Introduction to Pharmacology Terminology and Concepts

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Introduction to Pharmacology Terminology and
Concepts

• Dr. Pete Bill
• Purdue University
• School of Veterinary Medicine

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When your head hurts, how much Tylenol, or Advil
do you take?
Why dont you take 12 tablets? Does it work 30
seconds after you took the tablet? Does it last
for a week? If you sprain your ankle, how does
the drug know to go to your ankle?
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Dr. Bills 1 Rule
ALL DRUGS ARE POISONS The only thing that
determines if a drug provides a benefit or kills
a patient is how WE administer it
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Our Therapeutic Goal is to
Achieve drug concentrations at the site of action
(target tissue) that are sufficiently high
enough to produce the intended effect without
producing adverse drug reactions.
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Drug Concentrations in the Plasma
50 40 30 20 10
But whats missing here that is needed for this
info to be of any use?
Drug Concentration in Plasma (Cp) mcg/mL
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Time since administration of drug (hours)
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Drug Concentrations in the Plasma
50 40 30 20 10
Drug Concentration in Plasma (Cp) mcg/mL
Subtherapeutic Concentrations
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Time since administration of drug (hours)
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Only by giving the right amount of drug can we
achieve therapeutic concentrations
Too little
Too much
Just right
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Drug Dose

• Amount (mass) of drug given for a specific animal
  
• 100 mg (for a 15 pound poodle)
• 5 grams (for a 500 kg horse)
• 4 mL from the 2 mg/mL bottle

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Drug Dosage
Formula to determine the amount of drug to be
given to ANY ANIMAL
10 mg/kg
IM
q12h
PRN
Duration
Dose Interval
Amount of drug per body weight or surface area
Route of Administration
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Routes of Administration
Identify these routes IM
Intra-muscular
SQ
Sub cutaneous
PO
Per os (oral)
IV
Intra-venous
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Routes of Administration
IV bolus
All one injection IV push
IV infusion
Administered over time IV drip
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Routes of Administration
IP
Intraperitoneal Into the abdominal cavity
ID
Intradermal Into the skin
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Routes of Administration
topical
Onto skin surface
Aerosol
Inhaled
Extravascular Perivascular
Parenteral
around enteric canal Any injection IM, SQ,
etc.
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Dose Interval
Identify these intervals s.i.d. q12h b.i.d. qd t.
i.d. q6h
If something is given q6h, how many times a day
is that? Which is more frequent t.i.d. or
q.i.d.? What is q2d?
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So if I follow the dosing information correctly,
I should be okay, right?
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30 mg IV bolus stat
100 mcg IM qd
200
120 mg
25 mg q12h PO for 3d
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5 grains s.i.d. PO p.r.n.
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Dr. Bills Rule 2
ALL DOSES ARE GUESSES A dose gives an
approximation of the amount of drug needed to
reach therapeutic concentrations in a healthy
physiologically normal animal
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In order for a therapeutic agent to be effective,
it must be

• Absorbed
• Distributed
• Metabolized
• Eliminated

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• Absorbed properly

The drug must move from the point of
administration TO the systemic circulation

• Distributed to the appropriate site

Meaning the drug must move FROM circulation TO
the target tissue and be present in sufficient
concentrations to produce a beneficial effect
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• Metabolized appropriately (if required)

Meaning that if metabolized, the drug must be
broken down at a predictable rate to an inactive
form

• Eliminated at the correct rate

Meaning that the drug must move OUT of the body
at a predictable rate
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How do routes of administration affect
absorption?
It depends upon the barriers between where the
drug is administered and the systemic circulation
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IV drugs are 100 absorbed
No absorption phase because the drug is placed
directly into the blood Used for stat
administration of drugs
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Drug Concentrations in the Plasma
IV administration
50 40 30 20 10
IM administration
Drug Concentration in Plasma (Cp) mcg/mL
PO and SQ administration
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Time since administration of drug (hours)
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How does the drug molecule know where to go?
It doesnt! Drugs molecules go wherever
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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)
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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Facilitated Diffusion
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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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
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
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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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
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How do the drugs get out of the blood and into
the tissues?
Capillaries are NOT like a big solid oil pipeline
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Capillaries have gaps that allow drugs to be
distributed to the tissues
Drug molecules
Body Capillary
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Note the different sizes of drug molecules
compared to RBCs and the normal proteins found in
blood
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Body capillaries are different than brain
capillaries
Body Capillary
BLOOD BRAIN BARRIER
NO Fenestrations
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How does the drug know upon which cells to act?
The key to this is the cells RECEPTOR
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The way a drug produces an effect on a cell is
via the drug molecule combining with a
specialized protein in or on the cell
Drug A Molecule
receptor
Drug B Molecule
The drug a KEY and the receptor a LOCK
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The cells response is due toAffinity and
Intrinsic Activity
Drug A Molecule
receptor
Drug B Molecule
Drug A has a greater affinity for this receptor
than Drug B Drug A fits the receptor better than
Drug B
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The cells response is due toAffinity and
Intrinsic Activity
Drug A Molecule
25 of maximum capacity secretion
Drug B Molecule
75 of maximum capacity secretion
Drug B has a greater intrinsic activity for this
receptor than Drug A
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An AGONIST is a drug that combines with a
cellular receptor and exerts an effect
Drug A Molecule
25 of maximum capacity secretion
Drug B Molecule
75 of maximum capacity secretion
Drug A and Drug B are both AGONISTS because they
both exert an effect
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An ANTAGONIST combines with a receptor but does
not produce an effect (no intrinsic activity)
By blocking the receptor site from an AGONIST
molecule, the ANTAGONIST blocks the effect of
the agonist
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Drug molecules normally do not just sit on the
receptor
Drug A Molecule
receptor
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If there are two agonist drugs competing for the
same receptor, there is competitive antagonism
for the receptor site
receptor
Drug B has more molecules present so it is more
likely to occupy the receptors than Drug A
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Because Drug A and B have equal affinity to
occupy the site, this is competitive antagonism
receptor
If there were more Drug A molecules than Drug B
then the activity of the cell would be dictated
by the presence of Drug B on the receptor
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If Drug A had a greater affinity for the receptor
than Drug B, Drug A would have an advantage
receptor
Because Drug A has an advantage, this would be an
example of NON-COMPETITIVE antagonism
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Concept of Partial Agonist and Partial Antagonist
Drug A Molecule
25 of maximum capacity secretion
Drug B Molecule
75 of maximum capacity secretion
Now, lets say Drug B was given FIRST and is
causing the cell to produce 75 of its maximum
capacity to secrete
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Concept of Partial Agonist and Partial Antagonist
Drug B Molecule
75 of maximum capacity secretion
Drug B Molecule
75 of maximum capacity secretion
Drug B is a pretty strong AGONIST because of its
strong intrinsic activity on the cell
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Now lets inject Drug A (25 max secretion) into
the animal
Secretion level has DECREASED from 75 to 25
under the effect of Drug A Drug A has acted as an
ANTAGONIST to the effect of Drug B
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Although Drug A antagonized Drug B, it did not
totally eliminate the activity
Thus Drug A is a PARTIAL ANTAGONIST because it
only partially reversed the effect of Drug B
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Because Drug A has some intrinsic activity of its
own (but less than Drug B), it also is a partial
AGONIST
Thus Drug A is a PARTIAL AGONIST/ PARTIAL
ANTAGONIST relative to the effects of Drug B
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Why is metabolism important?How does it relate
to drug tolerance?
Drug metabolism is the conversion of a drug
molecule into something else
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Metabolism or Biotransformation
Performed by liver enzymes As exposure to drug
continues, the number of enzymes increases in
response More enzymes FASTER rate of
metabolism INDUCED metabolism DRUG TOLERANCE
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Cats dont metabolize drugs very well!
Cats have fewer enzymes and less raw material
to be combined with the drug molecule Very young
animals have poorly developed (immature) livers
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How does the drug leave the body?
Unless the out-go matches the in-flow you
have trouble
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Two major elimination organs are the liver and
the kidney
Renal elimination goes into the urine
Liver elimination goes into the bile duct and
small intestine
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Renal elimination
MORE blood pressure MORE flow
Blood flows into kidney
Urine and drug flows into the ureter, then the
bladder, and out
MORE flow MORE filtered
MORE filtered QUICKER elimination
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In HYPOTENSION renal elimination decreases
MORE blood pressure MORE flow
Blood flows into kidney
Urine and drug flows into the ureter, then the
bladder, and out
MORE flow MORE filtered
MORE filtered QUICKER elimination
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Bottom Line

• KNOW this terminology for your anesthesia and
  pharmacology classes

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Thanks for your attention
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All drugs absorbed across the wall of the GI
tract enter the hepatic portal system
Therefore, all PO administered drugs must pass
through the liver prior to entering systemic
circulation
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Some drugs are excreted by the liver before they
reach systemic circulation
This is called the FIRST PASS EFFECT
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In the case of PO administered diazepam in the
dog, 97-99 is removed by the First Pass Effect
Only 1-3 reaches systemic circulation
Avoid using drugs with 1st pass effect via PO
route
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97-99
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Loading Dose versus Maintenance Dose
Loading dose bigger than normal
dose Establishes effective drug concentrations in
the body
Maintenance dose smaller doses Keeps
concentrations sufficiently high after
established by loading dose
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Half Life of Elimination and Clearance
Both terms refer to a measurement of how quickly
a drug leaves the body
Clearance is the VOLUME of drug cleared per unit
time (e.g. 0.5 Liters per hour)
Half life is the TIME it takes for drug
concentrations to drop by HALF (e.g. 3 hrs)
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Drugs highly protein bound have much of their
molecules stuck in the blood
Only the free form of the drug molecules can
distribute to tissues
Drug Molecules
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Normal blood and normal protein binding of
protein-bound drugs
Free Drug Molecules
Protein Bound Drug
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Normal blood and normal protein binding of
protein-bound drugs
Protein Bound Drug
Hypoproteinemic Blood and Binding
Protein Bound Drug
Free Drug Molecules