Pharmacology for Nurses: A Pathophysiologic
Approach
Fifth Edition
Chapter 5
Pharmacodynamics
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Pharmacodynamics and Interpatient
Variability
• 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 experience will
guide safe treatment
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Frequency Distribution Curve
• Graphical representation of number of patients
responding to a drug action at different doses
• Peak of curve indicates largest number of patients
responding to drug
• Does not show magnitude of response
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Figure 5.1 Frequency Distribution Curve:
Interpatient Variability in Drug Response
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Median Effective Dose (ED
E D sub 50)
50
• 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
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Nurse’s Skill Critical in Determining if
Average Dose is Effective
• Patient observation
• Taking of vital signs
• Monitoring lab data
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Median Lethal Dose (LD
L D sub 50)
50
• 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
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Median Toxicity Dose (TD 50 )
T D sub50
• 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
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Therapeutic Index
• Measure of a drug's safety margin
• The higher the value, the safer the drug
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Calculating Therapeutic Index
median lethal dose LD50
Therapeutic index
median effective dose ED50
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Example of Therapeutic Index
• Therapeutic index of 4: need error four times dose to be
lethal
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Figure 5.2 Therapeutic Index
(a) drug X has a therapeutic index of 4; (b) drug Z has a
therapeutic index of 2. In a human clinical study, LD50
is labeled as TD50 .
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Graded Dose-Response Relationship
• 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
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Three Phases of Graded Dose–Response
Curve (1 of 2)
• Phase 1: occurs at lowest dose
– Few target cells affected by drug
• Phase 2: straight-line portion of curve
– Most desirable range
– Linear relationship between amount of drug
administered and degree of patient response
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Three Phases of Graded Dose–Response
Curve (2 of 2)
• Phase 3: plateau reached
– Increasing dose has no therapeutic effect
– Increased dose may produce adverse effects
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Figure 5.3 Dose–Response Relationship
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Two Ways to Compare Medications
• Potency
• Efficacy
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Potency
• Drug with higher potency produces a therapeutic effect
at a lower dose, compared with another drug in the
same class
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Efficacy
• Magnitude of maximal response that can be produced
from a particular drug
• From a pharmacotherapeutic perspective, efficacy
almost always more important than potency
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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
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Receptor 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
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Drug Attaches to Receptor
• Comparable to how thumb drive docks to USB port in a
computer
• May trigger second messenger events
– e.g., activation of specific G proteins and associated
enzymes
• Initiates drug action
• Can stimulate or inhibit normal activity
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Figure 5.5 Cellular Receptors
The red triangle represents the drug binding directly with
receptors.
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Receptor Subtypes Still Being Discovered
• Permit “fine-tuning” of pharmacology
• Two basic receptor types
– Alpha
– Beta
• Drugs affect each subtype differently
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Nonspecific Cellular Responses
• Caused by drugs that act independently of receptors
• Example: changing the permeability of cellular
membranes
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Drugs That Act as Agonists
• Bind to receptor
• Produce same response as endogenous chemical
• Sometimes produce greater maximal response
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Drugs That Act as Partial Agonists
• Bind to receptor
• Produce weaker, less effective response than agonists
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Drugs 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
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In the Future: Customized Drug Therapy
• End of single-drug, one-size-fits-all policy
• DNA test before receiving drug
• Prevention of idiosyncratic (unpredictable and
unexplained) drug reactions
• Pharmacogenetics—area of pharmacology that
examines role of heredity in drug response
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Copyright
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