Chapter 4
Pharmacokinetics
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• The term pharmacokinetics is derived
from two Greek words: pharmakon
(drug or poison) and kinesis (motion)
• Pharmacokinetics is the study of drug
movement throughout the body
• Pharmacokinetics also includes drug
metabolism and drug excretion
Pharmacokinetics
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Absorption
Distribution
Metabolism
Excretion
Time course of drug responses
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P-Glycoprotein
P-glycoprotein: Transmembrane protein that transports a
wide variety of drugs out of cells
Liver: Transports drugs into the bile for elimination
Kidney: Pumps drugs into the urine for excretion
Placenta: Transports drugs back into the maternal blood
Brain: Pumps drugs into the blood to limit drugs’ access to
the brain
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4
Passage of Drugs
Across Membranes
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•
Movement of a drug from its site of
administration into the blood
•
•
The rate of absorption determines how
soon effects will begin
Absorption
The amount of absorption helps
determine how intense the effects will
be
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• Rate of dissolution
• Surface area
• Blood flow
• Lipid solubility
• pH partitioning
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Factors
Affecting
Drug
Absorption
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Intravenous
Characteristics
of Commonly
Used Routes of
Administration
•
•
•
•
Barriers to absorption
Absorption pattern
Advantages
Disadvantages
Intramuscular
•
•
•
•
Barriers to absorption
Absorption pattern
Advantages
Disadvantages
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Subcutaneous
• No significant barriers to
absorption
Characteristics
of
Commonly
Used Routes of
Administration
(Cont.)
Oral
• Barriers to absorption
• Absorption pattern
• Drug movement after
absorption
• Advantages
• Disadvantages
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Additional
Routes of
Administration
• Topical
• Transdermal
• Inhaled
• Rectal
• Vaginal
• Direct injection to a specific
site—for example, heart, joints,
nerves, central nervous system
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10
Distribution
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• Movement of drugs
throughout the body
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• Drugs are carried by the blood
to tissues and organs of the
body
• Blood flow determines the rate
of delivery
• Abscesses and tumors
• Low regional blood flow
affects therapy
• Pus-filled pockets rather
Blood
Flow to
Tissues
than internal blood vessels
• Solid tumors have a limited
blood supply
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Tight junctions between the cells that
comprise the walls of most capillaries
in the central nervous system
BloodBrain
Barrier
Drugs must be able to pass through
the cells of the capillary wall
Only drugs that are lipid soluble or
that have a transport system can
cross the blood-brain barrier to a
significant degree
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13
•
Membranes of the placenta do NOT
constitute an absolute barrier to the
passage of drugs
•
•
Movement is determined in the
same way as it is for other
membranes
Risks with drug transfer
•
•
Birth defects: Mental retardation,
gross malformations, low birth
weight
Placental
Drug
Transfer
Mother’s use of habitual opioids:
Birth of drug-dependent baby
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• Drugs can form reversible
bonds with various proteins
• Plasma albumin is the most
abundant and important
protein
• Large molecule that
Protein
Binding
always remains in the
bloodstream
• Affects drug distribution
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Some drugs must enter cells to reach
the site of action
Entering
Cells
Most drugs must enter cells to
undergo metabolism and excretion
Many drugs produce their effects by
binding with receptors on the
external surface of the cell membrane
• These do not need to cross the cell membrane
to act
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16
• Also known as
biotransformation
• Defined as the enzymatic
alteration of drug structure
• Most often takes place in
Drug
Metabolism
the liver
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17
Accelerated renal drug
excretion
Drug inactivation
Therapeutic
Consequences
of Drug
Metabolism
Increased therapeutic action
Activation of prodrugs
Increased or decreased toxicity
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Defined as the removal of
drugs from the body
Excretion
Drugs and their metabolites
can exit the body through
urine, sweat, saliva, breast
milk, or expired air
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Plasma Drug Levels
• Clinical significance of plasma drug levels
• Two plasma drug levels defined
•
•
Minimum effective concentration
Toxic concentration
• Therapeutic range
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Therapeutic Range
• The objective of drug dosing is to maintain plasma drug
levels within the therapeutic range
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21
Half-Life
• Defined as the time required for the amount of drug in
the body to decrease by 50%
• Percentage versus amount
• Determines the dosing interval
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Question 1
A nurse is preparing to administer epinephrine to a patient who is
having a severe allergic reaction. Which route of administration
should the nurse use to provide the fastest and most complete
absorption of epinephrine?
A.
B.
C.
D.
Intravenous
Intramuscular
Subcutaneous
Oral
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Question 2
When preparing to administer a sustained-release capsule to a patient,
the nurse understands that which of the following is true for sustainedrelease capsules?
A.
B.
C.
D.
They are usually most costly than pills.
They are rapidly absorbed.
They need to be crushed for appropriate absorption to take place.
They need to be taken at regular intervals throughout the day.
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Question 3
The nurse identifies which patient as being at highest risk
for slow drug metabolism?
A. A 2-year-old boy who is prescribed an oral antibiotic
B. A 14-year-old girl who takes four prescription drugs
C. A 56-year-old man who has chronic hepatic disease
D. A 76-year-old woman who has an elevated temperature
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Question 4
Digoxin has a half-life of 36 to 48 hours. Because of the length of
the half-life, the nurse expects dosing to occur how often?
A.
B.
C.
D.
4 times per day
3 times per day
2 times per day
Once a day
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