Pharmacology has 2 main areas:
pharmacodynamics and pharmacokinetics.
Pharma: drug
Dynamics: action
Kinetic: motion
So, pharmacodynamics is the action of the
drug on the body, which includes biochemical
and physiological effects of the drug,
including the mechanism of action, interaction
with receptors as well as adverse effects.
Pharmacokinetics is what the body does to
the drug. The drug is not the master in the
body; it acts on the body and the body acts on
it. These include absorption, distribution,
biotransformation (metabolizing) and
excretion of the drug.
Actions of the body on the drug are:
1- Absorption: It is the movement of
drug molecules from the site of
administration into the circulation. An
example of site of administration is in
the intestines. When a patient takes a
drug orally, the drug is absorbed in the
intestines and is moved to the
circulation.
2- Distribution: Once in the circulation,
the drug goes to the rest of the body.
The movement of molecules from the
circulation to tissues and between
different parts of the body is called
distribution. The drug is distributed to
its site of action, elimination organs
and other tissues.
3- Biotransformation: If a drug reaches
to the liver which is a metabolizing
agent, it is metabolized.
Biotransformation is the biological
conversion in the drug from one
chemical structure to another by the
action of metabolic enzymes.
4- Excretion: It is the movement of drug
from the circulation to outside of the
body through feces or urine. If the
drug is secreted by the kidneys, then
it would be excreted as urine. If it
was secreted in bile, then it is
secreted as feces.
In explaining the relation between the two
concepts: pharmacodynamics and
pharmacokinetics, the drug follows the rule
of mass action. Rule of mass action can be
simply referred to as random diffusion. An
example that explains this law is illustrated
in adding a drop of blue ink to a large tank
of water. The drop diffuses rapidly, and
begins to fade out until it fully disappears.
At the end, we have a mixture of water and
blue ink in which the blue ink is not visible.
In the same way, the drug in the circulation
is distributed throughout the body, going to
the kidneys, liver, heart, intestines, etc…
Dosage form is the form of the administrated
drug. That can be either in a form of a
capsule or a tablet, or as liquid or
suppositories. If we take the solid form of a
tablet of drug, the drug is not absorbed to the
circulation as a tablet. The drug undergoes
disintegration. The disintegration of the drug
is the job of water. Water in the intestines
causes swelling of the tablet, until it
disintegrates. After disintegration, the drug
dissolves in water. So, before absorption of a
drug taken orally to the circulation it must
go through two steps: disintegration and
dissolution. After this the drug can be
absorbed to the systematic circulation.
After being circulated, the drug reaches its
site of action. It reaches also to the tissue of
distribution and elimination organs. The
drug is distributed randomly. Some of its
molecules go directly to the site of action;
some goes to the liver, kidneys, etc…
The site of action is the site where the drug
performs its pharmacological effect, which

is either desirable (efficacy) or undesirable
(toxicity).
Drug in elimination organs undergoes
excretion or metabolizing.
Works of drug on the site of action:
In order for a drug to work on its site of action
only, we should have some selectivity. Drug
receptors can grant this selectivity. These
receptors are not in the body to receive these
drugs originally; they work on substances
inside the body such as hormones. Drugs
modify body functions, so, they act on the
receptor either by stimulating or inhibiting
them.
A drug receptor is a component of the cell that
interacts with a drug and initiates a chain of
events leading to drug's action. The binding of
the drug alone is not enough to produce the
effect; it initiates a chain of events that leads
to the effect.
The receptors are responsible for the drug
selectivity; otherwise, the drug will affect all
the body and we will have undesirable results.
The receptors also determine the quantitative
relation between the drug concentration and
pharmacological effect. The effect is
proportional to the concentration. A specific
concentration leads to specific receptor
occupancy, and specific effect. If we raise the
concentration to a limit where all the receptors
are occupied, then the effect will turn to be
constant upon increasing of drug dose. The
extra drug molecules that have no receptors
will remain free, and will have toxic or no
effect, depending on the drug type.
Example: When you give a dose of 10 μg of a
certain drug, it will occupy 50% of the whole
count of receptors on the site of action, and
will have 50% effect. If you give 20 μg of the
same drug, it will have 100% occupancy,
and 100% effect. If you give the patient 30
μg of that drug, it will still have 100%
occupancy, and 100% effect, but the
remaining 10 μg will remain in the body in
its free form and will have undesirable
effect.
The receptors function can be modified by
agonists and antagonists. If a receptor is
stimulated by a drug, we call that drug an
agonist. On the other hand, if the receptor is
inhibited by a drug, we call that drug an
antagonist. The antagonist works by
inhibiting the agonist effect. So, the
antagonists interfere with the ability of the
agonist to activate the receptor.
- Receptors in most cases are proteins.
1- The best characterized drug
receptors are regulatory proteins,
which mediate the actions of
endogenous (from inside the body)
chemical signals such as
neurotransmitters, autacoids and
hormones. If we deficiency in
hormone activity, we give agonists
to stimulate receptors. If we have
excessive hormone activity, we give
antagonists to inhibit the role of
hormone.
2- Some receptors include enzymes
that could be inhibited by drugs.
(dihydrofolate reductase and
trimethoprim). Dihydrofolate
reductase is an enzyme involved in
folic acid synthesis. Folic acid is a
vitamin necessary for cell
proliferation by stimulation of DNA
synthesis. So, if we inhibit
dihydrofolate reductase, we inhibit
cell proliferation. We have some
drugs that inhibit dihydrofolate
reductase such as trimethoprim and
methotrexate. Deficiency in folic
acid causes anaemia.
3- Some receptors are transport
proteins (Na+/K+ ATPase and

digitalis). Na+/K+ ATPases regulate
the amount of potassium and sodium
on the two side of the membrane. This
ATPase is inhibited by digitalis.
4- Some receptors are structural
proteins (tubulin and colchicine).
Tubulin is a kind of protein that is
polymerized into microtubules.
Microtubules are responsible for
movement of substances throughout
the cell in addition of being the
cytoskeleton in the cell. If we inhibit
the transformation of tubulin into
microtubules, microtubules are not
formed. Therefore, this kind of
inhibition is used in the cases of
inflammation and gout. Gout is caused
by the presence of uric acid secreted
but inflamed cells. As we inhibit the
formation of microtubules, we kill the
cells causing pain and we can
overcome the situation. Microtubules
are also responsible for the formation
of mitotic spindle in cell division. If
we inhibit tubulin polymerization, we
inhibit chromosomal separation and
cell division.
Signaling Mechanisms: (Illustrated in the
figure below)
1- The drug molecule can go across the
membrane, but it should be lipid
soluble to cross the lipid bilayer. The
receptor should be intracellular. The
receptor is either in the nucleus, or in
the cytoplasm. In both ways, the drug
is transmitted into the nucleus.
When the drug binds to the receptor,
it stimulates gene transcription,
which in turn stimulates mRNA
synthesis. mRNA synthesis result at
the end in protein synthesis, which
is the basis of the drug effect. The
drug in this case effects the cell by
synthesizing proteins.
2- In this case the drug molecule is not
lipid soluble, but it binds to a
receptor that traverses through the
membrane. So, a part is facing the
outside of the cell (receptor portion),
and the other is facing the cytoplasm
(enzymatic portion). Once the drug
binds to its receptor, the receptor
performs a catalytic reaction acting
as an enzyme; converting A to B. B
initiates the pharmacological effect
of the drug.
3- This is similar to the second type,
but in this case another protein is
involved. The drug's interaction
with the receptor causes binding of
another protein to the receptor
which acts as an enzyme that
initiates phosphorylation. This is a
more complex mechanism, which
requires the control of the drug and
the receptor and the catalytic
protein.
4- This initiates the opening or closing
of an ion channel allowing or
inhibiting electrolytes to move.
5- This is the most complex
mechanism, as it involves control of
so many subunits. In this receptor-
  

In diagram A below, we realize that:

catalyst complex, we have three
components. The binding site binds to
the drug. The catalytic site is on the
membrane but not related to the
binding protein. Both components are
related to each other through a third
component name G-Protein
(reGulatory protein). Once the drug
binds to the receptor, G-Protein is
activated, and relates the catalytic site
to the binding site. Finally the
complex causes the catalytic site to
convert C to D, where D is the
molecule that initiates the
pharmacological effect of the drug.
This is the hardest one to control.
- Drug effect depends on drug
concentration. This is explained by
receptors' occupancy. Effect is
proportional mainly to receptor
occupancy.
- At 100% occupancy, the drug effect
reaches 1.0 unit. The drug here
reaches its maximal effect.
Pharmacologists prefer linear curves, so
they used logarithm of concentration of
drug. The resulting curve is a sigmoid
curve, as follows:
In diagram B below, we realize that:

- The diagram is not linear at all parts,

Drug Receptor Interaction but it is linear in a specific region.
- At a certain concentration, the drug
Agonist: A drug that binds to and reaches its maximal effect. If we
activates the receptor to bring about the raise the concentration of the drug at
pharmacological effect. It can be a full or that point, no change on effect
a partial antagonist, depending on its occurs.
ability to produce 100% effect. - In the partial agonist curve, at the
100% occupancy concentration, the
A full agonist produces maximal response is 40%. That is why it is
pharmacological response with full called partial agonist.
receptor occupancy.
Antagonist: A drug that binds to the
A partial agonist produces less than
receptor but does not activate it. It prevents
maximal (lower) pharmacological
the agonist from binding to the receptor and
response with full receptor occupancy.
prevents its activation and the generation of
Because a partial agonist is not a 100%
pharmacological effect. It can be reversible
agonist, it can be considered a partial
antagonist.
  

or irreversible, competitive or noncompetitive. - If we took the log of the

Some antagonists are called "inverse
agonists". They reduce receptor activity below
basal levels observed in the absence bound
ligand (drug).
Competitive Antagonist: In the presence of a
fixed concentration of agonist, increasing the
concentration of a reversible competitive
antagonist progressively inhibit the agonist
response; high antagonist concentrations
prevent response completely.
Conversely, sufficiently high concentrations of
agonist can completely overcome the effect of
a given concentration of the antagonist.
concentration (Slide 24), the
sigmoid curve is shifted to the right.
That means that there is no change
on the full effect of the drug, but
there is a change in the
concentration of the drug needed for
100% effect.
- As the competitive antagonist
concentration is increased, the curve
is shifted to the right further more.
(Slide 25)
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Because the antagonism is competitive, the

presence of antagonist increases the agonist
concentration required for a given degree
response, and so the agonist concentration
effect curve is shifted to the right.

The diagram below shows the competitive

antagonist effect:

- The competitive antagonist decreases

the effect of the agonist.
- At the end, at high concentrations, the
two curves meet. That means that the
100% efficiency is not changed. And
that can be explained by the definition
of the competitive antagonist: the
effect of the antagonist can be
overcome by increasing the
concentration of the agonist.