Pharmacology

Pharmacology is the science of drugs and medications,^[1] including a substance's origin, composition and interaction with biological systems; specifically through pharmacokinetics, pharmacodynamics, therapeutic use, and toxicology. The discipline examines these interactions through pharmacokinetics (what the body does to the drug) and pharmacodynamics (what the drug does to the body), both of which determine how a substance alters normal or abnormal biochemical function.^[2] Substances with medicinal properties are classified as pharmaceuticals, while the term drug encompasses any chemical agent that alters biological processes.

The field encompasses drug composition and properties, functions, sources, medicinal chemistry, drug design, molecular and cellular mechanisms, organ/systems mechanisms, signal transduction/cellular communication, molecular diagnostics, interactions, chemical biology, therapy, medical applications, toxicology, 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 receptors, and pharmacokinetics discusses the liberation, absorption, distribution, metabolism, and excretion (LADME) of chemicals from the biological systems.

Pharmacology is not synonymous with pharmacy, though the two terms are frequently confused. Pharmacology is a branch of medical and biological sciences which encompasses the research, discovery, and characterization of chemicals exhibiting biological effects, alongside 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, pharmaceutics, medicinal chemistry, pharmacognosy, clinical pharmacy and others 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 distinction between direct-patient care, pharmacy practice, and the science-oriented research field, driven by pharmacology.

The word pharmacology is derived from Greek word φάρμακον, pharmakon, meaning "drug" or "poison", together with another Greek word -λογία, logia with the meaning of "study of" or "knowledge of"^[3][4] (cf. the etymology of pharmacy). Pharmakon is related to pharmakos, the ritualistic sacrifice or exile of a human scapegoat or victim in Ancient Greek religion.

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 antagonists, but also enzyme inhibitors (such as monoamine oxidase inhibitors).^[5]

The origins of clinical pharmacology date back to the Middle Ages, with pharmacognosy, Avicenna's The Canon of Medicine, Peter of Spain's Commentary on Isaac, and John of St Amand's Commentary on the Antedotary of Nicholas.^[9] Early pharmacology focused on herbalism and natural substances, mainly plant extracts while medicines were compiled in books called pharmacopoeias. Crude drugs have been used since prehistory as a preparation of substances from natural sources. However, the active pharmaceutical ingredient (API) of crude drugs are not purified and the substance is adulterated with other substances.

Traditional medicine varies between cultures and may be specific to a particular culture, such as in traditional Chinese, Mongolian, Tibetan, and Korean medicine. However much of this has since been regarded as pseudoscience. Pharmacological substances known as entheogens may have spiritual and religious use and a historical context.^[10]

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.^[11] Pharmacology as a scientific discipline did not further advance until the mid-19th century amid the great biomedical resurgence of that period.^[12] 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.^[13] The first pharmacology department was set up by Rudolf Buchheim in 1847, at the University of Tartu, in recognition of the need to understand how therapeutic drugs and poisons produced their effects.^[12] Subsequently, the first pharmacology department in England was set up in 1905 at University College London.^[14]

Pharmacology developed in the 19th century as a biomedical science that applied the principles of scientific experimentation to therapeutic contexts.^[15] 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 binding affinity of drugs at chemical targets.^[16] 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.

The discipline of pharmacology can be divided into many sub disciplines each with a specific focus.^[17]

Pharmacology can focus on specific 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 and peripheral nervous systems; immunopharmacology in the immune system. Other divisions include cardiovascular, renal, and endocrine pharmacology. Psychopharmacology is the study of the use of drugs that affect the psyche, mind, and behavior (e.g. antidepressants) in treating mental disorders (e.g. depression).^[18][19] 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. The related field of neuropsychopharmacology focuses on the effects of drugs at the overlap between the nervous system and the psyche.

Pharmacometabolomics, also known as pharmacometabolomics, is a field which stems from metabolomics, the quantification and analysis of metabolites produced by the body.^[20][21] 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.^[20][21] 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.^[22] Pharmacomicrobiomics is concerned with the interaction between drugs and the gut microbiome. Pharmacogenomics is the application of genomic technologies to drug discovery and further characterization of drugs related to an organism's entire genome. For pharmacology regarding individual genes, pharmacogenetics studies how genetic variation gives rise to differing responses to drugs.Lua error: Internal error: The interpreter has terminated with signal "24". Lua error: Internal error: The interpreter has terminated with signal "24".

Pharmacokinetics is the study of the bodily absorption, distribution, metabolism, and excretion of drugs.^[61]

When describing the pharmacokinetic properties of the chemical that is the active ingredient or active pharmaceutical ingredient, pharmacologists are often interested in L-ADME:

• Liberation – How is the active pharmaceutical ingredient disintegrated (for solid oral forms (breaking down into smaller particles), dispersed, or dissolved from the medication?
• Absorption – How is the active pharmaceutical ingredient absorbed (through the skin, the intestine, the oral mucosa)?
• Distribution – How does the active pharmaceutical ingredient spread through the organism?
• Metabolism – Is the active pharmaceutical ingredient converted chemically inside the body, and into which substances. Are these active (as well)? Could they be toxic?
• Excretion – How is the active pharmaceutical ingredient excreted (through the bile, urine, breath, skin)?

Drug metabolism is assessed in pharmacokinetics and is important in drug research and prescribing.

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 that 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 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.

Apart from classical pharmacological targets, drugs may exert effects through direct or indirect gene expression modulation, or even introduce persistent state changes through epigenetic reprogramming.

Therefore, drugs should be screened for off-target activity by gene expression profiling, in addition to conventional ligand binding, enzyme assays, etc.

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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:

1. 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).
2. The drug must meet safety criteria by being subject to animal and controlled human testing.

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.^[62]

The safety and effectiveness of prescription drugs in the U.S. are regulated by the federal Prescription Drug Marketing Act of 1987.

The Medicines and Healthcare products Regulatory Agency (MHRA) has a similar role in the UK.

Medicare Part D is a prescription drug plan in the U.S.

The Prescription Drug Marketing Act (PDMA) is an act related to drug policy.

Prescription drugs are drugs regulated by legislation.

The International Union of Basic and Clinical Pharmacology, Federation of European Pharmacological Societies, and European Association for Clinical Pharmacology and Therapeutics are organizations representing standardization and regulation of clinical and scientific pharmacology.

Systems for medical classification of drugs with pharmaceutical codes have been developed. These include the National Drug Code (NDC), administered by Food and Drug Administration;^[63] Drug Identification Number (DIN), administered by Health Canada under the Food and Drugs Act; 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, a hierarchical classification number published by MediSpan and SNOMED, C axis. Ingredients of drugs have been categorized by Unique Ingredient Identifiers.

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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.^[45] 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 organizations 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.

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• American Society for Pharmacology and Experimental Therapeutics
• British Pharmacological Society
• International Conference on Harmonisation
• US Pharmacopeia
• International Union of Basic and Clinical Pharmacology
• IUPHAR Committee on Receptor Nomenclature and Drug Classification
• IUPHAR/BPS Guide to Pharmacology

• Textbook of Receptor Pharmacology. 2010. doi:10.1201/9781420052558. ISBN 978-0-429-14730-2. 
• Brunton, Laurence (2011). Brunton, L. L.; Chabner, Bruce; Knollmann, Björn C.. eds. Goodman and Gilman's The Pharmacological Basis of Therapeutics (12 ed.). New York: McGraw-Hill. ISBN 978-0-07-162442-8. 
• Whalen, Karen (2014). Lippincott Illustrated Reviews: Pharmacology. 

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