Pharmacodynamics definition

So far, this series has considered how drugs are absorbed, distributed and excreted by the body the pharmacokinetic phase of drug action. To produce therapeutic or toxic effects, drugs interact with receptors in the body the pharmacodynamic phase of drug action. The drug in the tissues, where drug-receptor interactions usually occur, is in equilibrium with the unbound drug in the plasma. Drugs usually interact in a structurally specific way with a protein receptor. This activates a second messenger system which produces a biochemical or physiological response, e.g. changes in intracellular calcium concentrations result in muscle contraction or relaxation. The most common receptors are transmembrane receptors linked to guanosine triphosphate binding proteins (G proteins) which activate second messenger systems such as adenylylcyclase (beta adrenoceptors) or the inositoltriphosphate pathway (alpha adrenoceptors). A drug which binds to a receptor and produces a maximum response is called a full agonist; a drug which binds and produces less than a maximal response is called a partial agonist. Drugs which bind but do not activate second messenger systems are called antagonists. Antagonists can only produce effects by blocking the access of the natural transmitter (agonist) to the receptor. Thus, beta blockers produce relatively little change in heart rate when given to subjects at rest as there is low sympathetic tone and little noradrenaline (the natural agonist) to be antagon...

Alright, so in order to have an effect, most medications have to reach their target cells and bind to a receptor. Receptors are specialized proteins both on the Now, that ligand could be an agonist, which is a molecule that binds and activates a receptor. This means the receptor changes its shape or activity, and that gives rise to a signal cascade of intracellular molecules - the second messengers, which ultimately results in some change in the cell’s function. Okay, now if we massively expose the receptors to their agonists, we will get a huge downstream signal cascade and cellular response. But if we continuously or persistently flood that receptor with the same agonist at the same dose, what will happen, is that the ability of the agonist to produce that response will drop. This is actually a defense mechanism, whereby cells prevent their overstimulation by agonists. If this happens very rapidly, like within a few minutes, it’s called desensitization or If this happens more gradually, like over the course of days to weeks, it’s called tolerance. Desensitization can occur with the initial dose of a medication, while tolerance typically happens with repeated doses. Alright, so, there are several mechanisms responsible for these phenomena. First, chronic exposure to agonists cause a decrease in the number of receptors. The decrease in the number of the receptors could result from the reduced synthesis of new receptors, also known as downregulation. Also, chronic exposure ...

\( \newcommand\) • • • • • • • • • • • • • The ability of a drug to carry its metabolic action (response)depends on two general phase. One phaseis the ability of the drug to reach its siteof action (receptor) in a particular cell. This processbegins with the administration of the drug, itsabsorption, distribution, metabolization,and excretionthrough the body. This phase of drug actionis called pharmacokinetics. Once at its action site, the ability of the drug to bind to the receptor depends on the chemical interactions between the chemical groups in the receptor and the drug(drug-receptor affinity). This phase of drug action is called pharmacodynamics. In order for a drug to be effective, it needs to exhibit acceptable pharmacokinetic and pharmacodynamic properties. Pharmacokinetics and Pharmacodynamic stages of Drug Action. Image by A. Pharmacokinetics Pharmacokinetics deals with the absorption, distribution, biotransformation (metabolization), and excretion of drugs. These factors, coupled with dosage, determine the concentration of a drug at its sites of action and, hence, the intensity of its effects as a function of time. Many basic principles of biochemistry and enzymology and the physical and chemical principles that govern the active and passive transfer and the distribution of substances across biological membranes are readily applied to the understanding of this important aspect of medicinal chemistry. Drug Absorption: Absorption occurs after drugs enter the body...

Pharmacodynamics Pharmacodynamics is defined as the effects of the interaction of the drug with the body, or ‘what does the drug do to the body?’ From: Encyclopedia of Forensic and Legal Medicine (Second Edition), 2016 Related terms: • Combination Therapy • Patient • Inpatient • Biological Marker • Drug Therapy Melinda Marian, Wolfgang Seghezzi, in Nonclinical Development of Novel Biologics, Biosimilars, Vaccines and Specialty Biologics, 2013 Pharmacodynamics, PK/PD Methods and Examples Pharmacodynamics (PD) is the quantitative study of the relationship between drug exposure (concentrations or dose) and pharmacologic or toxicologic responses. PK/PD analysis combines PK and PD model components to describe the dose–concentration–response time course. PK/PD models are especially useful for biopharmaceuticals since dose- and time-dependent effects on PK and responses are common. PK/PD models for biopharmaceuticals (and small molecules) have become increasingly sophisticated, and newer mechanistic PK/PD models not only empirically describe the data, but can include pertinent aspects of physiology which allow extrapolation across species and disease indications. PK/PD models can also provide simulations and hypothesis testing of potential drug impacts on biology and can be of great value in early molecule design and engineering, particularly for “biobetter” molecules where improvements in specific molecule characteristics (i.e. stability, improved FcRn binding) or target interac...

Pharmacodynamics (sometimes described as what a drug does to the body) is the study of the biochemical, physiologic, and molecular effects of drugs on the body and involves Drug–Receptor Interactions Receptors are macromolecules involved in chemical signaling between and within cells; they may be located on the cell surface membrane or within the cytoplasm (see table Some Types of Physiologic... read more (including receptor sensitivity), postreceptor effects, and Chemical Interactions Some drugs produce effects without altering cellular function and without binding to a receptor. For example, most antacids decrease gastric acidity through simple chemical reactions; antacids... read more . Pharmacodynamics, with Overview of Pharmacokinetics Pharmacokinetics, sometimes described as what the body does to a drug, refers to the movement of drug into, through, and out of the body—the time course of its absorption, bioavailability, distribution... read more (what the body does to a drug, or the fate of a drug within the body), helps explain the relationship between the Dose-Response Relationships Regardless of how a drug effect occurs—through binding or chemical interaction—the concentration of the drug at the site of action controls the effect. However, response to concentration may... read more , ie, the drug's effects. The pharmacologic response depends on the drug binding to its target. The concentration of the drug at the receptor site influences the drug’s effect. Disorder...

Sub-Disciplines of Pharmacology • Pharmacodynamics: effects and mechanisms of drug action • Drug-Receptor Interactions • Dose-Response Relationships • Signal Transduction • Pharmacokinetics: movement of drug throughout the body including: • Absorption • Distribution • Metabolism • Excretion • Pharmacogenetics: genetic factors play a role in the following: • Rate of Drug Metabolism • Drug-Induced Toxicity • Drug-Induced Allergies Pharmacology and the Pharmacist Key Questions you should be asking as a Pharmacist: • Where is the molecular site of action? • What are the body function changes caused by a drug (pharmacodynamics)? • What is the relationship between the Dose vs. Effect? • How does a drug produce its effect? • What is the fate of the drug once it enters the body (pharmacokinetics)? • What is the interplay between genetic makeup and drug response? Example: Beta 1 Blocker: Metoprolol Succinate (oral) Drug Action: selective binding to cardiac muscle beta 1 adrenergic receptors that respond to norepinephrine (at higher doses, also inhibits bronchial and vascular smooth muscle by acting on beta 2 adrenergic receptors) to inhibit the binding of norepinephrine. Drug Effect: reduced inotropic effect (contractility) and chronotropic effect (heart rate) Fate of the Drug (pharmacokinetics): 12% protein binding and distribution 5.6 L/kg: hepatic metabolism (CYP2D6 mainly): <5% renal excretion: t 1/23-7 hours