Introduction to
Pharmacodynamics
Dr. Preeti
Ashok
Learning Objectives
By the end of this activity students will be able
to understand
Important terminologies related
pharmacodynamics
Definition of Pharmacodynamics
Drug Receptors with types
Different mechanisms of actions
Properties of receptors
Conceptual Terminologies
Agonist: A drug which binds with receptor and
produce maximum response.
A drug which has affinity as well as efficacy.
Partial agonist: A drug which binds with receptor and
produce minimum or low response. Low intrinsic
activity.
Inverse agonist: A drug that converts the active
form of a receptor(R*) into an inactive form(R). It has
intrinsic activity <0 and exerts opposite
pharmacological effect of agonists.
Antagonist: A drug which binds to receptors but can
not produce response or it inhibits the effects of an
agonist.
Definition
Study of the effects of the drug
on the body is known as
pharmacodynamics.
It includes the mechanism of
action and side effects of the
drug.
Mechanism of action of
drug
Most drugs interact with
macromolecular component
called receptors of a cell or
organism to begin a biochemical
and physiologic changes that
produce the drug’s observed
effect or response.
Other Mechanisms of Action
Pumps and Transporters: e. g PPIs,
SSRIs
Ion Channels: Calcium channel
blockers, Local anesthetics
Enzyme Inhibition: ACE Inhibitors
Chemical Reaction: Antacid +HCl
Bacterial cells and organelles:
Erythromycin(Protein synthesis
Inhibition) Penicillin (Inhibition of Cell
wall Synthesis)
Receptors
These are the biological regulatory
molecules to which the drug binds
and produces a measureable
response.
Receptors may be enzymes, Nucleic
acids and structural proteins.
Majority of the receptors are proteins
that transduce the extracellular
signals into intracellular response.
Types of receptors
Ligand gated Ion channel:
G Protein coupled receptors:
Enzyme linked Receptors:
Intracellular receptors:
Types of receptors
Ligand gated Ion channel:
These receptors are located in the cell
membrane extracellular portion of these
receptors binds with the drug and
regulates the shape of the pore
permitting or inhibiting the flow of ions.
Agonist produces depolarization or
hyperpolarization
Ion receptors are confined to excitable
tissues (CNS, NMJ, etc)
E.g. GABA receptors, nicotinic receptors,
glutamine receptors and glycine
G Protein coupled receptors:
These are transmembrane receptors with
extracellular and intracellular domain to
interact with the drug and G-protein
respectively
G proteins are of many types but 3 are most
important Gs, Gi and Gq. Receptor examples
(D1, M2, M3)
Effectors include adenylyl cyclase stimulated
by Gs followed by generation of the 2nd
messenger cAMP and inhibited by Gi.
Gq activates phospholipase C that generates
two 2nd messengers IP3 and DAG.
cAMP and DAG activate different protein
Enzyme linked Receptors
:
These receptors are located on the
plasma membrane and linked to
Tyrosine kinase which when
stimulated get auto phosphorylated
and causes phosphorylation of the
tissue specific substrates.
E.g. Insulin receptors, EGF, IGF-1.
Intracellular receptors
These are intracellular receptors and
lipophilic drugs pass through the
membrane .
Their primary targets are transcription
factors activating or deactivating them
thus affecting the transcription of DNA into
RNA and translation of RNA into proteins.
The response ranges from hours to days
E.g. estrogen, progesterone,
glucocorticoid, T3, T4 and Vit D.
Receptors signaling
pathway
Second messengers:
cAMP, cGMP, IP3, DAG.
Ions (Ca2+ Na+, K+, Cl-)
DNA binding — Transcription
regulation.
Phosphorylated proteins and enzyme
via tyrosine kinase receptors
Properties of receptors
1. Signal amplification:
It is the property of receptor to amplify the
signal intensity and duration. A single drug-
receptor complex can interact many G-
proteins thus multiplying the original signal
many folds. Activated G-proteins persist for
longer duration as compared to the drug –
receptor complex
Properties of receptors
[Link] and Down regulation:
When a receptor is repeatedly exposed to
an agonist it becomes desensitized
(Decreased response) the process is known
as tachyphylaxis.
3. Hypersensitization and Upregulation:
When a receptor is repeatedly exposed to
an antagonist it becomes hyper sensitized
for its agonist.
Properties of receptors
4. Specificity: Receptors are specific for
their agonists and do not bind to other types
of agonists.
States of receptors: Receptors exist in two
states 1. Inactive state (R) 2. Active
state (R*)
Spare Receptors: Unoccupied receptor are
known as spare receptors e.g99% receptors
for insulin are spare while 5%-10% of the
beta receptors on the heart are spare
receptors.
Conceptual Terminologies
Affinity: ability of the drug to bind to receptor.
Efficacy(Intrinsic activity): ability of the drug to
produce response.
Potency: Comparative measure refers to different doses
of two drugs that are needed to produce same effect.
EC50: The concentration of an agonist that produces
half response as compared to the maximum response.
ED50: The dose of a drug which cures 50% animal
population
TD50: The dose of a drug which produces toxicity in 50%
animal population
LD50: The dose of a drug which kills 50% of the
experimental animals
Maximal Effect
EFFECT
EFFICACY
POTENCY
ED50
Log [Dose]
A B C D
EFFECT
Log [Dose]
RANK ORDER OF POTENCY: A > B > C > D
Potency and efficacy
A C
B
D
RESPONSE
ED50
RANK ORDER OF POTENCY: A > B > C > D
RANK ORDER OF EFFICACY: A = C > B > D
