PCOL Prelims Lecture 5
toxicity
Site of administration Systemic Circulation Site of action
Effective Drug Concentration
Concentration of the drug at the receptor
The concentration of a drug thats free, unchanged,
unbound only exerts its action at the site of action
Drug Receptor
Component of a cell or organism that interacts with a drug
and initiate the chain of events leading to the drugs
observed effects
Receives the free, unchanged, and unbound drug molecule
Types of Drug Receptors:
1. Regulatory Proteins: mediates the actions of endogenous
chemical signals(drugs, hormones, etc.) such as:
Enzymes may be inhibited by binding to a drug
Transport proteins
Structural proteins
2. Non-regulatory Protein: a receptor that receives a
molecule, but there is no change
Inert binding site
Characteristics of a Receptor
1. Selective
Outside the receptor, there are plenty of ligands
(signals), if its not selective, anything can bind to it
Its to avoid constant activation and promiscuous
binding of different signals
Bawal maging malandi si receptor
2. Modifiable
A receptor upon binding to a drug molecule should be
able to modify/change its function
If it cant be modified no change happens
It can be activated or inactivated
Drug Receptor Bonds
1. Covalent strongest bond and irreversible
2. Electrostatic most common but weak (between a cation
and an anion)
3. Hydrophobic weakest bond (between a lipid-soluble drug
and the lipid bilayer)
Effectors Signaling Mechanism:
1. Lipid soluble ligand that crosses the membrane and acts on
an intracellular receptor
2. Transmembrane receptor protein whose activity is
regulated by the proteins extracellular domain
3. Transmembrane receptor that stimulates a protein tyrosine
kinase
4. A ligand-gated transmembrane ion channel
5. A transmembrane receptor protein that stimulates a G
protein
Drug Dose and Response
How to measure a change and response of a drug use a
Dose Response Curve (the left graph; dont mind the right
graph)
What dose will produce maximal benefit and minimal
Ec50
Effective concentration at 50% or Effective dose
at 50% ( Ed50 ) both are the same
Drug concentration or dose that produces 50% of
the maximum response
Plot it by finding the half way mark of the curve
then draw a straight line down
Emax
The greatest effect an agonist can produce if the
dose is taken to the highest tolerated level.
Maximum response that a drug can produce
Concentration is immaterial
Therefore the concentration of a drug is not
important, because were only looking for
the maximum response
Regardless the concentration, it just needs
to be tolerable.
if its not tolerable, it means that its toxic
which is not under Emax anymore
Potency
Refers to the concentration of a drug required to produce
50% of thats drugs maximal effect Ec50
Always consider the dose when finding potency
Example:
Drug A at 30 mg produces 50% of maximal response
Drug B at 50 mg produces 50% of maximal response
Which among them is more potent?
Drug A, because it has a lesser dose that produces half the
maximum response.
Maximal Efficacy Emax: the greatest to effect an organism can
produce if the dose is taken to the highest tolerated level
Which is more potent, Drug C or Drug D?
Look for Ec50 which has a lower one? Drug C is more
potent because at a lower concentration, it reaches the half
maximal response
Which is more potent, Drug B or Drug A?
Look for Ec50 which has a lower one? Drug B is
more potent, because at a lower concentration it reaches the
half maximal response
Which is more effective, Drug C or Drug A?
Look for Emax dont mind the concentration, which has
a higher maximal response? Same, they both are effective
Which is more effective, Drug B or Drug A?
Look for Emax dont mind the concentration, which has
a higher maximal response? Drug A is more effect, has a
higher Emax
Drug Receptor Interaction
Regardless the molecule before reaching the receptor, the
receptor Can either be active ( Ra ) or inactive (
Ri )
 Allosteric receptor (another binding site) effect is
inhibitory

Chemical Antagonism
1. Interacts directly to the drug binding antagonized
2. To prevent the drug from binding to its receptor
Chelators Like magnets, attracts drugs to excrete to the
urine before they bind to a receptor
Beneficial vs. Toxic Effect
If a receptor is active, it has the potential to produce a No drug causes only a single, specific effect
minimal effect (at steady state) Drugs are only selective, rather than specific
If a drug binds to an inactive receptor no effect Selectivity is usually considered by their beneficial or
If a drug binds to activate a receptor theres an effect & therapeutic effects versus toxic or adverse effects
the effect is greater compared to the steady state

Development of Drugs

Constitutive Activity
Active receptor that gives a minimal response
Theres already a response even without a drug
binding/activating it, and its already able to give a minimal
response by themselves because of their active state

Agonist
Binds to a receptor and activates it
Full
o A drug that is capable of activating the receptors
o Can reach the maximal efficacy/activity
o Has higher affinity to active receptors
Partial
o A drug that has equal affinity to active and
inactive receptors
o Drugs bind to active receptors only
Inverse
o A drug that has affinity to inactive receptors
o Diminished activity no constitutive activity

Antagonist
Antagonist only exits if theres an agonist (kontrabida siya)
Compete with and prevent binding by other molecules

Pharmacologic Antagonism
Reversible antagonist
Competes with a molecule on the same receptor
Reversible Drug A (agonist) can still counteract or
surmount the effect of Drug B (antagonist) by
increasing its dosage
Example: Drug A 10 mg administration Drug B attaches
to receptor hindering the effect of Drug A Drug A then
increases dose to 30 mg to counteract and surmount the
effect of Drug B to achieve the same effect
Irreversible
Drug A (agonist) cannot counteract or remove the
effect of Drug B (antagonist) diminished activity
and effect of Drug A
No matter how much Drug A increases its dosage, it
cannot surmount Drug Bs action and effect

Physiologic Antagonism
Antagonism between endogenous regulatory pathways
mediated by different receptors