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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 -
British Journal of Clinical Pharmacology Jan 2004Advancing age is characterized by impairment in the function of the many regulatory processes that provide functional integration between cells and organs. Therefore,... (Review)
Review
Advancing age is characterized by impairment in the function of the many regulatory processes that provide functional integration between cells and organs. Therefore, there may be a failure to maintain homeostasis under conditions of physiological stress. The reduced homeostatic ability affects different regulatory systems in different subjects, thus explaining at least partly the increased interindividual variability occurring as people get older. Important pharmacokinetic and pharmacodynamic changes occur with advancing age. Pharmacokinetic changes include a reduction in renal and hepatic clearance and an increase in volume of distribution of lipid soluble drugs (hence prolongation of elimination half-life) whereas pharmacodynamic changes involve altered (usually increased) sensitivity to several classes of drugs such as anticoagulants, cardiovascular and psychotropic drugs. This review focuses on the main age-related physiological changes affecting different organ systems and their implications for pharmacokinetics and pharmacodynamics of drugs.
Topics: Aging; Biological Availability; Digestive System; Heart; Humans; Kidney; Metabolic Clearance Rate; Neurosecretory Systems; Pharmacokinetics; Pharmacology; Protein Binding
PubMed: 14678335
DOI: 10.1046/j.1365-2125.2003.02007.x -
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 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 -
The American Journal of Geriatric... Sep 2007Older individuals experience physiologic changes in organ function related to aging or to specific disease processes. These changes can affect drug pharmacodynamics in... (Review)
Review
BACKGROUND
Older individuals experience physiologic changes in organ function related to aging or to specific disease processes. These changes can affect drug pharmacodynamics in older adults.
OBJECTIVE
The goal of this article was to review age-related changes in pharmacodynamics and their clinical relevance.
METHODS
PubMed and International Pharmaceutical Abstracts were searched (January 1980-June 2006) for the following combination of terms: pharmacodynamic and elderly, geriatric or aged. References cited in other reviews were also evaluated. The current review focused on age-related pharmacodynamic changes in agents affecting the central nervous system (CNS), cardiovascular, and endocrine functions.
RESULTS
Older adults frequently demonstrate an exaggerated response to CNS-active drugs. This is in part due to an underlying age-related decline in CNS function and in part due to increased pharmacodynamic sensitivity for some benzodiazepines, anesthetics, and opioids. The most important pharmacodynamic differences with age for cardiovascular agents are the decrease in effect for beta-adrenergic agents. This decline in response in vascular, cardiac, and pulmonary tissue may be due to a decrease in Gs protein interactions. Most studies indicate there is no decrease in cx-receptor sensitivity with age. Angiotensin-converting enzyme inhibitors do not show age-related differences in elderly patients. With the dihydropyridine calcium channel blockers, there was a slight increase in effect for older adults, but this was only for treatment-naive patients and was transient. Nondihydropyridines did not show an age- associated change in pharmacodynamic effect; however, in the elderly, there appeared to be a decrease in the PR interval prolongation normally seen with these agents. Studies of diuretics indicated that the changes in diuretic and natriuretic effects seen in the elderly were associated with pharmacokinetic changes and were not pharmacodynamic in nature. There was a lack of consistent evidence regarding whether sulfonylureas show age-related changes in pharmacodynamic effect.
CONCLUSIONS
There is a general trend of greater pharmacodynamic sensitivity in the elderly; however, this is not universal, and these age-related changes must be investigated agent-by-agent until further research yields greater understanding of the molecular mechanisms underlying the aging process.
Topics: Age Factors; Aged; Aged, 80 and over; Aging; Cardiovascular Agents; Central Nervous System Agents; Controlled Clinical Trials as Topic; Endocrine System; Female; Humans; Male; Pharmacology
PubMed: 17996666
DOI: 10.1016/j.amjopharm.2007.10.001 -
Advances in Therapy Feb 2020While there is considerable evidence about sex-related differences between men and women in drug metabolism, efficacy and safety of frequently prescribed drugs such as... (Comparative Study)
Comparative Study Review
While there is considerable evidence about sex-related differences between men and women in drug metabolism, efficacy and safety of frequently prescribed drugs such as analgesics, tranquillizers, statins and beta-blockers, clinicians' awareness of the implications on dosing and adverse event monitoring in routine practice is inadequate. Some drugs are more effective in men than women (e.g. ibuprofen) or vice versa (e.g. opioids, benzodiazepine), typically owing to pharmacodynamic causes. The 5-hydroxytryptamine (5-HT) receptor 3 antagonist alosetron is approved for women only since it largely lacks efficacy in men. For statins, equal efficacy was demonstrated in secondary prevention of cardiovascular events, but primary prevention is still under debate. For some drugs (e.g. paracetamol, metoprolol), women are at significantly higher risk of adverse effects. Therefore, considering sex-specific features in clinical trials and therapeutic guidelines is warranted to ensure efficacy and safety of medicines.
Topics: Adult; Aged; Aged, 80 and over; Biopharmaceutics; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Middle Aged; Pharmacogenomic Variants; Sex Factors
PubMed: 31873866
DOI: 10.1007/s12325-019-01201-3 -
Science Translational Medicine Mar 2012The emerging discipline of systems pharmacology aims to combine analysis and computational modeling of cellular regulatory networks with quantitative pharmacology... (Review)
Review
The emerging discipline of systems pharmacology aims to combine analysis and computational modeling of cellular regulatory networks with quantitative pharmacology approaches to drive the drug discovery processes, predict rare adverse events, and catalyze the practice of personalized precision medicine. Here, we introduce the concept of enhanced pharmacodynamic (ePD) models, which synergistically combine the desirable features of systems biology and current PD models within the framework of ordinary or partial differential equations. ePD models that analyze regulatory networks involved in drug action can account for a drug's multiple targets and for the effects of genomic, epigenomic, and posttranslational changes on the drug efficacy. This new knowledge can drive drug discovery and shape precision medicine.
Topics: Decision Making; Models, Theoretical; Pharmacology; Systems Biology
PubMed: 22440734
DOI: 10.1126/scitranslmed.3003563 -
Clinical Pharmacokinetics 2007Drug development is a complex, lengthy and expensive process. Pharmaceutical companies and regulatory authorities have recognised that the drug development process needs... (Review)
Review
Drug development is a complex, lengthy and expensive process. Pharmaceutical companies and regulatory authorities have recognised that the drug development process needs optimisation for efficiency in view of the return on investments. Pharmacokinetics and pharmacodynamics are the two main principles determining the relationship between dose and response. This article provides an update on integrated approaches towards drug development by linking pharmacokinetics, pharmacodynamics and disease aspects into mathematical models. Gradually, a transition is taking place from a rather empirical approach towards a modelling- and simulation-based approach to drug development. The main learning phases should be phases 0, I and II, whereas phase III studies should merely have a confirmatory purpose. In model-based drug development, mechanism-based mathematical models, which are iteratively refined along the path of development, incorporate the accumulating knowledge of the investigational drug, the disease and their mutual interference in different subsets of the target population. These models facilitate the design of the next study and improve the probability of achieving the projected efficacy and safety endpoints. In this article, several theoretical and practical aspects of an integrated approach towards drug development are discussed, together with some case studies from different therapeutic areas illustrating the application of pharmacokinetic/pharmacodynamic disease models at different stages of drug development.
Topics: Clinical Trials as Topic; Drug Delivery Systems; Drug Design; Drug Industry; Humans; Models, Biological; Pharmaceutical Preparations; Pharmacokinetics; Pharmacology, Clinical
PubMed: 17713971
DOI: 10.2165/00003088-200746090-00001 -
Clinics in Geriatric Medicine May 1990The importance of age-related changes in drug sensitivity is increasingly appreciated. More conclusive evidence is now being presented in combined kinetic and dynamic... (Review)
Review
The importance of age-related changes in drug sensitivity is increasingly appreciated. More conclusive evidence is now being presented in combined kinetic and dynamic studies. The type, intensity, and duration of drug action may be affected, ranging from therapeutic failure to major drug toxicity. Alterations in physiologic and homeostatic systems, including the autonomic system, baroreceptors, thermoregulation, and balance, have been described. These may explain the propensity to postural hypotension, falls, hypothermia, and confusion, particularly following drug-induced decrements in these systems. Studies on the sensitivity to individual drugs produce a varied picture emphasizing the danger of generalizations. An increased sensitivity to many agents affecting the central nervous system, including benzodiazepines, halothane, metoclopramide, and narcotic analgesics, is becoming apparent. For the latter this may also be accompanied by an age-associated qualitative difference in toxicity. Whereas there is conclusive evidence of a reduced responsiveness to propranolol, the data are conflicting for calcium antagonists. The increased hypotensive response to ACE inhibitors is more likely due to kinetic factors. The anticoagulant response to warfarin is enhanced. Evidence is also emerging of a wide divergence in the sensitivity of different systems to the same drug--with aging the inotropic effect of theophylline is increased, but the bronchodilator response is decreased. It is becoming clear also that there is a need to separately study certain subgroups of the elderly population.
Topics: Aged; Aging; Dose-Response Relationship, Drug; Homeostasis; Humans; Pharmacokinetics; Pharmacology; Pharmacology, Clinical
PubMed: 2184923
DOI: No ID Found