Introduction to Pharmacology Course Coordinator Jamaluddin Shaikh, Ph.D. School of Pharmacy, University of Nizwa Lecture-1 September 17, 2011
What is Pharmacology? Study of how drugs function inside the body Composition Use Effects
What is Drug? Chemical substance Used in the treatment, cure and diagnosis of diseases
Pharmacokinetics and Pharmacodynamics Pharmacokinetics (PK) : Effects of body on the drugs Absorption Distribution Metabolism Excretion Pharmacodynamics (PD): Effects of the drugs on body
Bound Free Free Bound ABSORPTION Free Drug EXCRETION Bound Drug LOCUS OF ACTION “RECEPTORS” TISSUE RESERVOIRS Bound Free Free Bound ABSORPTION Free Drug EXCRETION SYSTEMIC CIRCULATION Bound Drug BIOTRANSFORMATION
PK vs PD Dose Site of action Plasma Concentration Effects PK PD
How Do Drugs Work? Work by interact with endogenous protein Some antagonize, block or inhibit endogenous proteins Some activate endogenous proteins A few endogenous proteins have unconventional mechanisms of action
Receptor Macromolecular endogenous protein Primarily located on the plasma membrane It binds the drugs and initiates its effects
Ligand Molecules that bind to receptor is called ligand A ligand may be Peptides Neurotransmitters Hormones Drugs
Drug-Receptor Binding Drug-receptor interaction produce pharmacological response Pharmacological response depends on: Nature of the drug No. of receptors Amount of drug at the receptor site
Agonist and its Action Chemical binds to a receptor of a cell Triggers a response by the cell Can be endogenous or exogenous Types of agonists Full agonist Partial agonist Inverse agonist
Antagonist and its Action Binds to receptor but produce no biological response Blocks the agonist mediated effects Interactions are reversible or irreversible Can compete with endogenous ligands
Agonists vs Antagonist Receptor Effect No Effect
How Do Agonist Interacts with Receptors? Extracellular Compartment Unbound Endogenous Activator (Agonist) Cell Membrane Inactive Receptor Intracellular Compartment
How Do Agonist Interact With Receptors? Extracellular Compartment Bound Endogenous Activator (Agonist) Cell Membrane Active Receptor Intracellular Compartment Cellular Response
How Do Agonist Drugs Produce Cellular Activity Displaced Endogenous Activator ( Agonist) Extracellular Compartment Bound Agonist of Receptor (Drug) Cell Membrane Active Receptor Intracellular Compartment Cellular Response
How Do Drugs Work by Antagonizing Receptors? Displaced Endogenous Activator ( Agonist) Extracellular Compartment Bound Antagonist of Receptor (Drug) Cell Membrane Inactive Receptor Intracellular Compartment
Two Drugs Given Together: Different Effects Work independently and produce own effects May produce similar effects Addition Synergism Potentiation May produce opposite effects Competitive antagonism Non-competitive antagonism Chemical antagonism Functional or physiological antagonism
Competitive Antagonism Common drug antagonism Antagonist competes with agonists for same receptors Pharmacological effects depends on the concentration of either agonists or antagonists Antagonism may be reversible or irreversible Reversible: loose binding Example: antihistamines, β-blocker Irreversible: covalent bonding Example: phenoxybenzamine
Non-competitive Antagonism Antagonists and agonists bind to the different sites
Competitive vs Non-competitive Antagonism Antagonist Antagonist Agonist Agonist Antagonist Competitive Antagonism Binds same site Chemical similarity Maximum response with increasing dose of agonist Non-competitive Antagonism Binds different site No chemical similarity Maximum response with increasing dose of agonist
Chemical Antagonism Involves a direct interaction between an agonist and antagonist in such a way that the effect of agonist is lost
Physiological Antagonism A form of antagonism which occurs when two drugs, each tends to oppose or cancel the effects of other