Pharmacodynamics Notes (PDF)

HSHG 2090 – Basic Principles of Pharmacology Pharmacodynamics Learning Outcomes 4.1 Define pharmacodynamics 4.2 Explain types of drug receptors, including: 4.2.1 Receptors for hormones and neurotransmitters 4.2.2 Enzymes 4.2.3 Membrane transport molecules 4.2.4 Other ma...

HSHG 2090 – Basic Principles of Pharmacology Pharmacodynamics Learning Outcomes 4.1 Define pharmacodynamics 4.2 Explain types of drug receptors, including: 4.2.1 Receptors for hormones and neurotransmitters 4.2.2 Enzymes 4.2.3 Membrane transport molecules 4.2.4 Other macromolecules 4.3 Explain drug-receptor interactions 4.4 Define terms related to drug-receptor interactions, including: 4.4.1 Agonists 4.4.2 Antagonists Examples What effect can drugs have on the human body? 4 Pharmacodynamics Defined as the study of the mechanism of action by which drugs produce their pharmacologic effects effects of drugs and the mechanism of their action “What the drug does to the body” Pharmacokinetics vs Pharmacodynamics If Pharmacokinetics is what the body does to the drug THEN Pharmacodynamics is what the drug does to the body Question Time Pharmacodynamics can be summarized as “what the body does to the drug”. a) True b) False Drug Actions Drugs work by a variety of chemical mechanisms Body continually fights to maintain a state of homeostasis (stability) achieved by a system of control and feedback mechanisms Drugs can be used to restore and maintain homeostasis Mechanisms of Drug Action Drugs act in many different ways Most common is the drug-receptor interaction Other MOA’s include: Interacting with nucleic acids, transport proteins, enzymes Interfering with osmotic cell balance Drug – Receptor Interaction To produce therapeutic or toxic effects drugs interact with receptors in the body – the pharmacodynamic phase of drug action. “Lock and key” 11 Receptor (Lock) Tissues use receptors to distinguish between chemical messengers/drugs Receptors are protein molecules within the cell or the cell membrane (cell wall) which receive and interact with specific hormones or neurotransmitters Drug Receptors Receptors bind with the “chemical messenger” Drugs produce their effects by interacting with receptors Drug Receptors (cont’d) Most receptors are “keyed” to one or more endogenous substances (i.e. neurotransmitters or hormones) Normal activation of the receptor results from the appropriate substance binding with the protein molecule on the cell wall. Binding reaction transduces into a signal to the cell Cell then responds accordingly Drug Receptors (cont’d) For some drugs, binding to a receptor or other target initiates a molecular chain of events called The Signal Transduction Pathway. A cascade of events caused by the activated receptor which ultimately results in a physiologic effect sample pathway: binding > structural change in receptor > interaction with effector molecule (if any) > secondary messenger molecules > chemical or structural change in target cell > change in cell function Types of Receptors 1. Receptors for hormones and neurotransmitters 2. Enzymes 3. Membrane transport molecules 4. Other macromolecules Hormones and Neurotransmitters Hormones Chemical substances produced and secreted by glands Control certain cells and organs Affect processes from growth to mood Hormones and Neurotransmitters (cont’d) Neurotransmitters Chemical substances that transfers impulses from one nerve cell to another Hormones and Neurotransmitters (cont’d) Neurotransmitters Released from the presynaptic neuron during excitation, crosses the synapse, and stimulates the postsynaptic neuron Receptors for Hormones and Neurotransmitters Ligands: drugs, hormones, neurotransmitters Bind to protein molecules in the cell wall Receptor is part of the protein that sticks out above the surface of the cell wall Receptors are classified according to the ligand they interact with May form a bond that is weak and reversible or one that is strong Receptors for Hormones and Neurotransmitters (cont’d) Ligand binding to exterior protrusion of protein causes change in receptor that signals the cell Receptors for Hormones and Neurotransmitters (cont’d) Can create opening in the membrane to allow passage of specific substance Receptors for Hormones and Neurotransmitters (cont’d) Can pass through cell membrane and bind with receptors within the cell Enzymes 5 types Proteins which act on other intra- or extracellular substances Protein in the membrane acts like a receptor but binding directly affects the cell Membrane Transport Molecules Proteins which facilitate passage of the bound agent through the membrane (into or out of the cell) Proteins that allow charged particles through a channel when stimulated Channels can be affected by Ligand binding with receptor Electrical charge within the cell Membrane Transport Molecules Neurotransmitter transporters – prevent neurotransmitters from spilling out of synapse and returns them to presynaptic neuron Other Macromolecules Steroid receptors transport within the cell directly to the nucleus DNA functions as receptor for agents that bind directly to amino acids Various lipid and phospholipid molecules which make up the cell membrane act as receptors for specific substances Drug-Receptor Interactions Binding: to initiate a cellular response a drug must bind to a receptor drug forms a weak bond with the protein molecule bond is reversible so the drug can disassociate from the receptor as tissue concentration declines Receptor Selectivity Drug & Specificity Drug – Receptor Interactions Affinity The ability of a drug to bind to a receptor Efficacy The ability of a drug to have the intended cellular effect Potency Determined primarily by affinity of a drug to receptor Drug – Receptor Interactions Affinity: tendency of a drug to combine with its receptor strength of attraction between drug and receptor the higher the affinity the lower the concentration needed to activate the same number of receptors affinity is therefore the primary determinant of drug potency Drug – Receptor Interactions Efficacy: the ability of a drug to initiate a cellular effect not directly related to affinity, differs among various drugs that bind to a receptor and start the pathway drugs with both affinity and efficacy are agonists drugs with affinity but low efficacy are antagonists Agonists Agonists drugs with both affinity for the receptor and efficacy are agonists binds with receptor and produces physiological response Drug – Receptor Interactions Drug tolerance Repeated dose of the same agonist drug can desensitize or reduce receptors Antagonist Antagonists Drugs with affinity but low efficacy are antagonists Blocking/antagonizing action (as with silent antagonists), the drug binds the receptor, but does not activate it (The key goes in but it can not turn the lock) Class Activity Refer to the HMCAS CPGs and list the drugs that are classified as agonists or antagonists. Assignment #2 Summary Types of receptors Receptors for hormones and neurotransmitters Enzymes Membrane transport molecules Other macromolecules Drug – receptor interactions Agonists / antagonists Questions? References 1. Brenner, G., et al. Pharmacology, 4th ed., 2013, Elsevier, Philadelphia, PA 2. Casem, M.L., Case Studies in Cell Biology, 2016, Elselvier 3. Focke PJ, Wang X, Larsson HP. Neurotransmitter transporters: structure meets function. Structure. 2013;21(5):694-705. doi:10.1016/j.str.2013.03.002 4. Medical Dictionary for the Health Professions and Nursing, 2012. Accessed at https://medical-dictionary.thefreedictionary.com/Neurotransmitter 5. US National Library of Medicine, Hormone. September, 2020. Accessed at https://medlineplus.gov/hormones.html 6. Van Meer, G. et al. Membrane lipids: where they are and how they behave. 2008. Nature Reviews Molecular Cell Biology 9;112-124