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

occurs 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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