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Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action,where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemical or physiological effect on the cell, tissue, organ, or organism (sometimes the word pharmacon is used as a term to encompass these endogenous and exogenous bioactive species). More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function. If substances have medicinal properties, they are considered pharmaceuticals.
The field encompasses drug composition and properties, synthesis and drug design, molecular and cellular mechanisms, organ/systems mechanisms, signal transduction/cellular communication, molecular diagnostics, interactions, 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 receptors, and pharmacokinetics discusses the absorption, distribution, metabolism, and excretion (ADME) of chemicals from the biological systems.
Pharmacology is not synonymous with pharmacy and the two terms are frequently confused. Pharmacology, a 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.
The word pharmacology is derived from Greek φάρμακον , pharmakon, "drug, poison" and -λογία , -logia "study of", "knowledge of" (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).
The origins of clinical pharmacology date back to the Middle Ages, with pharmacognosy and 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.Early pharmacology focused on herbalism and natural substances, mainly plant extracts. 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 ingredient 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 historical context.
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.Pharmacology as a scientific discipline did not further advance until the mid-19th century amid the great biomedical resurgence of that period. 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. The first pharmacology department was set up by Rudolf Buchheim in 1847, in recognition of the need to understand how therapeutic drugs and poisons produced their effects. Subsequently, the first pharmacology department in England was set up in 1905 at University College London.
Pharmacology developed in the 19th century as a biomedical science that applied the principles of scientific experimentation to therapeutic contexts.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. 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.
Pharmacology can also 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). [ citation needed ] The related field of neuropsychopharmacology focuses on the effects of drugs at the overlap between the nervous system and the psyche.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.
Pharmacometabolomics, also known as pharmacometabonomics, is a field which stems from metabolomics, the quantification and analysis of metabolites produced by the body. [ citation needed ] For pharmacology regarding individual genes, pharmacogenetics studies how genetic variation gives rise to differing responses to drugs.[ citation needed ] Pharmacoepigenetics studies the underlying epigenetic marking patterns that lead to variation in an individual's response to medical treatment.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. 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.
Pharmacology can be applied within clinical sciences. Clinical pharmacology is the basic science of pharmacology focusing on the application of pharmacological principles and methods in the medical clinic and towards patient care and outcomes.[ citation needed ] An example of this is posology, which is the study of how medicines are dosed.[ citation needed ]
Pharmacology is closely related to toxicology. Both pharmacology and toxicology are scientific disciplines that focus on understanding the properties and actions of chemicals.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.
Pharmacological knowledge is used to advise pharmacotherapy in medicine and pharmacy.
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Drug discovery is the field of study concerned with creating new drugs. It encompasses the subfields of drug design and development.[ citation needed ] Drug discovery starts with drug design, which is the inventive process of finding new drugs. In the most basic sense, this involves the design of molecules that are complementary in shape and charge to a given biomolecular target.[ citation needed ] After a lead compound has been identified through drug discovery, drug development involves bringing the drug to the market.[ citation needed ] Drug discovery is related to pharmacoeconomics, which is the sub-discipline of health economics that considers the value of drugs Pharmacoeconomics evaluates the cost and benefits of drugs in order to guide optimal healthcare resource allocation.[ citation needed ] The techniques used for the discovery, formulation, manufacturing and quality control of drugs discovery is studied by pharmaceutical engineering, a branch of engineering. Safety pharmacology specialises in detecting and investigating potential undesirable effects of drugs.
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 standards set by the United States Pharmacopoeia. In the European Union, the main body that regulates pharmaceuticals is the EMA, and they enforce standards set by the European Pharmacopoeia.
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.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. 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.
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:
The inverse benefit law describes the relationship between a drugs therapeutic benefits and its marketing.
When designing drugs, the placebo effect must be considered to assess the drug's true therapeutic value.
Drug development uses techniques from medicinal chemistry to chemically design drugs. This overlaps with the biological approach of finding targets and physiological effects.
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.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. 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.
Drugs may also have ethnocultural importance, so ethnopharmacology studies the ethnic and cultural aspects of pharmacology.
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.This is done to ultimately achieve control when and where drugs are active in a reversible manner, to prevent side effects and pollution of drugs into the environment.
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 receptors, to design chemicals that act on specific cellular signaling or metabolic pathways by affecting sites directly on cell-surface receptors (which modulate and mediate cellular signaling pathways controlling cellular function).
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).
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 ligands and include acetylcholine, adrenaline, glutamate, GABA, dopamine, histamine, serotonin, cannabinoid and opioid.
Molecular targets in pharmacology include receptors, enzymes and membrane transport proteins. 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.
Pharmacodynamics is defined as how the body reacts to the drugs. Pharmacology models include the Hill equation, Cheng-Prusoff equation and Schild regression. Pharmacodynamics theory often investigates the binding affinity of ligands to their receptors.
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 antiepileptics, aminoglycoside antibiotics). Most anti-cancer drugs have a narrow therapeutic margin: toxic side-effects are almost always encountered at doses used to kill tumors.
The effect of drugs can be described with Loewe additivity.[ clarification needed ]
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Pharmacokinetics is the study of the bodily absorption, distribution, metabolism, and excretion of drugs.
When describing the pharmacokinetic properties of the chemical that is the active ingredient or active pharmaceutical ingredient (API), pharmacologists are often interested in L-ADME:
Drug metabolism is assessed in pharmacokinetics and is important in drug research and prescribing.
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:
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.
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.
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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.
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.;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 (GPI), a hierarchical classification number published by MediSpan and SNOMED, C axis. Ingredients of drugs have been categorised by Unique Ingredient Identifier.
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. Modern pharmacology is interdisciplinary and relates to biophysical and computational sciences, and analytical chemistry. A pharmacist needs to be well-equipped with knowledge on pharmacology for application in pharmacy practice and pharmaceutical research. Whereas, pharmacologists usually work in a laboratory setting. 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.
Pharmacy is the clinical health science that links medical science with chemistry and it is charged with the discovery, production, disposal, safe and effective use, and control of medications and drugs. The practice of pharmacy requires excellent knowledge of drugs, their mechanism of action, side effects, interactions, mobility and toxicity. At the same time, it requires knowledge of treatment and understanding of the pathological process. Some specialties of pharmacists, such as that of clinical pharmacists, require other skills, e.g. knowledge about the acquisition and evaluation of physical and laboratory data.
The therapeutic index is a quantitative measurement of the relative safety of a drug. It is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxicity. The related terms therapeutic window or safety window refer to a range of doses which optimize between efficacy and toxicity, achieving the greatest therapeutic benefit without resulting in unacceptable side-effects or toxicity.
Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs. The effects can include those manifested within animals, microorganisms, or combinations of organisms.
In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation.
Buspirone, sold under the brand name Buspar, among others, is a medication primarily used to treat anxiety disorders, particularly generalized anxiety disorder. Benefits support its short-term use. It is taken by mouth, and it may take up to four weeks to have an effect.
Medicinal chemistry and pharmaceutical chemistry are disciplines at the intersection of chemistry, especially synthetic organic chemistry, and pharmacology and various other biological specialties, where they are involved with design, chemical synthesis and development for market of pharmaceutical agents, or bio-active molecules (drugs).
Aniracetam, also known as N-anisoyl-2-pyrrolidinone, is a racetam which is sold in Europe as a prescription drug. It is not approved by the Food and Drug Administration for use in the United States as a prescription medication or dietary supplement. Despite the FDA's lack of approval, the drug is readily available over-the-counter in the US as a dietary supplement.
Zopiclone, sold under the brand name Imovane among others, is a nonbenzodiazepine used to treat difficulty sleeping. Zopiclone is molecularly distinct from benzodiazepine drugs and is classed as a cyclopyrrolone. However, zopiclone increases the normal transmission of the neurotransmitter gamma-aminobutyric acid (GABA) in the central nervous system, via modulating benzodiazepine receptors in the same way that benzodiazepine drugs do.
Clinical pharmacology has been defined as "that discipline that teaches, does research, frames policy, gives information and advice about the actions and proper uses of medicines in humans and implements that knowledge in clinical practice". Clinical Pharmacology is inherently a translational discipline underpinned by the basic science of pharmacology, engaged in the experimental and observational study of the disposition and effects of drugs in humans, and committed to the translation of science into evidence-based therapeutics. It has a broad scope, from the discovery of new target molecules to the effects of drug usage in whole populations. The main aim of clinical pharmacology is to Generate data for optimum use of drug's and the practice of 'evidence based Medicine'.
Oxazepam is a short-to-intermediate-acting benzodiazepine. Oxazepam is used for the treatment of anxiety and insomnia and in the control of symptoms of alcohol withdrawal syndrome.
Biological half-life of a biological substance such as medication is the time it takes from its maximum concentration (Cmax) to half maximum concentration in human body, and is denoted by the abbreviation .
SB-649868 is a dual orexin receptor antagonist that was being developed by GlaxoSmithKline as a treatment for insomnia.
Brotizolam is a sedative-hypnotic thienotriazolodiazepine drug which is a benzodiazepine analog. It possesses anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties, and is considered to be similar in effect to other short-acting hypnotic benzodiazepines such as triazolam or midazolam. It is used in the short-term treatment of severe insomnia. Brotizolam is a highly potent and short-acting hypnotic, with a typical dose ranging from 0.125 to 0.25 milligrams, which is rapidly eliminated with an average half-life of 4.4 hours.
Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to determine the fate of substances administered to a living organism. The substances of interest include any chemical xenobiotic such as: pharmaceutical drugs, pesticides, food additives, cosmetics, etc. It attempts to analyze chemical metabolism and to discover the fate of a chemical from the moment that it is administered up to the point at which it is completely eliminated from the body. Pharmacokinetics is the study of how an organism affects a drug, whereas pharmacodynamics (PD) is the study of how the drug affects the organism. Both together influence dosing, benefit, and adverse effects, as seen in PK/PD models.
Zuclopenthixol, also known as zuclopentixol, is a medication used to treat schizophrenia and other psychoses. It is classed, pharmacologically, as a typical antipsychotic. Chemically it is a thioxanthene. It is the cis-isomer of clopenthixol. Clopenthixol was introduced in 1961, while zuclopenthixol was introduced in 1978.
Safety pharmacology is a branch of pharmacology specialising in detecting and investigating potential undesirable pharmacodynamic effects of new chemical entities (NCEs) on physiological functions in relation to exposure in the therapeutic range and above.
Deramciclane (EGIS-3886) is a non-benzodiazepine-type anxiolytic drug to treat various types of anxiety disorders. Deramciclane is a unique alternative to current anxiolytics on the market because it has a novel chemical structure and target. It acts as an antagonist at the 5-HT2A receptor, as an inverse agonist at the 5-HT2C receptor, and as a GABA reuptake inhibitor. The two serotonin receptors are G protein-coupled receptors and are two of the main excitatory serotonin receptor types. Their excitation has been implicated in anxiety and mood. Deramciclane does not affect CYP3A4 activity in metabolizing other drugs, but it is a weak inhibitor of CYP2D6. Some studies also show the drug to have moderate affinity to dopamine D2 receptors and low affinity to dopamine receptor D1. Researchers are looking for alternatives to benzodiazepines for anxiolytic use because benzodiazepine drugs have sedative and muscle relaxant side effects.
Pharmacotoxicology entails the study of the consequences of toxic exposure to pharmaceutical drugs and agents in the health care field. The field of pharmacotoxicology also involves the treatment and prevention of pharmaceutically induced side effects. Pharmacotoxicology can be separated into two different categories: pharmacodynamics, and pharmacokinetics.
Opiate is a term classically used in pharmacology to mean a substance derived from opium. Opioid, a more modern term, is used to designate all substances, both natural and synthetic, that bind to opioid receptors in the brain. Opiates are alkaloid compounds naturally found in the opium poppy plant Papaver somniferum. The psychoactive compounds found in the opium plant include morphine, codeine, and thebaine. Opiates have long been used for a variety of medical conditions with evidence of opiate trade and use for pain relief as early as the eighth century AD. Opiates are considered drugs with moderate to high abuse potential and are listed on various "Substance-Control Schedules" under the Uniform Controlled Substances Act of the United States of America.
Leon Aarons is an Australian pharmacist who researches and teaches in the areas of pharmacodynamics and pharmacokinetics. He lives in the United Kingdom and from 1976 has been a professor of pharmacometrics at the University of Manchester. In the interest of promoting the effective development of drugs, the main focus of his work is optimizing pharmacological models, the design of clinical studies, and data analysis and interpretation in the field of population pharmacokinetics. From 1985 to 2010 Aarons was an editor emeritus of the Journal of Pharmacokinetics and Pharmacodynamics and is a former executive editor of the British Journal of Clinical Pharmacology.
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