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Chapter 2
Drugs in the Body
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Chapter 2
Topics
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Atoms and Molecules
Acids and Bases
Pharmacodynamics
Pharmacokinetics
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Atoms and Molecules
Atoms
• Is the basic unit of matter
• Ninety-two types of atoms, or elements, occur naturally on
Earth
• The periodic table of the elements
 Made up of naturally-occurring elements and those
synthesized in the lab
 Groups atoms by their chemical properties and
arranges them in rows and columns in the table
 Elements in the same column and group have similar
properties
Behave similarly when combining with other
elements
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Atoms and Molecules
The Periodic Table of the Elements
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Atoms and Molecules
Atomic Structure
• Consists of a nuclear center
and an outer shell
• Nucleus is a core of solid
matter, including protons and
neutrons
• Outer shell is an orbital space
where electrons circulate
• Has a unique number of
electrons and protons
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Atoms and Molecules
Atomic Structure (continued)
• Protons
 Have a positive electrical charge in the nucleus
• Neutrons
 Are neutral in the nucleus
• Electrons
 Have a negative charge
 Seek to balance the electrical charge of an atom
 Equal the number of protons normally
 Determine the chemical activity of an element and
how it combines with other atoms
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Atoms and Molecules
Atomic Structure (continued)
• Ions
 Are atoms or molecules with an electrical charge
 Examples include sodium (Na+), potassium (K+),
chloride (Cl–), which are found in the body
• Positively charged ion
 Forms when electrons separate from an atom, energy is
released
• Negatively charged ion
 Forms when an extra electron is added to an atom’s
orbit
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Atoms and Molecules
Chemical Bonds
• Occur when atoms combine by exchanging electrons in
their outer shells
• Covalent bond (strong bond)
 Forms when atoms share electrons and create a
neutrally charged molecule
• Ionic bond (weak bond)
 Forms when an atom transfers electrons to another
element and electromagnetic attraction connects the
two ions
 One atom is positively charged; the other is negative
 Most molecules in the body have covalent bonds
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Atoms and Molecules
Covalent Bond
Electrons share orbitals
around the nucleus
Ionic Bond
Sodium (+) and chloride (–)
combine by ionic bonds to
make table salt
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Atoms and Molecules
Molecules and Functional Groups
• Molecules
 Form when two or more atoms combine by covalent or
ionic bonds
• Carbon backbone
 Chains of atoms strung together or in ring-like
structures
 Forming rings is a unique property of carbon
• Functional groups
 Are on each backbone; these side portions of a
molecule give it unique chemical properties
• Molecules react only with those receptors in the
body shaped similarly, much like a lock and key
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Atoms and Molecules
Functional Groups
• A drug’s activity is based
on its molecular shape
and functional groups
• Amino functional group
in ampicillin is shown as
NH2
• Carboxyl functional
group in ampicillin is
shown as COOH
ampicillin
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Atoms and Molecules
Molecules and Functional Groups (continued)
• Isomers
 Are compounds with the same chemical makeup, but
are not arranged the same way
 Are often mirror images of each other (stereoisomers)
• A drug may contain a mix of stereoisomers, one having
more drug activity and the other causing more side effects
• The most common molecules in the body are
carbohydrates, peptides, lipids, and nucleic acids
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Atoms and Molecules
Carbohydrates Are an essential part of nutrition; breaking
these bonds produces energy the body uses
Peptides
Made up of amino acids; are the building blocks
of protein molecules. Proteins are most often
used to build tissue and can be used for energy
Lipids
Are made up of molecules that form long chains
of covalently bonded carbon and hydrogen
atoms. Lipids are soluble in fat and are used to
create hormones and other biochemicals
Nucleic acids
Are part of DNA which forms the genetic
material contained in the nucleus of each cell
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Acids and Bases
The pH Scale
• A way to measure acidic
and basic properties of
substances
• Low pH (below 7) are acids,
and high pH (over 7) are
bases
• Acidic molecules donate
protons to other molecules
• Basic molecules easily
accept protons
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Acids and Bases
The pH Scale (continued)
• Most drugs are weak acids or weak bases
 These properties affect how drug molecules enter and
behave in the body
• When acids and bases exchange protons, the remaining
molecules become positively or negatively charged ions
• Ionization
 Affects drug activity
 Ionic molecules cannot easily cross membranes and
enter the bloodstream
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Pharmacodynamics
Drug Receptor Theory
• Drugs mimic, enhance, or block the activity of substances
that are already present in the body
• Drug receptor theory
 Explains the process of drug molecules interacting with
receptors on the surface or inside of specific cells
 Based on a lock and key mechanism
Receptors (locks) are on the surface of body cells,
and various substances (keys) fit exactly into them
Keys are produced or processed within the body
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Pharmacodynamics
Drugs and Receptors
• Drug molecules are
similar to (but not
exactly the same as)
endogenous
molecules
• These slight
differences can be
the reason why side
effects occur
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Pharmacodynamics
Study of Drug Receptor Theory
• Pharmacodynamics
 Studies how drugs act on the body (mechanism of
action) at the molecular level
• Drug receptor theory is a way to explain drug activity
• Receptor agonist drugs
 Stimulate a specific response when binding to receptors
• Receptor antagonist drugs
 Block a response by binding to receptors in one of two
ways
Directly inactive a receptor, or
Bind to a receptor to keep other agonist molecules
from binding
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Pharmacodynamics
Dose-Response Relationship
• For a drug to be effective, enough of it must reach its site
of action to produce a measurable effect (response)
 Also known as the drug concentration in the blood
• Proper dosing (safety of use)
 Achieving the desired effect and few unwanted effects
• Dose-response curve
 Graphic representation of dose and effect relationship
• Ceiling effect
 Occurs when an increase in dose does not produce
more response
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Pharmacodynamics
Dose-Response Curve (Relationship)
• Graph shows the
drug concentration
in the bloodstream
over time
• Curve shows that
increases in dose
result in increased
response
• Eventually, a ceiling
effect is reached
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Pharmacodynamics
Dose-Response Relationship (continued)
• Therapeutic range of a drug
 Aims for blood concentrations in the middle of the
dose-response curve
• Minimum therapeutic range
 Lower threshold of the therapeutic range
• Toxic concentration
 Upper edge of the therapeutic range
Toxic effects may outweigh any benefit of the drug
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Pharmacodynamics
Time-Response Curve (Relationship)
• Some drugs have
a narrow
therapeutic range;
i.e., the minimum
therapeutic range
and toxic levels
are close
• Then drug dosing
is monitored
closely
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Pharmacodynamics
Dose-Response Relationship: Efficacy and Potency
• Can be determined using the dose-response curve
• When a dose-response curve is lower in vertical height for
one drug than another, the first drug is less effective
• When the curve is shifted horizontally left or right
compared with another drug, the potency differs
 Example: A drug that has the same response as another
drug but at a lower dose (left shift) is more potent
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Pharmacodynamics
Dose-Response Relationship: Timing of Doses
• Is important to achieve a constant concentration in the
therapeutic range
• Steady state
 Is when constant concentration is maintained
Up to five, timed doses may be needed to reach
steady state
• Loading dose
 Is a large enough dose to bring blood concentrations up
to the therapeutic range right away
Subsequent doses keep levels at steady state
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Your Turn
Question 1: A patient has started a prescription for digoxin, a
medication used to control heart rate. What is the reason the
patient is taking a loading dose?
Answer: The loading dose brings the blood concentration of
digoxin up to the therapeutic range immediately for
controlling the heart rate of the patient.
Question 2: How is the function of receptor agonists different
than the function of receptor antagonists?
Answer: Receptor agonists stimulate a response, whereas
receptor antagonists block a response.
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Pharmacodynamics
Dose-Response Relationship: Trough and Peak
• Trough
 Is the point at which a drug is at its lowest
concentration between doses
• Peak
 Is when the concentration of the drug is at its highest
• Drug levels help prescribers make certain that patients get
maximum benefit of drugs, but avoid toxicity
• Technicians sometimes are asked to help pharmacists in
retrieving drug concentration levels from lab data
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Pharmacokinetics
Pharmacokinetic Process
• Pharmacokinetics
 Studies how drugs are
absorbed, distributed,
and eliminated from
the bloodstream
• Process is four phases:
 absorption
distribution
metabolism
elimination (excretion)
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Pharmacokinetics
Absorption
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Is how drugs enter the bloodstream
Is the upward-sloping part of the time-response curve
Affects the onset and extent of drug action
Is affected by route of administration
 Oral drug administration is often used because of good
systemic absorption through the small intestines
 IV drug administration goes directly into the
bloodstream
 Topical routes of drugs limit absorption to a local area
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Pharmacokinetics
Absorption (continued)
• Is affected by dosage form
 Slower dosage forms include solids, transdermal
patches, and coated tablets
 Faster dosage forms include liquids and ODTs
• Is affected by acidic and basic properties of drugs
 Basic drugs in an acidic environment dissociate into
ionic particles that cannot cross membranes easily
 Acidic drugs in an acidic environment do not easily
dissociate, so more drug is absorbed
• Is affected by transport mechanisms that drugs use to
cross membranes
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Pharmacokinetics
Absorption (continued)
• Crossing membranes between the site of administration
and the circulatory system is necessary for drug activity
• Molecules cross membranes by active and passive
transport mechanisms
• Active transport mechanisms
 Use energy to bring drug molecules across a membrane
Example: sodium/potassium exchange pump
• Passive transport mechanisms
 Molecules move across membranes on their own
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Pharmacokinetics
Absorption (continued)
• Passive transport is often driven by concentration
gradients
 Drugs move from high concentration (administration
site) to an area of low concentration (the bloodstream)
 Many drugs are absorbed because molecules move
along a concentration gradient
 Higher drug doses typically produce greater absorption
• Blood flow and surface area affect absorption
 The great amount of surface area and good blood flow
from the GI tract to the small intestine
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Pharmacokinetics
Transport Mechanisms
In simple diffusion, molecules move either directly through the
membrane itself or through an open channel
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Pharmacokinetics
Distribution
• Is the process by which drugs move around in the
bloodstream and reach other body tissues
 Is highly affected by blood flow
• Vd
 Indicates how a drug is distributed within body
compartments
• One-Compartment Model (example)—the bloodstream is a
main compartment for water-soluble drug distribution
• Two-Compartment Model (example) —a highly fat-soluble
drug is stored in fatty tissue, then is slowly released back
into the bloodstream over time
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Pharmacokinetics
Distribution (continued)
• Is affected by protein binding
 When 90% or more of a drug’s molecules bind to
proteins in the blood, they cannot reach the action site
• Is affected by BBB
 A physical layer of cells that affects distribution of drugs
to the CNS
 Allows only select molecules through, such as oxygen
and carbon dioxide
 Most larger drug molecules cannot pass the BBB
Can limit access for drug therapy
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Pharmacokinetics
Elimination
• Is the process by which drugs leave the body
• Is measured as the rate and extent to which a drug leaves
the bloodstream
• Is the downward sloping part of the time-response curve
• Half-life (t1/2)
 Is the time it takes for half (50%) of a drug to be cleared
from the blood
 Complete elimination from the body takes about eight
half-lives
 Is affected by metabolism and excretion
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Pharmacokinetics
Elimination: Metabolism
• Enzymes in the liver metabolize drugs and other substances
in the body; this detoxifies the blood
• The liver is the primary site of drug metabolism
 Drug metabolism depends on blood flow to the liver
and the function of liver enzymes
 Prodrugs rely on metabolism to activate them
• First-pass effect
 Is the liver metabolizing drugs as they “pass,” or travel
through it
 Full drug dose may not reach the body due to first-pass
If problematic, ways to bypass the liver are used
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Pharmacokinetics
Elimination: Metabolism (continued)
• Cytochrome P450 liver enzyme system
 Most frequently deactivates drugs
 Causes many drug interactions
• Two drugs given together that use the same enzyme
system compete for elimination and can increase toxicity
Elimination: Excretion
• Is the process by which drug molecules are removed from
the bloodstream
• Occurs mainly in the kidneys; also via bile, feces, sweat,
and exhalation
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Pharmacokinetics
Special Populations
• Characteristics of individual patients affect the
pharmacokinetic properties of drugs they take
• Most problems are due to differences in age and function
of the liver and kidneys
• Females have more body fat and slower metabolism rates
than males, which affect drug distribution
• In pregnancy, GI motility slows allowing more time for
absorption and urination increases which affects
elimination
• In severe CV disease, blood flow decreases, altering blood
supply to the liver and kidneys
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Pharmacokinetics
Special Populations: Age
• Young patients
 Have higher body water content, so highly water-soluble
drugs distribute well; increases toxicity potential
 Liver function is not fully developed which affects
absorption, distribution, and metabolism
• Older patients
 Have higher body fat so highly fat-soluble drugs may
distribute well and accumulate
 Kidney and liver function decrease and elimination drops
Doses are decreased and dosing intervals increased
due to altered absorption, distribution, and
elimination
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Pharmacokinetics
Special Populations: Liver Disease
• Can greatly affect drugs eliminated via metabolism (occurs
in the liver)
 Cirrhosis, hepatitis, and other liver diseases can
severely affect liver function
 Doses are adjusted downward
Special Populations: Kidney Disease
• Greatly affects drug elimination (excretion occurs mostly
through kidneys)
 Doses are adjusted downward
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Your Turn
Question 1: A drug manufacturer has developed a new drug.
How can you tell if the drug is fast-acting and in oral form?
Answer: The drug was developed as a liquid so that it is
absorbed through the small intestines.
Question 2: A patient has acute (sudden) kidney failure. What
changes to his medications are likely to happen?
Answer: The doses will probably be decreased.
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Summary
• The functional groups and behavior of drugs determine
what happens to them in the body
• Pharmacodynamics studies how drugs act in the body at
the molecular level
• Pharmacokinetics studies how drugs move in the body
• The four phases of pharmacokinetics are absorption,
distribution, metabolism, and excretion
• Various factors affect individual patient drug therapy and
dosing
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