Pharmokinetics

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Pharmokinetics

• CHAPTER 3 - 2
• Dr. Dipa Brahmbhatt VMD MpH
• dbrahmbhatt_at_vettechinstitute.edu

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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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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
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Passive Diffusion
Movement is random from areas of higher to areas
of lower concentration Eventually the drug
molecules are equally distributed
(equilibrium) Once equilibrium reached, molecules
still moving around but no net direction of
movement
High concentration in this area
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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
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Passive Diffusion

• Movement of particles (atom, ion, molecules) from
  an area of high concentration to an area of low
  concentration
• Rapid for small, lipophilic, nonionic particles
• The drug must dissolve and pass through in the
  cell membrane
• No energy / carrier
• Temperature depended
• Oxygen, carbondioxide

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Passive Diffusion

• Rate of diffusion is dependent on
• Drug molecule size smaller gt faster
• Lipophilic dissolve in PL bilayer
• Temperature Low slower rate
• Thickness of membrane

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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
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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
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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
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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
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Facilitated Diffusion

• Passive diffusion that uses a special carrier
  molecule
• Usually transport protein in PL bilayer
• Good for bigger molecules that are not lipid
  soluble
• No energy is needed for a facilitated diffusion
• Glucose and insulin

Revolving door analogy
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Facilitated Diffusion
Passive Diffusion
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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
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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
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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
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Active Transport

• Molecules move against the concentration gradient
  
• Carrier molecule
• Energy ATP
• Good for accumulation of drugs within a part of
  the body
• Electrolytes Na, K proton pump
• Creates pH gradient
• Move acidic/alkaline substance into urine

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Active Transport
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Carrier molecules

• Saturated carrier molecules are full
• Cant move any faster
• Transportation maximum t-max
• Drugs arrive at rate that exceeds t-max, drug jam

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Pinocytosis/Phagocytosis

• Molecules are physically taken in or engulfed by
  a cell
• Pinocytosis (cell drinking) is engulfing liquid
  particles (insulin)
• Phagocytosis (cell eating) is engulfing solid
  particles (nutrients)
• Good for bigger molecules (proteins) or liquids

Active transport
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Mechanisms of Drug Movement
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Terminology

• Lipophilic drugs Fat loving (cell membrane
  phospholipids e.g. intestinal mucosa)
• Hydrophilic drugs Water loving, chemicals
  dissolved in water IM hydrophilic faster
  absorption
• Ionized /- charge depended on pH. Mostly
  hydrophilic form
• Non-ionized No charge, neutral. Mostly
  lipophilic form
• Polarized charges at the end of the molecule

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Phospholipid Bilayer

• Lipophilic in nature
• Nonpolarized/ nonionized molecules

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DRUG MOVEMENT

• PHARMACOKINETICS is the physiological movement of
  drugs.
• 4 Steps therapeutic range
• Absorption
• Distribution
• Biotransformation
• (metabolism)
• Excretion

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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
  (IV is directly in blood)
• Drug factors include bioavailability, route of
  administration, lipophilic/ hydrophilic, pH of
  the environment, ion trapping, dissolution, first
  pass effect, perfusion
• Patient factors include the animals age, health,
  metabolic rate, genetic factors, sex, and species

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Bioavailability

• Bioavailability of drug administered
• that actually enters the systemic circulation
• IV/IA 100 available, bioavailability F 1
• lt 1 Drugs that are partially absorbed
• LOWER the bioavailability gt the LESS drug in
  circulation gt LESS drug in the tissue
• Exceptions where you dont want high
  bioavailability local drugs, enteral drugs

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Route of Administration

• IV (F1) stat gt IM gt SC gt PO
• Plasma (serum concentration) of drugs pg. 57
  figure 3-6
• IV rapid high peak conc. for short period of
  time. If toxic CRI e.g. digoxin bolus gt toxic
  vomiting, arrhythmias

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Lipophilic/ Hydrophilic

• SQ/ IM hydrophilic gt extracellular fluid (ECF) gt
  capillaries
• In GI lumen (outer) Deworming agents or
  antibiotics for GI tract
• PO lipophilic gt lumen GI tract
• SQ/IM slow release drug

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References

• Romich, J.A. Pharmacology for Veterinary
  Technicians, 2nd edition. 2010.
• Bill, R.L. Clinical Pharmacology and Therapeutics
  for the Veterinary Technician, 3rd edition. 2006.
• Ahearn Gregory, Life on Earth, 5th edition, 2008.