of patients. To improve the safety of drug therapy, 197 publicly accessible court rulings from Germany were systemically analyzed in various dimensions according to the PRISMA 2020 statement. Particular attention was paid to the three active ingredients that were mentioned most frequently in connection with allegations of medication errors in court. According to the results of our keyword search, current as of April 2024, these are heparin, acetylsalicylic acid, and oxytocin. Cases involving MOR agonists and benzodiazepines were intentionally excluded from this study. Even though heparin and acetylsalicylic acid (ASA) are two active ingredients commonly used across a range of disciplines, the errors were ultimately similar in their recurrence. The occurrence of thromboembolic events and bleeding complications, as well as the development of the feared heparin-induced thrombocytopenia, repeatedly raised questions about the appropriate extent of monitoring during heparin therapy. Preoperative management in the case of antiplatelet therapy with ASA was likewise discussed in several trials, as bleeding and thromboembolic events had primarily occurred in connection with this active ingredient. Although oxytocin is used almost exclusively in obstetrics, the consequences of its administration can be equally dramatic. Difficulties with dosage were repeatedly identified, resulting in hypoxia in the child in almost all cases, and even requiring subsequent resuscitation in one of them. The latter, as well as the overall finding that the patients in our study suffered moderate or severe long-term damage, with a notable proportion of them dying, underscores the assumption that court rulings tend to deal with more serious cases. The most common alleged errors were identified as incorrect indication or overlooking of contraindication (50.8

The Schmiedeberg Medal, awarded by the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT), is the highest honour for excellent pharmacologists and has been awarded to 47 recipients until 2024. The first medal was awarded to Wolfgang Heubner in 1956, the most recent of our analysis to Franz Hofmann in June 2024. This is the first profound analysis of the prize winners: Most of the prize winners (63.83%) were born in Germany, and more than half (53.19%) came from academic families. Notably, only two women (4.26%), Edith Bülbring and Marthe Vogt, have received the award, although the presence of women in medicine and among members of the DGPT is on the rise. Almost 90% of the award winners studied medicine, and 29.79% spent part of their studies in Berlin. The award winners enjoyed exceptional quality of life and consistently surpassed the average life expectancy, with an average age of 86.26 years. On average, their careers spanned 50.65 years, with the Schmiedeberg Medal being awarded 20.74 years after the peak of their careers. Over time, the number of publications and productivity, co-authors, and senior authorships increased, while first authorships decreased. This shift reflects the growing importance of collaborative scientific work as opposed to solo endeavours. The overall publication productivity also increased during the observation period, with the Naunyn–Schmiedeberg’s Archives of Pharmacology being the most prominent journal for these publications, although its influence decreased over time. The predominant language of publication was English, accounting for 72.28% of the articles, a trend that has increasingly replaced German since the 1970s. The most common research focus was the cholinergic and adrenergic systems. Thus, Schmiedeberg Medal recipients are an outstandingly productive group of scientists enjoying a long scientific career and a long high-quality life. In addition, Schmiedeberg Medal recipients encountered numerous societal and scientific challenges which they mastered excellently. The gender gap for this award is dramatic, reflecting the very low number of eligible female pharmacologists for this award.

Antimicrobial resistance is a major threat to public health, with a well-established link between antibacterial consumption and bacterial resistance. Stewardship needs to focus on reducing overall consumption and optimising the quality of prescribing. The European Union’s ‘One Health’ approach aims for at least 65

β-Adrenergic receptors (βxAR) are G protein-coupled receptors with major physiological and therapeutic relevance in cardiovascular and respiratory conditions. Although numerous ligands have been investigated, binding affinities and functional annotations remain incomplete and fragmented across databases. This review systematically integrates ligand binding affinities and functional profiles at recombinant human βxAR from the Psychoactive Drug Screening Program Ki database and the International Union of Basic and Clinical Pharmacology/British Pharmacological Society (IUPHAR/BPS), with a focus on clinically important ligands, receptor selectivity, and characteristic patterns. Database agreement, affinity patterns, stereoisomer-specific information and concordance with primary literature are evaluated. In total, 156 ligands with pKi ≥ 5 were collected. Median pKi values were 6.6 for hβ1AR, 6.15 for hβ2AR, and 5.8 for hβ3AR. A pronounced overlap between hβ1AR and hβ2AR was observed, reflected in similar median affinities and shared ligand profiles, whereas hβ3AR showed narrower data coverage and a more distinct affinity distribution. Most ligands were listed for more than 1 hβxAR, and 37 ligands had binding data for all 3 hβxAR. Functional characterization was available for 90 ligands, whereas 61 lacked annotations. Database comparison revealed low overlap in ligand listings (28.8%). Stereoisomer data were highly incomplete, and in several cases, affinity-based stereoisomer comparisons differed from literature-reported stereoisomeric superiority. Summarized, substantial similarity between hβ1AR and hβ2AR ligand binding patterns is observed, whereas hβ3AR appears less extensively characterized. Considerable fragmentation, incomplete receptor profiling and methodological heterogeneity limit the evaluation of receptor and ligand characteristics. Binding affinity and functional behavior must be interpreted as context-dependent parameters influenced by experimental systems, G protein coupling conditions and stereochemical specification. Significance Statement This analysis systematically integrates ligand binding affinities and functional labels at recombinant human βxAR from the Psychoactive Drug Screening Program (PDSP) Ki database and the International Union of Basic and Clinical Pharmacology/British Pharmacological Society (IUPHAR/BPS) Guide to Pharmacology, providing a structured and comprehensive overview of ligand profiles. It identifies substantial data fragmentation, incomplete receptor and stereoisomer characterization, and limited concordance between databases. For clinically relevant ligands, it was demonstrated that therapeutic subtype classification does not always correspond to strict affinity-based receptor selectivity.

Black box warnings represent the most severe U.S. Food and Drug Administration (FDA) safety alerts. Currently, they are fragmented across individual product labels and not systematically accessible at the level of drugs or drug classes. This study provides a comprehensive overview of drugs with black box warnings and identifies class- and category-specific patterns of adverse effects, aiming to support risk–benefit assessments and rational treatment. 626 drugs across 250 drug classes were identified as carrying black box warnings. Drug classes were unevenly distributed, with many classes represented by a single drug, while a small number of large classes accounted for a substantial proportion of entries, e.g., μ-opioid receptor (MOR) agonists, cyclooxygenase (COX) inhibitors, angiotensin-converting enzyme (ACE) inhibitors or kinase inhibitors. Across all drugs, 1016 adverse effect category listings were identified, demonstrating that multiple serious risks are frequently combined within a single boxed warning. Cardiac and cardiovascular adverse effects are the most prevalent category (18.7%), followed by immunologic and allergic reactions (11.4%), beside drug category-specific patterns. The standardized adverse effect count ranged from 1.1 in endocrine system drugs to 2.1 in cytotoxic treatments, indicating marked differences in the density and variety of serious adverse effects between drug categories. Black box warnings reveal pronounced heterogeneity across drugs, but show consistent, mechanism-related patterns at the level of drug classes and categories. These patterns allow estimation of probable, high-risk adverse effects and risk profiles. A structured, drug-class-based overview of black box warnings can improve awareness of safety risks and support rational prescribing.

Black box warnings represent the most severe US Food and Drug Administration safety alerts. Currently, they are fragmented across individual product labels and not systematically accessible at the level of drugs or drug classes. This study provides a comprehensive overview of drugs with black box warnings and identifies class- and category-specific patterns of adverse effects, aiming to support risk benefit assessments and rational treatment. Six hundred twenty-six drugs across 250 drug classes were identified as carrying black box warnings. Drug classes were unevenly distributed, with many classes represented by a single drug, whereas a small number of large classes accounted for a substantial proportion of entries, for example, μ-opioid receptor agonists, cyclooxygenase inhibitors, angiotensin-converting enzyme inhibitors and kinase inhibitors. Across all drugs, 1016 adverse effect category listings were identified, demonstrating that multiple serious risks are frequently combined within a single boxed warning. Cardiac and cardiovascular adverse effects are the most prevalent category (18.7%), followed by immunologic and allergic reactions (11.4%), beside drug category-specific patterns. The standardized adverse effect count ranged from 1.1 in endocrine system drugs to 2.1 in cytotoxic treatments, indicating marked differences in the density and variety of serious adverse effects between drug categories. Black box warnings reveal pronounced heterogeneity across drugs, but show consistent, mechanism related patterns at the level of drug classes and categories. These patterns allow estimation of probable, high-risk adverse effects and risk profiles. A structured, drug class-based overview of black box warnings can improve awareness of safety risks and support rational prescribing. SIGNIFICANCE STATEMENT: Black box warnings are the most severe US Food and Drug Administration safety alerts, but they are fragmented across individual product labels. By systematically analyzing US Food and Drug Administration boxed warnings across drugs, drug classes, and adverse effect categories, this study reveals pronounced heterogeneity across individual drugs, but consistent, mechanism related risk patterns, with cardiovascular and immunologic adverse effects being most prevalent. A structured, drug class-based overview enables identification of high-risk profiles, supporting risk benefit assessment and rational prescribing.

Drug-induced gingival overgrowth (DIGO) is becoming an increasingly important issue due to high prescription rates of inducing pharmaceuticals. Therefore, the main focus of this study was to determine what experiences dentists in Germany have had with DIGO and which active ingredients cause this ADR in their patients. The conducted online survey was sent to all 17 German dental associations asking them to forward the survey to their members. Five associations complied with the request. Out of 25,562 dentists who were potentially eligible, 118 questionnaires were evaluated, resulting in a response rate of 0.46%. Furthermore, the 24 questions were designed to shed light on the frequency with which this adverse drug reaction (ADR) occurs, as well as patient factors, treatment strategies and potential risks. Amlodipine, nifedipine and ciclosporin were cited as the most frequent triggers of DIGO. In addition, no gender-specific differences were found among the affected patients. Sixty-nine percent of respondents were able to successfully treat this condition, using the following treatment options in descending order: "oral hygiene instruction", "change in medication", and "surgical procedures". Accordingly, it is difficult to determine a precise prevalence with which a particular active substance leads to gingival overgrowth. It is therefore advisable to specify a narrow percentage range with which the prevalence can be reliably described. In addition, the underlying parameters of the source under consideration should be examined very carefully, as different sources may come to very different results.

ABSTRACT Salmonella enterica serovars Typhimurium (STM) and Paratyphi A (SPA) cause clinically distinct diseases, yet the molecular bases for their different lifestyles remain incompletely understood. Genome degradation, a hallmark of typhoidal Salmonella , results in extensive pseudogenization across multiple functional pathways. Here, we investigate how such gene inactivation rewires cyclic-di-GMP (c-di-GMP) signaling and flagellar motility regulation in SPA vs. STM. We show that YhjH, a conserved phosphodiesterase (PDE), is required for motility in STM but not in SPA, despite retaining PDE activity in both serovars. We demonstrate that this functional divergence is caused by pseudogenization of ycgR in SPA, which truncates the flagellar brake protein YcgR to a nonfunctional peptide, severing the link between c-di-GMP levels and flagellar motor control. Site directed mutagenesis in the YhjH active site and ectopic expression of intact YcgR from STM that restored YhjH-dependent motility regulation in SPA, confirmed this molecular mechanism. Additionally, using a bacterial two-hybrid (BACTH) genetic screen, we identified a serovar-specific interaction between YhjH and the general stress protein YciG in SPA, but not in STM. Computational RNA folding analysis predicted substantial differences in mRNA secondary structure and stability between the SPA and STM yhjH alleles, suggesting a potential role for synonymous mutations in this serovar-specific interaction. Together, these findings reveal how genome degradation can rewire regulatory networks, uncovering a fundamental difference in motility control between typhoidal and non-typhoidal Salmonella and suggest that these differences allow SPA motility under conditions that suppress motility in STM. IMPORTANCE Salmonella enterica serovars Typhimurium (STM) and Paratyphi A (SPA) cause fundamentally different diseases in humans, yet the molecular basis for their distinct lifestyles and pathogenicity remains poorly understood. Genome degradation is a hallmark of typhoidal Salmonella , but its functional consequences for regulatory networks are largely unexplored. Here, we demonstrate that pseudogenization of ycgR in SPA dismantles c-di-GMP-mediated flagellar motor control, liberating SPA from an inhibitory brake that suppresses motility in STM. Additionally, we uncover a serovar-specific interaction between the phosphodiesterase YhjH and the general stress protein YciG in SPA, demonstrating that genome degradation can drive regulatory network rewiring beyond simple gene loss. These differences in motility regulation may facilitate the systemic pathogenesis and unique lifestyle of SPA.

Drug supply shortages are increasingly becoming a critical topic in the treatment of patients. Not only the reasons for the supply shortages are important but also their consequences for the medical profession. Firstly, this paper identifies which drug shortages have particularly affected medical doctors. Secondly, the additional time required for medical doctors due to supply shortages is analysed. A survey was conducted with 895 physicians from Germany and Austria using a purposive sampling method. The survey targets the supply shortages and its consequences for the medical profession of 20 commonly used drugs. All survey questions referred to the time span from November 2022 to January 2024. Penicillin V and amoxicillin emerged as the drugs most seriously affected by drug supply shortage although the severity to which physicians were affected by the individual 20 drug shortages varied regionally (Germany/Austria), depending on the place of work (practice/clinic) and the physicians’ specialty. Drug shortages reported by survey participants did not necessarily match official reporting of drug shortage. There was also a substantial increase in time required for medical doctors handling drug shortages. The most additional time burden per affected drug was recognised in haematology/oncology with 46 min, followed by psychiatry (37 min), nephrology (37 min), and general medicine (28 min). The identification of specific critical drugs, specific disciplines, and defined time-consuming factors offer starting points for improvements. Moreover, exact reporting of drug shortages by official authorities is important. Encouraging more judicious prescribing practices may help reduce perceived shortages.

Drugs removed from the US market after approval can be either discontinued by the manufacturer or withdrawn by the US Food and Drug Administration (FDA). However, a systematic overview is currently lacking. This minireview provides a comprehensive analysis of removed drugs, identifies patterns regarding drug classes, indications, adverse effects, and scientific interest, and compares US removals with the European Union and FDA boxed warnings. A total of 166 drugs were removed between 1955 and 2026, including 88 discontinued and 78 withdrawn drugs. Removed drugs represented a wide range of therapeutic fields, with certain drug classes occurring repeatedly, particularly cyclooxygenase inhibitors and fluoroquinolones. Market removals were frequently associated with serious adverse effects such as hepatotoxicity, cardiotoxicity, and hematologic toxicity. The prominent drug classes and adverse effect categories also occurred frequently among drugs carrying boxed warnings. While withdrawn drugs were typically banned by the FDA because of severe safety concerns, discontinued drugs were often removed because of commercial decisions or obsolescence, sometimes in combination with safety considerations. The analysis of publication peaks showed that for most drugs, scientific interest peaked before market removal, while in other cases, publication peaks occurred around or after withdrawal, indicating renewed scientific interest. Drug removals from the US market represent a heterogeneous group of drugs, indications, and underlying causes. While withdrawals and discontinuations differ in their regulatory implications, they share overlapping characteristics and safety considerations. Integration of European Union availability and FDA boxed warning comparisons highlights international differences and patterns requiring precautionary attention, with recurring drug classes and adverse effects. SIGNIFICANCE STATEMENT: This minireview provides a comprehensive overview of US postmarketing drug removals, covering drugs and causes, as well as evaluating and comparing their characteristics. Patterns and characteristics are identified and compared between discontinued and withdrawn drugs. The analysis of publication peaks and the derived patterns allow an evaluation of changes in scientific interest. This analysis provides information on past drug safety decisions and guides future risk-benefit assessments, while identifying prevalent drug classes and adverse effects that require precaution.

Women tend to be underrepresented in almost all scientific fields in Germany. This study analyses publications of scientists in a German pharmaceutical non-peer-reviewed journal over a period of 50 years (1972–2021). The journal Pharmakon (previously named Pharmazie in unserer Zeit) is the member journal of the German Pharmaceutical Society (DPhG). We performed a gender analysis of the journal and analysed 1577 articles by 2509 authors. Overall, the percentage of women is 26

Anaphylaxis can be life-threatening-due to its rapid-progressing and often unpredictable nature. Especially in such medical emergencies, robust clinical trials regarding adjunctive therapies can be scarce and recommendations across literature may vary. Hence, the aim of this study is to investigate the evolution of recommendations for the pharmacological management of anaphylaxis in established pharmacology textbooks over time. The following German textbook series were included: Aktories, Lüllmann, and Karow. The US standard work Goodman & Gilman was reviewed for an international comparison. This study focuses on epinephrine, H1R-antagonists, H2R-antagonists, and GCR-agonists-analyzing their potential use in anaphylaxis via predefined criteria and contextualizing it using the current AWMF anaphylaxis guideline. Epinephrine is continuously recommended as first-line treatment in anaphylaxis across textbooks and decades-with a shift towards i.m. use. Differences prevail regarding the anaphylaxis grade at which epinephrine is indicated vs. when H1R-antagonists are considered sufficient. Overall, H1R-antagonists are noted as adjuncts in at least more severe anaphylaxis. H2R-antagonists appear to lack clinical relevance and are inconsistently discussed as adjunctive add-ons. While GCR-agonists are consistently recommended as adjuncts in anaphylaxis, the included US literature deviates from the German consensus of a high-dose approach. Moreover, there are differences regarding fluid resuscitation-some textbooks merely predate the guideline's recommendation to refrain from colloids, whereas others remain at odds with it even in their latest editions. While there is general agreement on epinephrine's central role in anaphylaxis management, recommendations in literature regarding the specific roles of certain adjunctive measures vary-likely reflecting the limited evidence.

The Frankfurter Allgemeine Zeitung (F.A.Z.) is one of the most important national daily newspapers in Germany and serves as a source of information for more than 818,000 readers every day. The newspaper has high journalistic standards, which is why it should be assumed that pharmacological content is also presented correctly. Specifically, the differentiation between trade names and active ingredient names of drugs should be correct to inform readers, avoid surreptitious advertising and contribute to drug therapy safety. In this study, 345 articles from 2014 to 2023 from the online archive of the Frankfurter Allgemeine Zeitung were analyzed regarding the correct use of trade names using the example of Aspirin®. If the trade name is used incorrectly, suggestions are made to improve journalism about pharmacological content in the long term. The study shows that the trade name is used many times more frequently in the articles analyzed than the active ingredient name. In addition, the trade name is repeatedly mentioned in contexts where there is no need for it. This analysis shows that even in a renowned newspaper, mistakes are made in the correct naming of drugs. On this basis, further trade names and newspapers should be analyzed to counteract the "genericide" of drug names. The use of generic drug names is important for drug therapy safety.

The European Medicines Agency (EMA) is an institution of the European Union (EU), responsible for the authorization and pharmacovigilance of medicinal products. In our study, we present a systematic analysis of the 1,985 centralized EMA marketing authorization procedures (MAP) between 1995 and 2025. The analysis mainly includes EMA marketing authorizations, withdrawals of marketing authorizations, and revocations of marketing authorizations or refusals of drug applications. With regard to the analysis period, it is evident that the number of marketing authorizations recommended by the EMA increased significantly between 1996 (first fully published evaluation year) and 2025. Among the active substances (International Nonproprietary Names, INNs) in centralized EMA MAPs, clopidogrel and denosumab are the most frequently represented. On the other hand, antineoplastic agents and immunosuppressants are the most common therapeutic subgroups according to the Anatomical Therapeutic Chemical Classification (ATC) in MAPs. Notably, special MAPs for medicines such as generics, biosimilars, and medicines for the treatment of rare diseases (orphan medicines) account for more than 30