General Pharmacology

DEMYSTIFYING
PHARMACOKINETICS -
PHARMACODYNAMICS

Maulana A. Empitu, dr., MSc

Department of Pharmacology
Faculty of Medicine
Universitas Airlangga
Any question about this lecture…
Contact:

08155 94 90 95 (no call)

m.a.empitu@gmail.com
maulana.antiyan@fk.unair.ac.id
What does Pharmacology means?
What is pharmacology?
“Pharmacology is the science of drug action on biological systems. It is
a science that is basic not only to medicine, but also to pharmacy,
nursing, dentistry and veterinary medicine. Pharmacological studies
range from those that determine the effects of chemical agents upon
subcellular mechanisms, to those that deal with the potential hazards
of pesticides and herbicides, to those that focus on the treatment and
prevention of major diseases by drug therapy.” American Society of
Pharmacology
 The story of
the Puppet-master:
a Human Bender

How do you
become a Human
Bender?
Pharmacology & Therapeutics: The basis of
Human Bender

Sympathomimetic Drug
Administration

Sympathetic effect
Why should we learn
pharmacology?
Big part of pharmacology:
1.Pharmacokinetics – What
happens with the drug after we
ingest it?
2.Pharmacodynamics – How do
the drug work?
 Administering the drugs is only the beginning, it
take rigorous process before initiating the effect!
Circulation Drug – Receptor
Drug interaction →
Administration: ABSORPTION: DISTRIBUTED Clinical Effect
• Oral entering blood to various
• im, sc stream tissues
• Inhalation
• Rectal /
Vaginal Metabolized Metabolized
• Percutaneous and
• Parenteral Eliminated

Pharmacokinetics Pharmacodynamics
 So, learn Pharmacology…
But, pharmacology is massive like ocean!
How should we learn?
Learn from various
Be enthusiastic, resources:
like when you - Journal
were kid! - Textbook
- Peer-discussion
- Medical cases
Every good result - Clinical round
comes from a - Conference/seminar
good investment - Advertisement
of time! - SocMed
“Long life learning” - Lecture is just <0.001%
 Aims of the session:
1. Telling the story of pharmacokinetics process (“the fate of the
drugs”), including but not limited to:
Absorption | distribution | metabolism | elimination
2. Explaining the concept of pharmacokinetics parameters and its
importance in clinical application, including: Volume distribution,
clearance, half life, and bioavailability - bioequivalent.
3. Emphasizing the receptors concept in pharmacology, drug- receptor
interaction, clinical effect, side effect, and drug toxicity.
 Pharmacokinetics –
Dynamics: The basis of
Pharmaco-therapeutics

Route of
administration

Molecular
level
Cellular level
Tissue Level
Organ Level
Systemic
Clinical Effect
Pharmacokinetics
Scheme
Administering the drugs:
The beginning of pharmacokinetics
process
 Pharmacokinetics and Pharmacodynamics Variables

Subject Independent Dependent

Variable variable
Pharmacokinetics Time Concentration
Pharmacodynamics Time Effect
Kinetics – dynamics Concentration Effect
Modelling
 Multiple factors
influence the
Benefit
response to drug
Therapeutic

Drug Clinical
Pharmacokinetics
Administration Effect

Right?
• Dose
• Preparation Toxicity
• Route of
administration
Risk
• Indication
• Patients
 Absorption

“All route require

Absorption
(from site of
administration into
blood circulation),
except
intravascular
administrations.”
In i.v. injection, Cmax is achieved in the beginning of
drug administration
Drugs Absorption require the ability to permeate
multiple barriers via:
Passive Diffusion | Facilitated Transport | Active
Transport
Absorption Fick’s Law of Difussion
Absorption Influence of pH
Pharmacokinetics
Scheme
Distribution Blood Flow Distribution to Organ
Distribution Volume Distribution (Vd)

• Imaginary
• Not the sum of anatomic volume
• Quantitatively reflect peripheral tissue uptake
• Related to lipid solubility
 Distribution Protein Bound in Plasma

Protein bound
decrease the
distribution to
tissue, site of
action, and
kidney
excretion.

Acid drugs bind to Albumin

Base drugs bind to alpha-acid glycoprotein
Pharmacokinetics
Scheme
Biotransformation

Site:
• Liver
• Lung
• GI Track
• Brain
Biotransformation
Biotransformation

Contribution of
Various CYP
Subsets
Biotransformation Fraction of loss in
oral dose
Pharmacokinetics – Dynamics: The basis
of Pharmaco-therapeutics
 Terminology:
Everybody should know this…
Receptor Efficacy Spare Receptor

Ligand Potency Intrinsic

Activity
Constitutive
Affinity Specificity
Activity

KD Selectivity EC50
Maulana A. Empitu - FAT301 Lecture 37
 Receptor - Ligand

Receptor Ligand
Type of
Selectivity, Bound Specificity,
Physiologic Could be
alteration endogenous
(hormones, TF
activator) or
Resources list of Receptor-Ligand interaction study: Exogenous
https://sites.google.com/site/receptorligandbinding/
(drugs)
 Receptor Location

Maulana A. Empitu - FAT301 Lecture 40

Receptor type

GPCR

Maulana A. Empitu - FAT301 Lecture 41

 Receptor type
Ligand-gated ion Ligand-regulated
channel enzyme

Maulana A. Empitu - FAT301 Lecture 42

Receptor type

Maulana A. Empitu - FAT301 Lecture 43

 Drug-Receptor Interaction Theory

1. Central Dogma of Receptor Pharmacology: Drug

Occupation Theory
• Affinity & Efficacy concept
2. Rate Dependent Theory: Association –
Dissociation
• The concept of Full Agonist, Partial Agonist & Antagonist
are viewed from the Association – Dissociation rate

Maulana A. Empitu - FAT301 Lecture 44

Drug Occupational Vs Rate Dependent Theory:
Analogy of Hand & Sprayer

Maulana A. Empitu - FAT301 Lecture 45

 After drug arrived at the site of action,
what will happen?

Drug Receptor Effector R E

D
(D) (R) (E)
complex
D R D R E molecule
Coupling E
D R D R
molecule molecule EFFECT
D R- Enzyme E molecule↗
Inhibition of
metabolism Maulana A. Empitu - FAT301 Lecture 46
 Concentration,
Kd, and
Binding
Relationship

Maulana A. Empitu - FAT301 Lecture 47

 Orthosteric Vs Allosteric

Maulana A. Empitu - FAT301 Lecture 48

 Constitutive Activity
Non Functional Functional
Receptor Receptor

Maulana A. Empitu - FAT301 Lecture 49

 Full, Partial, and
Inverse Agonist

Maulana A. Empitu - FAT301 Lecture 50

 Relative Relative Efficacy
Potency
Different Emax
Equal Emax
Can be equal
Different EC50
EC50

Maulana A. Empitu - FAT301 Lecture 51

Antagonism – Drug Effect Relationship

Maulana A. Empitu - FAT301 Lecture 52

 Adverse Drug Reactions
Possible mechanism:
1. Overdose
2. Increased sensitivity
3. Lack of Selectivity
4. Allergy

Maulana A. Empitu - FAT301 Lecture 53

Adverse Drug Reactions

Maulana A. Empitu - FAT301 Lecture 54

Adverse Drug Reactions

Maulana A. Empitu - FAT301 Lecture 55

Adverse Drug Reactions

Maulana A. Empitu - FAT301 Lecture 56

Adverse Drug Reactions

Maulana A. Empitu - FAT301 Lecture 57

 Summary of the lecture

1. Drug act through coupling with receptor

2. Drug-Receptor coupling initiates response cascade
3. Drugs can act by antagonism or synergism in
competitive or non-competitive manners
4. Drug could cause adverse reaction due to
overdose, altered sensitivity, lack of specificity, and
allergic reaction

Maulana A. Empitu - FAT301 Lecture 58

Thank You! See You Next Time!

Maulana A. Empitu - FAT301 Lecture 59