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Introduction to Pharmacology
Terminology and Concepts
Dr. Pete Bill
Purdue University
School of Veterinary Medicine
Drug Dose
• Amount (mass) of drug given at
ONE TIME (one administration)
• 100 mg
• 5 grams
• 4 mL from the 2 mg/mL bottle
Drug Dosage
Amount of drug to be given to ANY ANIMAL
10 mg/kg IM q12h PRN
Duration
Amount of drug Dose
per body Route of Interval
weight or Administration
surface area
Routes of
Administration
Identify these routes:
IM ID
SQ topical
IV bolus aerosol
IV infusion perivascular
extravascular
PO
parenteral
IP
Dose Interval
Identify these intervals:
s.i.d.
q12h
b.i.d.
qd
t.i.d.
q6h
Loading Dose
versus
Maintenance Dose
Loading dose – bigger than
normal dose
Establishes effective
concentrations immediately
Maintenance dose – smaller
dose
Keeps concentrations
sufficiently high after
established by loading dose
Movement of Drug Molecules
This process is
called passive
Drug
diffusion
molecules
move No cellular effort
randomly is needed to
from one transport the
point to molecules (hence
another the process is
passive)
Passive Diffusion
Movement is
random from
areas of higher to
areas of lower
High
concentration
concentration
in this area Eventually the
drug molecules
are equally
distributed
(equilibrium)
Passive Diffusion
C
e But drug
l molecules will
l only cross by
M passive
Drug molecules
e diffusion if they
may move from
m can dissolve in
one side of a
b the membrane
cell membrane
to another by r
passive a
diffusion n
e
Facilitated Diffusion
C
e These drug
l molecules need
l a carrier to get
M across the
These
e membrane
molecules can’t
pass through m
the membrane b
without help r
a
n
e
Facilitated Diffusion
C
e
When the drug
l
molecule
l
encounters the
M carrier protein,
e it “carries” it
m across
Here is the
carrier protein b
molecule in the r
membrane a
n
e
Facilitated Diffusion
C
e
When the drug
l
molecule
l
encounters the
M carrier protein,
e it “carries” it
m across
Here is the
carrier protein b
molecule in the r
membrane a
n
e
Facilitated Diffusion
C
e
When the drug
l
molecule
l
encounters the
M carrier protein,
e it “carries” it
m across
Here is the
carrier protein b
molecule in the r
membrane a
n
e
Facilitated Diffusion
C The carrier
e molecule then
l resets itself
l
No cellular
M energy is used
e to transport the
Here is the m molecule across
carrier protein b
Only the
molecule in the r
concentration
membrane a
gradient moves
n
the molecules
e
Active Transport
C The drug
e molecule
l encounters the
l carrier molecule
M The cell
e expends energy
Involves a m to PUMP the
carrier molecule b molecule across
again r the membrane
a to the other side
n
e
Active Transport
C The drug
e molecule
l encounters the
l carrier molecule
M The cell
e expends energy
Involves a m to PUMP the
carrier molecule b molecule across
again r the membrane
a to the other side
n
e
Active Transport
C Unlike diffusion,
e active transport
l is not dependent
l upon
concentration
M
gradient
e
Involves a m
carrier molecule b All of the
again r molecules can
a end up on this
n side
e
Phagocytosis and Pinocytosis
Foreign Cell
particle
Phagocytosis – the cell flows around large
particles and engulfs it
Pinocytosis – cell takes in molecules
through invaginations in the membrane
Drug Concentrations in the
Plasma
50 But what’s
missing here
Drug 40 that is needed
Concentration
for this info to
in Plasma (Cp)
30 be of any use?
mcg/mL
20
10
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Time since administration of drug
(hours)
Drug Concentrations in the
Plasma
Toxic
50 Concentrations
Drug 40
Concentration Therapeutic
in Plasma (Cp)
30 Concentrations
mcg/mL (Therapeutic Range)
20
Subtherapeutic
10 Concentrations
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Time since administration of drug
(hours)
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.
Dr. Bill’s #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
In order for a therapeutic agent to
be effective, it must be:
• Absorbed
• Distributed
• Metabolized
• Eliminated
In order for a drug to achieve
appropriate therapeutic
concentrations at the target site,
it must be:
• Absorbed properly
Meaning … the drug must move
from the point of administration TO
the systemic circulation
IV drugs are 100% absorbed
No absorption phase
because the drug is placed
directly into the blood
Used for stat administration
of drugs
Drug Concentrations in the
Plasma
IV
50 administration
Drug 40 IM
Concentration administration
in Plasma (Cp) PO and SQ
30
administration
mcg/mL
20
10
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Time since administration of drug
(hours)
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
Some drugs are excreted by the
liver before they reach systemic
circulation
This is called
the FIRST
PASS EFFECT
In the case of PO administered
diazepam in the dog, 97-99% is
removed by the First Pass Effect
Avoid using Only 1-3%
drugs with 1st reaches systemic
pass effect via circulation
PO route
100%
97-99%
In order for a therapeutic agent to
be effective, it must be:
• 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
Capillaries have gaps that
allow drugs to be distributed
to the tissues
Drug molecules
Body Capillary
Note the different sizes of drug
molecules compared to RBCs
and the normal proteins found
in blood
Body Capillary
RBC Drug Protein
Molecules
Body capillaries are different
than brain capillaries
Body Capillary
Fenestrations (windows)
Brain Capillary Neuroglia
cells
BLOOD
BRAIN
BARRIER
NO Fenestrations
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
Body Capillary
RBC Drug
Protein
Molecules
Normal blood and normal protein
binding of protein-bound drugs
Protein Free Drug
Bound Drug Molecules
Normal blood and normal protein
binding of protein-bound drugs
Protein
Bound Drug
Hypoproteinemic Blood and Binding
Protein Free Drug
Bound Drug Molecules
In order for a therapeutic agent to
be effective, it must be:
Metabolized appropriately
(if required)
Meaning that if metabolized, the
drug must be broken down at a
predictable rate to an inactive form
Metabolism or
Biotransformation
Drug Meta
A bolite
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
Cats don’t 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
In order for a therapeutic agent to
be effective, it must be:
Eliminated at the correct rate
Meaning that the drug must move
OUT of the body
at a predictable rate
Two major elimination organs are
the liver and the kidney
Liver elimination Renal
goes into the bile elimination goes
duct and small into the urine
intestine
Renal elimination
MORE blood pressure =
MORE flow
Water, drugs,
Blood flows small molecules
into kidney filtered out in
glomerulus
Urine and drug
MORE flow =
flows into the
MORE filtered
ureter, then the
bladder, and out MORE filtered =
QUICKER elimination
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)
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 Cell
Molecule
receptor
Drug B
Molecule
The drug = a KEY and the receptor = a LOCK
The cell’s response is due to
Affinity and Intrinsic Activity
Drug A Cell
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
The cell’s response is due to
Affinity and Intrinsic Activity
Drug A
Molecule 25% of maximum
capacity secretion
Drug B 75% of maximum
Molecule capacity secretion
Drug B has a greater intrinsic activity for this
receptor than Drug A
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 75% of maximum
Molecule capacity secretion
Drug A and Drug B are both AGONISTS
because they both exert an effect
An ANTAGONIST combines with a
receptor but does not produce an
effect (no intrinsic activity)
Antagonist
Drug
Cell
Molecule
By blocking the receptor site from an
AGONIST molecule, the ANTAGONIST
“blocks” the effect of the agonist
Drug molecules normally do not
just “sit” on the receptor
Drug A Cell
Molecule
receptor
If there are two agonist drugs
competing for the same receptor,
there is competitive antagonism for
the receptor site
Cell
receptor
Drug B has more molecules present so it is
more likely to occupy the receptors than Drug A
Because Drug A and B have equal
affinity to occupy the site, this is
competitive antagonism
Cell
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
If Drug A had a greater affinity for
the receptor than Drug B, Drug A
would have an advantage
Cell
receptor
Because Drug A has an advantage, this would
be an example of NON-COMPETITIVE
antagonism
Concept of Partial Agonist and
Partial Antagonist
Drug A
Molecule 25% of maximum
capacity secretion
Drug B 75% of maximum
Molecule capacity secretion
Now, let’s say Drug B was given FIRST and is
causing the cell to produce 75% of its
maximum capacity to secrete
Concept of Partial Agonist and
Partial Antagonist
Drug B
75% of maximum
Molecule
capacity secretion
Drug B 75% of maximum
Molecule capacity secretion
Drug B is a pretty strong AGONIST because of
its strong intrinsic activity on the cell
Now lets inject Drug A (25%
max secretion) into the animal
B
Drug A
75% of maximum
25% of maximum
Molecule
capacity secretion
capacity secretion
Drug A
Drug B 75% of maximum
25% of maximum
Molecule
Molecule capacity secretion
capacity secretion
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
Although Drug A antagonized
Drug B, it did not totally
eliminate the activity
Drug A
Molecule 25% of maximum
capacity secretion
Drug A
Molecule 25% of maximum
capacity secretion
Thus Drug A is a PARTIAL ANTAGONIST because it
only partially reversed the effect of Drug B
Because Drug A has some intrinsic
activity of its own (but less than
Drug B), it also is a partial AGONIST
Drug A
Molecule 25% of maximum
capacity secretion
Drug A
Molecule 25% of maximum
capacity secretion
Thus Drug A is a PARTIAL AGONIST/ PARTIAL
ANTAGONIST relative to the effects of Drug B
Bottom Line
KNOW this terminology for your
anesthesia and pharmacology
classes
Thanks for your attention
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