Drug-Receptor Concepts 1 (2023-24) PDF

WEEK 11 MPharm Programme Drug-Receptor Concepts 1 Dr Gabriel Boachie-Ansah [email protected] Dale 113 ext. 2617 MPharm PHA112 Drug Receptor Concepts WEEK 11 Outline of Lectures What is Pharmacology? Drug-Receptor Concepts Drug-Receptor Interactions Drug-Drug Interactio...

WEEK 11 MPharm Programme Drug-Receptor Concepts 1 Dr Gabriel Boachie-Ansah [email protected] Dale 113 ext. 2617 MPharm PHA112 Drug Receptor Concepts WEEK 11 Outline of Lectures What is Pharmacology? Drug-Receptor Concepts Drug-Receptor Interactions Drug-Drug Interactions Variation in Drug Responsiveness Clinical Selectivity Slide 2 of 76 MPharm PHA112 Drug Receptor Concepts WEEK Learning Outcomes 11 At the end of this lecture, you should be able to: Define and distinguish between ‘pharmacology’, ‘pharmacodynamics’ & ‘pharmacokinetics’ Explain how drugs act to produce their effects Describe the various types of drug targets or receptors Define and distinguish between an agonist, a partial agonist & an antagonist Describe how drug-receptor binding translates into a biological effect Define & discuss the importance of therapeutic index Slide 3 of 76 MPharm PHA112 Drug Receptor Concepts WEEK 11 Basic Principles of Drug Action What is Pharmacology? Drugs & The Human Body Drug taking initiates 2 processes action of the drug on the body action of the body on the drug Slide 4 of 76 MPharm PHA112 Drug Receptor Concepts WEEK Drug-Body Interactions 11 “When we have a headache, we take for granted that after taking some aspirin, our headache will probably disappear within 15 to 30 minutes. We also take for granted that, unless we take more aspirin later, the headache may recur within a few hours. This familiar scenario reveals the primary events of pain relief: The first is the administration and absorption of the drug into the body; the second is the distribution of the drug throughout the body; the third is the interaction of the drug with relevant functional components of the body, which are responsible for the drug’s actions; and the fourth is the elimination of the drug from the body”. RM Julien Slide 5 of 76 MPharm PHA112 Drug Receptor Concepts WEEK 11 Basic Principles of Drug Action What is Pharmacology? Drugs & The Human Body Drug taking initiates 2 processes action of the drug on the body action of the body on the drug Study of this ‘drug-body interaction’ called ‘pharmacology’ Slide 6 of 76 MPharm PHA112 Drug Receptor Concepts WEEK 11 Branches of Pharmacology (Traditional) Pharmacology ‘The study of the interaction between drugs & the living body’ Pharmacodynamics Pharmacokinetics ‘The study of the effects of drugs on the living body and how the effects are produced’ ‘The study of how the body deals with or handles drugs’ Pharmacotherapeutics ‘The study of the use of drugs in the treatment & prevention of disease’ Slide 7 of 76 MPharm PHA112 Drug Receptor Concepts WEEK 11 Drug-Receptor Concepts How Do Drugs Act? Slide 8 of 76 MPharm PHA112 Drug Receptor Concepts WEEK How Do Drugs Act? 11 Drugs interact with biological systems in ways that mimic, or otherwise affect, the natural chemical messengers or processes of the body Two types of drug action Non-specific drug action Some drugs act in a simple physical or chemical manner – e.g. antacids, osmotic diuretics, osmotic laxatives lack any specific structure-activity relationship require large doses of drug for effect Slide 9 of 76 MPharm PHA112 Drug Receptor Concepts WEEK How Do Drugs Act? 11 Two types of drug action Specific drug action Most drugs act in a highly specific manner – e.g. phenylephrine, salbutamol, atropine, digoxin they interact with or bind to specific macromolecular or cellular targets in the body, called ‘receptors’ show clear-cut structure-activity relationship produce biological effects at very low doses Slide 10 of 76 MPharm PHA112 Drug Receptor Concepts WEEK 11 The Idea of the Drug ‘Receptor’ The Drug Receptor Concept ‘Most drugs produce their biological effects by interacting with specific macromolecules in the body, called receptors’ The Receptor ‘The specialised component of the cell or organism that interacts with a drug, and initiates the chain of biochemical events leading to the drug's observed biological effects’ Slide 11 of 76 MPharm PHA112 Drug Receptor Concepts WEEK 11 The Drug Target or ‘Receptor’ Drug receptors are protein or glycoprotein molecules Most drug receptors are located on the cell membrane e.g. atenolol, chlorphenamine, cimetidine, codeine Some drug receptors are located inside the cell e.g. oestrogen, testosterone, vitamin D, etc Slide 12 of 76 MPharm PHA112 Drug Receptor Concepts WEEK 11 Drug Targets or Receptors are Protein or Glycoprotein Entities 1-adrenergic Receptor GABAA Receptor Slide 13 of 76 MPharm PHA112 Drug Receptor Concepts WEEK Drug Targets or ‘Receptors’ 11 Multiple Types of Drug Targets or ‘Receptors’ ‘Classical’ receptors – regulatory protein or binding sites for endogenous or natural chemical messengers, such as neurotransmitters & hormones Ion channels – e.g. lidocaine, diazepam, amiodarone Enzymes – e.g. NSAIDs, Statins, ACE inhibitors Carrier or transport proteins – e.g. digoxin, PPIs, SSRIs Slide 14 of 76 MPharm PHA112 Drug Receptor Concepts WEEK 11 Drug-Receptor Interactions How do drugs and receptors interact? Slide 15 of 76 MPharm PHA112 Drug Receptor Concepts Drug-Receptor Interactions WEEK 11 Drugs bind to receptors because the drug’s molecular structure & shape are similar to those of the natural chemical messengers the body produces to target those receptors There must be a complementary fit between the drug molecule & the binding site on the receptor Drug & receptor interact to form a drug-receptor (D-R) complex via a reversible chemical reaction The drug-receptor interaction is governed by the Law of Mass Action We can relate drug concentration & biological effect to the fraction of receptors occupied by the drug Slide 16 of 76 MPharm PHA112 Drug Receptor Concepts WEEK 11 Drug-Receptor Interactions The ‘Lock and Key’ Relationship basis of selectivity of drug action chemical selectivity biological or tissue selectivity Slide 17 of 76 MPharm PHA112 Drug Receptor Concepts WEEK 11 Drug-Receptor Interactions Drug & receptor interact to form a D-R complex via a reversible chemical reaction Drug + Receptor  Drug-receptor complex k1 D + R == DR k2 The fraction of receptors occupied by the drug is a function of: the concentration of drug in the biophase the equilibrium dissociation constant (KD) for drugreceptor complex Slide 18 of 76 MPharm PHA112 Drug Receptor Concepts WEEK Fractional Occupancy 11 Drug Concentration-Receptor Occupancy Curve Concentration of drug Slide 19 of 76 MPharm PHA112 Drug Receptor Concepts Drug-Receptor Interactions WEEK 11 The ‘Receptor Occupancy Theory’ Assumptions drug effect is proportional to the fraction of receptors occupied maximum drug effect (Emax) occurs when all receptors in the system are occupied by the drug Slide 20 of 76 MPharm PHA112 Drug Receptor Concepts Drug Concentration-Effect Curve WEEK 11 E Emax Drug Concentration Slide 21 of 76 MPharm PHA112 Drug Receptor Concepts WEEK 11 Log Drug Concentration-Effect Curve E Emax Log Drug Concentration Slide 22 of 76 MPharm PHA112 Drug Receptor Concepts