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Pharmacological Research Apr 2024Here we present an account on the history of pharmacology in Spain. Pharmacology as an independent science in Europe began with the creation of university chairs. Of...
Here we present an account on the history of pharmacology in Spain. Pharmacology as an independent science in Europe began with the creation of university chairs. Of particular relevance was the appointment in 1872 of Osswald Shmiedeberg as chairman of an Institute of Pharmacology at the University of Strassbourg, Germany. Teófilo Hernando pioneered in Spain the new emerging pharmacology at the beginning of the XX Century. He made a posdoctoral stay in the laboratory of Schmiedeberg, working on digitalis. In 1912 he won the chair of "Materia Médica y Arte de Recetar" at "Universidad Central of Madrid" (today, "Universidad Complutense de Madrid", UCM). He soon decided to transform such subject to the emerging modern pharmacology, with the teaching of experimental pharmacology in the third course of medical studies and clinical therapeutics (today clinical pharmacology) in the sixth course. This was the status of pharmacology in 1920, supporting the view that Hernando was a pioneer of clinical pharmacology. However, the Spanish Civil War and the II Word War interropted this division of preclinical and clinical pharmacology; only in the 1980's was clinical pharmacolgy partially developed in Spain. From a scientific point of view, Hernando directly trained various young pharmacologists that extended the new science to various Spanish universities. Some of his direct disciples were Benigno Lorenzo Velázquez, Francisco García Valdecasas, Rafael Méndez, Tomás Alday, Gabriel Sánchez de la Cuesta, Dámaso Gutiérrez or Ramón P é rez-Cirera. One of the central research subject was the analysis of the effects of digitalis on the cat and frog heart. In the initiation of the 1970 s pharmacologists trained by those Hernando's students grew throughout various universities and the "Consejo Superior de Investigaciones Científicas" (CSIC). And hence, in 1972 the "Sociedad Española de Farmacología" (SEF) emerged. Later on, in the 1990's the "Sociedad Española de Farmacología Clínica (SEFC) also emerged. The relationship between the two societies is still weak. Out of the vast scope of the pharmacological sciences, Spanish pharmacologists have made relevant contributions in two areas namely, neuropsychopharmacology and cardiovacular pharmacology. Nonetheless, in other areas such as smooth muscle, gastroenterology, pharmacogenetics and hepatic toxicity, Spanish pharmacologists have also made relevant contributions. A succint description of such contributions is made. Finally, some hints on perspectives for the further development of preclinical and clinical pharmacology in Spain, are offered.
Topics: Humans; Spain; Europe; Pharmacology, Clinical; Pharmacogenetics; Pharmacology
PubMed: 38364957
DOI: 10.1016/j.phrs.2024.107104 -
Frontiers in Pharmacology 2023
PubMed: 37614312
DOI: 10.3389/fphar.2023.1267344 -
Genes Sep 2023Health equity means the opportunity for all people and populations to attain optimal health, and it requires intentional efforts to promote fairness in patient...
Health equity means the opportunity for all people and populations to attain optimal health, and it requires intentional efforts to promote fairness in patient treatments and outcomes. Pharmacogenomic variants are genetic differences associated with how patients respond to medications, and their presence can inform treatment decisions. In this perspective, we contend that the study of pharmacogenomic variation within and between human populations-population pharmacogenomics-can and should be leveraged in support of health equity. The key observation in support of this contention is that racial and ethnic groups exhibit pronounced differences in the frequencies of numerous pharmacogenomic variants, with direct implications for clinical practice. The use of race and ethnicity to stratify pharmacogenomic risk provides a means to avoid potential harm caused by biases introduced when treatment regimens do not consider genetic differences between population groups, particularly when majority group genetic profiles are assumed to hold for minority groups. We focus on the mitigation of adverse drug reactions as an area where population pharmacogenomics can have a direct and immediate impact on public health.
Topics: Humans; Pharmacogenetics; Health Equity; Ethnicity; Pharmacogenomic Variants; Minority Groups
PubMed: 37895188
DOI: 10.3390/genes14101840 -
Frontiers in Psychiatry 2023Pharmacological therapy represents one of the essential approaches to treatment of Major Depressive Disorder (MDD). However, currently available antidepressant... (Review)
Review
Pharmacological therapy represents one of the essential approaches to treatment of Major Depressive Disorder (MDD). However, currently available antidepressant medications show high rates of first-level treatment non-response, and several attempts are often required to find an effective molecule for a specific patient in clinical practice. In this context, pharmacogenetic analyses could represent a valuable tool to identify appropriate pharmacological treatment quickly and more effectively. However, the usefulness and the practical effectiveness of pharmacogenetic testing currently remains an object of scientific debate. The present narrative and critical review focuses on exploring the available evidence supporting the usefulness of pharmacogenetic testing for the treatment of MDD in clinical practice, highlighting both the points of strength and the limitations of the available studies and of currently used tests. Future research directions and suggestions to improve the quality of available evidence, as well as consideration on the potential use of pharmacogenetic tests in everyday clinical practice are also presented.
PubMed: 38025425
DOI: 10.3389/fpsyt.2023.1307473 -
Clinical Pharmacokinetics Nov 2023Side effects of irinotecan treatment can be dose limiting and may impair quality of life. In this study, we investigated the correlation between single nucleotide...
BACKGROUND AND OBJECTIVE
Side effects of irinotecan treatment can be dose limiting and may impair quality of life. In this study, we investigated the correlation between single nucleotide polymorphisms (SNPs) in genes encoding enzymes involved in the irinotecan metabolism and transport, outside UGT1A1, and irinotecan-related toxicity. We focused on carboxylesterases, which are involved in formation of the active metabolite SN-38 and on drug transporters.
METHODS
Patients who provided written informed consent at the Erasmus Medical Center Cancer Institute to the Code Geno study (local protocol: MEC02-1002) or the IRI28-study (NTR-6612) were enrolled in the study and were genotyped for 15 SNPs in the genes CES1, CES2, SLCO1B1, ABCB1, ABCC2, and ABCG2.
RESULTS
From 299 evaluable patients, 86 patients (28.8%) developed severe irinotecan-related toxicity. A significantly higher risk of toxicity was seen in ABCG2 c.421C>A variant allele carriers (P = 0.030, OR 1.88, 95% CI 1.06-3.34). Higher age was associated with all grade diarrhea (P = 0.041, OR 1.03, 95% CI 1.00-1.06). In addition, CES1 c.1165-41C>T and CES1 n.95346T>C variant allele carriers had a lower risk of all-grade thrombocytopenia (P = 0.024, OR 0.42, 95% CI 0.20-0.90 and P = 0.018, OR 0.23, 95% CI 0.08-0.79, respectively).
CONCLUSION
Our study indicates that ABCG2 and CES1 SNPs might be used as predictive markers for irinotecan-induced toxicity.
Topics: Humans; Irinotecan; Camptothecin; Pharmacogenomic Testing; Quality of Life; Genotype; Glucuronosyltransferase; Antineoplastic Agents, Phytogenic; Liver-Specific Organic Anion Transporter 1
PubMed: 37715926
DOI: 10.1007/s40262-023-01279-7 -
Pharmacogenetics and Genomics Sep 2023The association of SLCO1B1 c.521T>C with simvastatin-induced muscle toxicity is well characterized. However, different statins are subject to metabolism and transport...
OBJECTIVE
The association of SLCO1B1 c.521T>C with simvastatin-induced muscle toxicity is well characterized. However, different statins are subject to metabolism and transport also by other proteins exhibiting clinically meaningful genetic variation. Our aim was to investigate associations of SLCO1B1 c.521T>C with intolerance to atorvastatin, fluvastatin, pravastatin, rosuvastatin, or simvastatin, those of ABCG2 c.421C>A with intolerance to atorvastatin, fluvastatin, or rosuvastatin, and that of CYP2C9*2 and *3 alleles with intolerance to fluvastatin.
METHODS
We studied the associations of these variants with statin intolerance in 2042 patients initiating statin therapy by combining genetic data from samples from the Helsinki Biobank to clinical chemistry and statin purchase data.
RESULTS
We confirmed the association of SLCO1B1 c.521C/C genotype with simvastatin intolerance both by using phenotype of switching initial statin to another as a marker of statin intolerance [hazard ratio (HR) 1.88, 95% confidence interval (CI) 1.08-3.25, P = 0.025] and statin switching along with creatine kinase measurement (HR 5.44, 95% CI 1.49-19.9, P = 0.011). No significant association was observed with atorvastatin and rosuvastatin. The sample sizes for fluvastatin and pravastatin were relatively small, but SLCO1B1 c.521T>C carriers had an increased risk of pravastatin intolerance defined by statin switching when compared to homozygous reference T/T genotype (HR 2.11, 95% CI 1.01-4.39, P = 0.047).
CONCLUSION
The current results can inform pharmacogenetic statin prescribing guidelines and show feasibility for the methodology to be used in larger future studies.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Rosuvastatin Calcium; Pravastatin; Cytochrome P-450 CYP2C9; Fluvastatin; Pharmacogenetics; Simvastatin; Liver-Specific Organic Anion Transporter 1; ATP Binding Cassette Transporter, Subfamily G, Member 2; Neoplasm Proteins
PubMed: 37490620
DOI: 10.1097/FPC.0000000000000504 -
Genes Nov 2023Dementia is a syndrome of global and progressive deterioration of cognitive skills, especially memory, learning, abstract thinking, and orientation, usually affecting... (Review)
Review
Dementia is a syndrome of global and progressive deterioration of cognitive skills, especially memory, learning, abstract thinking, and orientation, usually affecting the elderly. The most common forms are Alzheimer's disease, vascular dementia, and other (frontotemporal, Lewy body disease) dementias. The etiology of these multifactorial disorders involves complex interactions of various environmental and (epi)genetic factors and requires multiple forms of pharmacological intervention, including anti-dementia drugs for cognitive impairment, antidepressants, antipsychotics, anxiolytics and sedatives for behavioral and psychological symptoms of dementia, and other drugs for comorbid disorders. The pharmacotherapy of dementia patients has been characterized by a significant interindividual variability in drug response and the development of adverse drug effects. The therapeutic response to currently available drugs is partially effective in only some individuals, with side effects, drug interactions, intolerance, and non-compliance occurring in the majority of dementia patients. Therefore, understanding the genetic basis of a patient's response to pharmacotherapy might help clinicians select the most effective treatment for dementia while minimizing the likelihood of adverse reactions and drug interactions. Recent advances in pharmacogenomics may contribute to the individualization and optimization of dementia pharmacotherapy by increasing its efficacy and safety via a prediction of clinical outcomes. Thus, it can significantly improve the quality of life in dementia patients.
Topics: Humans; Aged; Pharmacogenetics; Quality of Life; Alzheimer Disease; Antidepressive Agents; Cognition
PubMed: 38002991
DOI: 10.3390/genes14112048 -
Cambridge Prisms. Precision Medicine 2023Precision medicine envisages the integration of an individual's clinical and biological features obtained from laboratory tests, imaging, high-throughput omics and... (Review)
Review
Precision medicine envisages the integration of an individual's clinical and biological features obtained from laboratory tests, imaging, high-throughput omics and health records, to drive a personalised approach to diagnosis and treatment with a higher chance of success. As only up to half of patients respond to medication prescribed following the current one-size-fits-all treatment strategy, the need for a more personalised approach is evident. One of the routes to transforming healthcare through precision medicine is pharmacogenomics (PGx). Around 95% of the population is estimated to carry one or more actionable pharmacogenetic variants and over 75% of adults over 50 years old are on a prescription with a known PGx association. Whilst there are compelling examples of pharmacogenomic implementation in clinical practice, the case for cardiovascular PGx is still evolving. In this review, we shall summarise the current status of PGx in cardiovascular diseases and look at the key enablers and barriers to PGx implementation in clinical practice.
PubMed: 38550953
DOI: 10.1017/pcm.2023.17 -
Pharmacological Research Jul 2023Herbal organic compounds (HOCs) are bioactive natural products from medicinal plants and some traditional Chinese medicines (TCMs). Recently, ingestion of a few HOCs...
Herbal organic compounds (HOCs) are bioactive natural products from medicinal plants and some traditional Chinese medicines (TCMs). Recently, ingestion of a few HOCs with low bioavailability has been associated with alterations in gut microbiota, but the extent of this phenomenon remains unclear. Here, we systematically screened 481 HOCs against 47 representative gut bacterial strains in vitro and found that almost one-third of the HOCs exhibited unique anticommensal activity. Quinones showed a potent anticommensal activity, while saturated fatty acids exhibited stronger inhibition of the Lactobacillus genus. Flavonoids, phenylpropanoids, terpenoids, triterpenoids, alkaloids and phenols displayed weaker anticommensal activity, but steroids, saccharides and glycosides had hardly any effect on strain growth. Notably, S-configuration HOCs demonstrated stronger anticommensal activity than R-configuration HOCs. The strict screening conditions ensured high accuracy (95%) through benchmarking validation. Additionally, the effects of HOCs on human fecal microbiota profiling were positively correlated with their anticommensal activity against bacterial strains. Molecular and chemical features such as AATS3i and XLogP3 were correlated with the anticommensal activity of the HOCs in the random forest classifier. Finally, we validated that curcumin, a polyhydric phenol with anticommensal activity, improved insulin resistance in HFD mice by modulating the composition and metabolic function of gut microbiota. Our results systematically mapped the profile of HOCs directly affecting human gut bacterial strains, offering a resource for future research on HOC-microbiota interaction, and broadening our understanding of natural product utilization through gut microbiota modulation.
Topics: Humans; Mice; Animals; Bacteria; Plants, Medicinal; Terpenes; Alkaloids; Flavonoids; Phenols
PubMed: 37244386
DOI: 10.1016/j.phrs.2023.106804 -
Psychological Medicine Dec 2023Psychotropic medication efficacy and tolerability are critical treatment issues faced by individuals with psychiatric disorders and their healthcare providers. For some... (Review)
Review
Psychotropic medication efficacy and tolerability are critical treatment issues faced by individuals with psychiatric disorders and their healthcare providers. For some people, it can take months to years of a trial-and-error process to identify a medication with the ideal efficacy and tolerability profile. Current strategies (e.g. clinical practice guidelines, treatment algorithms) for addressing this issue can be useful at the population level, but often fall short at the individual level. This is, in part, attributed to interindividual variation in genes that are involved in pharmacokinetic (i.e. absorption, distribution, metabolism, elimination) and pharmacodynamic (e.g. receptors, signaling pathways) processes that in large part, determine whether a medication will be efficacious or tolerable. A precision prescribing strategy know as pharmacogenomics (PGx) assesses these genomic variations, and uses it to inform selection and dosing of certain psychotropic medications. In this review, we describe the path that led to the emergence of PGx in psychiatry, the current evidence base and implementation status of PGx in the psychiatric clinic, and finally, the future growth potential of precision psychiatry via the convergence of the PGx-guided strategy with emerging technologies and approaches (i.e. pharmacoepigenomics, pharmacomicrobiomics, pharmacotranscriptomics, pharmacoproteomics, pharmacometabolomics) to personalize treatment of psychiatric disorders.
Topics: Humans; Pharmacogenetics; Psychiatry; Mental Disorders; Psychotropic Drugs; Algorithms
PubMed: 37772416
DOI: 10.1017/S0033291723002817