Loewe Additivity
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Loewe Additivity
In toxicodynamics and pharmacodynamics, Loewe additivity (or dose additivity) is one of several common reference models used for measuring the effects of drug combinations. Definition Let d_1 and d_2 be doses of compounds 1 and 2 producing in combination an effect e. We denote by D_ and D_ the doses of compounds 1 and 2 required to produce effect e alone (assuming this conditions uniquely define them, i.e. that the individual dose-response functions are bijective). D_/D_ quantifies the potency of compound 1 relatively to that of compound 2. d_2 D_/D_ can be interpreted as the dose d_2 of compound 2 converted into the corresponding dose of compound 1 after accounting for difference in potency. Loewe additivity is defined as the situation where d_1 + d_2 D_/D_ = D_ or d_1 / D_ + d_2/D_ = 1. Geometrically, Loewe additivity is the situation where isoboles are segments joining the points (D_,0) and (0,D_) in the domain (d_1,d_2). If we denote by f_1(d_1), f_2(d_2) and f_ ...
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Toxicodynamics
Toxicodynamics, termed pharmacodynamics in pharmacology, describes the dynamic interactions of a toxicant with a biological target and its biological effects.Boelsterli, 2003 A biological target, also known as the site of action, can be binding proteins, ion channels, DNA, or a variety of other receptors. When a toxicant enters an organism, it can interact with these receptors and produce structural or functional alterations. The mechanism of action of the toxicant, as determined by a toxicant’s chemical properties, will determine what receptors are targeted and the overall toxic effect at the cellular level and organismal level. Toxicants have been grouped together according to their chemical properties by way of quantitative structure-activity relationships (QSARs), which allows prediction of toxic action based on these properties. endocrine disrupting chemicals (EDCs) and carcinogens are examples of classes of toxicants that can act as QSARs. EDCs mimic or block transcripti ...
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Pharmacodynamics
Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms (for example, infection). Pharmacodynamics and pharmacokinetics are the main branches of pharmacology, being itself a topic of biology interested in the study of the interactions between both endogenous and exogenous chemical substances with living organisms. In particular, pharmacodynamics is the study of how a drug affects an organism, whereas pharmacokinetics is the study of how the organism affects the drug. Both together influence dosing, benefit, and adverse effects. Pharmacodynamics is sometimes abbreviated as PD and pharmacokinetics as PK, especially in combined reference (for example, when speaking of PK/PD models). Pharmacodynamics places particular emphasis on dose–response relationships, that is, the relationships between d ...
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Drug
A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insufflation (medicine), inhalation, drug injection, injection, smoking, ingestion, absorption (skin), absorption via a dermal patch, patch on the skin, suppository, or sublingual administration, dissolution under the tongue. In pharmacology, a drug is a chemical substance, typically of known structure, which, when administered to a living organism, produces a biological effect. A pharmaceutical drug, also called a medication or medicine, is a chemical substance used to pharmacotherapy, treat, cure, preventive healthcare, prevent, or medical diagnosis, diagnose a disease or to promote well-being. Traditionally drugs were obtained through extraction from medicinal plants, but more recently also by organic synthesis. Pharmaceutical drugs may be used ...
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P-value
In null-hypothesis significance testing, the ''p''-value is the probability of obtaining test results at least as extreme as the result actually observed, under the assumption that the null hypothesis is correct. A very small ''p''-value means that such an extreme observed outcome would be very unlikely under the null hypothesis. Reporting ''p''-values of statistical tests is common practice in academic publications of many quantitative fields. Since the precise meaning of ''p''-value is hard to grasp, misuse is widespread and has been a major topic in metascience. Basic concepts In statistics, every conjecture concerning the unknown probability distribution of a collection of random variables representing the observed data X in some study is called a ''statistical hypothesis''. If we state one hypothesis only and the aim of the statistical test is to see whether this hypothesis is tenable, but not to investigate other specific hypotheses, then such a test is called a null ...
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Monte Carlo Simulation
Monte Carlo methods, or Monte Carlo experiments, are a broad class of computational algorithms that rely on repeated random sampling to obtain numerical results. The underlying concept is to use randomness to solve problems that might be deterministic in principle. They are often used in physical and mathematical problems and are most useful when it is difficult or impossible to use other approaches. Monte Carlo methods are mainly used in three problem classes: optimization, numerical integration, and generating draws from a probability distribution. In physics-related problems, Monte Carlo methods are useful for simulating systems with many coupled degrees of freedom, such as fluids, disordered materials, strongly coupled solids, and cellular structures (see cellular Potts model, interacting particle systems, McKean–Vlasov processes, kinetic models of gases). Other examples include modeling phenomena with significant uncertainty in inputs such as the calculation of risk in b ...
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