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

Introduction to Pharmacology

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

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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

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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.

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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

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Breaking Through the Barriers

 Many biological barriers

 Tissue  Cell membranes

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Tissue Barriers

 Reaching the site of action (brain)

 Intestinal epithelium  Capillaries  Liver

 First pass effect (metabolism)

 General circulation  Blood brain barrier  Brain capillaries

 Brain tissue

 Exiting the body

 Brain capillaries  Blood brain barrier  General circulation  Liver

 Metabolism (biotransformation)

 General circulation  Kidney

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Absorption Distribution Metabolism Excretion

Cellular Transport – Cell Membrane barriers

 Transcellular

 Passive diffusion

 Transporters  Carrier mediated transport

 Facilitated diffusion  Active transport  Transcytosis

 Paracellular

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Passive Diffusion Diffusion – The natural tendency for molecules to move from an area of higher concentration to lower concentration *no energy required*

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Area of high concentration Area of low concentration Equilibrium

Passive Diffusion

Diffusion – The natural tendency for molecules to move from an area of higher concentration to lower concentration

Hydrophilic

 Water loving  Lipophobic

Hydrophobic

 Water resistant  Lipophilic

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Passive Diffusion

Diffusion – The natural tendency for molecules to move from an area of higher concentration to lower concentration

Hydrophilic substances Lipophilic substances

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 Hydrophilic channels  Through the lipid bilayer Water like environment Oil like environment

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

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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

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Facilitated Diffusion

Facilitated diffusion – a carrier medicate process that

• ccurs only when a concentration gradient exists *no

energy required*

 Facilitated diffusion

 Factors

 Concentration gradient  Transporter concentration  Affinity

 Types

 Uniporter

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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

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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

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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

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More Than 1 Way to Skin a Cat

 Substances or molecules are able to transport through biological membranes by more than 1 transport mechanism

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Break….

 May be a good time to take a break

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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

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Receptor proteins

 Receive and process chemical signals from outside the cell  Example of drugs that target receptor proteins

 Zyrtec  Alpha Blockers

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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

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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

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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

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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

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Enzymes

 An enzymes job is to catalyze biochemical and metabolic reactions  Examples of drugs that bind to enzymes

 Celecoxib  Aspirin

 Examples of enzymes

 ProteASE  SynthASE  TranscriptASE

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Transporters

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

 Prozac  Cocaine

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Bonds

 Drugs form bonds at the site of action  Types of bonds

 Covalent  Ionic  Hydrogen bonds  Hydrophobic interactions

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Covalent Bonds

 Covalent bonds – sharing of electrons  Covalent bonds in pharmacology

 “Irreversible”

 Aspirin and cyclooxygenase

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Ionic bonds

 Ionic bonds - the transferring of electrons between two atoms  Ionic bonds in pharmacology (AKA electrostatic bond)

 “Reversible”

 Lidocaine

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Hydrogen bonds

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

 Lactulose

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Hydrophobic bonds

 Hydrophobic interactions – interactions driven by the tendency to avoid water  Hydrophobic interactions in pharmacology

 Weak  Flagyl

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Questions

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