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