Introduction to Introduction to Pharmacology and Pharmacology and PharmacokineticsPharmacokinetics

Pharmacology 49.222Pharmacology 49.222Bill Diehl-Jones RN, PhDBill Diehl-Jones RN, PhD

Faculty of Nursing and Department Faculty of Nursing and Department of Zoologyof Zoology

AgendaAgenda The instructorThe instructor The courseThe course

organizationorganization expectations/gradingexpectations/grading

IntroductionIntroduction Purpose of drug therapyPurpose of drug therapy

Principles of PharmacokineticsPrinciples of Pharmacokinetics

The InstructorThe Instructor

Office: 333 Helen Office: 333 Helen GlassGlass

Lab: 336 Helen GlassLab: 336 Helen Glass Phone: 474-7136Phone: 474-7136 Email:Email:

Bill_Diehl-Bill_Diehl-Jones@umanitoba.caJones@umanitoba.ca

Office Hours:Office Hours: by appointmentby appointment

The CourseThe Course

Introductory level course designed Introductory level course designed for nursing studentsfor nursing students

Lecture notes are available on my Lecture notes are available on my websitewebsite

Physiological and pharmacological Physiological and pharmacological principles will be integratedprinciples will be integrated

Optional TextOptional Text It is currently in It is currently in

the U of M the U of M bookstorebookstore

Primary text: Primary text: Lilly and Aucker, Lilly and Aucker,

20012001

Core ConceptsCore ConceptsIntroduction to Introduction to

PharmacologyPharmacology

General PrinciplesGeneral Principles

PharmacotherapeuticsPharmacotherapeutics

The Role of the NurseThe Role of the Nurse

Drug Issues in SocietyDrug Issues in Society

Evaluation MethodsEvaluation Methods Mid Term Test Mid Term Test - 25%- 25% Final Exam Final Exam - 35%- 35% Patient Information Pamphlet Patient Information Pamphlet - 20% - 20% Pop Quizzes (x 4)Pop Quizzes (x 4) - 10%- 10%

Test/exam will be multiple choice, true false and matchingTest/exam will be multiple choice, true false and matching

WhyWhy Do We Study Do We Study Pharmacology?Pharmacology?

A. It’s good for youA. It’s good for you B. You will be able to use fancy B. You will be able to use fancy

terms like ’bioavailabilty’terms like ’bioavailabilty’ C. My instructor likes tortureC. My instructor likes torture D. A competent nurse must D. A competent nurse must

understand why his/her patient is understand why his/her patient is getting a medication, and HOW IT getting a medication, and HOW IT WORKSWORKS

Purpose of Drug TherapyPurpose of Drug Therapy “… “… to prevent, control or cure to prevent, control or cure

various disease states.”various disease states.” To achieve this, the right drug dose To achieve this, the right drug dose

must be delivered to the tissuesmust be delivered to the tissues Every nurse must know…Every nurse must know…

speed of onset of drug actionspeed of onset of drug action intensity of drug effectintensity of drug effect duration of drug actionduration of drug action

A Graphical Example:A Graphical Example:

Time in Hours

Dru

g C

once

ntra

tion

Therapeutic

RangeSub-

Therapeutic

LethalDose

Peak Onset

Duration

HowHow Do We Study Do We Study Pharmacology?Pharmacology?

General ConceptsGeneral ConceptsDrug Dose

Administration

Drug Effect or Response

Pharmaceutical

Pharmacokinetics

Pharmacodynamics

Pharmacotherapeutics

Disintegrationof Drug

Absorption/distribution

metabolism/excretionDrug/Receptor

Interaction

How are Drugs How are Drugs Administered?Administered?

Routes of Drug DeliveryRoutes of Drug DeliveryParenteral

(IV)Inhaled

Oral

Transdermal

Rectal

TopicalParenteral(SC, IM)

What Happens After What Happens After Drug Administration?Drug Administration?

Drug at site Drug at site of administrationof administration

Drug in plasmaDrug in plasma

Drug/metabolitesDrug/metabolitesin urine, feces, bilein urine, feces, bile

Drug/metabolitesDrug/metabolites

in tissuesin tissues

1. Absorption

2. Distribution

4. Elimination

3. Metabolism

Modified from Mycek et al. (1997)

We are now talking We are now talking about …about …

Pharmacokinetics

Factors Affecting Drug Factors Affecting Drug AbsorptionAbsorption

TransportTransport active vs. passiveactive vs. passive

pHpH Physical factorsPhysical factors

blood flowblood flow surface areasurface area contact timecontact time

ATP

ADP + Pi

A-

BH+

What Factors Affect What Factors Affect Distribution?Distribution?

Blood flowBlood flow brain vs. fatbrain vs. fat

Capillary Capillary permeabilitypermeability differences in differences in

capillary structurecapillary structure Binding to proteinsBinding to proteins

role of albuminrole of albumin

Endothelial cellsin liver capillary

Endothelial cellsin brain capillary Glial cell

An Important Concept:An Important Concept:BIOAVAILABIITYBIOAVAILABIITY

Def’n:Def’n: Fraction of a drug that Fraction of a drug that

reaches systemic reaches systemic circulation after a circulation after a particular route of admin’nparticular route of admin’n

Affected by:Affected by: 1st pass metabolism 1st pass metabolism

(eg: Lidocaine, propranolol)(eg: Lidocaine, propranolol) SolubilitySolubility Instability Instability

(eg: Penicillin G, insulin)(eg: Penicillin G, insulin)Se

rum

Con

cent

ratio

n

Time

Injected Dose

Oral Dose

Volume of Drug Volume of Drug DistributionDistribution

Drugs may distribute Drugs may distribute into any or all of the into any or all of the following following compartments:compartments: PlasmaPlasma Interstitial FluidInterstitial Fluid Intracellular FluidIntracellular Fluid

Plasma(4 litres)

Interstitial Fluid(10 litres)

Intracellular Fluid(28 litres)

So What?So What?

Most drugs distribute into Most drugs distribute into several compartments; several compartments; however …however …

Some drugs distribute into Some drugs distribute into only one or two only one or two compartmentscompartments

Eg: Aminoglycoside Eg: Aminoglycoside antibioticsantibiotics StreptomycinStreptomycin GentamycinGentamycin Arggh! I can’t fit through these

darn fenestrations!

More “So What?”More “So What?” It takes time for a drug to distribute in the bodyIt takes time for a drug to distribute in the body Drug distribution is affected by eliminationDrug distribution is affected by elimination

Time

Seru

m C

once

ntra

tion

0

0.5

1.0

1.5

0

Elimination Phase

Distribution Phase Drug is eliminated

Drug is not eliminated

Albumin Affects Albumin Affects DistributionDistribution

Drugs bind Drugs bind differentially to albumin differentially to albumin

2 drug classifications:2 drug classifications: Class IClass I: dose less than : dose less than

available binding sites available binding sites (eg: most drugs)(eg: most drugs)

Class IIClass II: dose greater : dose greater than binding sites than binding sites (eg: sulfonamide)(eg: sulfonamide)

The problem:The problem: one drug may out-one drug may out-

compete the othercompete the other

Sulfonamide

Drug X

Albumin

Drug MetabolismDrug Metabolism(we’re still talking about (we’re still talking about

Pharmacokinetics)Pharmacokinetics)

Drug MetabolismDrug Metabolism First passFirst pass

metabolism of drugs may occur as they metabolism of drugs may occur as they cross the intestine or transit the livercross the intestine or transit the liver eg: nitroglycerineg: nitroglycerin

Other drugs may be destroyed before Other drugs may be destroyed before absorptionabsorption

eg: penicillineg: penicillin Such reactions decrease delivery to Such reactions decrease delivery to

the target tissuesthe target tissues

Drug Metabolism Drug Metabolism (cont’d)(cont’d)

Two Phases: I and IITwo Phases: I and II Phase I: conversion Phase I: conversion

to lipophilic cpdsto lipophilic cpds Phase II: conjugationPhase II: conjugation

Phase I involves the Phase I involves the cytochrome P-450 cytochrome P-450 systemsystem

Ultimate effect is to Ultimate effect is to facilitate eliminationfacilitate elimination

Drug

Phase I

Phase II

OxidationReductionHydrolysis

Activation/Inactivation

Conjugation Products

Glucuronidation

An Example of Phase I An Example of Phase I and IIand II

Biotransformation:Biotransformation:-OC2H5CH3CON-

H

-OHCH3CON- H

-O-CH3CON- H

-OH

OH

COOH

HOO

PHASE I

PHASE II

Phenacetin

Paracetamol

Glucuronic AcidConjugate

An Example of Drug An Example of Drug MetabolismMetabolism

First Pass Metabolism First Pass Metabolism Occurs Primarily in the Occurs Primarily in the

Liver and GutLiver and Gut

Drug EliminationDrug Elimination Most important route is the kidneyMost important route is the kidney

May also involve bile, intestine, lung, May also involve bile, intestine, lung, breast milkbreast milk

What clinical scenarios may affect What clinical scenarios may affect drug elimination?drug elimination?

Elimination of a drug is Elimination of a drug is usually linked to renal usually linked to renal filtration, secretion and filtration, secretion and

reabsorption.reabsorption.

Food for ThoughtFood for Thought What conditions might affect renal What conditions might affect renal

function (and therefore drug function (and therefore drug elimination)?elimination)?

What other organ systems are What other organ systems are involved in drug clearance?involved in drug clearance?

Important PointImportant Point The pharmacokinetic profile of a The pharmacokinetic profile of a

drug also depends on its mode of drug also depends on its mode of administration …administration …

Example: Intravenous Example: Intravenous InfusionsInfusions

Plasma Plasma concentration rises concentration rises until elimination until elimination = input= input

Faster infusions get Faster infusions get more drugs on more drugs on board, but does not board, but does not change the time to change the time to achieve a steady achieve a steady statestate

Plas

ma

Con

cent

ratio

n

Time

Slow Infusion

Fast Infusion

Time at whichsteady state is achieved

Example: Intravenous Example: Intravenous InjectionInjection

Peak plasma Peak plasma concentration of concentration of the drug is the drug is achieved at time achieved at time = 0= 0

There is no There is no steady state steady state concentration. concentration. Why?Why?

Plas

ma

Con

cent

ratio

n

Time

100 mg injected

50 mg injected

Example: Oral DoseExample: Oral Dose

A single oral dose will A single oral dose will give you a single peak give you a single peak plasma concentrationplasma concentration

The drug The drug concentration then concentration then continuously declinescontinuously declines

Repeated doses result Repeated doses result in oscillations in in oscillations in plasma concentrationplasma concentration Pl

asm

a C

once

ntra

tion

Time

Are We Having Fun Yet?Are We Having Fun Yet?