1. Chapter 5
Pharmacodynamics 1

2. Pharmacodynamics
The study of the biochemical and physiologic effects of drugs and the molecular mechanisms by which those effects are produced
The study of what drugs do to the body and how they do it 2

3. Therapeutic Objective
To accomplish the therapeutic objective, nurses must have a basic understanding of pharmacodynamics
Educating patients about their medications
Making PRN decisions
Evaluating patients for drug responses (both beneficial and harmful)
Collaborating with physicians about drug therapy 3

4. Pharmacodynamics Dose-response relationships
Drug-receptor interactions
Drug responses that do not involve receptors
Interpatient variability in drug responses
The therapeutic index 4

5. Dose-Response Relationships
Relationship between the size of an administered dose and the intensity of the response produced
Determines
The minimum amount of drug we can use
The maximum response a drug can elicit
How much we need to increase the dosage to produce the desired increase in response 5

6. Dose-Response Relationships
As the dosage increases, the response becomes progressively larger.
Tailor treatment by increased/decreased dosage until desired intensity of response is achieved.
Three phases occur (see Figure 5-1). 6

7. Fig. 5-1. Basic components of the dose-response curve.
A, A dose-response curve with dose plotted on a linear scale. B, The same dose-response
relationship shown in A but with the dose plotted on a logarithmic scale. Note the three
phases of the dose-response curve: Phase 1, The curve is relatively flat; doses are too low to
elicit a significant response. Phase 2, The curve climbs upward as bigger doses elicit a
corresponding increase in response. Phase 3, The curve levels off; bigger doses are unable
to elicit a further increase in response. (Phase 1 is not indicated in A because very low doses
cannot be shown on a linear scale.) 7

8. Maximal Efficacy and Relative Potency
These two characteristic properties of drugs are revealed in dose-response curves.
Maximal efficacy
The largest effect that a drug can produce (height of the curve; see Fig. 5-2A)
Match the intensity of the response with the patient’s need.
Very high maximal efficacy is not always more desirable. Don’t hunt squirrels with a cannon. 8

9. Fig. 5-2. Dose-response curves demonstrating efficacy and potency.
A, Efficacy, or “maximal efficacy,” is an index of the maximal response a drug can produce. The
efficacy of a drug is indicated by the height of its dose-response curve. In this example,
meperidine has greater efficacy than pentazocine. Efficacy is an important quality in a drug.
B, Potency is an index of how much drug must be administered to elicit a desired response.
In this example, achieving pain relief with meperidine requires higher doses than with morphine.
We would say that morphine is more potent than meperidine. Note that, if administered in
sufficiently high doses, meperidine can produce just as much pain relief as morphine. Potency is
usually not an important quality in a drug. 9

10. Maximal Efficacy and Relative Potency
The amount of drug we must give to elicit an effect (see Fig. 5-2B)
Rarely an important characteristic of the drug
Can be important if lack of potency forces inconveniently large doses
Implies nothing about maximal efficacy – refers to dosage needed to produce effects 10

11. Drug-Receptor Interactions
Drugs
Chemicals that produce effects by interacting with other chemicals
Receptors
Special chemicals in the body that most drugs interact with to produce effects 11

12. Receptor
A receptor is any functional macromolecule in a cell to which a drug binds to produce its effects.
Technically, receptors can include enzymes, ribosomes, tubulin, etc.
The term receptor is generally reserved for the body’s own receptors for
Hormones, neurotransmitters, and other regulatory molecules 12

13. Receptor Binding
Binding of a drug to its receptor is usually reversible.
Receptor activity is regulated by endogenous compounds.
When a drug binds to a receptor, it will mimic or block the action of the endogenous regulatory molecules and increase or decrease the rate of physiologic activity normally controlled by that receptor. 13

14. Fig. 5-3. Interaction of drugs with receptors for norepinephrine.
Under physiologic conditions, cardiac output can be increased by the binding of
norepinephrine (NE) to receptors (R) on the heart. Norepinephrine is supplied to
these receptors by nerves. These same receptors can be acted on by drugs,
which can mimic the actions of endogenous NE (and thereby increase
cardiac output) or block the actions of endogenous NE (and thereby reduce
cardiac output). 14

15. Important Properties of Receptors
Receptors are normal points of control of physiologic processes.
Under physiologic conditions, receptor function is regulated by molecules supplied by the body.
Drugs can only mimic or block the body’s own regulatory molecules.
Drugs cannot give cells new functions. 15

16. Important Properties of Receptors
Drugs produce their therapeutic effects by helping the body use its preexisting capabilities.
In theory, it should be possible to synthesize drugs that can alter the rate of any biologic process for which receptors exist. 16

17. Four Primary Receptor Families
Cell membrane–embedded enzymes
Ligand-gated ion channels
G protein–coupled receptor systems
Transcription factors 17

18. Fig. 5-4. The four primary receptor families.
1, Cell membrane–embedded enzyme. 2, Ligand-gated ion channel. 3, G protein–coupled
receptor system (G = G protein). 4, Transcription factor. (See text for details.) 18

19. Receptors and Selectivity of Drug Action
The more selective a drug is, the fewer side effects it will produce.
Receptors make selectivity possible.
Each type of receptor participates in the regulation of just a few processes. 19

20. Receptors and Selectivity of Drug Action
Lock and key mechanism
Does not guarantee safety
Body has receptors for each:
Neurotransmitter
Hormone
All other molecules in the body used to regulate physiologic processes 20

21. Fig. 5-5. Interaction of acetylcholine with its receptor.
A, Three-dimensional model of the acetylcholine molecule. B, Binding of acetylcholine to its
receptor. Note how the shape of acetylcholine closely matches the shape of the receptor.
Note also how the positive charges on acetylcholine align with the negative sites on the receptor. 21

22. Theories of Drug-Receptor Interaction
Simple occupancy theory
Modified occupancy theory
Affinity
Strength of the attraction
Intrinsic activity
Ability of the drug to activate a receptor upon binding 22

23. Fig. 5-6. Model of simple occupancy theory.
The simple occupancy theory states that the intensity
of response to a drug is proportional to the number of
receptors occupied; maximal response is reached with
100% receptor occupancy. Because the hypothetical
cell in this figure has only four receptors, maximal
response is achieved when all four receptors are
occupied. (Please note: Real cells have thousands
of receptors.) 23

24. Drug-Receptor Interactions
Agonists, antagonists, and partial agonists
Agonists
Antagonists
Noncompetitive vs. competitive antagonists
Partial agonists 24

25. Agonists Agonists are molecules that activate receptors.
Endogenous regulators are considered agonists.
Agonists have both affinity and high intrinsic activity.
Dobutamine mimics norepinephrine at cardiac receptors.
Agonists can make processes go “faster” or “slower.” 25

26. Antagonists
Produce their effects by preventing receptor activation by endogenous regulatory molecules and drugs
Affinity but no intrinsic activity
No effects of their own on receptor function 26

27. Antagonists
Do not cause receptor activation but cause pharmacologic effects by preventing the activation of receptors by agonists
If there is no agonist present, an antagonist will have no observable effect. 27

28. Noncompetitive vs. Competitive Antagonists
Noncompetitive antagonists
Bind irreversibly to receptors
Reduce the maximal response that an agonist can elicit (fewer available receptors)
Impact not permanent (cells are constantly breaking down “old” receptors and synthesizing new ones) 28

29. Noncompetitive vs. Competitive Antagonists
Compete with agonists for receptor binding
Bind reversibly to receptors
Equal affinity: receptor occupied by whichever agent is present in the highest concentration 29

30. Fig. 5-7. Dose-response curves in the presence of competitive and noncompetitive
antagonists.
A, Effect of a noncompetitive antagonist on the dose-response curve of an agonist.
Note that noncompetitive antagonists decrease the maximal response achievable with an
agonist. B, Effect of a competitive antagonist on the dose-response curve of an agonist.
Note that the maximal response achievable with the agonist is not reduced. Competitive
antagonists simply increase the amount of agonist required to produce any given intensity of
response. 30

31. Partial Agonists
These are agonists that have only moderate intrinsic activity.
The maximal effect that a partial agonist can produce is less than that of a full agonist.
Can act as antagonists as well as agonists 31

32. Regulation of Receptor Sensitivity
Receptors are dynamic cell components.
Number of receptors on cell surface and sensitivity to agonists can change in response to
Continuous activation
Continuous inhibition 32

33. Regulation of Receptor Sensitivity
Continuous exposure to agonist
Desensitized or refractory
Down-regulation
Continuous exposure to an antagonist
Hypersensitive 33

34. Drug Responses That Do Not Involve Receptors
Simple physical or chemical interactions with other small molecules
Examples of receptorless drugs
Antacids, antiseptics, saline laxatives, chelating agents 34

35. Interpatient Variability in Drug Responses
The dose required to produce a therapeutic response can vary substantially among patients.
Measurement of interpatient variability (see Fig. 5-8)
The ED50 35

36. Fig. 5-8. Interpatient variation in drug responses.
A, Data from tests of a hypothetical acid suppressant in 100 patients. The goal of the study is to
determine the dosage required by each patient to elevate gastric pH to 5. Note the wide
variability in doses needed to produce the target response for the 100 subjects. B, Frequency
distribution curve for the data in A. The dose at the middle of the curve is termed the ED50—the
dose that will produce a predefined intensity of response in 50% of the population. 36

37. Interpatient Variability in Drug Responses
Clinical implications of interpatient variability
The initial dose of a drug is necessarily an approximation.
Subsequent doses must be “fine tuned” based on the patient’s response.
ED50 in a patient may need to be increased or decreased after the patient response is evaluated. 37

38. Therapeutic Index Measure of a drug’s safety
Ratio of the drug’s LD50 (average lethal dose to 50% of the animals treated) to its ED50
The larger/higher the therapeutic index, the safer the drug.
The smaller/lower the therapeutic index, the less safe the drug. 38

39. Fig. 5-9. The therapeutic index.
A, Frequency distribution curves indicating the ED50 and LD50 for drug “X.” Because its LD50 is much greater than its ED50, drug X is relatively safe. B, Frequency distribution curves indicating the ED50 and LD50 for drug “Y.” Because its LD50 is very close to its ED50, drug “Y” is not very safe. Also note the overlap between the effective-dose curve and the lethal-dose curve. 39