Transcript Chapter 4 - Pharmacokinetics

Fundamentals of Pharmacology
for Veterinary Technicians
Chapter 4
Pharmacokinetics
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
Pharmacokinetics
• Pharmacokinetics is the
physiological movement of drugs
• Four steps:
– Absorption
– Distribution
– Biotransformation (metabolism)
– Excretion
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
Movement of Drugs Across the
Cell Membrane
• Pharmacokinetics includes the
movement of substances across cell
membranes
• Basic mechanisms:
– Passive diffusion
– Facilitated diffusion
– Active transport
– Pinocytosis/phagocytosis
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
Movement of Drugs Across the
Cell Membrane
• Passive diffusion: movement of particles
from an area of high concentration to an
area of low concentration
– Good for small, lipophilic, nonionic
particles
• Facilitated diffusion: passive diffusion that
uses a special carrier molecule
– Good for bigger molecules that are not
lipid soluble
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
Movement of Drugs Across the
Cell Membrane
• 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
• Pinocytosis/phagocytosis: molecules are
physically taken in or engulfed.
Pinocytosis is engulfing liquid;
phagocytosis is engulfing solid particles
– Good for bigger molecules or liquids
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
Movement of Substances
Across the Cell Membrane
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
Drug Absorption
• Drug absorption is the movement of 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
and health status
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
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
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
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
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
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
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
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
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
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
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
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
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
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
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
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
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
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
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
Receptors
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
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
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
Agonist vs. Antagonist
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.