Pharmacology for Nurses: A Pathophysiological Approach

Third Canadian Edition

Chapter 4
Pharmacodynamics

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Learning Outcomes (1 of 3)
1. Apply principles of pharmacodynamics to clinical
practice.
2. Discuss how frequency response curves may be
used to explain how clients respond differently to
medications.
3. Explain the importance of the median effective
dose (ED50) to clinical practice.

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Learning Outcomes (2 of 3)
4. Compare and contrast median lethal dose (LD 50)
and median toxicity dose (TD50).
5. Correlate a drug's therapeutic index to its margin
of safety.
6. Identify the significance of the graded dose‒
response relationship to clinical practice.

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Learning Outcomes (3 of 3)
7. Compare and contrast the terms potency and
efficacy.
8. Distinguish between an agonist, partial agonist,
and antagonist.
9. Explain the relationship between receptors and
drug action.
10.Explain possible future developments in the field
of pharmacogenetics.

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Pharmacodynamics (1 of 2)
• Refers to what the drug does to the body to create
a response
– Related to the mechanism of action of a drug
– Related to how a drug interacts with a target tissue
 Altering the activity of a cell through interactions with receptor
 Altering the activity of an enzyme

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Pharmacodynamics (2 of 2)
• Nursing Process
– Recognizing that there is considerable variation in
client response to a particular dose of a drug
– Recognizing consequences of giving too much or too
little of a drug in terms of therapeutic response, risk of
adverse effects
– Application of pharmacodynamics critical for safe and
responsible administration of medications

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Interpatient Variability
• Response to dose of drug is normally distributed
across a population
– Some people require a very small dose to produce a
therapeutic response (left side of curve in figure 4.1)
– Some people require a very large dose to produce a
therapeutic response (right side of curve)
– Most require a dose in the middle to produce a
therapeutic response

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Median Effective Dose (ED50)

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Interpatient Variability – ED50
• Dose at which 50% of a population exhibit desired
therapeutic response
• Clinical implications
– predicts dose range to achieve therapeutic response
– ED50 may be toxic for some patients and may not
produce a meaningful response in others
– Critical to monitor patient response to assess if dosage
adjustment is indicated

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TD50 and LD50
• Normal frequency distributions exist for both the
dose of drug at which it is toxic and at which it is
lethal for test subjects
– TD50 refers to median toxic dose
 Dose at which 50% of test subjects exhibit a response
indicative of toxicity
– LD50 refers to median lethal dose
 Dose at which 50% of test subjects are killed by drug

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Therapeutic Index (TI)
• Measure that compares LD50 to ED50 using a ratio
• TI = LD50 / ED50
• If a drug has a large TI, it is considered to be safer
(upper panel of figure 4.2) than a drug with a
smaller TI (lower panel of figure 4.2)

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Therapeutic Index

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Margin of Safety (MOS)
• Dose of drug that is lethal to 1% (LD 1; left tail of
orange curve in figure 4.2) of animals divided by
dose of drug that produces a therapeutic effect in
99% (ED99; right tail of green curve in figure 4.2) of
animals
– MOS = LD1 / ED99
– Drugs with a large TI will also have a larger MOS

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Graded Dose-Response Relationship (1 of 4)
• Describes relationship between dose of drug and
intensity of drug response
– See figure 4.3
• Sinusoidal curve with three distinct phases
– Phase 1: occurs at low doses; very little change in
response as dose increases
– Phase 2: linear phase; sharp increase in response as
dose is increased
– Phase 3: plateau phase; no change in response as
dose increases

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Graded Dose-Response Relationship (2 of 4)

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Graded Dose-Response Relationship (3 of 4)
• Phase 2 is best range of doses to achieve a safe,
therapeutic effect
• Response to drug usually due to several
mechanisms
– More receptors being affected by drug
– More enzymes being affected by response
– Patient symptoms affected by drug
 ie patient has a headache and feels better after taking
medication

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Graded Dose-Response Relationship (4 of 4)
• Phase 1
– Few receptors or enzymes affected, therefore response
is minimal
• Phase 2 – linear phase
– As more receptors or enzymes are affected, intensity of
response increases
• Phase 3 – plateau phase
– Drug is bound to all receptors or enzymes, or
symptoms have been alleviated. Increasing dose has
no further effect

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Potency and Efficacy (1 of 3)
• Even within a pharmacologic class, not all drugs
produce the same intensity of response
• Two measures are commonly used to quantify and
compare elements of graded dose-response
curves
– Potency
– Efficacy

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Potency and Efficacy (2 of 3)
• Potency
– Amount of drug required to produce a particular
intensity of response
– drug that requires lowest dose to produce particular
intensity of response is most potent (see figure 4.4,
upper panel)
• Efficacy
– Maximum intensity of response produced by a
particular dose of drug
– Drug with greatest intensity of response has highest
efficacy (figure 4.4, lower panel)
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Potency and Efficacy (3 of 3)

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Receptor Theory (1 of 2)
• Most drugs influence biological response through
interactions with cellular receptors
• Receptor
– Cellular molecule to which a medication binds to
produce its effects
– Intrinsic activity – ability of drug to bind receptor and
produce biological response
– Most drugs enhance or inhibit a physiological process.

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Receptor Theory (2 of 2)
• Receptors are only activated or inhibited by
chemicals that bind like lock and key
• When receptor is bound by its ligand, intracellular
response is triggered
– Responses carried out by second messenger systems
within the cell
– Responses can be short term (opening of channels)
– Responses can be long term (transcription and
translation of genes)

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Agonists and Antagonists (1 of 2)
• Within a pharmacologic class, some drugs are
better at stimulating intracellular responses than
others
• Agonist
– Mimics the action of endogenous substances;
response may be greater than endogenous activity.
• Partial Agonist
– Produces weaker responses than endogenous
substances

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Agonists and Antagonists (2 of 2)
• Antagonists
– Prevent action of endogenous substances, usually by
competing with endogenous ligand and/or agonist for
receptor binding sites
– Sometimes used to prevent adverse effects of
overdoses
– Antagonists do not usually have intrinsic activity

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Pharmacogenetics
• Branch of pharmacology that studies the role of
genetic variation in drug responses.
• Considers underlying genetic expression as
reason for why drug therapy not effective for
everyone
• Using data from human genome project, genetic
differences in drug-metabolizing enzymes have
been discovered; opens door to individualized
drug therapy

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