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l. VanValkenburg, RVT, BAS

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Pharmacokinetics CHAPTER 4 L. VanValkenburg, RVT, BAS Drug Elimination Terminology Drug residue: amount of drug that can be detected in tissues after administration ... – PowerPoint PPT presentation

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Title: l. VanValkenburg, RVT, BAS


1
Pharmacokinetics
  • CHAPTER 4
  • l. VanValkenburg, RVT, BAS

2
DRUG MOVEMENT
  • PHARMACOKINETICS is the physiological movement of
    drugs.
  • 4 Steps
  • Absorption
  • Distribution
  • Biotransformation
  • (metabolism)
  • Excretion

3
DRUG MOVEMENT
  • Pharmacokinetics includes the movement of
    substances across cell membranes.
  • Basic mechanisms
  • Passive diffusion
  • Facilitated diffusion
  • Active transport
  • Pinocytosis/phagocytosis

4
How do drug molecules know where to go?
They dont! Drugs molecules go wherever
5
Movement of Drug Molecules
This process is called passive diffusion No
cellular effort is needed to transport the
molecules (hence the process is passive)
Drug molecules move randomly from one point to
another
6
Passive Diffusion
Movement is random from areas of higher to areas
of lower concentration Eventually the drug
molecules are equally distributed (equilibrium)
High concentration in this area
7
Passive Diffusion
Cell Membrane
But drug molecules will only cross by passive
diffusion if they can dissolve in the membrane
Drug molecules may move from one side of a cell
membrane to another by passive diffusion
8
Facilitated Diffusion
Cell Membrane
Cell Membrane
These drug molecules need a carrier to get across
the membrane
These molecules cant pass through the membrane
without help
9
Facilitated Diffusion
Cell
When the drug molecule encounters the carrier
protein, it carries it across
Membrane
Here is the carrier protein molecule in the
membrane
10
Facilitated Diffusion
Cell
When the drug molecule encounters the carrier
protein, it carries it across
Membrane
Here is the carrier protein molecule in the
membrane
11
Facilitated Diffusion
Cell
The carrier molecule then resets itself No
cellular energy is used to transport the molecule
across Only the concentration gradient moves the
molecules
Membrane
Here is the carrier protein molecule in the
membrane
12
Active Transport
Cell
The drug molecule encounters the carrier molecule
Membrane
The cell expends energy to PUMP the molecule
across the membrane to the other side
Involves a carrier molecule again
13
Active Transport
Cell
The drug molecule encounters the carrier molecule
The cell expends energy to PUMP the molecule
across the membrane to the other side
Membrane
Involves a carrier molecule again
14
Active Transport
Cell
Unlike diffusion, active transport is not
dependent upon concentration gradient
Membrane
Involves a carrier molecule again
All of the molecules can end up on this side
15
Phagocytosis and Pinocytosis
Foreign particle
Cell
Phagocytosis the cell flows around large
particles and engulfs it
Pinocytosis cell takes in molecules through
invaginations in the membrane
16
In summary.
17
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

18
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

19
Active Transport
  • Molecules move against the concentration gradient
    from areas of low concentration of molecules to
    areas of high concentration of molecules
  • Involves a carrier molecule and energy
  • Good for accumulation of drugs within a part of
    the body

20
Phagocytosis and Pinocytosis
  • Molecules are physically taken in or engulfed.
    Pinocytosis is engulfing liquid phagocytosis is
    engulfing solid particles
  • Good for bigger molecules or liquids

21
Getting In 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 drug solubility, pH and molecular
    size (see Table 4-2)
  • Patient factors include the animals age, health,
    metabolic rate, genetics, gender, and species
    (see Table 4-3)
  • Bioavailability is the percent of drug
    administered that actually enters the systemic
    circulation
  • IV and IA are 100 bioavailable and have a
    bioavailability of 1.
  • Drugs that are only partially absorbed have a
    bioavailability of less than 1.

22
Getting in DRUG ABSORPTION
23
Moving Around DRUG DISTRIBUTION
  • Drug distribution is the physiological movement
    of drugs from systemic circulation into the
    tissues.
  • Goal is for the drug to reach the target tissue
    or intended site of action
  • Factors affecting drug distribution
  • Membrane Permeability
  • Tissue Perfusion
  • Protein Binding
  • Volume of Distribution

24
Membrane Permeability
  • Capillary fenestrations allow movement of small
    molecules in and out of them.
  • Large molecules usually cannot pass through them
  • Exception Only lipophilic drugs can pass through
    the blood-brain barrier because it has no
    fenestrations and it has an extra layer of cells
    surrounding them (glial cells). However,
    fever/inflammation can make the membrane more
    permeable to some drugs.
  • Exception The placenta has the ability to block
    SOME drugs from affecting the fetus with its
    barrier.

25
TISSUE PERFUSION
  • Definition the relative amount of blood supply
    to an area or body system. It affects how rapidly
    drugs will be distributed.
  • Drugs travel rapidly to well perfused tissues
    (brain, heart, liver, kidneys).
  • May initially have high levels of drug
  • Drugs travel slowly to poorly perfused tissues
    (fat).
  • May inititially have low levels of drug
  • Can also be affected by blood flow rates that are
    altered via vasoconstriction or vasodilation.
  • Decreased rates decrease the amount and rate of
    the drug thats delivered to the tissues.

26
Protein Binding
  • Protein bound drugs in the blood become trapped
    in circulation because they cannot leave
    capillaries.
  • Free or unbound drugs are able to leave the
    capillaries.
  • INCREASED PROTEIN BINDING less free drug
    available to the tissues
  • DECREASED PROTEIN BINDING more free drug
    available to the tissues.
  • Equilibrium is typically established between
    bound and unbound drugs.
  • When given concurrently, protein bound drugs
    compete for binding sites.

27
Hypoalbuminemia
  • Albumin is the 1 transport protein in
    circulation and is made in the LIVER.
  • Animals with liver disease will have less protein
    in their body, thus more drug will be UNBOUND and
    available to the tissues.
  • DECREASED dosages or different medications should
    be chosen for patients with liver disease.
  • Also important because most drugs will be
    metabolized by the liver.

28
Volume of Distribution
29
Volume of Distribution
  • Volume of distribution is how well a drug is
    distributed throughout the body based on
    concentration of drug in the blood.
  • Assumes that the drug concentration in the blood
    is equal to the drug concentration throughout the
    rest of the body
  • NOTE THE LARGER THE Volume of Distribution,
  • THE LOWER THE DRUG CONCENTRATION IN
  • THE BLOOD AND OTHER TISSUES AFTER
  • DISTRIBUTION.
  • Lower concentrations may keep a drug out of
    therapeutic range and decrease its effectiveness.
  • Dose may need to be increased in cases of larger
    volumes of distribution.

30
Changing PHARMACOKINETICS
  • Biotransformation is also called drug metabolism,
    drug inactivation, and drug detoxification
  • Biotransformation is the chemical alteration of
    drug molecules by the body cells into a
    metabolite that is in an activated form, an
    inactivated form, and/or a toxic form.
  • Primary site of biotransformation is the liver.
  • Inhibition or induction of Cytochrome P450

31
Drug Interactions Affecting Drug Metabolism
  • Altered absorption one drug may alter the
    absorption of other drugs
  • Antacids alter pH of stomach.
  • 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
  • Diuretics increase production of urine and may
    affect drugs excreted via the kidneys.
  • Altered metabolism the same enzymes may be
    needed for biotransformation of two drugs that
    are prescribed at the same time for an animal
  • Enzyme saturated rate of metabolism decreased
    for both drugs

32
Other ways in which drug interactions affect drug
metabolism
  • Some drugs induce the enzyme system, altering
    metabolism by causing liver enzymes to become
    more efficient.
  • Ex Phenobarbital (may need to increase dose to
    maintain adequate therapeutic levels)
  • Liver damage or immaturity decreases enzyme
    production and ability to metabolize drugs
  • Doses may need to be decreased to avoid toxicity.
  • Tolerance is decreased response to a drug
    resulting from repeated use.
  • Metabolic drug metabolized more rapidly
  • Cellular down regulation decreased receptor
    response
  • Doses need to be increased.

33
Getting out PHARMACOKINETICS
  • Drug elimination (drug excretion) is removal of a
    drug from the body.
  • Most important routes kidneys and liver
  • Renal elimination of drugs involves
  • Glomerular filtration
  • Tubular secretion
  • Tubular reabsorption
  • Urine pH can also affect rate of drug excretion.
  • Weak acids better excreted in basic urine
  • Weak bases better excreted in acidic urine
  • Other elimination routes include the intestine
    and through milk.
  • Minor routes of elimination sweat, saliva, and
    pulmonary route.

34
Drug Elimination Terminology
  • Drug residue amount of drug that can be detected
    in tissues after administration ceases.
  • 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

35
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

36
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

37
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 animals
    body

38
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

39
RECEPTORS
40
AGONISTS VS ANTAGONISTS
  • 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

41
AGONISTS VS ANTAGONISTS
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