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PHARMACOLOGY FOR NURSES
A Pathophysiological Approach
FOURTH EDITION
CHAPTER
4
Pharmacokinetics
Copyright © 2014, © 2011, © 2008 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 that a drug faces
to reach target cells
Pharmacology for Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
Drugs in the Body
• Greatest barrier for many drugs is
crossing many membranes.
• Enteral route drugs are broken down by
stomach acids and enzymes.
• Organs attempt to excrete medicines.
• Phagocytes may attempt to remove
medicines seen as foreign.
Pharmacology for Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
Four Components of
Pharmacokinetics
•
•
•
•
Absorption
Distribution
Metabolism
Excretion
Pharmacology for Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
Figure 4.1
The four processes of pharmacokinetics: absorption, distribution, metabolism, and excretion
Pharmacology for Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
Drugs Cross Plasma Membranes
to Produce Effects
• Diffusion or passive transport
• Active transport
Pharmacology for Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
Diffusion or Passive Transport
• Molecules move from higher to lower
concentration.
• Usually small, nonionized, or lipidsoluble molecules
Pharmacology for Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
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 Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
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 Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
Factors Affecting Drug Absorption
•
•
•
•
•
•
Route of administration
Drug formulation
Drug dosage
Digestive motility
Digestive tract enzymes
Blood flow at administration site
Pharmacology for Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
Factors Affecting Drug Absorption
• 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 Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
Metabolism of Medications
•
•
•
•
•
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 Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
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 Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
Oral Drugs Enter Hepatic-Portal
Circulation (First-Pass Effect)
• Drug is 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 are rendered inactive by
first-pass effect.
Pharmacology for Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
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 Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
Metabolism and Pharmacotherapy
• Can be decreased metabolic activity in
some patients:
– Infants and elderly
– Patients with severe liver disease
– Patients with certain genetic disorders
– Dosages need to be adjusted in these
patients.
Pharmacology for Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
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.
Pharmacology for Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
Distribution of Medications
• Physical properties of drug have big
influence.
• Certain tissues, such as bone marrow,
have a high affinity, or attraction, for
certain medications.
Pharmacology for Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
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 Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
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 Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
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 Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
Distribution of Medications
• 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 Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
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 Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
Renal Failure Diminishes
Excretion of Medications
• Drugs are retained for extended times.
• Dosages must be reduced.
Pharmacology for Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
Other Organs Can Be Sites of
Excretion
• Respiratory system
• Glands
• Biliary system
Pharmacology for Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
Enterohepatic Recirculation
of Drugs
• Drugs are 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 Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
Figure 4.5
Enterohepatic recirculation
Pharmacology for Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
Drug Plasma Concentration and
Therapeutic Response
• Concentration of medication in target
tissue is often impossible to measure,
so it 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
Pharmacology for Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
Drug Plasma Concentration and
Therapeutic Response
• Concentration of medication in target
tissue is often impossible to measure,
so it must be measured in plasma.
– Therapeutic range—plasma drug
concentration between the minimum
effective concentration and the toxic
concentration
Pharmacology for Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
Plasma Half-Life (t½) 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 Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
How Drug Reaches and Maintains
Therapeutic Range
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•
•
•
Repeated doses of drug are given
Drug accumulates in bloodstream.
Plateau is reached.
Amount administered equals amount
eliminated.
Pharmacology for Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
Figure 4.6 Single-dose drug administration: pharmacokinetic values for this drug are as follows: onset of
action = 2 hours; duration of action = 6 hours; termination of action = 8 hours after administration; peak plasma
concentration = 10 mcg/mL; time to peak drug effect =5 hours; t½= 4 hours
Pharmacology for Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
Figure 4.7 Multiple-dose drug administration: drug A and drug B are administered every 12 hours; drug B
reaches the therapeutic range faster, because the first dose is a loading dose
Pharmacology for Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
Loading Dose
• Higher amount of drug given
• Plateau reached faster
• Quickly produces therapeutic response
Pharmacology for Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
Maintenance Dose
• Keeps plasma-drug concentration in
therapeutic range
Pharmacology for Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban