Array ( [0] => {{Short description|Branch of biology concerning drugs}} [1] => {{About|the science|the book type ("a pharmacology")|Materia medica|the journal|Karger Publishers#Journals{{!}}Pharmacology (journal)}} [2] => {{Redirect|Pharmacologist|the American Society for Pharmacology and Experimental Therapeutics newsletter|American Society for Pharmacology and Experimental Therapeutics#Publications{{!}}The Pharmacologist}} [3] => {{Use dmy dates|date=March 2014}} [4] => {{Infobox [5] => | abovestyle = background:pink; [6] => | above = Pharmacology [7] => | image = [[File:Constant tempertature bath for isolated organs Wellcome M0013241.jpg|250px]] [8] => | caption = Diagrammatic representation of organ bath used for studying the effect of isolated tissues [9] => | label1 = MeSH Unique ID [10] => | data1 = [https://www.ncbi.nlm.nih.gov/mesh/68010600 D010600] [11] => }} [12] => [13] => '''Pharmacology''' is the [[science]] of [[drug|drugs]] and [[medication]]s,{{cite journal | vauthors = Vallance P, Smart TG | title = The future of pharmacology | journal = British Journal of Pharmacology | volume = 147 Suppl 1 | issue = S1 | pages = S304–7 | date = January 2006 | pmid = 16402118 | pmc = 1760753 | doi = 10.1038/sj.bjp.0706454 }} including a substance's origin, composition, pharmacokinetics, pharmacodynamics, therapeutic use, and toxicology. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function.{{Cite web |title=Definition of PHARMACOLOGY |url=https://www.merriam-webster.com/dictionary/pharmacology |access-date=2023-02-28 |website=Merriam-Webster |language=en}} If substances have medicinal properties, they are considered [[Pharmaceutical drug|pharmaceuticals]]. [14] => [15] => The field encompasses drug composition and properties, functions, sources, synthesis and drug design, molecular and cellular [[mechanism of action|mechanisms]], organ/systems mechanisms, signal transduction/cellular communication, [[molecular diagnostics]], [[drug interaction|interaction]]s, [[chemical biology]], therapy, and medical applications and antipathogenic capabilities. The two main areas of pharmacology are [[pharmacodynamics]] and [[pharmacokinetics]]. Pharmacodynamics studies the effects of a drug on biological systems, and pharmacokinetics studies the effects of biological systems on a drug. In broad terms, pharmacodynamics discusses the chemicals with biological [[Receptor (biochemistry)|receptors]], and pharmacokinetics discusses the [[Absorption (pharmacology)|absorption]], distribution, [[metabolism]], and [[excretion]] (ADME) of chemicals from the biological systems. [16] => [17] => Pharmacology is not synonymous with [[pharmacy]] and the two terms are frequently confused. Pharmacology, a [[Biomedical sciences|biomedical science]], deals with the research, discovery, and characterization of chemicals which show biological effects and the elucidation of cellular and organismal function in relation to these chemicals. In contrast, pharmacy, a health services profession, is concerned with the application of the principles learned from pharmacology in its clinical settings; whether it be in a dispensing or clinical care role. In either field, the primary contrast between the two is their distinctions between direct-patient care, pharmacy practice, and the science-oriented research field, driven by pharmacology. [18] => [19] => ==Etymology== [20] => The word ''pharmacology'' is derived from [[Ancient Greek|Greek]] word {{lang|grc|[[wikt:φάρμακον|φάρμακον]]}}, ''pharmakon'', meaning "drug" or "[[poison]]", together with another Greek word {{lang|grc|[[wikt:-λογία|-λογία]]}}, ''logia'' with the meaning of "study of" or "knowledge of"{{cite web | url = http://www.etymonline.com/index.php?term=pharmacy | title = Pharmacy (n.) | work = Online Etymology Dictionary | access-date = 18 May 2017 | archive-date = 2 October 2017 | archive-url = https://web.archive.org/web/20171002165813/http://www.etymonline.com/index.php?term=pharmacy | url-status = live }}{{cite web | url = http://www.etymonline.com/index.php?term=pharmacology | title = Pharmacology | work = Online Etymology Dictionary | access-date = 18 May 2017 | archive-date = 2 October 2017 | archive-url = https://web.archive.org/web/20171002165736/http://www.etymonline.com/index.php?term=pharmacology | url-status = live }} (cf. the [[Pharmacy#Etymology|etymology of ''pharmacy'']]). Pharmakon is related to [[pharmakos]], the ritualistic sacrifice or exile of a human [[scapegoat]] or victim in [[Ancient Greek religion]]. [21] => [22] => The modern term ''pharmacon'' is used more broadly than the term ''[[drug]]'' because it includes [[endogenous]] substances, and biologically active substances which are not used as drugs. Typically it includes pharmacological [[agonists]] and [[Receptor antagonist|antagonists]], but also [[enzyme]] inhibitors (such as [[monoamine oxidase]] inhibitors).{{cite journal | pmid =8877846 |title = Interlaboratory study of log P determination by shake-flask and potentiometric methods | volume=14 | issue=11 | date=Aug 1996 | pages=1405–13|last1 = Takács-Novák |first1 = K. |last2 = Avdeef |first2 = A. |journal = Journal of Pharmaceutical and Biomedical Analysis |doi = 10.1016/0731-7085(96)01773-6 }} [23] => [24] => == History == [25] => {{main|List of drugs by year of discovery|History of pharmacy}} [26] => {{multiple image [27] => [28] => | align = [29] => | direction = vertical [30] => | background color = [31] => | width = [32] => | caption_align = [33] => [34] => [35] => | header_background = [36] => | header_align = [37] => | header = [38] => [39] => [40] => | image1 = Raw_opium.jpg [41] => | width1 = [42] => | alt1 = [43] => | link1 = [44] => | thumbtime1 = [45] => | caption1 = Naturally derived [[opium]] from [[Papaver somniferum|opium poppies]] has been used as a drug since before 1100 BCE.{{cite journal|title=The early history of the poppy and opium| vauthors = Kritikos PG, Papadaki SP |journal=Journal of the Archaeological Society of Athens|date=January 1, 1967}} [46] => [47] => | image2 = Morphin_-_Morphine.svg [48] => | width2 = [49] => | alt2 = [50] => | link2 = [51] => | thumbtime2 = [52] => | caption2 = Opium's major active constituent, [[morphine]], was first isolated in 1804 and is now known to act as an [[opioid agonist]].{{cite book |url = https://books.google.com/books?id=MtOiLVWBn8cC&pg=PA20 |page = 20 |title = Molecular, clinical and environmental toxicology |veditors = Luch A |publisher = Springer |year = 2009 |isbn = 978-3-7643-8335-0 |access-date = 21 July 2020 |archive-date = 6 August 2020 |archive-url = https://web.archive.org/web/20200806043108/https://books.google.com/books?id=MtOiLVWBn8cC&pg=PA20 |url-status = live }}{{cite journal | first = Friedrich | last = Sertürner | name-list-style = vanc | date = 1805 | url = https://books.google.com/books?id=8A09AAAAcAAJ&pg=PA229 | title = Untitled letter to the editor | archive-url = https://web.archive.org/web/20160817101928/https://books.google.com/books?id=8A09AAAAcAAJ&pg=PA229 | archive-date=17 August 2016 | journal = Journal der Pharmacie für Aerzte, Apotheker und Chemisten (Journal of Pharmacy for Physicians, Apothecaries, and Chemists) | volume = 13 | pages = 229–243 }}; see especially "III. Säure im Opium" (acid in opium), pp. 234–235, and "I. Nachtrag zur Charakteristik der Säure im Opium" (Addendum on the characteristics of the acid in opium), pp. 236–241. [53] => [54] => [55] => [56] => | footer_background = [57] => | footer_align = [58] => | footer = [59] => }} [60] => The origins of [[clinical pharmacology]] date back to the [[Middle Ages]], with [[pharmacognosy]] and [[Avicenna]]'s ''[[The Canon of Medicine]]'', [[Peter of Spain (author)|Peter of Spain]]'s ''Commentary on Isaac'', and [[John of St Amand]]'s ''Commentary on the Antedotary of Nicholas''.{{cite journal | vauthors = Brater DC, Daly WJ | title = Clinical pharmacology in the Middle Ages: principles that presage the 21st century | journal = Clinical Pharmacology and Therapeutics | volume = 67 | issue = 5 | pages = 447–50 | date = May 2000 | pmid = 10824622 | doi = 10.1067/mcp.2000.106465 | s2cid = 45980791 }} Early pharmacology focused on [[herbalism]] and natural substances, mainly plant extracts. Medicines were compiled in books called [[pharmacopoeia]]s. [[Crude drug]]s have been used since prehistory as a preparation of substances from natural sources. However, the [[active ingredient]] of crude drugs are not purified and the substance is adulterated with other substances. [61] => [62] => [[Traditional medicine]] varies between cultures and may be specific to a particular culture, such as in traditional [[Traditional Chinese Medicine|Chinese]], [[Traditional Mongolian medicine|Mongolian]], [[Traditional Tibetan medicine|Tibetan]] and [[Traditional Korean medicine|Korean medicine]]. However much of this has since been regarded as [[pseudoscience]]. Pharmacological substances known as [[entheogen]]s may have spiritual and religious use and historical context. [63] => [64] => In the 17th century, the English physician [[Nicholas Culpeper]] translated and used pharmacological texts. Culpeper detailed plants and the conditions they could treat. In the 18th century, much of clinical pharmacology was established by the work of [[William Withering]].{{cite book | first = Mannfred A. | last = Hollinger | name-list-style = vanc | date = 2003 | url = https://books.google.com/books?id=bx-WfLwrVH8C&pg=PA4 | title = Introduction to pharmacology | publisher = [[CRC Press]] | page = 4 | isbn = 0-415-28033-8 | access-date = 27 June 2015 | archive-date = 17 April 2021 | archive-url = https://web.archive.org/web/20210417050725/https://books.google.com/books?id=bx-WfLwrVH8C&pg=PA4 | url-status = live }} Pharmacology as a scientific discipline did not further advance until the mid-19th century amid the great biomedical resurgence of that period.{{cite journal | vauthors = Rang HP | title = The receptor concept: pharmacology's big idea | journal = British Journal of Pharmacology | volume = 147 Suppl 1 | issue = S1 | pages = S9-16 | date = January 2006 | pmid = 16402126 | pmc = 1760743 | doi = 10.1038/sj.bjp.0706457 }} Before the second half of the nineteenth century, the remarkable potency and specificity of the actions of drugs such as [[morphine]], [[quinine]] and [[digitalis]] were explained vaguely and with reference to extraordinary chemical powers and affinities to certain organs or tissues.{{cite journal | vauthors = Maehle AH, Prüll CR, Halliwell RF | s2cid = 205479063 | title = The emergence of the drug receptor theory | journal = Nature Reviews. Drug Discovery | volume = 1 | issue = 8 | pages = 637–41 | date = August 2002 | pmid = 12402503 | doi = 10.1038/nrd875 }} The first pharmacology department was set up by [[Rudolf Buchheim]] in 1847, at University of Tartu, in recognition of the need to understand how therapeutic drugs and poisons produced their effects. Subsequently, the first [[Department of Pharmacology at University College London, 1905 – 2007|pharmacology department]] in [[England]] was set up in 1905 at [[University College London]]. [65] => [66] => Pharmacology developed in the 19th century as a biomedical science that applied the principles of scientific experimentation to therapeutic contexts.{{cite book|title=Pharmacology| vauthors = Rang HP, Dale MM, Ritter JM, Flower RJ |publisher=[[Elsevier]]|year=2007|isbn=978-0-443-06911-6|location=[[China]]}} The advancement of research techniques propelled pharmacological research and understanding. The development of the [[organ bath]] preparation, where tissue samples are connected to recording devices, such as a [[myograph]], and physiological responses are recorded after drug application, allowed analysis of drugs' effects on tissues. The development of the [[ligand binding assay]] in 1945 allowed quantification of the [[affinity constant|binding affinity]] of drugs at chemical targets.{{cite book|title=Ligand-binding assays development, validation, and implementation in the drug development arena|year=2009|publisher=John Wiley & Sons|location=Hoboken, N.J.|isbn=978-0470541494|editor1=Masood N. Khan |editor2=John W. Findlay }} Modern pharmacologists use techniques from [[genetics]], [[molecular biology]], [[biochemistry]], and other advanced tools to transform information about molecular mechanisms and targets into therapies directed against disease, defects or pathogens, and create methods for preventive care, diagnostics, and ultimately [[personalized medicine]]. [67] => [68] => ==Divisions== [69] => The discipline of pharmacology can be divided into many sub disciplines each with a specific focus. [70] => [71] => === Systems of the body === [72] => [[Image:Pharmacologyprism.jpg|thumb|A variety of topics involved with pharmacology, including [[neuropharmacology]], renal pharmacology, human [[metabolism]], intracellular metabolism, and intracellular regulation]] [73] => Pharmacology can also focus on specific [[Human body#Systems|systems]] comprising the body. Divisions related to bodily systems study the effects of drugs in different systems of the body. These include [[neuropharmacology]], in the [[central nervous system|central]] and [[peripheral nervous system]]s; [[immune system|immunopharmacology]] in the immune system. Other divisions include [[Circulatory system|cardiovascular]], [[renal system|renal]] and [[endocrine system|endocrine]] pharmacology. [[Psychopharmacology]] is the study of the use of drugs that affect the [[psyche (psychology)|psyche]], mind and behavior (e.g. antidepressants) in treating mental disorders (e.g. depression).{{Cite web|title=Psychopharmacology {{!}} Psychology Today International|url=https://www.psychologytoday.com/intl/basics/psychopharmacology|access-date=2020-07-23|website=psychologytoday.com|archive-date=24 February 2022|archive-url=https://web.archive.org/web/20220224115628/https://www.psychologytoday.com/intl/basics/psychopharmacology|url-status=live}}{{Cite web|title=What is Psychopharmacology|url=https://ascpp.org/resources/information-for-patients/what-is-psychopharmacology/|access-date=2020-07-23|website=ascpp.org|date=29 November 2012 |archive-date=23 July 2020|archive-url=https://web.archive.org/web/20200723100542/https://ascpp.org/resources/information-for-patients/what-is-psychopharmacology/|url-status=live}} It incorporates approaches and techniques from neuropharmacology, animal behavior and behavioral neuroscience, and is interested in the behavioral and neurobiological mechanisms of action of psychoactive drugs.{{Citation needed|date=July 2019}} The related field of [[neuropsychopharmacology]] focuses on the effects of drugs at the overlap between the nervous system and the psyche. [77] => [78] => [[Pharmacometabolomics]], also known as pharmacometabonomics, is a field which stems from [[metabolomics]], the quantification and analysis of [[metabolites]] produced by the body. It refers to the direct measurement of [[metabolites]] in an individual's bodily fluids, in order to predict or evaluate the [[metabolism]] of [[pharmaceutical]] compounds, and to better understand the pharmacokinetic profile of a drug. Pharmacometabolomics can be applied to measure [[metabolite]] levels following the administration of a drug, in order to monitor the effects of the drug on metabolic pathways. [[Pharmacomicrobiomics]] studies the effect of microbiome variations on drug disposition, action, and toxicity.{{cite journal | vauthors = Rizkallah MR, Saad R, Aziz RK | title = The Human Microbiome Project, personalized medicine and the birth of pharmacomicrobiomics. | journal = Current Pharmacogenomics and Personalized Medicine | date = September 2010 | volume = 8 | issue = 3 | pages = 182–93 | doi = 10.2174/187569210792246326 }} Pharmacomicrobiomics is concerned with the interaction between drugs and the gut [[Microbiome of humans|microbiome]]. [[Pharmacogenomics]] is the application of genomic technologies to [[drug discovery]] and further characterization of drugs related to an organism's entire genome.{{Citation needed|date=July 2019}} For pharmacology regarding individual genes, [[pharmacogenetics]] studies how genetic variation gives rise to differing responses to drugs.{{Citation needed|date=July 2019}} [[Pharmacoepigenetics]] studies the underlying [[Epigenetics|epigenetic]] marking patterns that lead to variation in an individual's response to medical treatment.{{cite journal | vauthors = Gomez A, Ingelman-Sundberg M | title = Pharmacoepigenetics: its role in interindividual differences in drug response | journal = Clinical Pharmacology and Therapeutics | volume = 85 | issue = 4 | pages = 426–30 | date = April 2009 | pmid = 19242404 | doi = 10.1038/clpt.2009.2 | s2cid = 39131071 }} [79] => [80] => ===Clinical practice and drug discovery=== [81] => {{main|Drug development|Drug Discovery Hit to Lead}} [82] => [[File:Toxicology Research at FDA (NCTR 1193) (6009043040).jpg|thumb|right|255px|A [[Toxicology|toxicologist]] working in a lab]] [83] => Pharmacology can be applied within clinical sciences. [[Clinical pharmacology]] is the application of pharmacological methods and principles in the study of drugs in humans.{{cite web|url=https://www.ascpt.org/Resources/Knowledge-Center/What-is-Clinical-Pharmacology|title=What is Clinical Pharmacology?|website=ascpt.org|access-date=31 October 2021|archive-date=31 October 2021|archive-url=https://web.archive.org/web/20211031021835/https://www.ascpt.org/Resources/Knowledge-Center/What-is-Clinical-Pharmacology|url-status=live}} An example of this is posology, which is the study of how medicines are dosed.{{cite web|url=https://www.pharmamad.com/posology/|title=Posology, Factors Influencing Dose, Calculation of Doses|date=23 January 2019|access-date=31 October 2021|website=pharmamad.com|archive-date=31 October 2021|archive-url=https://web.archive.org/web/20211031021837/https://www.pharmamad.com/posology/|url-status=live}} [84] => [85] => Pharmacology is closely related to [[toxicology]]. Both pharmacology and toxicology are scientific disciplines that focus on understanding the properties and actions of chemicals.{{cite web|url=https://www.pharmtox.utoronto.ca/science-pharmacology-toxicology|title=The Science of Pharmacology & Toxicology|publisher=Faculty of Medicine, University of Toronto|access-date=July 16, 2019|archive-date=16 July 2019|archive-url=https://web.archive.org/web/20190716151155/https://www.pharmtox.utoronto.ca/science-pharmacology-toxicology|url-status=live}} However, pharmacology emphasizes the therapeutic effects of chemicals, usually drugs or compounds that could become drugs, whereas toxicology is the study of chemical's adverse effects and risk assessment. [86] => [87] => Pharmacological knowledge is used to advise [[pharmacotherapy]] in [[medicine]] and [[pharmacy]]. [88] => [89] => ==== Drug discovery ==== [90] => {{overly detailed|date=July 2019}} [91] => [[Drug discovery]] is the field of study concerned with creating new drugs. It encompasses the subfields of [[drug design]] and [[Drug development|development]].{{cite web|url=https://www.sciencedirect.com/topics/nursing-and-health-professions/drug-development/|access-date=31 October 2021|title=Drug Development|date=2013|website=sciencedirect.com|archive-date=31 October 2021|archive-url=https://web.archive.org/web/20211031021833/https://www.sciencedirect.com/topics/nursing-and-health-professions/drug-development/|url-status=live}} Drug discovery starts with drug design, which is the [[invention|inventive]] process of finding new drugs.{{cite book | last1 = Madsen | first1 = Ulf | last2 = Krogsgaard-Larsen | first2 = Povl | last3 = Liljefors | first3 = Tommy V | title = Textbook of Drug Design and Discovery | publisher = Taylor & Francis | location = Washington, DC | year = 2002 | isbn = 978-0-415-28288-8 | name-list-style = vanc }} In the most basic sense, this involves the design of molecules that are complementary in [[shape]] and [[electric charge|charge]] to a given biomolecular target.{{cite web|url=https://www.chem.uwec.edu/Chem491_W09/Topic7-2.pdf|title=Introduction to Drug Design|access-date=31 October 2021|archive-date=31 October 2021|archive-url=https://web.archive.org/web/20211031021835/https://www.chem.uwec.edu/Chem491_W09/Topic7-2.pdf|url-status=live}} After a [[lead compound]] has been identified through drug discovery, drug development involves bringing the drug to the market. Drug discovery is related to [[pharmacoeconomics]], which is the sub-discipline of [[health economics]] that considers the value of drugs{{cite journal | vauthors = Mueller C, Schur C, O'Connell J | title = Prescription drug spending: the impact of age and chronic disease status | journal = American Journal of Public Health | volume = 87 | issue = 10 | pages = 1626–9 | date = October 1997 | pmid = 9357343 | pmc = 1381124 | doi = 10.2105/ajph.87.10.1626 }}{{cite journal | vauthors = Arnold RJ, Ekins S | s2cid = 23088517 | title = Time for cooperation in health economics among the modelling community | journal = PharmacoEconomics | volume = 28 | issue = 8 | pages = 609–13 | year = 2010 | pmid = 20513161 | doi = 10.2165/11537580-000000000-00000 }} Pharmacoeconomics evaluates the cost and benefits of drugs in order to guide optimal healthcare resource allocation.{{cite web|url=https://www.sciencedirect.com/topics/nursing-and-health-professions/pharmacoeconomics|title=Pharmacoeconomics – an overview|access-date=31 October 2021|website=sciencedirect.com|archive-date=31 October 2021|archive-url=https://web.archive.org/web/20211031021834/https://www.sciencedirect.com/topics/nursing-and-health-professions/pharmacoeconomics|url-status=live}} The techniques used for the [[Drug discovery|discovery]], [[Pharmaceutical formulation|formulation]], manufacturing and quality control of drugs discovery is studied by [[pharmaceutical engineering]], a branch of [[engineering]].{{cite journal| vauthors = Reklaitis GV, Khinast J, Muzzio F |date=November 2010|title=Pharmaceutical engineering science—New approaches to pharmaceutical development and manufacturing|journal=Chemical Engineering Science|volume=65|issue=21|pages=iv–vii|doi=10.1016/j.ces.2010.08.041|bibcode=2010ChEnS..65D...4R }} [[Safety pharmacology]] specialises in detecting and investigating potential undesirable effects of drugs.{{Cite journal|last=Hite|first=Mark|date=2016-06-25|title=Safety Pharmacology Approaches|journal=International Journal of Toxicology|language=en|volume=16|pages=23–32|doi=10.1080/109158197227332|s2cid=71986376|doi-access=free}}{{AI4 | image = Drug discovery cycle.svg | annotations = | align = right | image-width = 300 | width = 300 | height = 225 | alt = Drug discovery cycle schematic | caption =The drug discovery cycle}} [92] => [[Drug development|Development of medication]] is a vital concern to [[medicine]], but also has strong [[economical]] and [[political]] implications. To protect the [[consumer]] and prevent abuse, many governments regulate the manufacture, sale, and administration of medication. In the [[United States]], the main body that regulates pharmaceuticals is the [[Food and Drug Administration]]; they enforce [[Technical standard|standards]] set by the [[United States Pharmacopoeia]]. In the [[European Union]], the main body that regulates pharmaceuticals is the [[European Medicines Agency|EMA]], and they enforce standards set by the [[European Pharmacopoeia]]. [93] => [94] => The metabolic stability and the reactivity of a library of candidate drug compounds have to be assessed for drug metabolism and toxicological studies. Many methods have been proposed for quantitative predictions in drug metabolism; one example of a recent computational method is SPORCalc.{{cite journal | vauthors = Smith J, Stein V | title = SPORCalc: A development of a database analysis that provides putative metabolic enzyme reactions for ligand-based drug design | journal = Computational Biology and Chemistry | volume = 33 | issue = 2 | pages = 149–59 | date = April 2009 | pmid = 19157988 | doi = 10.1016/j.compbiolchem.2008.11.002 }} A slight alteration to the chemical structure of a medicinal compound could alter its medicinal properties, depending on how the alteration relates to the structure of the substrate or receptor site on which it acts: this is called the structural activity relationship (SAR). When a useful activity has been identified, chemists will make many similar compounds called analogues, to try to maximize the desired medicinal effect(s). This can take anywhere from a few years to a decade or more, and is very expensive.{{cite book|title=Revise A2 Chemistry |url=https://www.google.com/books/edition/Revise_A2_Chemistry_for_Salters_OCR/4vtRp_03vFYC?hl=en&gbpv=1&pg=RA1-PA1 |last1=Newton|first1=David| first2 = Alasdair | last2 = Thorpe | first3 = Chris | last3 = Otter | name-list-style = vanc |publisher=[[Heinemann Educational Publishers]]|year=2004|isbn=0-435-58347-6|pages=1}} One must also determine how safe the medicine is to consume, its stability in the human body and the best form for delivery to the desired organ system, such as tablet or aerosol. After extensive testing, which can take up to six years, the new medicine is ready for marketing and selling. [95] => [96] => Because of these long timescales, and because out of every 5000 potential new medicines typically only one will ever reach the open market, this is an expensive way of doing things, often costing over 1 billion dollars. To recoup this outlay pharmaceutical companies may do a number of things: [97] => * Carefully research the demand for their potential new product before spending an outlay of company funds. [98] => * Obtain a patent on the new medicine preventing other companies from producing that medicine for a certain allocation of time. [99] => [100] => The [[inverse benefit law]] describes the relationship between a drugs therapeutic benefits and its marketing. [101] => [102] => When designing drugs, the [[placebo]] effect must be considered to assess the drug's true therapeutic value. [103] => [104] => Drug development uses techniques from [[medicinal chemistry]] to chemically design drugs. This overlaps with the biological approach of finding targets and physiological effects. [105] => [106] => === Wider contexts === [107] => Pharmacology can be studied in relation to wider contexts than the physiology of individuals. For example, [[pharmacoepidemiology]] concerns the variations of the effects of drugs in or between populations, it is the bridge between [[clinical pharmacology]] and [[epidemiology]].{{Cite book |title=Rang and Dale's pharmacology |first1=James |last1=Ritter |first2=Rod J. |last2=Flower |first3=G. |last3=Henderson |first4=David J. |last4=MacEwan |first5=Yoon Kong |last5=Loke |first6=H. P. |last6=Rang |publisher=Elsevier |year=2020|isbn=978-0-7020-8060-9|edition=Ninth|location=Edinburgh|oclc=1081403059}}{{Cite book|title=Textbook of pharmacoepidemiology|date=2013|publisher=Wiley Blackwell|editor-first1=Brian L. |editor-last1=Strom |editor-first2=Stephen E. |editor-last2=Kimmel |editor-first3=Sean |editor-last3=Hennessy |url=https://www.google.com/books/edition/Textbook_of_Pharmacoepidemiology/PaMRAAAAQBAJ?hl=en&gbpv=1&pg=PA21 |isbn=978-1-118-34484-2|edition=Second|location=Chichester, West Sussex, UK|pages=21–23|oclc=826123173}} [[Pharmacoenvironmentology]] or environmental pharmacology is the study of the effects of used pharmaceuticals and personal care products (PPCPs) on the environment after their elimination from the body.{{cite journal | vauthors = Rahman SZ, Khan RA, Gupta V, Uddin M | title = Pharmacoenvironmentology--a component of pharmacovigilance | journal = Environmental Health | volume = 6 | issue = 1 | pages = 20 | date = July 2007 | pmid = 17650313 | pmc = 1947975 | doi = 10.1186/1476-069X-6-20 | bibcode = 2007EnvHe...6...20R | doi-access = free }} Human health and ecology are intimately related so environmental pharmacology studies the environmental effect of drugs and [[pharmaceuticals and personal care products in the environment]].{{Cite journal|last1=Jena|first1=Monalisa|last2=Mishra|first2=Archana|last3=Maiti|first3=Rituparna|date=2019-03-26|title=Environmental pharmacology: source, impact and solution|url=http://www.degruyter.com/view/j/reveh.2019.34.issue-1/reveh-2018-0049/reveh-2018-0049.xml|journal=Reviews on Environmental Health|volume=34|issue=1|pages=69–79|doi=10.1515/reveh-2018-0049|pmid=30854834|s2cid=73725468|issn=2191-0308|access-date=4 February 2021|archive-date=24 February 2022|archive-url=https://web.archive.org/web/20220224115636/https://www.degruyter.com/document/doi/10.1515/reveh-2018-0049/html|url-status=live}} [108] => [109] => Drugs may also have ethnocultural importance, so [[ethnopharmacology]] studies the ethnic and cultural aspects of pharmacology.{{Cite web|title=International Society for Ethnopharmacology|url=https://ethnopharmacology.org/|access-date=2021-02-04|website=International Society for Ethnopharmacology|language=en-US|archive-date=21 January 2021|archive-url=https://web.archive.org/web/20210121205853/https://ethnopharmacology.org/|url-status=live}} [110] => [111] => === Emerging fields === [112] => [[Photopharmacology]] is an emerging approach in [[medicine]] in which drugs are activated and deactivated with [[light]]. The energy of light is used to change for shape and chemical properties of the drug, resulting in different biological activity.{{cite journal | vauthors = Ricart-Ortega M, Font J, Llebaria A | s2cid = 76664855 | title = GPCR photopharmacology | journal = Molecular and Cellular Endocrinology | volume = 488 | pages = 36–51 | date = May 2019 | pmid = 30862498 | doi = 10.1016/j.mce.2019.03.003 | url = http://www.sciencedirect.com/science/article/pii/S0303720719300796 | hdl = 10261/201805 | hdl-access = free | access-date = 17 July 2020 | archive-date = 24 February 2022 | archive-url = https://web.archive.org/web/20220224115642/https://www.sciencedirect.com/science/article/abs/pii/S0303720719300796 | url-status = live }} This is done to ultimately achieve control when and where drugs are active in a reversible manner, to prevent [[side effect]]s and pollution of drugs into the environment.{{cite journal | vauthors = Velema WA, Szymanski W, Feringa BL | title = Photopharmacology: beyond proof of principle | journal = Journal of the American Chemical Society | volume = 136 | issue = 6 | pages = 2178–91 | date = February 2014 | pmid = 24456115 | doi = 10.1021/ja413063e | url = https://www.rug.nl/research/portal/files/13153399/ja_2013_13063e_photopharma_revised.pdf | hdl = 11370/d6714f52-c2c8-4e48-b345-238e98bcc776 | s2cid = 197196311 | hdl-access = free | access-date = 24 September 2019 | archive-date = 24 September 2019 | archive-url = https://web.archive.org/web/20190924102955/https://www.rug.nl/research/portal/files/13153399/ja_2013_13063e_photopharma_revised.pdf | url-status = live }}{{cite journal | vauthors = Broichhagen J, Frank JA, Trauner D | title = A roadmap to success in photopharmacology | journal = Accounts of Chemical Research | volume = 48 | issue = 7 | pages = 1947–60 | date = July 2015 | pmid = 26103428 | doi = 10.1021/acs.accounts.5b00129 }} [114] => [115] => ==Theory of pharmacology== [116] => {{Expand section|date=July 2019}}[[File:Dose response antagonist.jpg|thumb|400px|right|A trio of [[dose response curve]]s. Dose response curves are studied extensively in pharmacology.]] [117] => The study of chemicals requires intimate knowledge of the biological system affected. With the knowledge of [[cell biology]] and [[biochemistry]] increasing, the field of pharmacology has also changed substantially. It has become possible, through molecular analysis of [[receptor (biochemistry)|receptors]], to design chemicals that act on specific cellular signaling or [[metabolic pathway]]s by affecting sites directly on cell-surface receptors (which modulate and mediate cellular signaling pathways controlling cellular function). [118] => [119] => Chemicals can have pharmacologically relevant properties and effects. [[Pharmacokinetics]] describes the effect of the body on the chemical (e.g. [[half-life]] and [[volume of distribution]]), and [[pharmacodynamics]] describes the chemical's effect on the body (desired or [[toxic]]). [120] => [121] => ===Systems, receptors and ligands=== [122] => {{Expand section|date=July 2019}}{{Main|Ligand (biochemistry)|List of drugs|Neurotransmitter}} [123] => [[File:Cholinergic synapse.svg|thumb|300px|The [[acetylcholine|cholinergic]] synapse. Targets in synapses can be modulated with pharmacological agents. In this case, [[cholinergic]]s (such as [[muscarine]]) and [[anticholinergic]]s (such as [[atropine]]) target receptors; [[Reuptake modulator|transporter inhibitors]] (such as [[hemicholinium]]) target membrane transport proteins and [[anticholinesterase]]s (such as [[sarin]]) target enzymes.]] [124] => [125] => Pharmacology is typically studied with respect to particular systems, for example endogenous [[neurotransmitter systems]]. The major systems studied in pharmacology can be categorised by their [[ligand (biochemistry)|ligand]]s and include [[acetylcholine]], [[adrenaline]], [[glutamate]], [[GABA]], [[dopamine]], [[histamine]], [[serotonin]], [[cannabinoid]] and [[opioid]]. [126] => [127] => Molecular targets in pharmacology include [[receptor (biochemistry)|receptor]]s, [[enzyme]]s and [[membrane transport protein]]s. Enzymes can be targeted with [[enzyme inhibitors]]. Receptors are typically categorised based on structure and function. Major receptor types studied in pharmacology include [[G protein coupled receptors]], [[ligand gated ion channels]] and [[receptor tyrosine kinases]]. [128] => [129] => Network pharmacology is a subfield of pharmacology that combines principles from pharmacology, systems biology, and network analysis to study the complex interactions between drugs and targets (e.g., receptors or enzymes etc.) in biological systems. The topology of a biochemical reaction network determines the shape of drug [[dose-response relationship|dose-response curve]]Roeland van Wijk et al., Non-monotonic dynamics and crosstalk in signaling pathways and their implications for pharmacology. Scientific Reports 5:11376 (2015) doi: 10.1038/srep11376 as well as the type of drug-drug interactions,Mehrad Babaei et al., Biochemical reaction network topology defines dose-dependent Drug–Drug interactions. Comput Biol Med 155:106584 (2023) doi: 10.1016/j.compbiomed.2023.106584 thus can help designing efficient and safe therapeutic strategies. The topology Network pharmacology utilizes computational tools and network analysis algorithms to identify drug targets, predict drug-drug interactions, elucidate signaling pathways, and explore the polypharmacology of drugs. [130] => [131] => ===Pharmacodynamics=== [132] => {{More citations needed section|date=November 2023}}{{main|Pharmacodynamics}} [133] => Pharmacodynamics is defined as how the body reacts to the drugs. Pharmacodynamics theory often investigates the [[binding affinity]] of [[ligand (biochemistry)|ligand]]s to their receptors. Ligands can be [[agonist]]s, partial agonists or [[Receptor antagonist|antagonists]] at specific receptors in the body. Agonists bind to receptors and produce a biological response, a partial agonist produces a biological response lower than that of a full agonist, antagonists have affinity for a receptor but do not produce a biological response. [134] => [135] => The ability of a ligand to produce a biological response is termed [[Intrinsic activity|efficacy]], in a dose-response profile it is indicated as percentage on the y-axis, where 100% is the maximal efficacy (all receptors are occupied). [136] => [137] => Binding affinity is the ability of a ligand to form a ligand-receptor complex either through [[Van der Waals force|weak attractive forces]] (reversible) or [[covalent bond]] (irreversible), therefore efficacy is dependent on binding affinity. [138] => [139] => [[Potency (pharmacology)|Potency]] of drug is the measure of its effectiveness, [[EC50|EC50]] is the drug concentration of a drug that produces an efficacy of 50% and the lower the concentration the higher the potency of the drug therefore EC50 can be used to compare potencies of drugs. [140] => [141] => Medication is said to have a narrow or wide ''[[therapeutic index]],'' [[certain safety factor]] or ''[[therapeutic window]]''. This describes the ratio of desired effect to toxic effect. A compound with a narrow therapeutic index (close to one) exerts its desired effect at a dose close to its toxic dose. A compound with a wide therapeutic index (greater than five) exerts its desired effect at a dose substantially below its toxic dose. Those with a narrow margin are more difficult to dose and administer, and may require [[therapeutic drug monitoring]] (examples are [[warfarin]], some [[antiepileptic]]s, [[aminoglycoside]] [[antibiotics]]). Most anti-[[cancer]] drugs have a narrow therapeutic margin: toxic side-effects are almost always encountered at doses used to kill [[tumor]]s. [142] => [143] => The effect of drugs can be described with [[Loewe additivity]] which is one of several common reference models. [144] => [145] => Other models include the [[Hill equation (biochemistry)|Hill equation]], [[Cheng-Prusoff equation]] and [[Schild regression]]. [146] => [147] => ===Pharmacokinetics=== [148] => {{Multiple issues|section=yes| [149] => {{expand section|date=July 2019}} [150] => {{cleanup section|reason=Content needs to be generalised to encompass pharmacokinetics as a whole, not just individual ideas.|date=July 2019}} [151] => }} [152] => {{main|Pharmacokinetics}} [153] => [154] => [[Pharmacokinetics]] is the study of the bodily absorption, distribution, metabolism, and excretion of drugs.{{cite web |url= https://www.merriam-webster.com/dictionary/pharmacokinetics |title= Pharmacokinetics |website= Merriam-Webster |access-date= July 16, 2019 |archive-date= 16 July 2019 |archive-url= https://web.archive.org/web/20190716151748/https://www.merriam-webster.com/dictionary/pharmacokinetics |url-status= live }} [155] => [156] => When describing the pharmacokinetic properties of the chemical that is the active ingredient or [[Active ingredient|active pharmaceutical ingredient]] (API), pharmacologists are often interested in ''L-ADME'': [157] => * [[Liberation (pharmacology)|Liberation]] – How is the API disintegrated (for solid oral forms (breaking down into smaller particles), dispersed, or dissolved from the medication? [158] => * [[Absorption (digestive)|Absorption]] – How is the API absorbed (through the [[human skin|skin]], the [[intestine]], the [[oral mucosa]])? [159] => * [[Distribution (pharmacology)|Distribution]] – How does the API spread through the organism? [160] => * [[Drug metabolism|Metabolism]] – Is the API converted chemically inside the body, and into which substances. Are these active (as well)? Could they be toxic? [161] => * [[Excretion]] – How is the API excreted (through the bile, urine, breath, skin)? [162] => [163] => [[Drug metabolism]] is assessed in pharmacokinetics and is important in drug research and prescribing. [164] => [165] => Pharmacokinetics is the movement of the drug in the body, it is usually described as 'what the body does to the drug' the physico-chemical properties of a drug will affect the rate and extent of absorption, extent of distribution, metabolism and elimination. The drug needs to have the appropriate molecular weight, polarity etc. in order to be absorbed, the fraction of a drug the reaches the systemic circulation is termed bioavailability, this is simply a ratio of the peak plasma drug levels after oral administration and the drug concentration after an IV administration(first pass effect is avoided and therefore no amount drug is lost). A drug must be lipophilic (lipid soluble) in order to pass through biological membranes this is true because biological membranes are made up of a lipid bilayer (phospholipids etc.) Once the drug reaches the blood circulation it is then distributed throughout the body and being more concentrated in highly perfused organs. [166] => [167] => ==Administration, drug policy and safety== [168] => ===Drug policy=== [169] => {{Main|Drug policy}} [170] => In the [[United States]], the [[Food and Drug Administration]] (FDA) is responsible for creating guidelines for the approval and use of drugs. The FDA requires that all approved drugs fulfill two requirements: [171] => # The drug must be found to be effective against the disease for which it is seeking approval (where 'effective' means only that the drug performed better than placebo or competitors in at least two trials). [172] => # The drug must meet safety criteria by being subject to animal and controlled human testing. [173] => [174] => Gaining FDA approval usually takes several years. Testing done on animals must be extensive and must include several species to help in the evaluation of both the effectiveness and toxicity of the drug. The dosage of any drug approved for use is intended to fall within a range in which the drug produces a [[therapeutic effect]] or desired outcome.{{cite book|last1=Nagle|first1=Hinter | first2 = Barbara | last2 = Nagle | name-list-style = vanc |title=Pharmacology: An Introduction|year=2005|publisher=[[McGraw Hill]]|location=[[Boston]]|isbn=0-07-312275-0}} [175] => [176] => The safety and effectiveness of prescription drugs in the U.S. are regulated by the federal [[Prescription Drug Marketing Act (PDMA)|Prescription Drug Marketing Act of 1987]]. [177] => [178] => The [[Medicines and Healthcare products Regulatory Agency]] (MHRA) has a similar role in the UK. [179] => [180] => [[Medicare Part D]] is a prescription drug plan in the U.S. [181] => [182] => The [[Prescription Drug Marketing Act (PDMA)]] is an act related to drug policy. [183] => [184] => [[Prescription drug]]s are drugs regulated by legislation. [185] => [186] => == Societies and education == [187] => {{unreferenced section|date=February 2016}} [188] => [189] => === Societies and administration === [190] => The [[International Union of Basic and Clinical Pharmacology]], [[Federation of European Pharmacological Societies]] and [[European Association for Clinical Pharmacology and Therapeutics]] are organisations representing standardisation and regulation of clinical and scientific pharmacology. [191] => [192] => Systems for [[medical classification]] of drugs with [[pharmaceutical code]]s have been developed. These include the [[National Drug Code]] (NDC), administered by [[Food and Drug Administration]].;{{cite web|url=https://www.fda.gov/Drugs/InformationOnDrugs/ucm142438.htm|title=National Drug Code Directory|date=5 May 2017|website=U.S. Food and Drug Administration|access-date=28 May 2019|archive-date=27 May 2016|archive-url=https://web.archive.org/web/20160527135726/http://www.fda.gov/Drugs/InformationOnDrugs/ucm142438.htm|url-status=live}} [[Drug Identification Number]] (DIN), administered by [[Health Canada]] under the [[Food and Drugs Act]]; [[Department of Health (Hong Kong)#Hong Kong Drug Registration|Hong Kong Drug Registration]], administered by the Pharmaceutical Service of the [[Department of Health (Hong Kong)]] and [[National Pharmaceutical Product Index]] in South Africa. Hierarchical systems have also been developed, including the [[Anatomical Therapeutic Chemical Classification System]] (AT, or ATC/DDD), administered by [[World Health Organization]]; [[Generic Product Identifier]] (GPI), a hierarchical classification number published by MediSpan and [[SNOMED]], C axis. Ingredients of drugs have been categorised by [[Unique Ingredient Identifier]]. [193] => [194] => === Education === [195] => {{main|Medical education}} [196] => The study of pharmacology overlaps with [[biomedical sciences]] and is the study of the effects of drugs on living organisms. Pharmacological research can lead to new drug discoveries, and promote a better understanding of human [[physiology]]. Students of pharmacology must have a detailed working knowledge of aspects in physiology, pathology, and chemistry. They may also require knowledge of plants as sources of pharmacologically active compounds. Modern pharmacology is interdisciplinary and involves biophysical and computational sciences, and analytical chemistry. A pharmacist needs to be well-equipped with knowledge on pharmacology for application in pharmaceutical research or pharmacy practice in hospitals or commercial organisations selling to customers. Pharmacologists, however, usually work in a laboratory undertaking research or development of new products. Pharmacological research is important in academic research (medical and non-medical), private industrial positions, science writing, scientific patents and law, consultation, biotech and pharmaceutical employment, the alcohol industry, food industry, forensics/law enforcement, public health, and environmental/ecological sciences. Pharmacology is often taught to pharmacy and medicine students as part of a [[Medical School]] curriculum. [197] => [198] => == See also == [199] => {{Portal|Biology}} [200] => {{Columns-list|colwidth=30em| [201] => * [[Cosmeceuticals]] [202] => * [[List of abbreviations used in medical prescriptions]] [203] => * [[List of pharmaceutical companies]] [204] => * [[List of withdrawn drugs]] [205] => * [[Pharmaceutical company]] [206] => * [[Pharmaceutical formulation]] [207] => }} [208] => [209] => == References == [210] => {{Reflist|refs= [211] => {{cite journal | vauthors = Kaddurah-Daouk R, Kristal BS, Weinshilboum RM | title = Metabolomics: a global biochemical approach to drug response and disease | journal = Annual Review of Pharmacology and Toxicology | volume = 48 | pages = 653–83 | year = 2008 | pmid = 18184107 | doi = 10.1146/annurev.pharmtox.48.113006.094715 }} [212] => {{cite journal | vauthors = Kaddurah-Daouk R, Weinshilboum RM | title = Pharmacometabolomics: implications for clinical pharmacology and systems pharmacology | journal = Clinical Pharmacology and Therapeutics | volume = 95 | issue = 2 | pages = 154–67 | date = February 2014 | pmid = 24193171 | doi = 10.1038/clpt.2013.217 | s2cid = 22649568 }} [213] => }} [214] => [215] => == External links == [216] => {{Commons category}} [217] => * [http://www.aspet.org American Society for Pharmacology and Experimental Therapeutics] [218] => * [http://www.bps.ac.uk British Pharmacological Society] [219] => * [http://www.ich.org/ International Conference on Harmonisation] [220] => * [http://www.usp.org US Pharmacopeia] [221] => * [http://www.iuphar.org International Union of Basic and Clinical Pharmacology] [222] => * [http://www.iuphar-db.org IUPHAR Committee on Receptor Nomenclature and Drug Classification] [223] => * [http://www.guidetopharmacology.org/ IUPHAR/BPS Guide to Pharmacology] [224] => [225] => == Further reading == [226] => * {{cite book|url=https://books.google.com/books?id=Y9bsUpefYW0C&pg=PA51|title=Textbook of Receptor Pharmacology, Second Edition|last1=Foreman|first1=John C.|last2=Johansen|first2=Torben|last3=Gibb|first3=Alasdair J.| name-list-style = vanc |publisher=CRC Press|year=2009|isbn=9781439887578}} [227] => * {{cite book|title=[[Goodman and Gilman's The Pharmacological Basis of Therapeutics]] |edition=12 |year=2011|first1=Laurence |last1=Brunton |editor1-last=Brunton |editor1-first=L. L. |editor2-last=Chabner |editor2-first=Bruce |editor3-last=Knollmann |editor3-first=Björn C. | name-list-style = vanc |isbn=978-0-07-162442-8|location=New York |publisher=McGraw-Hill }} [228] => * {{cite book|title=Lippincott Illustrated Reviews: Pharmacology|first1=Karen|last1=Whalen| name-list-style = vanc |year=2014}} [229] => [230] => {{Pharmacology}} [231] => {{Pharmacomodulation}} [232] => {{Pharmacy}} [233] => {{Biology_nav}} [234] => {{Major drug groups}} [235] => {{Branches of biology}} [236] => {{Branches of chemistry}} [237] => [238] => {{Authority control}} [239] => [240] => [[Category:Pharmacology| ]] [241] => [[Category:Biochemistry]] [242] => [[Category:Life sciences industry]] [] => )
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Pharmacology

Pharmacology is a scientific discipline that focuses on the study of how drugs interact with the body. It encompasses various aspects including the discovery, development, and evaluation of drugs, as well as their mechanisms of action and therapeutic uses.

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It encompasses various aspects including the discovery, development, and evaluation of drugs, as well as their mechanisms of action and therapeutic uses. Pharmacologists aim to understand how drugs work at the molecular level, how they are absorbed, distributed, metabolized, and excreted by the body, and how different individuals may respond differently to the same drug. This information is crucial for designing effective and safe medications, as well as for evaluating the potential risks and benefits of drug therapy. Pharmacology integrates knowledge from various fields such as biochemistry, physiology, genetics, and pathology to provide a comprehensive understanding of drug actions. It has wide-ranging applications in medicine, as well as in other fields such as toxicology, pharmacy, and research.

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