1. Saddam Ansari
3rd year
Tbilisi State Medical University
Pharmacodynamics

2. Objectives
 Pharmacodynamics
 Major Receptor Families
 Dose –Response Relationships
 Quantal Dose – Response Relationships

3. Pharmacodynamics
Study of the biochemical and
physiological effects of drugs on the
Body
Microorganisms
Parasites within or on the body and
Mechanisms of drug action and the
relationship between drug
concentration and effect

4. Continued…
 “Action of Drugs on the Body”
 Abbreviated as PD
Effects on the Body (when drugs acts on body)
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 Stimulating action
 Depressing action
 Blocking action
 Exchanging action
 Direct beneficial chemical reaction
 Direct harmful chemical reaction

5. Continued…
Desired Effect
 Cellular membrane disruption
 Chemical reaction with downstream effects
 Interaction with enzyme proteins
 Interaction with structural proteins
 Interaction with carrier proteins
 Interaction with ion channels
 Ligand binding to receptors

6. Continued…
Undesirable effects
 Increased probability of cell mutation
(carcinogenic activity)
 Interaction (additive, multiplicative, or
metabolic)
 Induced physiological damage, or abnormal
chronic conditions

7. Receptor
 Receptor is a molecule found on the surface of a
cell, which receives specific chemical signals from
neighbouring cells or the wider environment
within an organism.

9. Ligands
 Is a substance that forms a complex with a
biomolecule to serve a biological purpose. “Signal
triggering molecules”

10. Ligand - Receptor Complex

11. Major Receptor Families
 Ligand-gated ion channels
 G protein- coupled receptors
 Enzyme-linked receptors
 Intracellular receptors
 Spare receptors
 Desensitization of receptors

12. Ligand-gated ion channels
(LGICs)
Are one type of ionotropic receptor or channel-linked
receptor. They are a group of transmembrane ion
channels that are opened or closed in response to
the binding of a chemical messenger (i.e., a
ligand),such as a neurotransmitter.
An ionotropic receptor, when activated, directly
affects the activity of a cell by directly opening ion
channels.

13. Continued…
Metabotropic receptor influences the
activity of a cell indirectly by first
initiating a metabolic change in the cell.
This metabolic change may ultimately
affect the opening or closing of an ion
channel or may alter some other activity
of the cell such as protein transcription.

15. G protein-coupled Receptors
G protein-coupled receptors (GPCRs),
also known as :
 seven-transmembrane domain receptors,
 7TM receptors,
 heptahelical receptors,
 serpentine receptor, and
 G protein-linked receptors (GPLR)

16. Continued…
 Comprise a large protein family of
transmembrane receptors that sense molecules
outside the cell and activate inside signal
transduction pathways and, ultimately, cellular
responses

17. Classes of GPCRs
 Class A (or 1) (Rhodopsin-like)
 Class B (or 2) (Secretin receptor family)
 Class C (or 3) (Metabotropic glutamate/pheromone)
 Class D (or 4) (Fungal mating pheromone receptors)
 Class E (or 5) (Cyclic AMP receptors)
 Class F (or 6) (Frizzled/Smoothened)

18. Second Messengers
 Second messengers are molecules that relay
signals from receptors on the cell surface to
target molecules inside the cell, in the cytoplasm
or nucleus.
 They relay the signals of hormones like
epinephrine (adrenalin), growth factors, and
others, and cause some kind of change in the
activity of the cell.

19. Types of Second Messenger
Hydrophobic molecules: water-insoluble
molecules, like: diacylglycerol,and
phosphatidylinositols,
are membrane-associated and
diffuse from the plasma membrane into
the intermembrane space where they
can reach and regulate membrane-
associated effector proteins

20. Continued…
Hydrophilic molecules: water-soluble
molecules, like:
 cAMP,
cGMP,
IP3, and
Ca2

21. Continued…
Gases:
nitric oxide (NO)
carbon monoxide (CO) and
hydrogen sulphide (H2S) (which
can diffuse both through cytosol
and across cellular membranes.)

22. Properties of Second
Messengers
 They can be synthesized/released and broken
down again in specific reactions by enzymes or
ion channels.
 Some (like Ca2+) can be stored in special
organelles and quickly released when needed.
 Their production/release and destruction can be
localized, enabling the cell to limit space and time
of signal activity.

23. Enzyme-linked Receptors
 An enzyme-linked receptor is a transmembrane
receptor, where the binding of an extracellular
ligand causes enzymatic activity on the
intracellular side.
 They have two important domains:
 Extra-cellular ligand binding domain
 Intracellular domain
The signaling molecule binds to the receptor
outside of the cell and causes a
conformational change on the Catalytic
function located on the receptor inside of the
cell

25. Examples of Enzymatic Action
 Receptor tyrosine kinase, as in fibroblast
growth factor receptor. Most enzyme-linked
receptors are of this type
 Serine/threonine-specific protein kinase, as in
bone morphogenetic protein
 Guanylate cyclase, as in atrial natriuretic
factor receptor

26. Intracellular Receptors
 Intracellular receptors are receptors located
inside the cell rather than on its cell membrane.
 Examples are the class of nuclear receptors
located in the cell nucleus and the IP3 receptor
located on the endoplasmic reticulum.
 The ligands that bind to them are usually
intracellular second messengers like (IP3) and
extracellular lipophilic hormones like steroid
hormones.

27. Intracellular Receptors : Types
Steroid hormone receptor:
Sex hormone receptors (sex
hormones)
 Estrogen receptor (α and β)
 Androgen receptor (one type)
Vitamin D receptor (vitamin D, one
type)
Glucocorticoid receptor
(glucocorticoids, one type)
Mineralocorticoid receptor
(mineralocorticoids, one type)

28. Continued…
 Thyroid hormone receptor (α and β)
 Retinoic acid receptor (vitamin A and related
compounds);
 Peroxisome proliferator-activated receptors
(PPARs, α, γ and δ)
 Retinoid X receptor
 Farnesoid X receptor
 Liver X receptor
 Constitutive androstane receptor

29. Spare Receptors
 Term used to describe the situation in which
maximum tissue response occurs when not all the
receptors of the tissue are occupied by the drug

30. Desensitization of Receptors
 The rapid signal attenuation in response to
the stimulation of cell by agonists or an
antagonists.
 Or, decrease in response due to over
administration of durgs
 Adptation
 Refractoriness
 Down regulation
It is of 2 types….