adams ch05 lecture
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PHARMACOLOGY FOR NURSESPHARMACOLOGY FOR NURSESA Pathophysiological ApproachA Pathophysiological Approach
CHAPTER
FOURTH EDITIONFOURTH EDITION
Copyright © 2014, © 2011, © 2008 by Pearson Education, Inc.All Rights Reserved
5Pharmacodynamics
Pharmacology for Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
Pharmacodynamics and Clinical Pharmacodynamics and Clinical PracticePractice
• Pharmacodynamics – how a medicine changes the body
• Helps to predict if drug will produce change
• Will ensure that drug will provide safe, effective treatment
• Combination of drug guides and intuitive knowledge will guide safe treatment
Pharmacology for Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
Frequency Distribution CurveFrequency Distribution Curve
• Graphical representation of number of patients responding to drugs at different doses
• Peak of curve indicates largest number of patients responding to drug.
• Does not show magnitude of response
Pharmacology for Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
Figure 5.1 Frequency distribution curve: interpatient variability in drug response
Pharmacology for Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
Median Effective Dose (EDMedian Effective Dose (ED5050))
• Middle of frequency distribution curve• Dose that produces therapeutic
response in 50% of a group• Sometimes called “average” or
“standard” dose• Many patients require more or less.
Pharmacology for Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
Skill of Nurse Critical in Determining if Skill of Nurse Critical in Determining if Average Dose Is EffectiveAverage Dose Is Effective
• Patient observation• Taking of vital signs• Monitoring lab data
Pharmacology for Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
Median Lethal Dose (LDMedian Lethal Dose (LD5050))
• 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 Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
Median Toxicity Dose (TDMedian Toxicity Dose (TD5050))
• Dose that will produce given toxicity in 50% of group of patients
• Value may be extrapolated from– Animal data– Adverse effects in patient clinical trials
• Needed because Median Lethal Dose cannot be tested in humans
Pharmacology for Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
Therapeutic IndexTherapeutic Index
• Measure of a drug's safety margin• The higher the value, the safer the drug
Pharmacology for Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
Calculating Therapeutic IndexCalculating Therapeutic Index
Pharmacology for Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
Example of Therapeutic IndexExample of Therapeutic Index
• Therapeutic index of 4: need error four times dose to be lethal
Pharmacology for Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
Figure 5.2 Therapeutic index: (a) drug X has a therapeutic index of 4; (b) drug Z has a therapeutic index of 2
Pharmacology for Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
Graded Dose–Responsive CurveGraded Dose–Responsive Curve
• Graphically visualizes differences in responses to medications in a single patient
• Obtained by observing and measuring patient's response at different doses of the drug
Pharmacology for Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
Three Phases of Graded Three Phases of Graded Dose–Response CurveDose–Response Curve
• Phase 1: occurs at lowest dose– Few target cells affected by drug
• Phase 2: linear relationship– Most desirable range– Linear relationship between amount of
drug administered and degree of patient response
Pharmacology for Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
Three Phases of Graded Three Phases of Graded Dose–Response CurveDose–Response Curve
• Phase 3: plateau reached– Increasing dose has no therapeutic
effect.– Increased dose may produce adverse
effects.
Pharmacology for Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
Figure 5.3 Dose–response relationship
Pharmacology for Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
Two Ways to Compare MedicationsTwo Ways to Compare Medications
• Potency• Efficacy
Pharmacology for Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
PotencyPotency
• Drug with higher potency produces a therapeutic effect at a lower dose, compared with another drug in the same class.
Pharmacology for Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
EfficacyEfficacy
• Magnitude of maximal response that can be produced from a particular drug
• From a pharmacotherapeutic perspective, efficacy is almost always more important than potency.
Pharmacology for Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
Figure 5.4 Potency and efficacy: (a) drug A has a higher potency than drug B; (b) drug A has a higher efficacy than drug B
Pharmacology for Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
Drugs That Act as AgonistsDrugs That Act as Agonists
• Bind to receptor• Produce same response as endogenous
substance• Sometimes produce greater maximal
response
Pharmacology for Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
Drugs That Act as Partial AgonistsDrugs That Act as Partial Agonists
• Bind to receptor• Produce weaker response than agonists
Pharmacology for Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
Drugs That Act as AntagonistsDrugs That Act as Antagonists
• Occupy receptor• Prevent endogenous chemical from
acting• Often compete with agonists for
receptor• Functional antagonists inhibit the
effects of an agonist not by competing for a receptor, but by changing pharmacokinetic factors.
Pharmacology for Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
Receptor Is MacromoleculeReceptor Is Macromolecule
• Molecule to which medication binds in order to initiate its effects
• Binds endogenous molecules– Hormones, neurotransmitters, growth
factors• Most drug receptors are protein
agonists.• Associated with plasma membrane or
intracellular molecules
Pharmacology for Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
Drug Attaches to ReceptorDrug Attaches to Receptor
• Like key to lock• May trigger second messenger events
– e.g., activation of specific G proteins and associated enzymes
• Initiates drug action• Can stimulate or inhibit normal activity
Pharmacology for Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
Receptor Subtypes Still Being Receptor Subtypes Still Being DiscoveredDiscovered
• Permit “fine-tuning” of pharmacology• Two basic receptor types
– Alpha– Beta
• Drugs affect each subtype differently.
Pharmacology for Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
Nonspecific Cellular ResponsesNonspecific Cellular Responses
• Caused by drugs that act independently of receptors
• Example: changing the permeability of cellular membranes
Pharmacology for Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
Figure 5.5 Cellular receptors
Pharmacology for Nursing: A Pathophysiology Approach, Fourth EditionMichael Patrick Adams | Leland N. Holland | Carol Urban
In the Future: Customized In the Future: Customized Drug TherapyDrug Therapy
• End of single-drug, one-size-fits-all policy
• DNA test before receiving drug• Prevention of idiosyncratic responses—
unpredictable and unexplained drug reactions
• Pharmacogenetics—area of pharmacology that examines role of heredity in drug response