introduction to pharmacology and pharmacokinetics pharmacology 49.222 bill diehl-jones rn, phd...
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The Instructor Office: 333 Helen Glass Office: 333 Helen Glass Lab: 336 Helen Glass Lab: 336 Helen Glass Phone: Phone: Bill_Diehl- Bill_Diehl- Office Hours: Office Hours: by appointment by appointmentTRANSCRIPT
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:
[email protected]@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?