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Chapter 6 Pharmacodynamics Pharmacology for Nurses: A Pathophysiologic Approach 2nd Ed. Michael Patrick Adams, Leland Norman Holland, Jr., and Paula Manuel Bostwick Know Principles of Pharmacodynamics and Clinical Practice • Helps to predict if drug will produce change • Will ensure that drug will provide safe, effective treatment Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Pharmacology for Nurses: A Pathophysiologic Approach 2nd Ed. Michael Patrick Adams, Leland Norman Holland, Jr., and Paula Manuel Bostwick Copyright ©2008 by Pearson Education, Inc. Pharmacology for Nurses: A Pathophysiologic Approach 2nd Ed. Michael Patrick Adams, Leland Norman Holland, Jr., and Paula Manuel Bostwick Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Frequency-Distribution Curve • Graphical representation of number of clients responding to drugs at different doses • Peak of curve indicates largest number of clients responding to drug Pharmacology for Nurses: A Pathophysiologic Approach 2nd Ed. Michael Patrick Adams, Leland Norman Holland, Jr., and Paula Manuel Bostwick Copyright ©2008 by Pearson Education, Inc. Skill of Nurse Critical in Determining if Average Dose Is Effective Median Effective Dose (ED50) • Middle of frequency-distribution curve • Dose that produces therapeutic response in 50% of a group • Sometimes called “average” or “standard” dose • Many clients require more or less Pharmacology for Nurses: A Pathophysiologic Approach 2nd Ed. Michael Patrick Adams, Leland Norman Holland, Jr., and Paula Manuel Bostwick Copyright ©2008 by Pearson Education, Inc. • • • Client observation Taking of vital signs Monitoring lab data Pharmacology for Nurses: A Pathophysiologic Approach 2nd Ed. Michael Patrick Adams, Leland Norman Holland, Jr., and Paula Manuel Bostwick Copyright ©2008 by Pearson Education, Inc. Median Lethal Dose (LD50) • • • • • Used to assess safety of a drug Shown on frequency-distribution curves Determined in preclinical trials Is lethal dose in 50% of group of animals Cannot be experimentally determined in humans Pharmacology for Nurses: A Pathophysiologic Approach 2nd Ed. Michael Patrick Adams, Leland Norman Holland, Jr., and Paula Manuel Bostwick Copyright ©2008 by Pearson Education, Inc. Therapeutic Index • Measure of a drug’s safety margin • The higher the value, the safer the drug Median Toxicity Dose (TD50) • Dose that will produce given toxicity in 50% of group of clients • Value may be extrapolated from – Animal data or – Adverse effects in client clinical trials Pharmacology for Nurses: A Pathophysiologic Approach 2nd Ed. Michael Patrick Adams, Leland Norman Holland, Jr., and Paula Manuel Bostwick Copyright ©2008 by Pearson Education, Inc. Calculating Therapeutic Index Therapeutic index = Median lethal dose LD50 Median effective dose ED50 Pharmacology for Nurses: A Pathophysiologic Approach 2nd Ed. Michael Patrick Adams, Leland Norman Holland, Jr., and Paula Manuel Bostwick Copyright ©2008 by Pearson Education, Inc. Example of Therapeutic Index Pharmacology for Nurses: A Pathophysiologic Approach 2nd Ed. Michael Patrick Adams, Leland Norman Holland, Jr., and Paula Manuel Bostwick Copyright ©2008 by Pearson Education, Inc. Figure 6.2 Therapeutic index: (a) drug X has a therapeutic index of 4: drug Z has a therapeutic index of 2. • Therapeutic index of 4: need error four times dose to be lethal Pharmacology for Nurses: A Pathophysiologic Approach 2nd Ed. Michael Patrick Adams, Leland Norman Holland, Jr., and Paula Manuel Bostwick Copyright ©2008 by Pearson Education, Inc. Pharmacology for Nurses: A Pathophysiologic Approach 2nd Ed. Michael Patrick Adams, Leland Norman Holland, Jr., and Paula Manuel Bostwick Copyright ©2008 by Pearson Education, Inc. Three Phases of Graded Dose-Response Curve • Phase 1: occurs at lowest dose – Few target cells affected by drug • Phase 2: linear relationship Three Phases of Graded Dose-Response Curve • Phase 3: plateau reached – Increasing dose has no therapeutic effect – Increased dose may produce adverse effects – Most desirable range – Linear relationship between amount of drug administered and degree of client response Pharmacology for Nurses: A Pathophysiologic Approach 2nd Ed. Michael Patrick Adams, Leland Norman Holland, Jr., and Paula Manuel Bostwick Copyright ©2008 by Pearson Education, Inc. Pharmacology for Nurses: A Pathophysiologic Approach 2nd Ed. Michael Patrick Adams, Leland Norman Holland, Jr., and Paula Manuel Bostwick Copyright ©2008 by Pearson Education, Inc. Two Ways to Compare Medications Figure 6.3 Dose – response relationship. • Potency • Efficacy Pharmacology for Nurses: A Pathophysiologic Approach 2nd Ed. Michael Patrick Adams, Leland Norman Holland, Jr., and Paula Manuel Bostwick Copyright ©2008 by Pearson Education, Inc. Pharmacology for Nurses: A Pathophysiologic Approach 2nd Ed. Michael Patrick Adams, Leland Norman Holland, Jr., and Paula Manuel Bostwick Copyright ©2008 by Pearson Education, Inc. Figure 6.4 Potency and efficacy: (a) drug A has a higher potency than drug B (b) drug A has a higher efficacy that drug B Potency • Lower dosage with therapeutic effect Pharmacology for Nurses: A Pathophysiologic Approach 2nd Ed. Michael Patrick Adams, Leland Norman Holland, Jr., and Paula Manuel Bostwick Copyright ©2008 by Pearson Education, Inc. Pharmacology for Nurses: A Pathophysiologic Approach 2nd Ed. Michael Patrick Adams, Leland Norman Holland, Jr., and Paula Manuel Bostwick Copyright ©2008 by Pearson Education, Inc. Efficacy Drugs That Act as Agonists • Magnitude of maximal response Pharmacology for Nurses: A Pathophysiologic Approach 2nd Ed. Michael Patrick Adams, Leland Norman Holland, Jr., and Paula Manuel Bostwick • Bind to receptor • Produce same response as endogenous chemical • Sometimes produce greater maximal response Pharmacology for Nurses: A Pathophysiologic Approach 2nd Ed. Michael Patrick Adams, Leland Norman Holland, Jr., and Paula Manuel Bostwick Copyright ©2008 by Pearson Education, Inc. Drugs That Act as Partial Antagonists • Bind to receptor • Produce weaker response than agonist Pharmacology for Nurses: A Pathophysiologic Approach 2nd Ed. Michael Patrick Adams, Leland Norman Holland, Jr., and Paula Manuel Bostwick Drugs That Act as Antagonists • • • • Receptor Is Macromolecule – Hormones, neurotransmitters, growth factors • Most drug receptors are proteins. • Associated with plasma membrane or intracellular molecules Pharmacology for Nurses: A Pathophysiologic Approach 2nd Ed. Michael Patrick Adams, Leland Norman Holland, Jr., and Paula Manuel Bostwick Copyright ©2008 by Pearson Education, Inc. Occupy receptor Prevent endogenous chemical from acting Compete with agonist for receptor Inhibit effects of agonist by changing pharmacokinetic factors Pharmacology for Nurses: A Pathophysiologic Approach 2nd Ed. Michael Patrick Adams, Leland Norman Holland, Jr., and Paula Manuel Bostwick Copyright ©2008 by Pearson Education, Inc. • Binds with endogenous molecules Copyright ©2008 by Pearson Education, Inc. Copyright ©2008 by Pearson Education, Inc. Drug Attaches to Receptor • • • • Like key to lock Triggers second messenger events Initiates drug action Can stimulate or inhibit normal activity Pharmacology for Nurses: A Pathophysiologic Approach 2nd Ed. Michael Patrick Adams, Leland Norman Holland, Jr., and Paula Manuel Bostwick Copyright ©2008 by Pearson Education, Inc. In the Future: Customized Drug Therapy Figure 6.5 Cellular receptors. • DNA test before receiving drug • Prevention of idiosyncratic responses Pharmacology for Nurses: A Pathophysiologic Approach 2nd Ed. Michael Patrick Adams, Leland Norman Holland, Jr., and Paula Manuel Bostwick Copyright ©2008 by Pearson Education, Inc. Pharmacology for Nurses: A Pathophysiologic Approach 2nd Ed. Michael Patrick Adams, Leland Norman Holland, Jr., and Paula Manuel Bostwick Copyright ©2008 by Pearson Education, Inc.