Theory of drug activity and drug receptor interaction pdf

The drug receptor interaction implies a mutual molding of drug and receptor like a lock and its matching key. A large category of them exerts their physiologic effects by binding with naturally selective receptor s and thus making the drug receptor interaction a widely studied subject, considering. This must be distinguished from the affinity, which is a measure of the ability of the drug to bind to its molecular target, and the ec 50, which is a measure of the potency of the drug and which is proportional to both efficacy and affinity. Drugreceptor interactions clinical pharmacology msd. Molecular pharmacology, structureactivity relations, gastric acid secretion, pp. Classification of drugs based on drugreceptor interactions. Receptor theory was propounded by alfred joseph clark, a theory of drug action based on occupation of receptors by specific drugs and the cellular function can be altered by interaction of the receptors with the drugs. Learn vocabulary, terms, and more with flashcards, games, and other study tools.

This theory also describes the behaviour of agonists and antagonist. A drugs ability to affect a given receptor is related to the drugs affinity probability of the drug occupying a receptor at any given instant and intrinsic efficacy intrinsic activitydegree to which a ligand activates receptors and leads to cellular response. The biological activity of drug is related to its affinity for the receptor. The driving force for the drugreceptor interaction can be considered as a low energy state of the drugreceptor complex, where kon is the rate constant for formation of the drugreceptor complex, which depends on the concentration of the drug and the receptor koff is the rate constant for breakdown of the complex, which depends on the. Feb 25, 2018 theories of drug receptor interaction 1. Drug action and pharmacodynamics pharmacology veterinary. A minimum three point attachment of a drug to a receptor site is required. The interaction of human haemoglobin with allosteric. Drug receptor interaction drugs interact with receptor sites localized in macromolecules which have proteinlike properties and specific three dimensional shapes. Pdf in presentday pharmacology and medicine, it is usually taken for granted.

The biological activity of drug is related to its affinity for the receptor, i. Receptors vary greatly in structure so a specific chemical structure is required for the receptor site and a. Receptor theory is the application of receptor models to explain drug behavior. Betagamma from gabab receptorcoupled gi has a higher affinity. A common example of an antagonistic drug interaction is the effect of concurrent zidovudine and stavu2b4 202 inducers inhibitors substrates 1a2 ritonavir, rifampin. The principles of drug design course aims to provide students with an understanding of the process of drug discovery and development from the identification of novel drug targets to the introduction of new drugs into clinical practice. Theories of drug receptor interaction receptor antagonist. For example, one drug may alter the pharmacokinetics of another. An important field of study in pharmacology comprises the investigation of drug target interaction kinetics.

The interaction of a drug molecule with its receptor can be represented in the manner shown in figure 22, where. The term drug action is used to describe the method by which the drug influences a cell and the term drug effect or response is a. The action of the benzodiazepines on the gaba receptor chapter 4 may be of this type. Agonist, antagonist and theories of drug receptor interaction presented by abhishek ghara 1st year m. Intrinsic activity ia and efficacy refer to the relative ability of a drugreceptor complex to produce a maximum functional response. A drug interaction is a change in the action or side effects of a drug caused by concomitant administration with a food, beverage, supplement, or another drug. Because this new class of drugs is extensively used, serious drugdrug interactions are an increasing risk. A theory of drug action is developed on the assumption that excitation by a stimulant drug is proportional to the rate of drugreceptor combination, rather than. Frontiers exploring drugreceptor interaction kinetics. A drugreceptor interaction occurs where a drug binds to a specific ligand for an endogenous regulatory substance.

A molecule can be composed of either single kind of element. Binding of drug to receptor is essentially the same as drug to enzyme as defined by the michelismenten equation. Theories of drug activity how drugs act drug times. Copeland dept of pharmacology october 17, 2008 concept of specific drug receptors most drugs combine with specific sites on macromolecules e. Drug receptor theory also furnishes the tools for quantifying the activity of drugs in a systemindependent manner, essential because drugs are almost always studied in test systems somewhat. Kinetics of drugreceptor interaction springer for research. Occupancy theory rests on the concept that the proportion of occupied receptors is related to the effect of the drug eg. Theories of drug activity last updated on tue, 03 sep 2019 how drugs act although there is no single uniform theory that can explain the activity of drugs, several theories have been advanced over the years in attempts to elucidate drug action. Drugreceptor interactions involve all known types of bond. In 2008 the most recent data available, 36,500 drug related deaths were reported. The drugreceptor interaction implies a mutual molding of drug and receptor like a lock and its matching key. Drug receptor interactions an overview sciencedirect topics.

Ppt receptor theory powerpoint presentation free to view. As noted above, drug receptor interaction can generally be defined as specific, doserelated and saturable. Quoting from kenakian 2008, receptor occupancy theory describes the quantitative relationships between drug concentrations and the responses that result from the interaction of those drugs with receptors. An illustration of the relationship between drug concentration and receptor occupancy by drug is shown in. The central dogma of receptor pharmacology is that a drug effect is directly proportional to the number of receptors that are occupied. The interaction of the ligand at its binding site on the. John newport langley and paul ehrlich introduced the concept of a receptor that would mediate drug action at the beginning of the 20th century. As the drug concentration is increased, a progressively higher fraction of available receptors will become occupied by drug until all available receptors become bound. Molecular orbital theory in drug research 1st edition. General theory of drugreceptor interactions springerlink. An antagonistic effect results when a drugs pharmacologic effect is reduced due to concurrent therapy. What are the historical origins of the receptor concept.

This stability is commonly measured by how difficult is for the complex to dissociate, which is measured by its kd, the dissociation constant for the drug receptor complex at. It is defined as the affinity of one for the other. Drugs with short duration of action generally have weaker. Drug it is a natural or synthetic substances which has a physiological effects when administered into the body. When the ligand approaches the receptor in an appropriate distance, a bond is formed, and then the drug action happens. The driving force for the drug receptor interaction can be considered as a low energy state of the drug receptor complex, where kon is the rate constant for formation of the drug receptor complex, which depends on the concentration of the drug and the receptor koff is the rate constant for breakdown of the complex, which depends on the.

The interaction of histaminomimetic compounds and of competitive antagonists of histamine with the histamine receptor. This statistic is a wide net and includes intentional overdose and illicit drug use, as well as adverse drug reac. If a drug does not dissociate due to a very tight binding such as a covalent bond, the effect continues to be produced as long as the receptordrug complex remains intact. Betagamma from gabab receptor coupled gi has a higher affinity for. An important field of study in pharmacology comprises the investigation of drugtarget interaction kinetics. Theories of drug receptor interaction free download as powerpoint presentation. Clarkes receptor occupation theory the occupancy model was the first model put forward by clark to explain the activity of drugs at receptors quantified the relationship between drug concentration and observed effect.

Mechanisms of drug interactions introduction the risk of dying from a drug related incident now exceeds the risk of dying in a traffic accident. Activity and molecular composition in the case of pharmacology, the fundamental postulate of chemistry reduces to the proposition that. Thus, assessing both the lifetime of the drug on its receptor i. When a drug is modelled on a hormone or a neurotransmitter, there is usually a need to develop selectivity so that the drug only interacts with specific receptors and not with all the receptors that are sensitive to a particular neurotransmitter. Pharmacodynamics is the study of the biochemical and physiologic effects of drugs and their mechanisms of action on the body or on microorganisms and other parasites within or on the body. But it can be 0 if intrinsic receptor activity exists b threshold dose drug dose or below which there is no appreciable in receptor activity with agonist binding important to note this hyperbolic relationship is the result of the dynamics of drugreceptor interaction see.

Explain the concept of drug action with respect to receptor theory, enzyme interactions and physicochemical interactions. Thus, an agonist has the properties of affinity and intrinsic activity. These characteristics of a drug at a receptor are described by k d and ed 50 and can be obtained from ligand binding and doseresponse curves. But it can be 0 if intrinsic receptor activity exists b threshold dose drug dose or below which there is no appreciable in receptor activity with agonist binding important to note this hyperbolic relationship is the result of the dynamics of drugreceptor interaction see law of mass action below. Allows one to determine a rough estimate of an unlabeled ligands affinity for a receptor. Drug receptor theory also furnishes the tools for quantifying the activity of drugs in a system. A drug that binds to a receptor and produces a biological response is an agonist.

A theory of drug action based on the rate of drugreceptor combination. Drugs interact with receptors in a reversible manner to produce a change in the state of the receptor, which is then translated into a physiological effect. Drug receptor interactions an overview sciencedirect. The biological activity is related to the drug affinity for the receptor, i. A drug that interacts with a single type of receptor that is expressed on only a limited number of differentiated cells will exhibit high specificity. Receptor theory of drug action deranged physiology. Mechanisms of drug interactions introduction the risk of dying from a drugrelated incident now exceeds the risk of dying in a traffic accident. Molecular orbital theory in drug research is a 12chapter text that emerged from a series of lectures presented to graduate students in medicinal chemistry at the university of michigan. A molecule is a small chemical element that is made up of two or more atoms held together by chemical bonds.

Drugreceptor interactions clinical pharmacology merck. The drugreceptor concept of drug action and the receptor occupation theory describe a graded doseeffect relationship, in which the responding system is capable of showing a progressively increasing effect with increasing dose or drug concentration. Balis, in principles of clinical pharmacology second edition, 2007. A drug that binds to a receptor but does not initiate a cellular response is an antagonist. The interaction between the drug d and receptor r is governed by the law of mass action. First of all some drugs have an effect by virtue of their overall physicochemical characteristics e. Classification of drugs based on drug receptor interactions. Pdf drugs by definition, are characterized as those agents that can bring a change in. The strength of the reversible interaction between a drug and its receptor. Drugdrug interactions with tyrosinekinase inhibitors. Drug receptor interactions receptor antagonist receptor. A drug receptor interaction occurs where a drug binds to a specific ligand for an endogenous regulatory substance. This molecular interaction with the receptor can be modeled mathematically and obeys the law of mass action.

The bond formed is so very strong that detachment of the ligand is very hard and nonspontaneous. The theoretical basis for using dipole moment as a free. The drug receptor interaction is usually reversible. Theories for relationship between drug receptor interaction. A drugs affinity and activity are determined by its chemical structure. J receptor theory and structureaction relationships. It covers the basic principles of how new drugs are discovered with. This type of bonding is the strongest form of bond that can be formed between a ligand and a receptor. The receptor theory is as important and basic to pharmacology as the atomic theory is to physical sciences.

In the past decade, many tyrosinekinase inhibitors have been introduced in oncology and haematooncology. Molecular pharmacology, structure activity relations, gastric acid secretion, pp. To find the interaction between drug molecule and receptor by performing docking studies. Pharmacologic analysis of drugreceptor interaction 2nd. Dissociation constant of the drugreceptor complex gives an idea a bout how potent is the drug. Intrinsic activity ia and efficacy refer to the relative ability of a drug receptor complex to produce a maximum functional response. Pharmacological receptor models preceded accurate knowledge of receptors by many years. The driving force for drugreceptor interaction is the low energy state of the drugreceptor complex. The classical interaction theory dictates that receptors occupation is directly. Over 300 group dipole moments for aromatic substituents were compiled using the dipole moments of monosubstituted benzene derivatives. Drugs can exert their pharmacological action in two different ways. It considers both drug action, which refers to the initial consequence of a drugreceptor interaction, and drug effect, which refers to the subsequent effects. Michael j curtis, pharmacologic analysis of drugreceptor interaction 2nd edition.