MT6314 Unit 2 - Drug Receptors and Pharmacodynamics PDF

MT6314 UNIT 2 - DRUG RECEPTORS AND PHARMACODYNAMICS Study online at https://quizlet.com/_glzdi5 These are actions or effects of the drug on the body. Pharmacodynamics Determines the...

MT6314 UNIT 2 - DRUG RECEPTORS AND PHARMACODYNAMICS Study online at https://quizlet.com/_glzdi5 These are actions or effects of the drug on the body. Pharmacodynamics Determines the group in which the drug is classified and plays a major role in deciding whether a group is appropriate therapy for symptom or disease The component of a cell or organism that interacts with a drug and Receptor initiates the chain of events leading to the drug's observed effects True or False True Receptors are specific molecules in a biologic system with which drugs interact to produce changes in the function of the system True or False False; they determine quantitative relations Receptors determine the qualitative relations between dose or concentration of drug and pharmacologic effects. To avoid constant activation by promiscuous binding of many Why is a receptor selective in choosing a drug molecule? different molecules True or False True Majority of the receptors are proteins. Receptor Site / Recognition Site This is a specific binding region of the macromolecule. Interaction between the drug and receptor It is the fundamental event that initiates the action of drug. 1. Regulatory Proteins 2. Enzymes What are the four classification of receptors? 3. Transport Proteins 4. Structural Proteins It is the best characterized drug receptors Regulatory Protein It mediates the effects of the most useful therapeutic agents Endogenous Chemical Signals (neurotransmitters, autacoids, What does regulatory protein mediate? and hormones) Enzymes Inhibited (or less commonly, activated) by binding a drug Facilitate the movement of molecules across biological mem- Transport Proteins branes. Structural Proteins These proteins provide support and stability to cells and tissues. Molecules that translate the drug-receptor interaction into a Effector change in cellular activity True or False True Some receptors are also effectors 1. Intracellular receptors 2. Ligand-regulated enzymes 3. Cytokine receptors What are the 5 basic transmembrane signaling mechanisms? 4. Ligand-gated transmembrane ion channel 5. G Protein-Coupled Receptors Intracellular receptors Ligands bind to these to regulate gene transcription in the nucleus. Cytokine Receptors Ligand binding induces receptor dimerization. Transmembrane receptor that binds and stimulates a protein ty- Ligand-Regulated Enzymes rosine kinase Ligand-Gated Ion Channels Regulates the opening of the ion channel Transmembrane receptor is coupled with an effector which mod- G Protein-Coupled Receptors ulates production of an intracellular second messenger 1/5  MT6314 UNIT 2 - DRUG RECEPTORS AND PHARMACODYNAMICS Study online at https://quizlet.com/_glzdi5 - Cyclic adenosine monophosphate - Calcium and phosphoinositides What are the second intracellular messengers? - Cyclic guanosine monophosphate cAMP (Cyclic Adenosine Monophosphate) Mediates hormonal responses Mobilization of stored energy (breakdown of carbohydrates in the Catecholamines liver) is stimulated by ______ Vasopressin Conservation of water by the kidneys mediated by _____ Parathyroid hormone This hormone is responsible for calcium homeostasis Beta-adrenergic catecholamines Stimulates heart rate and contraction Bind to receptors linked to G proteins while others bind to receptor Calcium and Phosphoinositides tyrosine kinases Stimulation of membrane enzyme phospholipase C What is the crucial step in calcium and phosphoinositides? Few signaling roles in a few cell types like the intestinal mucosa cGMP (Cyclic Guanosine Monophosphate) and vascular smooth muscle cells Kinase-Mediated Mechanism In cGMP, what causes the relaxation of vascular smooth muscles? Response of a particular receptor-effector system is measured against increasing concentration of a drug Graded Dose-Response Curve It tells the graph of the response versus the drug dose True or False True The smaller the EC50, the greater the potency of the drug. Efficacy (Emax) and Potency (EC50) These two are derived from the Graded Dose-Response Curve Maximal response that can be produced by a drug Emax This means that all receptors are occupied No response even if the dose is increased EC50 It is the concentration of drug that produces 50% of maximal effect It is the total number of receptor sites Bmax It means that all receptors have been occupied It is the equilibrium dissociation constant Kd Concentration of drug required to bind 50% of the receptors Affinity of a drug for its binding site on the receptor What does Kd measure? True or False False; Smaller Kd has greater affinity of drug to receptor Higher Kd means that there is a greater affinity of drug to receptor Curve A Agonist response occurs in the absence of antagonist Maximal response is preserved because the remaining available Curve B receptors are still in excess. Produced after larger concentration of antagonist, the available Curve C receptors are no longer "spare", sufficient to mediate an undimin- ished maximal response. With higher concentrations of antagonist, reduce the number of Curve D and E available receptors to the point that maximal response is dimin- ished. Transduction process between the occupancy of receptors and Coupling production of specific effect. When there is a full agonist and spare receptors How do you tell if there is highly efficient coupling? 2/5 MT6314 UNIT 2 - DRUG RECEPTORS AND PHARMACODYNAMICS Study online at https://quizlet.com/_glzdi5 Maximal drug response is obtained at less than maximal occupa- Spare Receptors tion of the receptors. True or False False; they will only produce low response. Drugs with low binding affinity for receptors will be able to produce high response even at low concentration. These are non-regulatory molecules of the body. Inert Binding Sites Binding with these molecules will result to no detectable change in the function of the biologic system. Agonist Binds to the receptor and directly or indirectly bring about an effect Produces less than the full effect, even when it has saturated the receptors Partial Agonist Acts as an inhibitor in the presence of a full agonist Binds but do not activate the receptors Antagonist Blocks or competes with agonist 1. Competitive Antagonist 2. Irreversible Antagonist What are the 4 classifications of antagonists? 3. Chemical Antagonist 4. Physiologic Antagonist Binds to the receptor reversibly without activating the effector system Competitive Antagonist Same maximal effect is reached Clinical response to a competitive antagonist depends on the Concentration of Agonist _______ that is competing for the binding receptor Binds with the receptor via covalent bonds Antagonist's affinity to the receptor maybe so high Irreversible Antagonist No increase in median effective dose (ED50) unless there are spare receptors Does not depend on interaction with the agonist's receptor Chemical Antagonism Drug that interacts directly with the drug being antagonized to remove it or to prevent it from reaching its target Makes use of the regulatory pathway Physiological Antagonism Binds to a different receptor producing an effect opposite to that produced by the drug it is antagonizing Response gradually diminishes even if the drug is still there (after Receptor Desensitization reaching an initial high level of response) Cells use more than one signaling mechanism to respond to the Structure Activity Relationship drug. Quantal Dose-Response Curve ED50 (Median Effective Dose) 50% of the individuals manifested the desired therapeutic effect TD50 (Median Toxic Dose) 50% of the individuals manifested the toxic effects the dose of a drug or toxic substance that causes death in 50% of LD50 (Lethal Dose) a tested population (usually in animal studies). Ratio of the TD50 (or LD50 ) to the ED50 determined from the Therapeutic Index quantal dose-response curves 3/5  MT6314 UNIT 2 - DRUG RECEPTORS AND PHARMACODYNAMICS Study online at https://quizlet.com/_glzdi5 True or False False; large toxic dose A very safe drug might be expected to have a smaller toxic dose. Dosage range between the minimum effective therapeutic con- Therapeutic Window centration or dose (MEC) and the minimum toxic concentration or dose (MTC) Maximal effect (Emax) an agonist can produce if the dose is taken to very high levels Maximal Efficacy Determined mainly by the nature of receptors and its associated effectors True or False True Maximal Efficacy is only measured with the graded dose-response curve. Potency Amount of drug needed to produce a given effect - 50% of the maximal effect and the dose (EC50) It is the effect chosen in the graded dose-response curve. In the quantal dose-response curve, what are the variables in 50% ED50, TD50, LD50 of the population? Caused by differences in metabolism (genetic) or immunologic mechanisms. Idiosyncratic Response Response to the drug is unknown or unusual Intensity of the drug is decreased Hyporeactive Response Large dose of the drug is needed to have an effect Hypereactive Response Intensity of the drug is increased or exaggerated Tolerance Decreased sensitivity acquired because of exposure to the drug Tachyphylaxis Tolerance develops after a few doses Down Regulation Decrease in the number of receptors. Up Regulation Increase in the number of receptors. Drug has been taken for a long time, then abruptly discontinued Overshoot Phenomenon/Rebound Hypertension Gradual decrease of taking the drug by decreasing/tapering the dose Clinical Sensitivity Give the drug that really acts on the disease True or False No drug causes a single specific effect only, they are selective but True never specific Beneficial and toxic effects may be mediated by the same recep- tor-effector mechanism ªGive low doses ªCarefully monitor the patient What to do to avoid/circumvent toxic effects of a drug? ªEmploy ancillary procedures ªUse a safer drug ªLow doses for prevention of blood clots Heparin ªVery high doses causes internal bleeding ªMonitor PT, PTT and bleeding parameters ªGive lowest dose possible Steroids ªGive adjunctive drugs ªAnatomic selectivity (lungs-by inhalation) 4/5  MT6314 UNIT 2 - DRUG RECEPTORS AND PHARMACODYNAMICS Study online at https://quizlet.com/_glzdi5 True or False False; they are mediated by different types of receptors Beneficial and toxic effects mediated by the same type of receptor 5/5