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Pharmacology for Nurses
A Pathophysiologic Approach
Third Edition
CHAPTER
4
Pharmacokinetics
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
NCLEX-RN Review
Question 1
A patient has an order for a tetracycline
antibiotic and has been instructed to avoid
taking the medication with foods, beverages,
or drugs that contain calcium, iron, or
magnesium. What stage of the
pharmacokinetic processes is behind the
rationale for this instruction?
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
NCLEX-RN Review
Question 1 – Choices
1.
2.
3.
4.
Absorption
Distribution
Metabolism
Excretion
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
NCLEX-RN Review
Question 1 – Answer
1.
2.
3.
4.
Absorption
Distribution
Metabolism
Excretion
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
NCLEX-RN Review
Question 1 – Rationale
Rationale: Some medications can be
affected by foods, beverages, or other
drugs. The effect of calcium, iron, and
magnesium on a tetracycline antibiotic is an
example of a food–drug interaction that
occurs in the absorption process.
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
NCLEX-RN Review
Question 2
The patient has a malignant brain tumor.
What property of pharmacokinetics may
cause difficulty in treating her tumor?
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
NCLEX-RN Review
Question 2 – Choices
1.
2.
3.
4.
Blood–brain barrier
Drug–protein complexes
Affinity for neoplasms
Lack of active transport
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
NCLEX-RN Review
Question 2 – Answer
1.
2.
3.
4.
Blood–brain barrier
Drug–protein complexes
Affinity for neoplasms
Lack of active transport
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
NCLEX-RN Review
Question 2 – Rationale
Rationale: The blood–brain barrier may
cause difficulty in treating tumors. Most
antitumor medications do not cross the
blood–brain barrier.
Cognitive Level: Analysis
Nursing Process: Assessment
Patient Need: Physiological Integrity
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
NCLEX-RN Review
Question 3
A patient with cirrhosis of the liver exhibits
decreased metabolic activity. This will
require what possible change in her drug
regimen?
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
NCLEX-RN Review
Question 3 – Choices
1. A reduction in the dosage of drugs
2. A change in the timing of medication
administration
3. An increased dose of prescribed drugs
4. All prescribed drugs must be given by
intramuscular injection.
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
NCLEX-RN Review
Question 3 – Answer
1. A reduction in the dosage of drugs
2. A change in the timing of medication
administration
3. An increased dose of prescribed drugs
4. All prescribed drugs must be given by
intramuscular injection.
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
NCLEX-RN Review
Question 3 – Rationale
Rationale: The liver is the primary site of
drug metabolism. Patients with severe liver
damage, such as that caused by cirrhosis,
will require reductions in drug dosage
because of the decreased metabolic activity.
Cognitive Level: Analysis
Nursing Process: Implementation
Patient Need: Physiological Integrity
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
NCLEX-RN Review
Question 4
Some drugs may be completely metabolized
by the liver circulation before ever reaching
the general circulation. This effect is known
as what?
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
NCLEX-RN Review
Question 4 – Choices
1.
2.
3.
4.
Conjugation of drugs
Hepatic microsomal enzyme system
Blood–brain barrier
First-pass effect
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
NCLEX-RN Review
Question 4 – Answer
1.
2.
3.
4.
Conjugation of drugs
Hepatic microsomal enzyme system
Blood–brain barrier
First-pass effect
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
NCLEX-RN Review
Question 4 – Rationale
Rationale: Some oral drugs are rendered
inactive by hepatic metabolic reactions,
during the process known as the first-pass
effect. An alternative route may need to be
assessed.
Cognitive Level: Application
Nursing Process: Implementation
Patient Need: Physiological Integrity
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
NCLEX-RN Review
Question 5
A patient who is in renal failure may have a
diminished capacity to excrete medications.
It is imperative that this patient be assessed
for what development?
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
NCLEX-RN Review
Question 5 – Choices
1.
2.
3.
4.
Increased creatinine levels
Increased levels of blood urea nitrogen
Drug toxicity
Increased levels of potassium
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
NCLEX-RN Review
Question 5 – Answer
1.
2.
3.
4.
Increased creatinine levels
Increased levels of blood urea nitrogen
Drug toxicity
Increased levels of potassium
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
NCLEX-RN Review
Question 5 – Rationale
Rationale: The kidneys are the primary site
of excretion. Renal failure increases the
duration of the drug’s action because of
decreased excretion. The patient must be
assessed for drug toxicity.
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
NCLEX-RN Review
Question 5 – Rationale (cont'd)
Cognitive Level: Analysis
Nursing Process: Assessment
Patient Need: Physiological Integrity
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
Application of Pharmacokinetics
to Clinical Practice
• Pharmacokinetics: the study of drug
movement throughout the body
• Know how the body handles medication
• Understand actions and side effects of
drugs
• Understand obstacles drug faces to reach
target cells
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
Drugs in the Body
• Greatest barrier for many drugs is crossing
many membranes
• Enteral route drugs broken down by
stomach acids and enzymes
• Organs attempt to excrete medicines
• Phagocytes may attempt to remove
medicines seen as foreign
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
Four Categories of
Pharmacokinetics
•
•
•
•
Absorption
Distribution
Metabolism
Excretion
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
Diffusion or Passive Transport
• Molecules move from higher to lower
concentration
• Usually small, nonionized, or lipid-soluble
molecules
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
Active Transport
• Chemicals move against concentration or
electrochemical gradient
• Usually large, ionized, or water-soluble
molecules
• Cotransport involves the movement of two
or more chemicals across the membrane
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
Absorption
• Movement from site of administration,
across body membranes, to circulating
fluids
• Primary factor determining length of time
for effect of drug to occur
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
Factors Affecting
Drug Absorption
•
•
•
•
•
•
Route of administration
Drug formulation
Drug dosage
Digestive motility
Digestive tract enzymes
Blood flow at administration site
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
Factors Affecting Drug
Absorption (cont'd)
• Degree of ionization of drug
– In acid of stomach, aspirin is nonionized and
easily absorbed by bloodstream
– In alkaline of small intestine, aspirin is ionized
and less likely to be absorbed
• pH of surrounding environment
• Drug-drug/drug-Food interactions
• Dietary supplement/herbal product–drug
interactions
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
Metabolism (Also Known as
Biotransformation)
•
•
•
•
Changes drug so it can be excreted
Involves biochemical reactions
Liver—primary site
Addition of side chains, known as
conjugates, makes drugs more water
soluble and more easily excreted by the
kidneys
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
Metabolism in the Liver
• Hepatic microsomal enzyme system (P450 system)
– Inactivates drug
– Accelerates drug excretion
– some agents, known as prodrugs, have no
pharmacologic activity unless first
metabolized to active form by body
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
Enzyme Induction
• A drug increases metabolic activity in the
liver
• Changes in the function of the hepatic
microsomal enzymes can significantly
affect drug metabolism
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
Oral Drugs Enter Hepatic-Portal
Circulation (First-Pass Effect)
• Drug absorbed
• Drug enters hepatic circulation, goes to
liver
• Drug is metabolized to inactive form
• Drug conjugates and leaves liver
• Drug is distributed to general circulation
• Many drugs rendered inactive by first-pass
effect
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
Figure 4.4 First-pass effect: (a) drugs are absorbed; (b) drugs enter hepatic portal circulation and go directly to liver;
(c) hepatic microsomal enzymes metabolize drugs to inactive forms; (d) drug conjugates, leaving liver; (e) drug is
distributed to general circulation.
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
Metabolism and
Pharmacotherapy
• Can be decreased metabolic activity in
some clients
– Infants and elderly
– Clients with severe liver disease
– Clients with certain genetic disorders
– Dosages need to be adjusted in these clients
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
Distribution of Medications
• Distribution involves the transport of
pharmacologic agents throughout the body
– Simplest factor determining distribution is the
amount of blood flow to body tissues
• Physical properties of drug have big
influence
• Certain tissues, such as bone marrow,
have a high affinity, or attraction, for
certain medications
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
Drugs Bind with Plasma Proteins
• Many drug molecules form drug–protein
complexes – binding reversibly to plasma
proteins – and thus never reach target
cells
• Cannot cross capillary membranes
• Drug not distributed to body tissues
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
Figure 4.3 Plasma protein binding and drug availability: (a) drug exists in a free state or bound to plasma protein; (b)
drug-protein complexes are too large to cross membranes.
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
Distribution of Medications
• Drugs and other chemicals compete for
plasma protein–binding sites
– Drug–drug and drug–food interactions may
occur when one drug displaces another from
plasma proteins
• Some have greater affinity
• Displaced drug can reach high levels
– Can produce adverse effects
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
Distribution of Medications
(cont'd)
• Blood-brain barrier and fetal-placenta
barrier: special anatomic barriers that
prevent many chemicals and medications
from entering
– Makes brain tumors difficult to treat
– Fetal-placenta barrier protects fetus; no
pregnant woman should be given medication
without strong consideration of condition
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
Primary Site of Excretion
of Drugs Is Kidneys
• Free drugs, water-soluble agents,
electrolytes, and small molecules are
filtered
• Drug-protein complexes are secreted into
distal tubule
• Secretion mechanism is less active in
infants and older adults
• pH of filtrate can increase excretion
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
Renal Failure Diminishes
Excretion of Medications
• Drugs retained for extended times
• Dosages must be reduced
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
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Other Organs Can Be
Sites of Excretion
• Respiratory system
• Glands
• Biliary system
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
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Enterohepatic Recirculation
of Drugs
• Drugs excreted in bile
• Bile recirculates to liver
• Percentage of drug recirculated numerous
times
• Prolongs activity of drug
– Activity of drug may last after discontinuation
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
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Drug Plasma Concentration and
Therapeutic Response
• Concentration of medication in target
tissue often impossible to measure, so
must be measured in plasma
– Minimum effective concentration - amount of
drug required to produce a therapeutic effect
– Toxic concentration - level of drug that will
result in serious adverse effects
– Therapeutic range - plasma drug
concentration between the minimum effective
concentration and the toxic concentration
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
All rights reserved.
Plasma Half-Life (t1/2)
of Drugs
• Length of time needed to decrease drug
plasma concentration by one half
• The greater the half-life, the longer it takes
to excrete
• Determines frequency and dosages
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
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How Drug Reaches and Maintains
Therapeutic Range
•
•
•
•
Repeated doses of drug given
Drug accumulates in bloodstream
Plateau reached
Amount administered equals amount
eliminated
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
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Loading Dose
• Higher amount of drug given
• Plateau reached faster
• Quickly produces therapeutic response
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
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Maintenance Dose
• Keeps plasma-drug concentration in
therapeutic range
Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition
Adams • Holland
Copyright ©2011 by Pearson Education, Inc.
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