processes.
It modifies an already existing
Definitions
l Definitions
Medical (or Clinical) Pharmacology: Is the
science that deals with the use of drugs
for diagnosis, prevention and treatment of
human disease.
• Toxicology: Is that aspect of
pharmacology which deals with adverse
effects of drugs and the toxic effects
produced by household, envb,nmental
and industrial chemicals. [poisons are
also drugs, why?)
function, and does not create a new
function.
Pharmacology: The science of drugs.
It is the knowledge of history, source,
physical and chemical properties,
absorption, distribution,
biotransformation, excretion, actions and
therapeutic uses of drugs (or toxic effects
on microbes),
Two aeneral principlesttt ev~ry
student should always r Jmember:
1. All substances can u~def certain
conditions be toxic. ' '
2. All dietary supplements and all
substances promoted as health-
enhancing should meet the same
standards of efficacy and safety.
.,;.!.,
1
 Definitions
• Pharmacotherapeutics: Is the use
of drugs in the prevention and
treatment of disease ( or the
medical uses of drugs).
• Chemotherapeutics: Is the use of
drugs to stop the growth or kill
microorganisms or cancer cells
Definitions
Idiosyncratic drug response:
Unusual response, infrequently observed in
most patients. Usually caused by genetic
differences in metabolism of drug, or by
immunologic mechanisms including allergic
reactions.
• Tolerance:
Is a decrease in the responsiveness to the
drug with continued drug administration.
• Tachyphylaxis:
Similar to tolerance but m9!e rapid.
Definitions
• Ph?rmacogenomics: The relation
between the individual's genetic
makeup to his/her response to
specific drugs (entire genome).
• Pharmacogenetics: Interindividual
variation in drug response that is
due to genetic influences (specific
gene).
Areas of Pharmacology
• Pharmacodynamics:
Is what the drug does to the body,
which includes the biochemical
and physiological effects of the
drug, including the mechanism of
action, interaction with receptors
as well as the adverse effects.
.J-'-
 Areas of Pharmacology
Pharmacokinetics:
Is what the body does to the drug.
Deals with absorption, distribution,
biotransformation and excretion of
drugs.
1. Absorption: Is the movement of drug
molecules from the site of
administration into the circulation.
Areas of Pharmacology
2. Distribution: Is the movement of drug
molecules from the circulation to tissues
and between different parts of the body.
3. Biotransformation: Is conversion of the
drug from one chemical structure into
another by the action of metabolic
enzymes (metabolism)
4. Excretion: Is the movement of drug
molecules out of the body.

Pharmacokinetics & Pharmacodynamics Pharmacokinetics & Pharmacodynamics

DNg in the systemic circulation

Dosage form I DI&tribullon

I
Disintegration
Drug in tissues of distribution

JOlstrlbution

I
Dissolution
Drug in elimination organs

J Excretion I"'.t.bolism

Kidney Uver Pharmacological effect

IAbSOrption I
CliniCil respros e
Drug in the systemic circulation
Efficacy Toxicity

1\ 11.-
'f
~
1
!
,~,
Drug Receptors Drug Receptors
A receptor is a component of the cell that Most receptors are 'protelns:
interacts with a drug and initiates a chain of 1. The best characterized drug receptors are
events leading to drug's action. regulatory proteins, which mediate the actions of
Receptors are responsible for selectivity of endogenous chemical signals such as
drug action. neurotransmitters, autacoids and hormones.
Receptors determine the quantitative 2. Some receptors Include enzymes that could be
relationship between drug concentration and Inhibited by drugs. (dihydrofolate reductase and
pharmacological effect. trimethoprim).
Receptor function can be modified by 3. Some receptors are transport proteins (Na' I K'
agomsts and antagonists. Antagonists ATPase and digitalis).
int'lrfere with the ability of the agonist to 4. Some receptors are structural proteins (tubulin and
activate the receptor. colchicine).
i

13

Signaling Mechanisms ®
Five basic transmembrane signaling
mechanisms are well understood:
1. A lipid-soluble chemical signal crosses the
plasma membrane and acts on an intracellular
receptor.
2. The signal binds to the extracellular domain of a
transmembrane protein, thereby activating an
enzymatic actiVity of its cytoplasmic domain.
3. The signal binds to the extracellular domain of a
transmembrane receptor bound to a protein
tyrosine kinase, which it activates.
4. The signal binds to and directly regUlates the
opening of an ion channel. "
5. The signal binds to a cell-surface receptor linked
to an effector enzyme by a G protein.
• J""

1-> /Co
 Drug Receptcr Interaction Drug Receptor Interacti9n
Definitions:
1.0 r-------------..,.
Agonist: A d"ug that binds to and
activates the receptor to bring about the
pharmacological effect.
1. A full agonist produces maximal
pharmacological response with full ,
I

receptor occupancy. I
I

2. A partial agonist produces less than : EC 50

maximal (lower) pharmacological i/ .
response with full receptor occupancy. It Drug concentration (C)
is also calleq partial antagonist.

Drug Receptor Interaction Drug Receptor Interaction

B • Antagonist: A drug that binds to the

1.0 receptor but does not activate it. It
0.8 ~ Partial agonist
prevents the agonist from binding to the
~ _ Full agonist receptor and prevents its activation and
~ 0.6
the generation of pharmacological effect
~ 0.4
&! It can be either reversible or irreversible,
0.2 - competitive or noncompetitive.
Some antagonists are called "inverse
0.0 _~.S·0=---'----~8;---"------';;6:-----''----' agonists". They reduce receptor activity
log (Full agonist or partial agonist) below basal levels observed in the
absence bound ligand (drug).
 Drug Receptor Interaction Drug Receptor Interaction

• Competitive Antagonist • Conversely, suffic::ilntly high

In the presence of a fixed
concentration of agonist, increasing
the concentrations of a reversible
competitive antagonist progressively
inhibit the agonist response; high
antagonist concentrations prevent
response completely.
concentrations of agonist can
completely overcome the effect of a
given concentration of the antagonist.
• Because the antagonism is
competitive, the presence of antagonis
increases the a~onist concentration
required for a given degree of
response, and so the agonist
concentration effect curve is shifted to
the right.

Drug Receptor Interaction Drug with non- Drug with

competitive, competitive
~ntagon;'.?t
A antagonist
----...,,~ D,ug
)
\
l
Q~

"
~
alone "" _

~ Agonist
I -to
competilive antagoni,st

i
1
,/
c' _ C (1 -+-

AgonlGt concf'tntrntlon
hi ] I K i) Drug concentration

t
.
",., Drug Receptor Interaction

• Irreversible Antagonist:
FIGURE 2.5
Id~aliled dosc-rcsoonse cun'li:s of an agonist in tfIE.
absence Ie) and lhc presence (b. c. d} of incrt:a~in6 oose-s
of ilr'l cquilibnum-eonll'Ctil,\,C antacofllst.
Some anta~onists bind to the receptor in
an irreversible fashion either by forming
covalent bond with the receptor or
binding tightly to it, so that the receptor
not available for a~onist binding. Th)
remaining unoccupied receptors bind
agonist normally, but might not be
enough to elicit an adequateresponse.
The duration of action of the irreversible
antagonist is more dependent on recepto
turnover than antagonist elimination.

Drug Receptor Interaction Drug Receptor Interaction

B
----~.,--
• Another way of noncompetitive
antagonism is binding to the
receptor on a different site that
binds the agonist, thereby
preventing receptor activation by --~------,,....--
~ Agonist ..
the agonist without blocking noncompAlilivo anla{)oni~t

agonist binding. This is also called

,
"allosteric modulation". : EC sa
:/ /
Agonist concentration
 Drug with
competitive
antagonist'

c:;
Drug
alone ~
~
Q;
u
'51
o
.0 FIGURE 2.6
'iii Idealized dose-resixmse CUf\!CS of an agonist in the
nos-eoce ial ;,no tnc Df'escO(",c (b. c. d! 01 increasing uoses
.! of ;l non-eQuilil>nw!KCmiX'(llive anlCigonist.
Dr~g concentration

Drug Receptor Interaction Spare Receptors

Other mechanisms of drug
antagonism:
1. Chemical antagonism: heparin &
protamine.
2. Physiologic antagonism: Insulin
and glucocorticoids effects on
blood glucose.
• Occupation of a receptor by an agonis
is only the first of many steps required
to bring about the pharmacologic
effect.
The transduction process that links
drug occupancy of receptors and
pharmacologic response is termed
coupling.

31
 Spare Receptors
Sometirr,es the effect of the drug is linearly
related to the number of receptor bound.
100%
In other cases, the effect increases
disproportionately to the number of
receptors occupied by drug.
Effect
Receptors are said to be "spare" for a given
pharmacolo£ic response if a maximal
response is elicited at an agonist
concentration that does not result in full
occupancy of receptors.- 0%