Introduction to Pharmacology 1 University of Hawaii Hilo Pre - PowerPoint PPT Presentation

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

Learning Objectives 2  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

Definitions 3  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.

Types of drugs 4  Endogenous  Produced in the body  Hormones  Neurotransmitters  Exogenous  Not produced in the body  Poisons  Drugs with almost only harmful effects  Toxins  Naturally occurring poisons

Breaking Through the Barriers 5  Many biological barriers  Tissue  Cell membranes

Tissue Barriers 6 A bsorption M etabolism  Exiting the body  Reaching the site of action (brain)  Intestinal epithelium  Brain capillaries  Blood brain barrier  Capillaries  General circulation  Liver  Liver  First pass effect (metabolism)  General circulation  Metabolism (biotransformation)  General circulation  Blood brain barrier  Brain capillaries  Kidney  Brain tissue D istribution E xcretion

Cellular Transport – Cell Membrane 7 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

Passive Diffusion 9 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

Passive Diffusion 10 Diffusion – The natural tendency for molecules to move from an area of higher concentration to lower concentration Water like environment Hydrophilic substances Lipophilic substances  Hydrophilic channels  Through the lipid bilayer Oil like environment

Passive Diffusion 11  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

Transporters 12  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

Facilitated Diffusion 13 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

Active Transport 14 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

Transcytosis 15 Transcytosis (vesicular transport) – is a process by which certain substances are transported across cell membranes by the use of vesicles.  Endocytosis  Pinocytosis  Phagocytosis  Exocytosis

Paracellular Transport 16 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

More Than 1 Way to Skin a Cat 17  Substances or molecules are able to transport through biological membranes by more than 1 transport mechanism 

Break…. 18  May be a good time to take a break 

Regulatory Proteins (Receptors) 19  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

Receptor proteins 20  Receive and process chemical signals from outside the cell  Example of drugs that target receptor proteins  Zyrtec  Alpha Blockers

Ion channel proteins 21  Ion channels control the passage of ions through a cell‟s membrane  Example of drugs that target ion channels  Calcium channel blockers  Digoxin

Ion channel proteins 22  Ion channels control the passage of ions through a cell‟s membrane  Example of drugs that target ion channels  Calcium channel blockers  Digoxin

Ion channel proteins 23  Ion channels control the passage of ions through a cell‟s membrane  Example of drugs that target ion channels  Calcium channel blockers  Digoxin

Ion channel proteins 24  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  Prote ASE  Synth ASE  Celecoxib  Transcript ASE  Aspirin

Transporters 26  Transporters help to transport substances across a cells membrane  Examples of drugs that target transporters  Prozac  Cocaine

Bonds 27  Drugs form bonds at the site of action  Types of bonds  Covalent  Ionic  Hydrogen bonds  Hydrophobic interactions

Covalent Bonds 28  Covalent bonds – sharing of electrons  Covalent bonds in pharmacology  “Irreversible”  Aspirin and cyclooxygenase

Ionic bonds 29  Ionic bonds - the transferring of electrons between two atoms  Ionic bonds in pharmacology (AKA electrostatic bond)  “Reversible”  Lidocaine

Hydrogen bonds 30  Hydrogen bonds – A weak electrostatic bond  Hydrogen bonds in pharmacology  Lactulose

Hydrophobic bonds 31  Hydrophobic interactions – interactions driven by the tendency to avoid water  Hydrophobic interactions in pharmacology  Weak  Flagyl

Questions 32