Pharmacology Lec 4 PDF

PHARMACOLOGY 1 FACULTY OF DENTISTRY 1  Receptors are macromolecules present Receptor-mediated either on the cell surface, cytoplasm, or in the nucleus with which the drug binds Mechanisms and interacts to produce cellular chan...

PHARMACOLOGY 1 FACULTY OF DENTISTRY 1  Receptors are macromolecules present Receptor-mediated either on the cell surface, cytoplasm, or in the nucleus with which the drug binds Mechanisms and interacts to produce cellular changes.  For example, adrenergic receptors, and cholinergic receptors. Affinity: The ability of the drug to get bound to the receptor is known as affinity. Intrinsic activity: The ability of the drug to produce pharmacological action after combining with the receptor is known as the intrinsic activity of the drug. Agonist: A drug that can produce pharmacological action after binding to the receptor is called an agonist. Agonist has high affinity + high intrinsic activity (e.g., adrenaline).  Competitive Antagonist: A drug that binds to receptors but is not capable of producing pharmacological action is called an antagonist. Antagonist has high affinity without intrinsic activity (e.g., atropine). It produces receptor blockade  Partial agonist A drug that binds to the receptor but produces an effect less than that of an agonist is called a partial agonist. It has affinity + less activity  Inverse agonist It has a full affinity towards the receptor but produces an effect opposite to that of an agonist. It has an affinity and intrinsic activity between 0 and −1.  Receptor Families 1. Ligand-gated ion channels (inotropic receptors). 2. G-protein-coupled receptors (metabotropic receptors). 3. Enzymatic receptors. 4. Receptor regulating gene expression (transcription factors) or the nuclear receptor.  https://www.youtube.com/watch?v=WORIhbaRABg  Ligand-gated Ion Channels (Inotropic Receptors) Examples are ✓ nicotinic (NM) acetylcholine receptors, ✓ GABA receptors in the central nervous system. Nicotinic acetylcholine receptor, a ligand-gated natural ion channel.  G-Protein-Coupled Receptors (Metabotropic Receptors) They are coupled to intracellular effectors through G-proteins. G-proteins are membrane proteins and have three subunits (α,β,γ) with GDP bound to -subunit.  Effector pathways and second messengers: G-protein-coupled receptors control cell function via: ✓ Adenylyl cyclase, ✓Phospholipase C, ✓Ion channels. The agonist that binds to the receptor is the first messenger resulting in the generation or recruitment of molecules (second messengers) that initiate the signaling mechanism in a cell. Examples of second messengers are: cAMP (generated by adenylyl cyclase), cGMP (generated by guanylyl cyclase), Ca2+, inositol triphosphate–diacylglycerol (IP3–DAG) (generated by phospholipase C  https://www.youtube.com/watch?v=Glu_T6DQuLU Enzyme-linked Receptors For example, receptors for insulin (receptor tyrosine kinase)  Nuclear Receptors Examples are receptors for sex steroids and glucocorticoids.  Regulation of Receptors Receptors can be regulated by various mechanisms resulting in either their ✓up-regulation or ✓downregulation. Regulation of Receptors