Pharmacodynamics

- Eg. Steroid hormones, thyroid hormones,

vitamin D

A. Definition: study of the physiologic and biochemical

d. Protein Kinase
effects of drugs in the body, including their
- Produced by hypothalamus and is needed for
mechanisms of action
cell growth and differentiation
- Location: cell membrane
B. Receptors
- Eg. Growth factors, insulin, peptide
- A structural protein molecule on the cell surface or
hormones
within the cytoplasm that binds to a specific factor,
such as a drug, hormone, antigen, or neurotransmitter
Summary:
- Macromolecules involved in chemical signaling
between and within cells

- Ligands:
- Molecules (drugs, neurotransmitter, hormones)
that bind to receptors
- May activate or inactivate a receptor
- Each ligand may interact with multiple
receptor subtypes

1. Types of Receptors

a. Ligand-Gated Ion Channel Receptors

- Found in highly excitable cells (eg. Heart,
skeletal muscles, nerves)
- Used to regulate the flow of ions/electrolytes
through cellular membranes
- Location: extracellular (cell surface
transmembrane)
- Eg. Acetylcholine (nicotinic), epinephrine,
dopamine, GABA, glutamate, glycin 2. Concepts of Drug-Receptor Interactions

b. Guanosine Phosphate Protein (G-Protein a. Factors Affecting Drug’s Ability to Affect

Coupled) Receptors
- Regulates activity of enzymes and ligands
- Location: cytoplasmic (inner) face of the
cell membrane
- Eg. Alpha and Beta adrenergic receptors,
eicosanoids, acetylcholine (muscarinic)
Receptors
i. Affinity: probability of a drug occupying a
receptor at a given instant
- Receptors, in a way, are selective
- Several drugs can have the same action

c. Intracellular Receptors ii. Intrinsic activity: degree to which a ligand

- Activated by hormones, and regulate activates receptors and leads to cellular
expression of hormonal activity response
- Location: inside the cells - Drugs interacting with a receptor can
either activate it or inhibit it
 - The effect exerted is quantitative
(increase or decrease) and not
qualitative (no new function is
produced)

iii. Residence time: duration of time that the

drug-receptor complex persists. The longer
the residence time, there is a higher potential
for toxicity
- Not all receptors need to be occupied at
a given time for a drug to take effect
- Potent drugs may be effective a low
concentrations occupying only a
fraction of the receptors

iv. Drug Shape: complementary to that of the

receptor site
- Receptors have specific molecular
i. Full Agonist
conformation corresponding to certain
- Agonists which activate receptors to a
kinds of dugs
maximum extent of which the system is
- Drugs adjust to receptor sites to fit
capable
- Eg. Acetylcholine
v. Bonds: Drug-receptor complex is formed
from electrostatic bonds than covalent bonds
ii. Indirect-acting Agonists
- Forces must be present to attract and
- Agonist that inhibit their binding molecules
hold a drug in contact with a receptor so
- Mimic agonist drugs by inhibiting the
a drug may exert its effects
molecules responsible for terminating the
action of an endogenous agonist
C. Types of Drug-Receptor Interactions
- Eg. Acetylcholinesterase inhibitors

iii. Allosteric Binding

- Drugs that bind to the same receptor
1. Agonists
molecule but do not prevent binding of the
- Drugs bind to and activate the receptor in some
agonist
fashion which directly or indirectly brings about the
- May enhance or inhibit the action of the
effect
agonist molecule
- Allosteric inhibition is not overcome by
- Direct: receptors incorporate effector machinery in
increasing the dose of agonist
the same molecule, bringing about a direct effect
- Eg. Epinephrine
iv. Partial Agonists
- Bind to the same receptors and activate them
- Indirect: Some receptors may be linked through one
in the same way but do not evoke as great a
or more intervening coupling molecules to a separate
response, no matter how high the
effector molecule
concentration
- Eg. Guanylyl cyclase increases cAMP concentrations
- Agonists, but because of low intrinsic
activity, do not activate the receptor as fully
 as full agonists. May serve as antagonists in
the presence of a more potent agonist
- Eg. Pindolol (+ Epinephrine)
v. Inverse Agonists
- Agonists which when bound to receptors,
reduces constitutive effects, producing
opposing effects that are opposite of the
effects produced by conventional agonists at
that receptor
- Eg. GABA at chloride channels
2. Antagonist
- Compete with and prevent binding by other
molecules by binding to a receptor
- Stabilizes he receptor in its inactive state
A. Mechanisms of Antagonism
i. Antagonists binding to same receptor binding
site
- Binds to receptor sites where endogenous
substances bind to
- Binding results to a diminished or blocked
response from endogenous substrates
- Eg. Atropine to acetylcholine
ii. Antagonists binds to extracellular sites
- Binds to sites other than the main receptor
binding site
- Binding results to an opposing effect or
inhibition of response from endogenous
substrates
- Eg. Epinephrine to acetylcholine
iii. Antagonists intercepting responses
- Drug dissolves through cell membrane
resulting to a blockade in the effects
generated by endogenous substances inside
the cell
B. Types of Antagonists
i. Competitive Antagonist
- Antagonist that has similar affinity to the
receptor site like the agonist and will inhibit
or prevent a response (by blocking the
access of agonists to the receptor) when its
concentration is greater than the agonist
- No change is observed during antagonism so
that the drug will appear to be without effect
- Action can be overcome by increasing the
concentration of agonist
- Eg. Naloxone for opioid poisoning
ii. Non-Competitive Antagonist
- Antagonist that inactivates or binds tightly
to the receptor resulting to an irreversible or
prolonged antagonist-receptor binding
- An increase in concentration of an agonist
will no longer result to production of
maximal response
- Eg. Aspirin
D. Other Mechanisms of Drug Action
- Actions of drugs not mediated by receptors
1. Physical Mechanisms
i. Local Application
- Applicable for drugs applied topically which
produce several effects on superficial layer
of the skin
- Eg. Emollients, couterirritants, rubefacients,
pastes
ii. Physical Barriers
- Provide protective layering on mucous
membranes
- Eg. Milk, mucin
iii. Forms Bulk Inside the Body
- Increase the physical mass and size of
colonic contents
- Eg. Bran, psyllium fiber
iv. Promotes Osmosis
- Draws water to increase volume
- Eg. Mannitol, Urea, Sorbitol
 - May occur as a result of increased synthesis,
v. Adsorption stimulation of enzymatic activity, or reduced
- Adsorbing on surfaces of toxins degradation of an enzyme
- Eg. Activated charcoal, attapulgite, - Eg. Nitric oxide activating guanylyl cyclase
bentonite, pectin
xii. Inhibition of Enzymes
vi. Promote Physical Changes on Skin - Draws water to increase volume
- Action may induce drying or denaturation of - Eg. Acetylcholinesterase inhibitor,
superficial proteinaceous layers of skin disulfiram
- Eg. Astringents
3. Drug-Channel Interactions
vii. Lubrication and Softening
- Reduces friction in intestinal walls and xiii. Channel blockade
sotten stool - Drugs interfere with the flow of ions
- Eg. Liquid paraffin through the channels
- Eg. Lidocaine, nifedipine
2. Chemical Mechanisms
xiv. Channel opening
viii. Neutralization - Drugs increase the entry of ions through
- React chemically to promote neutralization channels
- Eg. Sodium bicarbonate, aluminum - Eg. Benzodiazepines
hydroxide
xv. Miscellaneous
- Binds to tubulin of microtubules
o Colchicine, vinca alkaloids
- Ionizing radiations
- Immunostimulation
o Levamisole
- Immunosuppression
o Suppresses growth of colonies
ix. Chelation
necessary for immune function
- Incorporation of metal ions in inner ring
- Therapeutic antibodies
structure to stabilize or neutralize a
o To supply immunoglobulins to the bo
compounds
- Eg. EDTA, BAL

x. Chemical reaction with poisons

- Drugs chemically react with poisons and
toxins to cause chemical changes which
directly inactivate the harmful effects
- Eg. Pralidoxime for organophosphate
poisoning

3. Drug-Enzyme Interactions

xi. Activation of Enzymes