Transcript Lecture 1: Introduction to Pharmacology

Introduction to Pharmacology
and Pharmacokinetics
Pharmacology 49.222
Bill Diehl-Jones RN, PhD
Faculty of Nursing and Department of Zoology
Agenda
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The instructor
The course
organization
 expectations/grading
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Introduction
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Purpose of drug therapy
Principles of Pharmacokinetics
The Instructor
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Office: 333 Helen Glass
Lab: 336 Helen Glass
Phone: 474-7136
Email:
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[email protected]
Office Hours:
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by appointment
The Course
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Introductory level course designed for nursing
students
Lecture notes are available on my website
Physiological and pharmacological principles
will be integrated
Optional Text
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It is currently in the U
of M bookstore
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Primary text:
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Lilly and Aucker, 2001
Core Concepts
Introduction to Pharmacology
General Principles
Pharmacotherapeutics
The Role of the Nurse
Drug Issues in Society
Evaluation Methods
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Mid Term Test
Final Exam
Patient Information Pamphlet
Pop Quizzes (x 4)
- 25%
- 35%
- 20%
- 10%
Test/exam will be multiple choice, true false and
matching
Why Do We Study Pharmacology?
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A. It’s good for you
B. You will be able to use fancy terms like
’bioavailabilty’
C. My instructor likes torture
D. A competent nurse must understand why
his/her patient is getting a medication, and
HOW IT WORKS
Purpose of Drug Therapy
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“… to prevent, control or cure various disease
states.”
To achieve this, the right drug dose must be
delivered to the tissues
Every nurse must know…
speed of onset of drug action
 intensity of drug effect
 duration of drug action
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Drug Concentration
A Graphical Example:
Lethal
Dose
Peak Onset

Therapeutic
Range
Duration
SubTherapeutic
Time in Hours
How Do We Study
Pharmacology?
General Concepts
Drug Dose
Administration
Pharmaceutical
Pharmacokinetics
Pharmacodynamics
Pharmacotherapeutics
Disintegration
of Drug
Absorption/distribution
metabolism/excretion
Drug/Receptor
Interaction
Drug Effect
or Response
How are Drugs
Administered?
Routes of Drug Delivery
Parenteral
(IV)
Inhaled
Oral
Transdermal
Topical
Parenteral
(SC, IM)
Rectal
What Happens After Drug
Administration?
Drug at site
of administration
1. Absorption
Drug in plasma
2. Distribution
Drug/metabolites
3. Metabolism
in tissues
Drug/metabolites
in urine, feces, bile
4. Elimination
Modified from Mycek et al. (1997)
We are now talking about …
Pharmacokinetics
Factors Affecting Drug
Absorption
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Transport
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active vs. passive
pH
Physical factors
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ATP
blood flow
surface area
contact time
ADP
+ Pi
ABH+
What Factors Affect Distribution?
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Blood flow
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Capillary permeability
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brain vs. fat
Endothelial cells
in liver capillary
differences in capillary
structure
Binding to proteins
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role of albumin
Endothelial cells
in brain capillary
Glial cell
Def’n:
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Fraction of a drug that
reaches systemic circulation
after a particular route of
admin’n
Affected by:
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1st pass metabolism
(eg:
Lidocaine, propranolol)
Solubility
Instability
(eg:
Penicillin G, insulin)
Serum Concentration
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An Important Concept:
BIOAVAILABIITY
Injected Dose
Oral Dose
Time
Volume of Drug Distribution
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Drugs may distribute into
any or all of the following
compartments:
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Plasma
Interstitial Fluid
Intracellular Fluid
Plasma
(4 litres)
Interstitial Fluid
(10 litres)
Intracellular Fluid
(28 litres)
So What?
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Most drugs distribute into
several compartments;
however …
Some drugs distribute into only
one or two compartments
Eg: Aminoglycoside antibiotics
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Streptomycin
Gentamycin
Arggh! I can’t fit through these
darn fenestrations!
More “So What?”
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Serum Concentration
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It takes time for a drug to distribute in the body
Drug distribution is affected by elimination
1.5
Drug is not eliminated
1.0
Elimination Phase
0.5
Distribution Phase
0
0
Time
Drug is eliminated
Albumin Affects Distribution
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Drugs bind differentially
to albumin
2 drug classifications:
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Albumin
Class I: dose less than
available binding sites (eg:
most drugs)
Class II: dose greater
than binding sites
(eg:
sulfonamide)
Drug X
The problem:
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one drug may outcompete the other
Sulfonamide
Drug Metabolism
(we’re still talking about
Pharmacokinetics)
Drug Metabolism
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First pass
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metabolism of drugs may occur as they cross the
intestine or transit the liver
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Other drugs may be destroyed before absorption
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eg: nitroglycerin
eg: penicillin
Such reactions decrease delivery to the target
tissues
Drug Metabolism (cont’d)
Drug
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Two Phases: I and II
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Phase I: conversion to
lipophilic cpds
Phase II: conjugation
Phase I involves the
cytochrome P-450 system
Ultimate effect is to
facilitate elimination
Phase I
Oxidation
Reduction
Hydrolysis
Activation/Inactivation
Phase II
Glucuronidation
Conjugation Products
An Example of Phase I and II
Biotransformation:
CH3CONH
PHASE I
-OC2H5
Phenacetin
CH3CONH
PHASE II
-OH
Paracetamol
OH
CH3CONH
-O- HO -OH
O COOH
Glucuronic Acid
Conjugate
An Example of Drug Metabolism
First Pass Metabolism Occurs
Primarily in the Liver and Gut
Drug Elimination
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Most important route is the kidney
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May also involve bile, intestine, lung, breast milk
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What clinical scenarios may affect drug
elimination?
Elimination of a drug is usually
linked to renal filtration,
secretion and reabsorption.
Food for Thought
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What conditions might affect renal function
(and therefore drug elimination)?
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What other organ systems are involved in drug
clearance?
Important Point
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The pharmacokinetic profile of a drug also
depends on its mode of administration …
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Plasma concentration
rises until elimination
= input
Faster infusions get
more drugs on board,
but does not change
the time to achieve a
steady state
Plasma Concentration
Example: Intravenous Infusions
Fast Infusion
Slow Infusion
Time
Time at which
steady state is achieved
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Peak plasma
concentration of the
drug is achieved at time
=0
There is no steady state
concentration. Why?
Plasma Concentration
Example: Intravenous Injection
100 mg injected
50 mg injected
Time
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A single oral dose will
give you a single peak
plasma concentration
The drug concentration
then continuously
declines
Repeated doses result
in oscillations in plasma
concentration
Plasma Concentration
Example: Oral Dose
Time
Are We Having Fun Yet?