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Methods in Molecular Biology (Clifton,... 2022Pain affects approximately 100 million Americans. Pain harms quality of life and costs patients billions of dollars per year. Clinically, nonpharmacologic and...
Pain affects approximately 100 million Americans. Pain harms quality of life and costs patients billions of dollars per year. Clinically, nonpharmacologic and pharmacologic therapies can alleviate acute and chronic pain suffering. Opioids are one type of medication used to manage pain. However, opioids can potentially create dependence and substance abuse, and the effects are not consistent in all patients. Pharmacogenomics is the study of the genome to understand the effects of drugs on individual patients based on their genetic information. Through pharmacogenomics, researchers can investigate genetic polymorphisms related to pain that maximize individual patient drug responses and minimize toxicity. This chapter discusses the pharmacogenomics of opioids to treat pain, including individual genetic differences to opioid treatments, opioid pharmacokinetics and pharmacodynamics, and the genetic polymorphisms associated with individual opioid medications.
Topics: Analgesics, Opioid; Chronic Pain; Humans; Pain Management; Pharmacogenetics; Quality of Life; United States
PubMed: 36068474
DOI: 10.1007/978-1-0716-2573-6_17 -
Journal of Veterinary Pharmacology and... Nov 2021Metabolomics is the large-scale study of low-molecular-weight substances in a biological system in a given physiological state at a given time point. Metabolomics can be... (Review)
Review
Metabolomics is the large-scale study of low-molecular-weight substances in a biological system in a given physiological state at a given time point. Metabolomics can be applied to identify predictors of inter-individual variability in drug response, provide clinicians with data useful for decision-making processes in drug selection, and inform about the pharmacokinetics and pharmacodynamics of a drug. It is, therefore, an exceptional approach for gaining new understanding effects in the field of comparative veterinary pharmacology. However, the incorporation of metabolomics into veterinary pharmacology and toxicology is not yet widespread, and this is probably, at least in part, a result of its highly multidisciplinary nature. This article reviews the potential applications of metabolomics in veterinary pharmacology and therapeutics. It integrates key concepts for designing metabolomics studies and analyzing and interpreting metabolomics data, providing solid foundations for applying metabolomics to the study of drugs in all veterinary species.
Topics: Animals; Metabolomics; Pharmacology
PubMed: 33719079
DOI: 10.1111/jvp.12961 -
Anesthesia and Analgesia May 2019Medications used in anesthesiology contain both pharmacologically active compounds and additional additives that are usually regarded as being pharmacologically... (Review)
Review
Medications used in anesthesiology contain both pharmacologically active compounds and additional additives that are usually regarded as being pharmacologically inactive. These additives, called excipients, serve diverse functions. Despite being labeled inert, excipients are not necessarily benign substances. Anesthesiologists should have a clear understanding of their chemical properties and the potential for adverse reactions. This report catalogs the excipients found in drugs commonly used in anesthesiology, provides a brief description of their function, and documents examples from the literature regarding their adverse effects.
Topics: Anesthesia; Anesthetics; Animals; Benzyl Alcohol; Chemistry, Pharmaceutical; Cresols; Drug Hypersensitivity; Edetic Acid; Excipients; Humans; Indocyanine Green; Injections, Spinal; Iodides; Mannitol; Models, Animal; Parabens; Perioperative Period; Propylene Glycol; Sulfites
PubMed: 29505449
DOI: 10.1213/ANE.0000000000003302 -
Currents in Pharmacy Teaching & Learning May 2022There is renewed research attention on the use of psychedelic drugs to treat psychiatric illnesses. If psychedelic drugs are approved for medical use in the United...
BACKGROUND AND PURPOSE
There is renewed research attention on the use of psychedelic drugs to treat psychiatric illnesses. If psychedelic drugs are approved for medical use in the United States, patients, professionals, and policy makers will look to pharmacists as medication experts for advice on the safe, effective, and ethical use of these substances. To help prepare a future generation of pharmacists in this therapeutic area, a psychedelic psychopharmacology elective was developed and piloted.
EDUCATIONAL ACTIVITY AND SETTING
Broadly, the objectives of the course were to train students to (1) analyze scientific literature, (2) engage in ethical discussions, and (3) make evidence-based clinical recommendations about the use of psychedelics. The pilot elective course was delivered synchronously online to 12 second- and third-year pharmacy students during spring 2021. Activities included journal clubs, textbook reading assignments, reflective structured dialogues, a monograph, and a term paper.
FINDINGS
The course was feasible for a single instructor and well-received by students. A mix of instructor-directed and self-directed learning approaches were utilized.
SUMMARY
The pilot psychedelic psychopharmacology elective was a success, providing a framework for future courses.
Topics: Hallucinogens; Humans; Learning; Mental Disorders; Psychopharmacology; Students, Pharmacy; United States
PubMed: 35715110
DOI: 10.1016/j.cptl.2022.04.019 -
Journal of Pharmaceutical and... Jan 2018Nuclear magnetic resonance (NMR) spectroscopy has a unique capability to probe the primary and higher order molecular structure and the structural dynamics of... (Review)
Review
Nuclear magnetic resonance (NMR) spectroscopy has a unique capability to probe the primary and higher order molecular structure and the structural dynamics of biomolecules at an atomic resolution, and this capability has been greatly fortified over the last five decades by an astonishing NMR instrumental and methodological development. Because of these factors, NMR has become a primary tool for the structure investigation of biomolecules, spawning a whole scientific subfield dedicated to the subject. This role of NMR is by now well established and broadly appreciated, especially in the context of academic research dealing with proteins that are purified and isotope-labeled in order to facilitate the necessary sophisticated multidimensional NMR measurements. However, the more recent industrial development, manufacturing, and quality control of biopharmaceuticals provide a different framework for NMR. For example, protein drug substances are not isotope-labeled and are present in a medium of excipients, which make structural NMR measurements much more difficult. On the other hand, biotechnology involves many other analytical requirements that can be efficiently addressed by NMR. In this respect the scope and limitations of NMR are less well understood. Having the non-expert reader in mind, herein we wish to highlight the ways in which modern NMR can effectively support biotechnological developments. Our focus will be on biosimilar proteins, pointing out certain cases where its use is probably essential. Based partly on literature data, and partly on our own hands-on experience, this paper is intended to be a guide for choosing the proper NMR approach for analytical questions concerning the structural comparability of therapeutic proteins, monitoring technology-related impurities, protein quantification, analysis of spent media, identification of extractable and leachable components, etc. Also, we focus on critical considerations, particularly those coming from drug authority guidelines, which limit the use of the well-established NMR tools in everyday practice.
Topics: Animals; Biopharmaceutics; Biosimilar Pharmaceuticals; Drug Industry; Humans; Nuclear Magnetic Resonance, Biomolecular
PubMed: 28760370
DOI: 10.1016/j.jpba.2017.07.004 -
Pharmaceutical Research May 2017Efficient drug delivery is dependent on the drug substance dissolving in the body fluids, being released from dosage forms and transported to the site of action. A... (Review)
Review
Efficient drug delivery is dependent on the drug substance dissolving in the body fluids, being released from dosage forms and transported to the site of action. A fundamental understanding of the interplay between the physicochemical properties of the active compound and pharmaceutical excipients defining formulation behavior after exposure to the aqueous environments and pharmaceutical performance is critical in pharmaceutical development, manufacturing and quality control of drugs. UV imaging has been explored as a tool for qualitative and quantitative characterization of drug dissolution and release with the characteristic feature of providing real-time visualization of the solution phase drug transport in the vicinity of the formulation. Events occurring during drug dissolution and release, such as polymer swelling, drug precipitation/recrystallization, or solvent-mediated phase transitions related to the structural properties of the drug substance or formulation can be monitored. UV imaging is a non-intrusive and simple-to-operate analytical technique which holds potential for providing a mechanistic foundation for formulation development. This review aims to cover applications of UV imaging in the early and late phase pharmaceutical development with a special focus on the relation between structural properties and performance. Potential areas of future advancement and application are also discussed.
Topics: Animals; Chemistry, Pharmaceutical; Drug Liberation; Excipients; Humans; Pharmaceutical Preparations; Polymers; Solubility; Spectrophotometry, Ultraviolet
PubMed: 27766463
DOI: 10.1007/s11095-016-2047-5 -
Chemical Reviews Dec 2019Reductive amination plays a paramount role in pharmaceutical and medicinal chemistry owing to its synthetic merits and the ubiquitous presence of amines among... (Review)
Review
Reductive amination plays a paramount role in pharmaceutical and medicinal chemistry owing to its synthetic merits and the ubiquitous presence of amines among biologically active compounds. It is one of the key approaches to C-N bond construction due to its operational easiness and a wide toolbox of protocols. Recent studies show that at least a quarter of C-N bond-forming reactions in the pharmaceutical industry are performed via reductive amination. This Review concisely compiles information on 71 medical substances that are synthesized by reductive amination. Compounds are grouped according to the principle of action, which includes drugs affecting the central nervous system, drugs affecting the cardiovascular system, anticancer drugs, antibiotics, antiviral and antifungal medicines, drugs affecting the urinary system, drugs affecting the respiratory system, antidiabetic medications, drugs affecting the gastrointestinal tract, and drugs regulating metabolic processes. A general synthetic scheme is provided for each compound, and the description is focused on reductive amination steps. The green chemistry metric of reaction mass efficiency was calculated for all reactions.
Topics: Amination; Amines; Chemistry, Pharmaceutical; Lewis Acids; Oxidation-Reduction; Pharmaceutical Preparations
PubMed: 31633341
DOI: 10.1021/acs.chemrev.9b00383 -
Experimental and Clinical... Jun 2023Co-use of alcohol and cannabis is highly prevalent and often problematic. However, mechanisms underlying their co-use remain unclear. This randomized and crossover study... (Randomized Controlled Trial)
Randomized Controlled Trial
Co-use of alcohol and cannabis is highly prevalent and often problematic. However, mechanisms underlying their co-use remain unclear. This randomized and crossover study tests cross-substance subjective craving for alcohol and cannabis. A community sample of nontreatment-seeking alcohol and cannabis co-users ( = 30 completers, 40% female) reporting high-risk levels of alcohol and cannabis use completed two experimental sessions in their homes and were monitored remotely using internet meeting technology (i.e., Zoom). The two counterbalanced and randomized sessions were as follows: (a) consumption of a standard alcoholic beverage followed by cannabis cue exposure and (b) consumption (i.e., smoking) of a miniature cannabis cigarette (containing 18%-22% tetrahydrocannabinol), followed by alcohol cue exposure. Participants rated their subjective craving for both alcohol and cannabis at baseline, following alcohol/cannabis administration, and following the presentation of cross-substance-related cues. Repeated measures analysis of variances revealed a statistically significant difference in cannabis craving across time, such that craving for cannabis was significantly higher following cannabis cue reactivity, compared to baseline and following alcohol administration ('s < .001). Similarly, there was a statistically significant difference in alcohol craving across time, such that craving for alcohol was significantly higher following alcohol cue reactivity, compared to baseline and following cannabis administration ('s < .001). Overall, results suggest that individuals who co-use alcohol and cannabis are most sensitive to the cue-induced, rather than the pharmacologically induced effects, of substance administration on cross-substance craving. This pattern of findings does not support a complementarity model. Conversely, these results may be interpreted as indicative of a substitution model for alcohol and cannabis co-use. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
Topics: Humans; Female; Male; Craving; Cannabis; Cues; Cross-Over Studies; Psychopharmacology; Hallucinogens; Cannabinoid Receptor Agonists; Ethanol
PubMed: 36534416
DOI: 10.1037/pha0000621 -
European Journal of Pharmaceutical... May 2016Impurities will be present in all drug substances and drug products, i.e. nothing is 100% pure if one looks in enough depth. The current regulatory guidance on... (Review)
Review
Impurities will be present in all drug substances and drug products, i.e. nothing is 100% pure if one looks in enough depth. The current regulatory guidance on impurities accepts this, and for drug products with a dose of less than 2g/day identification of impurities is set at 0.1% levels and above (ICH Q3B(R2), 2006). For some impurities, this is a simple undertaking as generally available analytical techniques can address the prevailing analytical challenges; whereas, for others this may be much more challenging requiring more sophisticated analytical approaches. The present review provides an insight into current development of analytical techniques to investigate and quantify impurities in drug substances and drug products providing discussion of progress particular within the field of chromatography to ensure separation of and quantification of those related impurities. Further, a section is devoted to the identification of classical impurities, but in addition, inorganic (metal residues) and solid state impurities are also discussed. Risk control strategies for pharmaceutical impurities aligned with several of the ICH guidelines, are also discussed.
Topics: Chemistry Techniques, Analytical; Chemistry, Pharmaceutical; Drug Contamination; Technology, Pharmaceutical
PubMed: 26690047
DOI: 10.1016/j.ejps.2015.12.007 -
European Journal of Drug Metabolism and... Jun 2017Up-regulation of arginase activity in several chronic disease conditions, including cancer and hypertension, may suggest new targets for treatment. Recently, the number... (Review)
Review
Up-regulation of arginase activity in several chronic disease conditions, including cancer and hypertension, may suggest new targets for treatment. Recently, the number of new arginase inhibitors with promising therapeutic effects for asthma, cancer, hypertension, diabetes mellitus, and erectile dysfunction has shown a remarkable increase. Arginase inhibitors may be chemical substances, such as boron-based amino acid derivatives, α-difluoromethylornithine (DMFO), and Nω-hydroxy-nor-L-arginine (nor-NOHA) or, of plant origin such as sauchinone, salvianolic acid B (SAB), piceatannol-3-O-β-D-glucopyranoside (PG) and obacunone. Despite their promising therapeutic potential, little is known about pharmacokinetics and pharmacodynamics of some of these agents. Several studies were conducted in different animal species and in vitro systems and reported significant differences in pharmacokinetics and pharmacodynamics of arginase inhibitors. Therefore, extra caution should be considered before extrapolating these studies to human. Physicochemical and pharmacokinetic profiles of some effective arginase inhibitors make it challenging to formulate stable and effective formulation. In this article, existing literature on the pharmacokinetics and pharmacodynamics of arginase inhibitors were reviewed and compared together with emphasis on possible drug interactions and solutions to overcome pharmacokinetics challenges and shortage of arginase inhibitors in clinical practice.
Topics: Animals; Arginase; Chemistry, Pharmaceutical; Drug Interactions; Enzyme Inhibitors; Humans
PubMed: 27734327
DOI: 10.1007/s13318-016-0381-y