Chapter 4

Pharmacokinetics
 Pharmacokinetics
 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
 Absorption
 Distribution
 Metabolism
 Excretion
 Time course of drug responses

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Passage of Drugs Across Membranes
 All four phases of pharmacokinetics involve drug
movement
 Three ways to cross a cell membrane
 Polar molecules
 Ions
 A general rule in chemistry states that “like
dissolves like”
 Cell membranes are composed primarily of
lipids; therefore, to directly penetrate
membranes, a drug must be lipid soluble
(lipophilic)
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Passage of Drugs Across Membranes
 For most drugs, movement throughout the body
is dependent on the drug’s ability to penetrate
membranes directly
 Most drugs are too large to pass through
channels or pores
 Most drugs lack transport systems to help them
cross all of the membranes that separate them
from their sites of action, metabolism, and
excretion

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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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 Absorption
 Movement of a drug from its site of
administration into the blood
 The rate of absorption determines how soon effects
will begin
 The amount of absorption helps determine how
intense the effects will be

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 Factors Affecting Drug Absorption
 Rate of dissolution
 Surface area
 Blood flow
 Lipid solubility
 pH partitioning (Ion trapping)

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 Characteristics of Commonly
Used Routes of Administration
(1 of 2)
 Intravenous
 Barriers to absorption
 Absorption pattern
 Advantages
 Disadvantages
 Intramuscular
 Barriers to absorption
 Absorption pattern
 Advantages
 Disadvantages

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 Characteristics of
Commonly Used Routes of
Administration (2 of 2)
 Subcutaneous
 No significant barriers to absorption
 Oral
 Barriers to absorption
 Absorption pattern
 Drug movement after absorption
 Advantages
 Disadvantages

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 Pharmaceutical Preparations
for Oral Administration
 Tablets
 Enteric-coated preparations
 Sustained-release preparations

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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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 Distribution
 Movement of drugs throughout the body

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 Blood Flow to Tissues
 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 than internal blood vessels
 Solid tumors have a limited blood supply

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 Exiting the Vascular System
 Typical capillary beds
 Drugs pass between capillary cells rather than
through them

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 Blood-Brain Barrier
 Tight junctions between the cells that comprise
the walls of most capillaries in the central
nervous system
 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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 Placental Drug Transfer
 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: Low birth weight, physical anomalies,
alterations in mental aptitude
 Mother’s use of habitual opioids: Birth of drug-
dependent baby

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 Protein Binding
 Drugs can form reversible bonds with various
proteins
 Plasma albumin is the most abundant and
important protein
 Large molecule that always remains in the
bloodstream
 Affects drug distribution

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 Entering Cells
 Some drugs must enter cells to reach the site of
action
 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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 Metabolism
 Also known as biotransformation
 Defined as the chemical alteration of drug
structure
 Most often takes place in the liver
 Hepatic drug-metabolizing enzymes
 Therapeutic consequences of drug metabolism
 Special considerations in drug metabolism

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 Hepatic Drug-
Metabolizing Enzymes
 Most drug metabolism that takes place in the
liver is performed by the hepatic microsomal
enzyme system, which is also known as the
P450 system
 Metabolism does not always result in a smaller
molecule

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 Therapeutic Consequences
of Drug Metabolism
 Accelerated renal drug excretion
 Drug inactivation
 Increased therapeutic action
 Activation of prodrugs
 Increased or decreased toxicity

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 Special Considerations
in Drug Metabolism
 Age
 Induction of drug-metabolizing enzymes
 First-pass effect
 Nutritional status
 Competition among drugs

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 Excretion
 Defined as the removal of drugs from the body
 Drugs and their metabolites can exit the body
through urine, sweat, saliva, breast milk, or
exhaled air

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 Drug Excretion

Renal Routes Nonrenal Routes

 Steps in renal drug  Breast milk
excretion  Other nonrenal routes of
 Glomerular filtration excretion
 Passive tubular  Bile
reabsorption • Enterohepatic recirculation
 Active tubular secretion  Lungs (especially
 Factors that modify renal anesthesia)
drug excretion  Sweat/saliva (small
 pH-dependent ionization amounts)
 Competition for active
tubular transport
 Age
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 Time Course of Drug Responses
 Plasma drug levels
 Single-dose time course
 Drug half-life
 Drug levels produced with repeated doses

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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
 The objective of drug dosing is to maintain plasma
drug levels within the therapeutic range

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 Single-Dose Time Course
 The duration of effects is determined largely by
the combination of metabolism and excretion
 For drug levels above the minimum effective
dose, the therapeutic response will be
maintained

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 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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 Drug Levels Produced
with Repeated Doses
 Process by which plateau drug levels are
achieved
 Time to plateau
 Techniques for reducing fluctuations in drug
levels
 Loading doses versus maintenance doses
 Decline from plateau

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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. Intravenous
B. Intramuscular
C. Subcutaneous
D. Oral

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When preparing to administer a sustained-release capsule
to a patient, the nurse understands that which statement is
true for sustained-release capsules?

A. They are usually most costly than pills.

B. They are rapidly absorbed.
C. They need to be crushed for appropriate absorption to
take place.
D. They need to be taken at regular intervals throughout
the day.

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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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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. 4 times per day

B. 3 times per day
C. 2 times per day
D. Once a day

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