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Introduction to Pharmacology 1 University of Hawai„I Hilo Pre-Nursing Program NURS 203 – General Pharmacology Danita Narciso Pharm D

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Introduction to Pharmacology 1 University of Hawai„I Hilo Pre-Nursing Program NURS 203 – General Pharmacology Danita Narciso Pharm D Introduction to Pharmacology 1 University of Hawai„i Hilo Pre-Nursing Program NURS 203 – General Pharmacology Danita Narciso Pharm D 2 Learning Objectives Understand the barriers that drug molecules must overcome to complete a cycle from absorption to excretion in the body (tissue and membrane) Understand the different ways drug molecules transport across membranes Know the different characteristics of binding sites Know the different characteristics of bonds 3 Definitions Pharmacology – The study of substances that interact with living systems through chemical processes. Medical pharmacology – The area of pharmacology concerned with the use of chemicals in the prevention, diagnosis, and treatment of disease, especially in humans. Toxicology – The area of pharmacology concerned with the undesirable effects of chemicals on biologic systems. Pharmacokinetics – Describes the effects of the body on drugs. Pharmacodynamics – Describes the effects of the drug on the body. 4 Types of drugs Endogenous Produced in the body Hormones Neurotransmitters Exogenous Not produced in the body Poisons Drugs with almost only harmful effects Toxins Naturally occurring poisons 5 Breaking Through the Barriers Many biological barriers Tissue Cell membranes 6 Tissue Barriers Absorption Reaching the site of action (brain) Exiting the body Metabolism Intestinal epithelium Brain capillaries Capillaries Blood brain barrier Liver General circulation First pass effect (metabolism) Liver General circulation Metabolism (biotransformation) Blood brain barrier General circulation Brain capillaries Kidney Brain tissue Distribution Excretion 7 Cellular Transport – Cell Membrane barriers Transcellular Passive diffusion Transporters Carrier mediated transport Facilitated diffusion Active transport Transcytosis Paracellular Passive Diffusion 8 Diffusion – The natural tendency for molecules to move from an area of higher concentration to lower concentration *no energy required* Area of high Area of low Equilibrium concentration concentration 9 Passive Diffusion Diffusion – The natural tendency for molecules to move from an area of higher concentration to lower concentration Hydrophilic Hydrophobic Water loving Water resistant Lipophobic Lipophilic 10 Passive Diffusion Diffusion – The natural tendency for molecules to move from an area of Water like higher concentration to lower concentration environment Hydrophilic substances Lipophilic substances Hydrophilic channels Through the lipid bilayer Oil like environment 11 Passive Diffusion Passive diffusion of Lipophilic substances Factors that alter Concentration gradient Surface area of the membrane Thickness of the membrane Charge Electric gradient Permeability Must be permeable to pass through a membrane 12 Transporters Transporters Membrane proteins with one or more active sites that move molecules across membranes Can be selective or non-selective Exist in the kidney, liver, intestines, and other tissues Carrier mediated transport Affinity 13 Facilitated Diffusion Facilitated diffusion – a carrier medicate process that occurs only when a concentration gradient exists *no energy required* Facilitated diffusion Factors Concentration gradient Transporter concentration Affinity Types Uniporter 14 Active Transport Active transport processes are able to transport molecules against their concentration gradient. *require energy* Active transport Against the concentration gradient Requires energy Use of transporters Uniport Symport Antiport Drug efflux transporters Efflux proteins Multidrug efflux 15 Transcytosis Transcytosis (vesicular transport) – is a process by which certain substances are transported across cell membranes by the use of vesicles. Endocytosis Pinocytosis Phagocytosis Exocytosis 16 Paracellular Transport Paracellular transport – the passing of substances through an epithelial or endothelial membrane by the use of cell junctions Types of paracellular transport Through epithelial membranes Gap junctions Smaller than 1 nm in diameter Through capillaries 5-30 nm in diameter Blood-Brain barrier Tight junctions Other enzymatic barriers Filtration Driven by hydrostatic pressure Leaky capillaries 50 -100 nm in diameter 17 More Than 1 Way to Skin a Cat Substances or molecules are able to transport through biological membranes by more than 1 transport mechanism 18 Break…. May be a good time to take a break 19 Regulatory Proteins (Receptors) Drugs must interact with the body in order to promote change Proteins that receive and pass on chemical messages Types of regulatory proteins Receptor proteins Ion channel proteins Enzymes Transporters Drugs are not the only substances that can bin to receptors 20 Receptor proteins Receive and process chemical signals from outside the cell Example of drugs that target receptor proteins Zyrtec Alpha Blockers 21 Ion channel proteins Ion channels control the passage of ions through a cell‟s membrane Example of drugs that target ion channels Calcium channel blockers Digoxin 22 Ion channel proteins Ion channels control the passage of ions through a cell‟s membrane Example of drugs that target ion channels Calcium channel blockers Digoxin 23 Ion channel proteins Ion channels control the passage of ions through a cell‟s membrane Example of drugs that target ion channels Calcium channel blockers Digoxin 24 Ion channel proteins Ion channels control the passage of ions through a cell‟s membrane Example of drugs that target ion channels Calcium channel blockers Digoxin Enzymes 25 An enzymes job is to catalyze biochemical and metabolic reactions Examples of enzymes Examples of drugs that bind to enzymes ProteASE Celecoxib SynthASE Aspirin TranscriptASE 26 Transporters Transporters help to transport substances across a cells membrane Examples of drugs that target transporters Prozac Cocaine 27 Bonds Drugs form bonds at the site of action Types of bonds Covalent Ionic Hydrogen bonds Hydrophobic interactions 28 Covalent Bonds Covalent bonds – sharing of electrons Covalent bonds in pharmacology “Irreversible” Aspirin and cyclooxygenase 29 Ionic bonds Ionic bonds - the transferring of electrons between two atoms Ionic bonds in pharmacology (AKA electrostatic bond) “Reversible” Lidocaine 30 Hydrogen bonds Hydrogen bonds – A weak electrostatic bond Hydrogen bonds in pharmacology Lactulose 31 Hydrophobic bonds Hydrophobic interactions – interactions driven by the tendency to avoid water Hydrophobic interactions in pharmacology Weak Flagyl 32 Questions .
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