Pharmacodynamics (part 1); Drug-receptor interaction & dose-response curves

Lecture’s note: https://www.mediafire.com/file/r7dppq... time codes 0:00 Introduction 2:25 Targets for drug actions 7:40 Types of drug-receptor interactions 18:40 Concept of dose-response curves 20:06 Graded dose response curve 31:48 Quantal dose response curve Pharmacodynamics refers to the mechanisms and effects of medications within the body. Or more simply, it’s what medications do to the body and how they do it. In order to have an effect, most medications have to reach their target cells and bind to a receptor. Receptors are specialized proteins both inside the cell and on the cell membrane that can bind to a ligand and get triggered to alter their shape or activity. The terms affinity, potency, and efficacy describe how a drug interacts with a specific receptor. Although each has unique characteristics, these terms also apply to other receptor classes, such as ligand-gated channels, tyrosine kinase-linked receptors, and nuclear receptors, in addition to G-protein coupled receptors. Affinity: The drug's binding to the receptor, which can be modeled and explained by a variety of terms, is the first stage of receptor interaction. The product of a drug's affinity (strong binding force) for a particular receptor and the rate at which the drug-receptor complex dissociates from the receptor is the drug's affinity. There is either very little or no dissociation due to the extremely strong nature of the binding between some drugs and ligands; Drugs and ligands that bind to receptors but do not activate the receptor are referred to as antagonists because they have affinity but lack efficacy. Even so, agonists' actions are blocked by antagonists, which still elicit a response. Antagonists can bind in a variety of ways, and their binding can be either irreversible or reversible. Potency, which can be determined using a concentration or dose-response curve and expressed as the EC50 or ED50, the effective concentration or dose to cause 50% of the maximal response, refers to the concentration range or dose range over which a drug produces a response. The difference between dose and concentration must be emphasized. Dose is the amount of a drug that is administered to a patient; it is usually measured in milligrams or micrograms. On the other hand, concentration is the amount of drug in a specific volume, measured in nanomolars or micromolars. Since dose is most commonly used in clinical practice, ED50 is the most appropriate parameter to use when modeling. Full agonists are defined as agonists that elicit the maximum tissue response, while partial agonists elicit less than the maximal response. Inverse agonists are medications that have the opposite effect of a classical agonist and lower specific cellular processes below a normal resting state or tone. The majority of inverse agonists are experimental medications, however some are important for anesthesia. For example, beta-carbolines act at benzodiazepine receptors but are anxiogenic as opposed to anxiolytic. A basic competitive antagonist can inhibit the action of an inverse agonist by shifting the response curve to the right. When it comes to opioid medications, buprenorphine is a partial agonist and fentanyl is a full agonist. Measuring the drug's maximum response is usually not a reliable way to determine drug efficacy because drug efficacy is more complex than this. In fact, using the maximal tissue response to a drug as a gauge of its effectiveness would be incorrect (instead, we will model "whole human" clinically relevant responses in this article). For instance, a group of drugs may not all be full agonists or have the same efficacy even if they all produced the greatest response in a particular tissue. To understand why this might be, it's critical to understand that in many receptor systems, a full agonist would not need to occupy all available receptors in order to produce a maximal response. types of receptors are mentioned dose response curves; graded dose response curve and quantal dose response curves are detailed. importance of slope is discussed. therapeutic index is explained easily. #pharmacodynamics #affinity #efficacy #receptor