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Lancet (London, England) Aug 2019Genomic medicine, which uses DNA variation to individualise and improve human health, is the subject of this Series of papers. The idea that genetic variation can be... (Review)
Review
Genomic medicine, which uses DNA variation to individualise and improve human health, is the subject of this Series of papers. The idea that genetic variation can be used to individualise drug therapy-the topic addressed here-is often viewed as within reach for genomic medicine. We have reviewed general mechanisms underlying variability in drug action, the role of genetic variation in mediating beneficial and adverse effects through variable drug concentrations (pharmacokinetics) and drug actions (pharmacodynamics), available data from clinical trials, and ongoing efforts to implement pharmacogenetics in clinical practice.
Topics: Clinical Trials as Topic; Drug-Related Side Effects and Adverse Reactions; Humans; Pharmacogenetics; Pharmacogenomic Variants
PubMed: 31395440
DOI: 10.1016/S0140-6736(19)31276-0 -
Journal of Nuclear Medicine Technology Sep 2018Pharmacology principles provide a key understanding that underpins the clinical and research roles of nuclear medicine practitioners. This article is the second in a... (Review)
Review
Pharmacology principles provide a key understanding that underpins the clinical and research roles of nuclear medicine practitioners. This article is the second in a series of articles that aims to enhance the understanding of pharmacologic principles relevant to nuclear medicine. This article will build on the introductory concepts, terminology, and principles of pharmacodynamics explored in the first article in the series. Specifically, this article will focus on the basic principles associated with pharmacokinetics. Article 3 will outline pharmacology relevant to pharmaceutical interventions and adjunctive medications used in general nuclear medicine; article 4, pharmacology relevant to pharmaceutical interventions and adjunctive medications used in nuclear cardiology; article 5, pharmacology relevant to contrast media associated with CT and MRI; and article 6, drugs in the emergency cart.
Topics: Animals; Humans; Pharmaceutical Preparations; Pharmacokinetics; Pharmacology
PubMed: 29724803
DOI: 10.2967/jnmt.117.199638 -
Anesthesiology Clinics Sep 2019An aging worldwide population demands that anesthesiologists consider geriatrics a unique subset of patients requiring customization of practice. This article reviews... (Review)
Review
An aging worldwide population demands that anesthesiologists consider geriatrics a unique subset of patients requiring customization of practice. This article reviews the current literature investigating physiologic changes of the elderly that affect pharmacokinetics and pharmacodynamics. Changes in drug absorption, distribution, metabolism, and excretion are discussed as well as the ultimate effects of medications. Implications for practice regarding specific anesthetic and analgesic drugs are addressed. Despite the immense body of research that contributes to understanding of geriatric pharmacology, elderly patients often are excluded from rigorous research trials, and further scientific investigation to inform best practices for this group of patients is needed.
Topics: Aged; Aged, 80 and over; Drug Therapy; Geriatrics; Humans; Pharmaceutical Preparations; Pharmacokinetics; Pharmacology; Population Dynamics
PubMed: 31337479
DOI: 10.1016/j.anclin.2019.04.007 -
Journal of Nuclear Medicine Technology Jun 2018There is an emerging need for greater understanding of pharmacology principles among technical staff. Indeed, the responsibility of dose preparation and administration,... (Review)
Review
There is an emerging need for greater understanding of pharmacology principles among technical staff. Indeed, the responsibility of dose preparation and administration, under any level of supervision, demands a foundational understanding of pharmacology. This is true for radiopharmaceuticals, contrast media, and pharmaceutical interventions or adjunctive medications. Regulation around the same might suggest a need to embed pharmacology theory in undergraduate education programs, and there is a need to disseminate that same foundational understanding to practicing clinicians. Moreover, pharmacology foundations can provide a key understanding of the principles that underpin quantitative techniques (e.g., pharmacokinetics). This article is the first in a series that aims to enhance the understanding of pharmacologic principles relevant to nuclear medicine. This article will deal with the introductory concepts, terminology, and principles that underpin the concepts to be discussed in the remainder of the series. The second article will build on the pharmacodynamic principles examined in this article with a treatment of pharmacokinetics. Article 3 will outline pharmacology relevant to pharmaceutical interventions and adjunctive medications used in general nuclear medicine, article 4 will cover pharmacology relevant to pharmaceutical interventions and adjunctive medications used in nuclear cardiology, and article 5 will discuss the pharmacology related to contrast media associated with CT and MRI. The final article (6) in the series will examine the pharmacology of drugs associated with the crash cart/emergency trolley.
Topics: Animals; Drug Interactions; Humans; Pharmaceutical Preparations; Pharmacology; Receptors, Cell Surface; Terminology as Topic
PubMed: 29599397
DOI: 10.2967/jnmt.117.199588 -
Journal of Clinical Pharmacology Jan 2024Small interfering RNAs (siRNAs) represent a new class of drugs with tremendous potential for battling previously "undruggable" diseases. After nearly 2 decades of... (Review)
Review
Small interfering RNAs (siRNAs) represent a new class of drugs with tremendous potential for battling previously "undruggable" diseases. After nearly 2 decades of efforts in addressing the problems of the poor drug profile of naked unmodified siRNAs, this new modality has finally come to fruition, with 5 agents (patisiran, givosiran, lumasiran, inclisiran, and vutrisiran) being approved since 2018, and with many others in the different phases of clinical development. Unlike small-molecule drugs and protein therapeutics, siRNAs have different sizes, distinct mechanisms of action, differing physicochemical and pharmacological properties, and, accordingly, a unique pharmacokinetic/pharmacodynamic (PK/PD) relationship. To support the continuous development of siRNAs, it is important to have a thorough and deep understanding of the PK/PD and clinical pharmacology related features of siRNAs. As most of the current siRNA products are conjugated by N-acetylgalactosamine (GalNAc), this review focuses on the PK/PD relationships and clinical pharmacology of GalNAc-conjugated siRNAs, including their absorption, distribution, metabolism, excretion (ADME) properties, PK/PD models, drug-drug interactions, clinical pharmacology in special populations, and safety evaluation. In addition, necessary background information related to the development of siRNAs as a therapeutic modality, including the mechanisms of action, the advantages of siRNAs, the problems of naked siRNAs, as well as the strategies used to enhance the clinical utility of siRNAs, have also been covered. The goal of this review is to serve as a "primer" on siRNA PK/PD, and I hope the readers, especially those who have a limited background on siRNA therapeutics, will have a fundamental understanding of siRNA PK/PD and clinical pharmacology after reading this review.
Topics: Humans; RNA, Small Interfering; Drug Interactions; Pharmacology, Clinical; Pharmacokinetics
PubMed: 37589246
DOI: 10.1002/jcph.2337 -
Therapeutic Drug Monitoring Apr 2023Therapeutic drug monitoring (TDM) and model-informed precision dosing (MIPD) have greatly benefitted from computational and mathematical advances over the past 60 years.... (Review)
Review
BACKGROUND
Therapeutic drug monitoring (TDM) and model-informed precision dosing (MIPD) have greatly benefitted from computational and mathematical advances over the past 60 years. Furthermore, the use of artificial intelligence (AI) and machine learning (ML) approaches for supporting clinical research and support is increasing. However, AI and ML applications for precision dosing have been evaluated only recently. Given the capability of ML to handle multidimensional data, such as from electronic health records, opportunities for AI and ML applications to facilitate TDM and MIPD may be advantageous.
METHODS
This review summarizes relevant AI and ML approaches to support TDM and MIPD, with a specific focus on recent applications. The opportunities and challenges associated with this integration are also discussed.
RESULTS
Various AI and ML applications have been evaluated for precision dosing, including those related to concentration or exposure prediction, dose optimization, population pharmacokinetics and pharmacodynamics, quantitative systems pharmacology, and MIPD system development and support. These applications provide an opportunity for ML and pharmacometrics to operate in an integrated manner to provide clinical decision support for precision dosing.
CONCLUSIONS
Although the integration of AI with precision dosing is still in its early stages and is evolving, AI and ML have the potential to work harmoniously and synergistically with pharmacometric approaches to support TDM and MIPD. Because data are increasingly shared between institutions and clinical networks and aggregated into large databases, these applications will continue to grow. The successful implementation of these approaches will depend on cross-field collaborations among clinicians and experts in informatics, ML, pharmacometrics, clinical pharmacology, and TDM.
Topics: Humans; Artificial Intelligence; Machine Learning; Models, Biological; Precision Medicine; Pharmacology, Clinical
PubMed: 36750470
DOI: 10.1097/FTD.0000000000001078 -
Nordic Journal of Psychiatry Sep 2018Ethnopharmacology relates to the study of substances used medicinally by different ethnic or cultural groups or handling of, drugs-based ethnicity or pharmacogenetics. (Review)
Review
BACKGROUND
Ethnopharmacology relates to the study of substances used medicinally by different ethnic or cultural groups or handling of, drugs-based ethnicity or pharmacogenetics.
AIMS
To review the key aspects of ethnopharmacology.
METHOD
This lecture gives an overview of the relationship between geography, culture, pharmacogenomics and prescribing.
RESULTS
Although the majority of antipsychotics, antidepressants and mood-stabilisers are widely and cheaply available in generic forms, prescription rates can vary. Clozapine is one such example with prescribing-rates ranging from less than 10 patients per 100,000 people to nearly 180 patients/100,000 people. Pharmacogenetic studies of antipsychotics and antidepressants concern gene polymorphisms that may affect both, pharmacodynamic or pharmacokinetic properties. Considerable genetic and ethnic variability has been seen for the P450 microsomal enzymes CYP 2D6 and 1A2.
CONCLUSIONS
With accelerated global mobility and increased understanding of medicinal substances at molecular level, understanding of ethnopharmacology will become increasingly important in routine clinical practice.
Topics: Ethnopharmacology; Humans; Pharmacogenetics; Polymorphism, Genetic
PubMed: 30688173
DOI: 10.1080/08039488.2018.1525636 -
Advances in Pharmacology (San Diego,... 2018Mental illness represents a major health issue both at the individual and at the socioeconomical level. This is partly due to the current suboptimal treatment options:... (Review)
Review
Mental illness represents a major health issue both at the individual and at the socioeconomical level. This is partly due to the current suboptimal treatment options: existing psychotropic medications, including antidepressants, antipsychotics, and mood stabilizers, are effective only in a subset of patients or produce partial response and they are often associated with debilitating side effects that discourage adherence. Pharmacogenetics is the study of how genetic information impacts on drug response/side effects with the goal to provide tailored treatments, thereby maximizing efficacy and tolerability. The first pharmacogenetic studies focused on candidate genes, previously known to be relevant to the pharmacokinetics and pharmacodynamics of psychotropic drugs. Results were mainly inconclusive, but some replicated candidates were identified and included as pharmacogenetic biomarkers in drug labeling and in some commercial kits. With the advent of the genomic revolution, it became possible to study the genetic variation on an unprecedented scale, throughout the whole genome with no need of a priori hypothesis. This may lead to the personalized prescription of existing medications and potentially to the development of innovative ones, thanks to new insights into the genetics of mental illness. Promising findings were obtained, but methods for the generation and analysis of genome-wide and sequencing data are still in evolution. Future pharmacogenetic tests may consist of hundreds/thousands of polymorphisms throughout the genome or selected pathways in order to take into account the complex interactions across variants in a number of genes.
Topics: Antidepressive Agents; Genome-Wide Association Study; Humans; Pharmacogenetics; Polymorphism, Genetic; Psychiatry; Psychotropic Drugs
PubMed: 29801579
DOI: 10.1016/bs.apha.2018.03.003 -
Trends in Pharmacological Sciences Sep 2018Pharmacological nomenclature has been continuously developed over the last century and taught to generations of medical, pharmacy, and science students. Many... (Review)
Review
Pharmacological nomenclature has been continuously developed over the last century and taught to generations of medical, pharmacy, and science students. Many pharmacological terms coined decades ago remain in textbooks and the scientific literature. With the advancement in the field and the identification of molecular drug targets, rethinking the pharmacological terms in the context of these new findings has become imperative. Some examples of such terms are antihistamine, beta blocker, calcium antagonist, disease-modifying antirheumatic drug (DMARD), and non-steroidal anti-inflammatory drug (NSAID). This opinion article is an attempt to generate discussion in the community that the better way forward to name/rename pharmacological terms would be according to their mechanism of action. A mechanism-based nomenclature provides important information about therapeutic and adverse effects of drugs. Abbreviations for drug classes have also been suggested. A parsimonious, practical, and mechanism-oriented pharmacological nomenclature will ultimately improve quality and safety of drug therapy.
Topics: Pharmaceutical Preparations; Pharmacology; Terminology as Topic
PubMed: 30025604
DOI: 10.1016/j.tips.2018.06.006 -
Handbook of Clinical Neurology 2018Pharmacogenetics is the study of how genetics influences drug treatment outcomes. Much research has been conducted to identify and characterize gene variants that impact... (Review)
Review
Pharmacogenetics is the study of how genetics influences drug treatment outcomes. Much research has been conducted to identify and characterize gene variants that impact the pharmacokinetic and pharmacodynamic aspects of medications used to treat neurologic and psychiatric disorders. This chapter reviews the current state of pharmacogenetic aspects of these treatments. Medications with supporting pharmacogenetic information in product labeling, clinical guidelines, or important mechanistic implications are discussed. At this time, clinically relevant genetic variation in drug metabolizing enzymes may inform drug dosing for a number of medications metabolized in the liver. Additionally, genetic variation in immunological genes may be tested to assess risk for severe hypersensitivity reactions to some anticonvulsant drugs. Finally, a growing body of research highlights that genetic polymorphisms in drug targets may influence symptom response or tolerability to some treatments.
Topics: Humans; Mental Disorders; Nervous System Diseases; Pharmacogenetics
PubMed: 29325628
DOI: 10.1016/B978-0-444-63233-3.00006-3