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Chapter 4
Pharmacokinetics
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Drug Movement
• Pharmacokinetics is the physiological
movement of drugs
• Four steps:
– Absorption
– Distribution
– Biotransformation (metabolism)
– Excretion
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Drug Movement
• Pharmacokinetics includes the movement
of substances across cell membranes
• Basic mechanisms:
– Passive diffusion
– Facilitated diffusion
– Active transport
– Pinocytosis/phagocytosis
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Passive Diffusion
• movement of particles from an area of high
concentration to an area of low concentration
– Good for small, lipophilic, nonionic particles
– The drug must dissolve and pass through in the cell
membrane
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Facilitated Diffusion
• passive diffusion that uses a special carrier
molecule
– Good for bigger molecules that are not lipid soluble
– No energy is needed for a facilitated diffusion
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Active Transport
• molecules move against the concentration
gradient from areas of low concentration of
molecules to areas of high concentration of
molecules; involves both a carrier molecule
and energy
– Good for accumulation of drugs within a part of
the body
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Pinocytosis/Phagocytosis
• molecules are physically taken in or engulfed.
Pinocytosis is engulfing liquid; phagocytosis is
engulfing solid particles
– Good for bigger molecules or liquids
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Movement of Substances
Across the Cell Membrane
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Drug Absorption
• Drug absorption is the movement of a drug from
the site of administration into the fluids of the
body that will carry it to its site(s) of action
• Drug factors include drug solubility, pH, and
molecular size
• Patient factors include the animal’s age, health,
metabolic rate, genetic factors, sex, and species
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Drug Absorption Terms
• Bioavailability: percent of drug administered that actually
enters the systemic circulation
• Ionization: the property of being charged
– Hydrophilic = ionized
– Lipophilic = nonionized
• Nature of the drug: pH of drug
– Weakly acid drugs = hydrophilic form in alkaline environment
– Weakly alkaline drugs = hydrophilic form in acid environment
• Ion trapping: when drugs change body compartments,
they may become ionized and trapped in the new
environment
• Drug form is important; oral drugs must have different
properties than parenteral drugs
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Drug Absorption
• Age
– Young animals may not have well developed
gastrointestinal tracts and less active enzyme
systems
• Health
– Sickness will affect the rate of absorption of certain
drugs
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Drug Absorption
• Metabolic rate
– Animals with a high metabolic rate may eliminate
drugs from their system quicker
• Genetic factors
– Individual variation in response to drugs may occur
because of genetic differences between animals
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Drug Absorption
• Sex
– Male and females have different body compositions
– These specific compositions may affect the action and
distribution of the drug
• Species
– Herbivores may have altered drug absorption due to
food in the gastrointestinal tract
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Drug Distribution
• Drug distribution is the physiological movement of drugs
from the systemic circulation to the tissues
• Goal of distribution is for the drug to reach the target
tissue or intended site of action
• Factors affecting drug distribution:
– Membrane permeability: large molecules cannot pass through
fenestrations of blood capillaries
– Tissue perfusion: relative amount of blood supply to an area or
body system
– Protein binding: drugs bound to proteins cannot leave the
capillaries due to the size of the protein
– Volume of distribution: how well a drug is distributed throughout
the body based on the concentration of drug in the blood
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Biotransformation
• Biotransformation is also called drug
metabolism, drug inactivation, and drug
detoxification
• Biotransformation is the chemical alteration of
drug molecules by the body cells of patients to a
metabolite that is in an activated form, an
inactivated form, and/or a toxic form
• Primary site of biotransformation is the liver
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Drug Interactions Affecting
Drug Metabolism
• Drug interactions may affect metabolism:
– Altered absorption: one drug may alter the absorption
of other drugs
– Competition for plasma proteins: drug A and drug B
may both bind to plasma proteins; one may have a
higher affinity than the other
– Altered excretion: some drugs may act directly on the
kidney and decrease the excretion of other drugs
– Altered metabolism: the same enzymes may be
needed for biotransformation of two drugs that are
prescribed at the same time for an animal
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Drug Interactions Affecting
Drug Metabolism
• Drug interactions may affect metabolism (cont.):
– Inducing the enzyme system: some drugs alter
metabolism by causing liver enzymes to become
more efficient
– Liver issues: the liver’s ability to metabolize drugs
may be impaired
– Tolerance: the animal may develop tolerance or
decreased response to a drug
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Drug Interactions Affecting
Drug Metabolism
• Tolerance
– Decreased response to a drug because of repeated use
– The two types of tolerance in animals are metabolic and cellular
• Metabolic tolerance
– Drug is metabolized more quickly because of chronic use
• Cellular tolerance
– Occurs when receptors adapt to the presence of the drug by
either reducing the number of receptors, or reducing their
sensitivity
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Drug Elimination
• Drug elimination is removal of a drug from the body
(excretion)
• Renal elimination of drugs involves
– Glomerular filtration
– Tubular secretion
– Tubular reabsorption
• Liver elimination of drugs is also important
• Other elimination routes include the intestine and
through milk
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Drug Elimination Terms
• Withdrawal time: period of time after drug administration
during which the animal cannot be sent to market for
slaughter and the eggs or milk must be discarded
because of the potential for drug residues
• Half-life: time required for the amount of drug in the body
to be reduced by half of its original level
• Steady state: point at which drug accumulation and
elimination are balanced
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Measuring Drug Action
• Graphic depiction of the plasma concentration of the
drug vs. time
– X axis represents time
– Y axis represents drug concentration in plasma
• Onset of action occurs when the drug enters the plasma
• The peak plasma level of the drug is when the
elimination rate of the drug is equivalent to its rate of
absorption
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Measuring Drug Action
• The time elapsed from the time of administration to the
time that the peak plasma level is reached is known as
the time to peak
– Important in making clinical judgments about the use of a drug
• From the peak plasma level the concentration declines
since the amount of drug being eliminated exceeds the
amount being absorbed
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How Do Drugs Work?
• Drugs work in a variety of ways:
– Drugs alter existing cellular functions
– Drugs alter the chemical composition of body fluids
– Drugs can form a chemical bond with specific cell
components on target cells within the animal’s body
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Receptors
• Receptors are three-dimensional proteins or
glycoproteins
– Located on the surface, in the cytoplasm, or within the
nucleus of cells
• Affinity is the strength of binding between a drug
and its receptor
– High-affinity drugs bind more tightly to a receptor than
do low-affinity drugs
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Receptors
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Agonist vs. Antagonist
• Agonist: drug that binds to a cell receptor and
causes action
• Antagonist: drug that inhibits or blocks the
response of a cell when the drug is bound to the
receptors
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Agonist vs. Antagonist
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