DRUG RECEPTOR INTERACTIONS Roselyn Aperocho-Naranjo Pharmacy Instructor University of Southern Philippines Foundation www.roselynnaranjo.vze.com
Definition of Terms • Receptors – are chemicals which binds to the drug to exert a pharmacologic effect. Formula: D + R = D-R ------ Drug Response Note:Binding of a drug to the receptor is usually reversible A Receptor is analogous to a switch in that it has two configurations: “ON” and “OFF”
Definition of Terms • Receptor Four Primary Receptor Families 1. Cell-membrane embedded proteins 2. Ligand-gated Ion Channel 3. G –protein coupled Receptor Systems 4. Transcription Factors
Definition of Terms • Agonist – are molecules that activates receptors. - a drug that has both affinity and high intrinsic activity. Many drugs produce their effects by acting as an agonist. For example: DOBUTAMINE - it mimics the action of norephenephrine at the receptors on the heart. Thereby causing the heart to contract and increase the heart beat.
Definition of Terms • Affinity– allows the agonist to bind to receptors. • Intrinsic Activity– allows the bound agonist to activate or turn on its receptor function.
Definition of Terms • Antagonist – molecules that acts against and blocks drug action Receptor receiver action Agonist Antagonist against
Types of Antagonism • Chemical Antagonism • Interaction of drug (agonist) with another chemical (antagonist) outside of receptor to form an inactive complex. • Competitive Antagonism • Drug (agonist) is displaced from drug-receptor binding by another chemical (antagonist). • It is reversible and depends on actual drug and antagonist concentration in the biophase. • Law of mass action
Types of Antagonism • Partial Antagonism • Antagonist has high affinity but low intrinsic activity • Non-equilibrium Antagonism • Antagonist forms irreversible receptor binding • Noncompetitive Antagonism • Agonist and antagonist bind to different receptors and have opposite pharmacologic actions
Types of Pharmacologic Action of the Drugs • Structural Non-specific Drugs - drugs which do not depend its pharmacologic action to the chemical structure of the drug. - only its structure affects its physicochemical property. - slight modification of its structure does not produce a change in its pharmacologic action.
Types of Pharmacologic Action of the Drugs • Structural Specific Drugs - drugs in which the pharmacologic action directly depend on its chemical structure - it attaches itself to a receptor in the biophase Three Prerequisites of the binding of drug to the receptor 1. chemical reactivity 2. presence of functional group 3. electronic distribution 4. mirror-like image of the receptor
Drug-Receptor Theories • Hypothesis of Clark “ The Pharmacologic effect of the drug depends on the percentage of the receptors occupied” If receptors are occupied, maximum effect is obtained. Chemical binding follow the Law of Mass Action.
Drug-Receptor Theories • Hypothesis of Ariens and Stephenson “ Effectiveness of a drug lasts as long as the receptor is occupied. Many substance possess different effect , some have high affinity for the receptor, some have low affinity and some are not effective, and those ineffective substances block or inhibit the receptor.” It is also called Occupation Theory.
Drug-Receptor Theories • Hypothesis of Paton “ Effectiveness of a drug does not depend on the actual occupation of the receptor but by obtaining proper stimulus” This is also known as the Rate Theory.
Drug-Receptor Theories • Lock and Key Hypothesis “ The drug molecule must fit into the receptor like a key fits into the lock” Known as the Intrinsic Activity.