PHARMACODYNAMICS

Faculty of Medicine University of Brawijaya

dr. Hikmawan W.S., Ph.D
2020
Definition
• the study of the biochemical and physiological effects of drugs
and their mechanisms of action.
Pharmacokinetics vs Pharmacodynamics

Pharmacokinetics
A: Administration
D: Distribution
M: Metabolism
E: Excretion

Pharmacodynamics
Mechanism of action
Drug interaction
Physiological effect
Mechanisms of Drug Action
• Action via non receptor
• Example: Antasida, normal saline for resuscitation, drug used for
constipation (stimulate water secretion)
• Action via receptor
• Ligand-Gated Ion Channels
• G-Protein Coupled Receptor
• Kinase-Linked Receptor
• Intracellular Receptor
Drug–Receptor Interaction
• The effects of most drugs result
from their interaction with
macromolecular components of
the organism (receptor).
• These interactions alter the
function of the pertinent
component and thereby initiate
the biochemical and
physiological changes that are
characteristic of the response to
the drug.
Drug–Receptor Interaction

Drugs

AFFINI Interaction: ionic, hydrogen, hydrophobic, van der Walls, and covalent
TY

Altered Biological Response Intrinsic Activity 

EFFICACY
Drug-Receptor Interactions
Drug-Receptor Interactions
Drug-Receptor Interactions
Some receptor in inactivated form (Ri)
& other in activated form (Ra)
Some Ra cause intrinsic activation
without agonist binding  constitutive
activity
Full Agonist: bind to Ra, maximal response

Partial Agonist: bind to Ra, partial

response
Antagonist: bind to Ra and Ri, but no
response
Inverse Agonist: bind to Ri > Ra, decrease
response
Drug Receptors
• Drugs that bind to physiological receptors and mimic the
regulatory effects of the endogenous signaling compounds are
termed agonists.
• Compounds with no stimulatory action of their own that still
may produce useful effects by inhibiting the action of an
agonist (e.g., by competition for agonist-binding sites) are
termed antagonists.
• Agents that are only partly as effective as agonists no matter
the amount employed are termed partial agonists,
Ligand-Gated Ion Channels
Structure of nicotinic receptor consists of 5 subunit

Ach (acetylcholine) binds to α

subunit
Channels opening

Sodium influx

Depolarization of neurons

RESPONSE

• Other examples: nicotinic receptor, GABA receptor,

serotonin (5-HT) receptor, glycine receptor, etc.
Diazepam

• Used for anti-anxiety, insomnia

• Allosteric activator of GABA receptor
• Mediates Cl- influx
• Inverse agonist cause agitation and anxiety
G-Protein Coupled Receptor
• GPCR located at plasma
membrane as a bundle of
seven helices
• G-protein consist of 3
subunit (α, β, and γ)
• α-subunit is activated
when it bind GTP
• α-subunit activates
effector protein
• β and γ could directly
activate K+ channels
• Consist of many subtype:
Gs, Gi, Gq, Golf, Gt
G-Protein Coupled Receptor Agonist-receptor binding

Activation of G-Protein

α-subunit exchange GDPGTP

Alteration of Effector Protein

• Adenylate cyclase
(ATPcAMP)
• Phospholipase C (PLC)
(PIP2 IP3 + DAG)
• Ion channel protein

Cellular Response
G-Protein Coupled Receptor
Norepinephrine (β1 Agonist) • Stimulation GPCR in
cardiac myocyte caused
increase of contractility
• NE bind to GPCR 
activate Gs  activate
adenylate cyclase 
increase of cAMP level 
activate PKA  release
of calcium from its
storage (sarcoplasmic
reticulum) and increase
influx of calcium 
contraction
• Effect on SA node 
tachycardia, Renal 
renin release, hepar 
glycogenolysis
Salbutamol (β2 agonist)

• Stimulation GPCR in lung

smooth muscle caused
bronchodilatation
• Salbutamol bind to GPCR
 activate Gs  activate
adenylate cyclase 
increase of cAMP level 
inhibition of MLC
(myosine light chain)
kinase  relaxation
GPCR, G-Protein, and Their Effectors
 Tyrosine Kinase

Binding of ligand

Dimerization of
receptor
Phosphorylation of
receptor
Activate downstream
signaling
RESPONSE

Example: Insulin Receptor (IR), epidermal growth factor (EGF), platelet-

derived
growth factor (PDGF), atrial natriuretic peptide (ANP), transforming
growth factor-β (TGF-β), and many other trophic hormones
Insulin Signaling
Intracellular Receptor
Ligand translocate to cytoplasmic
receptor
Binding of ligand-cytoplasmic
receptor
Homodimeric/ heterodimeric
receptor translocate to nucleus

Regulate gene expression

RESPONSE
Glucocorticoid Signaling
Graded-Dose Response

Concentration- Log [Concentration]-

Response Response
EC50 reflects effective concentration
needed for 50% response, efficacy has
Quantifying Agonism

Relative potency reflects EC50 of Relative efficacy reflects

drugs compared with other maximal response of drugs
drugs/ substances compared with other drugs/
substances
Side Effects vs Toxic Effect
• Toxic effects
occurred when
administered drugs
in higher/ toxic dose
• Side effects occurred
when administered
drugs in therapeutic
dose
Side Effect vs Toxic Effect
Selectivity of Drugs
Type of drug interaction
drug–drug interaction

drug–nutrient interaction
mechanism of drug-drug/ food-drug
interactions
1. Alteration of absorption
2. Alteration of distribution
3. Alteration of metabolism
4. Alteration of elimination
5. Potentiation
6. Inhibition
7. Direct chemical interaction
8. Competition at the site of action
 Potentiation
• Potentiation can be additive or synergistic
and refers to an increase in the effect of
one drug as a result of a second drug or
nutrient.
• The increased pain relief experienced when
acetaminophen is combined with a
narcotic (Vicodin®, Lortabs®) illustrates a
positive example of this effect.
• Adding bananas, potatoes, and other foods
rich in potassium to the diet at the same
time a patient is taking a prescribed
potassium supplement (e.g., Kaon-Cl®)
would cause an additive food–nutrient
effect with a therapeutic purpose.
 Inhibition
• Inhibition refers to the decrease of
effect when two substances have
opposite effects on a process.
• The decreased anticoagulant effect of
warfarin (Coumadin®) seen when
vitamin K intake is increased is a
negative example of this type of
interaction.
• Caffeine, a nonnutritive food
constituent, may oppose the
pharmacological effect of tranquilizers
Direct chemical interaction
• An example of a direct chemical interaction is the reaction
between dextrose and amino acids in parenteral nutrition. This
is the same reaction seen when meats are cooked and is known
as the Maillard reaction. The substrates involved tend to reduce
sugars and amino acids, and these factors limit the storage time
for parenteral nutrition solutions. The reaction results in a
darkening of the solution.
Competition at the site of action
• An example of competition at the site of action is best
illustrated by the effect of naloxone (Narcan®) on narcotics.
• Naloxone reverses the effects of narcotics at a receptor site.
This can be useful after surgery to reverse the effects of
intraoperative narcotics. Naloxone is also useful in the
treatment of narcotic overdoses.
Thank you