Transcript Pharmacodynamics

Pharmacodynamics
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The study of the biochemical and physiologic
effects of drugs and the molecular mechanisms
by which those effects are produced
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The study of what drugs
do to the body and
how they do it
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 prescribers about drug
therapy
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Dose-response relationships
Drug-receptor interactions
Drug responses that do not involve receptors
Interpatient variability in drug responses
The therapeutic index
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
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As the dosage increases, the response
becomes progressively larger.
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Tailor treatment by increased/decreased
dosage until desired intensity of
response achieved.
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Three phases occur
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 Figure 5-2, A).
* Match the intensity of the response with the
patient’s need.
* Very high maximal efficacy is not always more
desirable. Do not hunt squirrels with a cannon.
Potency
* The amount of drug we must give to elicit an effect
* 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
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Drugs
* Chemicals that produce effects by interacting
with other chemicals
Receptors
* Special chemicals in the body that most drugs
interact with to produce effects
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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.
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Drugs produce their therapeutic effects by
helping the body use its preexisting
capabilities
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In theory, it should be possible to synthesize
drugs that can alter the rate of any biologic
process for which receptors exist.
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Cell membrane-embedded enzymes
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Ligand-gated ion channels
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G protein–coupled receptor systems
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Transcription factors
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The more selective a drug is, the fewer
side effects it will produce.
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Receptors make selectivity possible.
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Each type of receptor participates in the
regulation of just a few processes.
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Lock and key mechanism
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Does not guarantee safety
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Body has receptors for each:
• Neurotransmitter
• Hormone
• All other molecules in the body used to regulate
physiologic processes
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Simple occupancy theory
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Modified occupancy theory
• Affinity
 Strength of the attraction
• Intrinsic activity
 Ability of the drug to activate a receptor upon
binding
Agonists, antagonists, and partial agonists
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Agonists
Antagonists
Noncompetitive versus competitive antagonists
Partial agonists
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Agonists are molecules that activate receptors.
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Endogenous regulators are considered agonists.
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Agonists have both affinity and high intrinsic
activity.
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Agonists can make processes go “faster” or
“slower.”
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e.g. Dobutamine mimics NE at cardiac receptors.
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Produce their effects by preventing receptor
activation by endogenous regulatory molecules
and drugs
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Affinity but no intrinsic activity
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No effects of their own on receptor function
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Do not cause receptor activation but cause
pharmacologic effects by preventing the
activation of receptors by agonists.
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If there is no agonist present, an antagonist will
have no observable effect.
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)
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
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These are agonists that have only moderate
intrinsic activity.
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The maximal effect that a partial agonist can
produce is less than that of a full agonist.
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Can act as antagonists as well as agonists.
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Receptors are dynamic cell components
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Number of receptors on cell surface and
sensitivity to agonists can change in response
to:
• Continuous activation
• Continuous inhibition
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Continuous exposure to agonist
• Desensitized or refractory
 Down-regulation
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Continuous exposure to an antagonist
• Hypersensitive
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Simple physical or chemical interactions
with other small molecules
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Examples of receptorless drugs
• Antacids, antiseptics, saline laxatives, chelating
agents
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The dose required to produce a therapeutic
response can vary substantially among patients
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Measurement of interpatient variability
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The ED50
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Clinical implications of interpatient
variability
• The initial dose of a drug is necessarily an
approximation.
• Subsequent doses must be “fine tuned” based
on patient’s response.
• ED50 in a patient may need to be increased or
decreased after evaluating the patient response.
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Measure of a drug’s safety
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The ratio of the drug’s LD50 (average lethal
dose to 50% of the animals treated) to its ED50
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The larger/higher the therapeutic index, the
safer the drug
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The smaller/lower the therapeutic index, the
less safe the drug