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IN THE NAME OF GOD
 Introduction
•
What is pharmacology
 Principles
•
•
•
•
of pharmacodynamics
Mechanism of Drug Actions
Drug-Receptor Interaction
Classification of Drugs
Dose-Response Relationships
What is Pharmacology?
Pharmakon = a drug or poison
Logos = discourse or study
The science that deals with:
 The
fate of drugs in the body
Pharmacokinetics
 The
actions of drugs on the body
Pharmacodynamics
Pharmacy
The science of preparation
of drugs
Pharmacotherapeutics
The treatment of diseases by
drugs
Textbooks
•
Basic & Clinical Pharmacology, 2004
Bertram G. Katzung
•
Goodman and Gilman’s The
pharmacological basis of therapeutics,
2001
(J.G. Hardman and L.E. Limbard, eds.)
New York: McGraw-Hill
• (first published in 1941)
Principles of
Pharmacodynamics
Pharmacodynamics
Mechanisms of drug action
& the relationship between
drug concentration and effect
Why to study Pharmacodynamics?
Scientific basis for the
selection & use of drugs
Mechanism of Drug Action
Basic Concept
Interaction of a drug with its target tissue
involves specific binding sites
Receptor
A macromolecular component of the cell to
which the drug binds and leads to an
effect on the cell
Nonspecific binding site
A biological component to which the drug
binds but does not lead to any effect
Nature of Drug Receptors
Proteins
Transmembrane proteins
Receptors for neurotransmitters
Transport proteins
Na+/K+ ATPase
Ion channels
digitalis glycosides
benzodiazepines
Structural proteins
Tubulin
colchicine
Enzymes
Cycloxygenase
ACE
acetylsalicylic acid
Captopril
Non-protein drug receptors
 Lipids
Anesthetics
Nystatin, Amphotericin
 Nucleotides
Antineoplastic drugs
Cyclophosphamide
Other Sites of Drug Action
Water
Osmotic Diuretics & Laxatives
Ions
Antacids
Changing urine pH
Chelators
Dimercaprol
Penicillamine
EDTA
Hg+2 , As+2
Cu+2
Pb2
Drug-Receptor
Interaction
Drug-Receptor Interaction
R+D
K1
R-D
Effect
K2
Affinity
The tendency of a drug to combine
with its receptor
Kd
The concentration of drug that binds to
50% of the receptors
Affinity= the reciprocal of the Kd
Drug-Receptor Interaction
R+D
K1
R-D
Effect
K2
Intrinsic Activity
The ability of a drug to initiate
a cellular effect
Receptor-Effector Coupling
o
Receptor conformational change
o
Coupling Efficiency
Drug-Receptor Binding
Concentration-Effect Relationship
Classification of drugs
Agonist
Full agonist
Partial agonist
Antagonist
Competitive antagonist
Non-competitive antagonist
Other Drug Antagonism
Chemical antagonists
Heparin & protamine
Physiologic antagonism
Glucocorticoids & Insulin
Dose-Response
Relationship
1. Graded dose-response
2. Quantal dose-response
Graded Dose-Response Relationship
Sigmoidal D-R Curve
Graded Dose-Response
Relations
Potency
Efficacy
Relative potency
Relative Efficacy
Agonists with different potency
Agonists with different efficacy
Competitive Antagonism
D-R Curve for Competitive
Antagonists
Non-Competitive Antagonism
Quantal D-R Curve
Quantal D-R Curve
Quantal D-R Curve
Quantal-Dose Response
 Median
Effective Dose (ED50)
 Median Toxic Dose (TD50)
 Median Lethal Dose (LD50)

Therapeutic index
LD50/ED50 or TD50/ED50
Signaling Mechanisms
&
Drug Action
Transmembrane Signaling
 Intracellular
receptors
 Enzyme-linked
 Ligand-gated
receptors
ion channels
 G-protein-coupled
receptors
Intracellular Receptors
Steroid Receptor Superfamily
Glucocorticoids
Mineralocorticoids
Sex hormones
Vitamin D
Thyroid hormone
Retinoic Acid
Therapeutically important
consequences
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Slow onset of action
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Persistence of effect following
withdrawal of the drug
Enzyme-Linked Receptors
Receptor Tyrosine Kinases
Insulin
Epidermal growth factor (EGF)
Platelet-derived growth factor (PDGF)
Receptor Tyrosine Kinases
Enzyme-Linked Receptors
Receptor Guanylyl Cyclase
Atrial natriuretic factor (ANF)
cGMP (Natriuresis; Vasodilation)
Receptor Serine Kinase
Transforming growth factor-beta
(TGF-b)
Cytokine Receptors
Cytokine Receptor
Ligand-gated Ion Channels
Acetylcholine nicotinic receptors
Neuromuscular blocking drugs
(tubucurarine)
Ganglion blockers
(Mecamylamine)
GABAA
Benzodiazepines (sedative-hypnotic)
Glutamate
Topiramate (anticonvulsant)
Ligand-gated Ion Channels
G Protein-Coupled Receptors