Baseline receptor density and the efficiency of stimulusresponse mechanisms vary from tissue to tissue. The binding of a drug to receptor depends on types of chemical bounds that can be established between drug and receptor. Conformational entropy in drugreceptor interactions. Introduction cannabis or marijuana is the most commonly used illegal substance in the world and approximately four percent of the worlds population has used cannabis at least once in the past year leggett. A chelator sequester of similar agent that interacts directly with the drug being antagonized to remove it or prevent it from binding its receptor. A drug that binds to a receptor but does not initiate a cellular response is an antagonist. If you conceptualize drug receptor interactions as a lock and key model, agonists are keys that fit into a lock receptor and open activate them, whereas antagonists fit into the lock and jam the mechanism. However, some drug effects are non receptor mediated and are caused by the particular physical or chemical properties of the drug molecule. 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. The interaction between the drug d and receptor r is governed by the law of mass action.
I pharmacodynamics in pharmacology terry kenakin encyclopedia of life support systems eolss pharmacodynamics in pharmacology terry kenakin glaxosmithkline research and development, usa keywords. Occupancy theory rests on the concept that the proportion of occupied receptors is related to the effect of the drug eg. Most drug effects are induced by the interaction of a drug molecule with specific molecular structures in the. Anytime you take more than one medication, or even mix it with certain foods, beverages, or overthecounter medicines, you are at risk of a drug interaction. A neurotransmitter has a specific shape to fit into a receptor site and cause a pharmacological response such as a nerve impulse being sent. To firmly grasp the concepts of how effects, both desired and. 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 there are many causes of drug interactions.
Ionic interactions are more reversible, compared to its covalent counterpart. 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. Clinical implications of drugdrug interactions with p2y12. According to conventional twostate drug receptor interaction model, binding of a ligand may initiate activity agonist with varying degrees of positive intrinsic activity or prevent the effect of an agonist antagonist with zero intrinsic activity. Drug interactions of antidiabetics part 1 diabetic patients take insulin andor other oral hypoglycemic and antihyperglycemic drugs to control their blood sugar levels. Law of mass action when a drug d combines with a receptor r, it does so at a rate which is dependent on the concentration of the drug and the concentration. Some drug interactions can be understood by looking at the properties of a single compound. When receptor sensitivity changes, the same concentration of a drug will produce a greater or lesser physiological response. Whereas various drug drug interactions have been described for clopidogrel and ticagrelor, prasugrel seems to have a lower potential for drug drug interactions. General theory of drugreceptor interactions springerlink. The simplest model of drugreceptor or more generally protein interaction is the law of mass action in which the drug binds reversibly to the protein at a single site. Drug discovery to drug development pipeline preexisting target literature target. Receptors are macromolecules involved in chemical signaling between and within cells. A drug that binds to a receptor and produces a biological response is an agonist.
A chemical antagonist does not depend on interaction with the agonists receptor although such interaction may occur. Amged sirelkhatim 2 when a drug interacts with a receptor, a. Drug receptor interactions abstract in presentday pharmacology and medicine, it is usually taken for granted that cells contain a host of highly specific receptors. In general, concomitant administration of strong cyp3a4 inhibitors or inducers should be avoided in patients treated with p2y 12 receptor. For example, if we know how cannabidiol cbd, a nonintoxicating component of cannabis, inhibits drug metabolizing enzymes, then we can foresee certain 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. Some of these interactions can occur even at moderate drinking levels and result in adverse health effects for the drinker. Mechanism of drug action drug receptor interactions howmed. Most drug interactions are not serious, but because a few are, it is important to understand the possible outcome before you take your medications. Receptor is a macromolecule in the membrane or inside the cell that specifically chemically bind a ligand drug. Pharmacology, psychoactive agents and drug interactions ureh nena lekwauwa, m. Most of the drugs binding receptors resemble the agonists but they cannot activate the receptors, and also prevent agonist binding. Pharmacological receptor models preceded accurate knowledge of receptors by many years. Functional groups, drugreceptor interactions and drug design.
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. Antagonists are drugs that bind to receptors without activating them, and consequently prevent the binding of other agonists. This type of bonding is the strongest form of bond that can be formed between a ligand and a receptor. Receptor types, mechanism, receptor pharmacology, drug receptor interactions, theories of receptor pharmacology, spare receptors and new concepts like biased a slideshare uses cookies to improve functionality and performance, and to provide you with relevant advertising. Receptor theory of drug action deranged physiology. Drugreceptor interactions clinical pharmacology msd. The biological activity is related to the drug affinity for the receptor, i. This means the drug is designed to specifically target and react with that specific biomolecule. Can glide retrieve known active compounds from a decoy set. Interaction between the drug and the biologic receptor would be expected to take place by utilizing the same bonding forces involved as thosewhensimple moleculesinteract. A drug molecule is considerably smaller in size than a receptor. Drug interactions between ccr5 antagonist and other drugs the information in the brief version is excerpted directly from the fulltext guidelines. The specific binding site on a receptor may be identified and studied. Drug receptor interactions last updated on mon, 05 mar 2018 medicinal chemistry although the hansch reasoning does apply to the interaction of a drug with its receptor, many of the factors that are considered relate to the substance crossing barriers and entering different cellular phases.
Activated receptors directly or indirectly regulate cellular biochemical processes eg, ion conductance, protein phosphorylation, dna transcription, enzymatic activity. This is usually through specific drug receptor sites known to be located on the membrane. Receptor theory is the application of receptor models to explain drug behavior. Introduction to structurebased drug design a practical guide tara phillips. Drug receptor interactions an overview sciencedirect. Ppt drugreceptor interactions powerpoint presentation. Mohamed, faculty of pharmacy, university of khartoum 2014 4. However, the latter process does not last too long because at some point the receptor drug complex is degraded and eliminated, and a new free receptor is synthesized. Alternatively, drug interactions may result from competition for a single receptor or signaling pathway. Dissociation constant of the drug receptor complex gives an idea a bout how potent is the drug. Ccr5 antagonist drug interactions drugdrug interactions. We show the role of the conformational component of the entropy in the complex formation between a substance and a specific neuroreceptor, using mcholinolytics and ligands of. Drugs, aging, genetic mutations, and disorders can increase upregulate or decrease downregulate the number and binding affinity of receptors. This type of interaction is usually not employed in drug action.
Thus, an agonist has the properties of affinity and intrinsic activity. Theories for relationship between drug receptor interaction. For example, clonidine downregulates alpha 2 receptors. After attachment to a receptor site, a drug may either initiate a response or prevent a response from occurring. The pharmacodynamic interactions of drug on drug can be divided into three broad groups. Under such conditions, regardless of the assay employed, ligand l binding to its receptor r at equilibrium is.
The medicinal chemistry course adme adsorption, distribution, metabolism and excretion of drugs drug receptor interactions development of drugs screening techniques combinatorial chemistry d. Drug receptor interactions the ability of a drug to produce an effect results from specific chemical interactions between the drug and specific sites lipoprotein receptors, enzymes, biomembranes, nucleic acids or small molecules. For example, one drug may alter the pharmacokinetics of another. This molecular interaction with the receptor can be modeled mathematically and obeys the law of mass action. To elaborate on these is the objective of this chapter. Copeland dept of pharmacology october 17, 2008 concept of specific drug receptors most drugs combine with specific sites on macromolecules e.
Experimental evidence indicates that drugs interact with receptor sites localized in macromolecules which have proteinlike properties and specific three dimensional shapes. The vast majority of drugs show a remarkably high correlation of structure and specificity to produce pharmacological effects. Drug receptor interactions may be modified by changes in receptor sensitivity, this being influenced by complex regulatory and homeostatic factors. Mechanisms of pharmacodynamic drugdrug interactions. The brief version is a compilation of the tables and boxed recommendations. Drugs act on the cell membrane by physical andor chemical interactions.
The driving force for drug receptor interaction is the low energy state of the drug receptor complex. The bond formed is so very strong that detachment of the ligand is very hard and nonspontaneous. 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 sequel to this action. Interactions between drugs can be classified as pharmacokinetic or pharmacodynamic. Here we will be focussing on two of the main biomolecules when it comes to drug target interaction, enzymes and receptors. A large category of them exerts their physiologic effects by binding with naturally selective receptor s and thus making the drugreceptor interaction a widely studied subject, considering particularly the complex intracellular biochemistry, pharmacology and energetics involved in the entire event. These are defined as proteins on or within the cell that bind with specificity to particular drugs, chemical messenger substances or hormones and mediate their effects on the body. The neurotransmitter is similar to a substrate in an enzyme interaction. These biomolecules could be proteins, nucleic acids, receptors, enzymes, hormones, ion channels etc. Along with antidiabetic medicines they may take drugs such as otc medicines, prescription medicines, treat other illnesses which may interact with them.
1079 1552 374 544 1148 1361 412 107 614 796 660 877 33 1069 778 455 642 815 742 426 996 656 1060 1516 1249 1522 187 916 497 1041 246 641 169 290 122 1086 1263 969 484