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Advances in Pharmacology (San Diego,... 2018Pain is an unpleasant feeling usually resulting from tissue damage that can persist along weeks, months, or even years after the injury, turning into pathological... (Review)
Review
Pain is an unpleasant feeling usually resulting from tissue damage that can persist along weeks, months, or even years after the injury, turning into pathological chronic pain, the leading cause of disability. Currently, pharmacology interventions are usually the first-line therapy but there is a highly variable analgesic drug response. Pharmacogenetics (PGx) offers a means to identify genetic biomarkers that can predict individual analgesic response opening doors to precision medicine. PGx analyze the way in which the presence of variations in the DNA sequence (single-nucleotide polymorphisms, SNPs) could be responsible for portions of the population reaching different levels of pain relief (phenotype) due to gene interference in the drug mechanism of action (pharmacodynamics) and/or its concentration at the place of action (pharmacokinetics). SNPs in the cytochrome P450 enzymes genes (CYP2D6) influence metabolism of codeine, tramadol, hydrocodone, oxycodone, and tricyclic antidepressants. Blood concentrations of some NSAIDs depend on CYP2C9 and/or CYP2C8 activity. Additional candidate genes encode for opioid receptors, transporters, and other molecules important for pharmacotherapy in pain management. However, PGx studies are often contradictory, slowing the uptake of this information. This is likely due, in large part, to a lack of robust evidence demonstrating clinical utility and to its polygenic response modulated by other exogenous or epigenetics factors. Novel therapies, including targeting of epigenetic changes and gene therapy-based approaches, broaden future options to improve understanding of pain and the treatment of people who suffer it.
Topics: Analgesics; Epigenesis, Genetic; Humans; Nociception; Pain; Pain Management; Pharmacogenetics
PubMed: 29801577
DOI: 10.1016/bs.apha.2018.04.004 -
Journal of Pharmaceutical Sciences Feb 2016
Topics: Humans; Pharmacology; Pharmacy
PubMed: 26869405
DOI: 10.1016/S0022-3549(15)00179-3 -
Journal of Pharmaceutical Sciences Sep 2017
Topics: Chemistry, Pharmaceutical; History, 21st Century; Japan; Pharmacology
PubMed: 28549904
DOI: 10.1016/j.xphs.2017.05.013 -
Molecular Pharmaceutics Mar 2018
Topics: Chemistry, Pharmaceutical; Drug Discovery; Humans; Metabolic Engineering; Pharmacology; Proteomics
PubMed: 29502427
DOI: 10.1021/acs.molpharmaceut.8b00067 -
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 -
Inflammopharmacology Apr 2021
Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; History, 20th Century; History, 21st Century; Inflammation; Periodicals as Topic; Pharmacology
PubMed: 33591472
DOI: 10.1007/s10787-021-00789-9 -
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 -
Biochemistry Oct 2017Genetics and pharmacology are often seen as two distinct approaches to interrogating, elucidating, and manipulating biological systems. The former is renowned for its... (Review)
Review
Genetics and pharmacology are often seen as two distinct approaches to interrogating, elucidating, and manipulating biological systems. The former is renowned for its precision whereas the latter for its fast kinetics, reversibility, and practicality. Here, we show that both can be joined as "tethered pharmacology", wherein a genetically programmed bioconjugation site provides selectivity and a tethered pharmacophore provides function. The speed of onset, and especially cessation, of pharmacological activity can be greatly enhanced by incorporating photoswitches and using light as the trigger ("tethered photopharmacology"). Genetically encoded, tethered photopharmacology is a variant of optogenetics and could even play a role in medicine wherever gene therapy is viable. However, gene therapy may not be necessary if sufficiently selective tethering strategies that operate on wild-type receptors can be developed.
Topics: Humans; Optogenetics; Pharmacology; Time Factors
PubMed: 28876905
DOI: 10.1021/acs.biochem.7b00687 -
Current Medicinal Chemistry 2017Sex is one of several factors influencing pharmacological responses, but research on its effects on pharmacokinetics and pharmacodynamics, although emerging remarkably,... (Review)
Review
Sex is one of several factors influencing pharmacological responses, but research on its effects on pharmacokinetics and pharmacodynamics, although emerging remarkably, remains poor and contains many methodological issues. In this review, the current state of knowledge about sex differences in pharmacokinetics and some hints to pharmacogenomics were evaluated. Moreover, considering that many pharmacological responses are monitored through biomarkers, the influence of sex on some biomarkers has been reported. Finally, we report sex differences in pharmacodynamics, particularly analysing opioids and their use during pregnancy, labor and breastfeeding. In conclusion, a more precise sex- and genderbased approach appears necessary to achieve more evidence-based therapy in men and women.
Topics: Biomarkers; Humans; Pharmacogenetics; Sex Characteristics
PubMed: 27697075
DOI: 10.2174/0929867323666161003124616 -
Molecules (Basel, Switzerland) Jun 2020Thanks to the progress made in chemical technology (particularly in the methodologies of stereoselective syntheses and analyses) along with regulatory measures, the... (Review)
Review
Thanks to the progress made in chemical technology (particularly in the methodologies of stereoselective syntheses and analyses) along with regulatory measures, the number of new chiral drugs registered in the form of pure enantiomers has increased over the past decade. In addition, the pharmacological and pharmacokinetic properties of the individual enantiomers of already-introduced racemic drugs are being re-examined. The use of the pure enantiomer of a drug that has been used to date in the form of a racemate is called a "chiral switch". A re-examination of the properties of the pure enantiomers of racemates has taken place for local anesthetics, which represent a group of drugs which have long been used. Differences in () and ()-enantiomers were found in terms of pharmacodynamic and pharmacokinetic activity as well as in toxicity. Levobupivacaine and robivacaine were introduced into practice as pure ()-(-)-enantiomers, exhibiting more favorable properties than their ()-(+)-stereoisomers or racemates. This overview focuses on the influence of chirality on the pharmacological and toxicological activity of local anesthetics as well as on individual HPLC and capillary electrophoresis (CE) methods used for enantioseparation and the pharmacokinetic study of individual local anesthetics with a chiral center.
Topics: Anesthetics, Local; Chemistry, Pharmaceutical; Levobupivacaine; Stereoisomerism
PubMed: 32545678
DOI: 10.3390/molecules25122738