Introduction to Pharmacology and Pharmacokinetics

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Introduction to Pharmacology and Pharmacokinetics

• Pharmacology 49.222
• Bill Diehl-Jones RN, PhD
• Faculty of Nursing and Department of Zoology

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Agenda

• The instructor
• The course
• organization
• expectations/grading
• Introduction
• Purpose of drug therapy
• Principles of Pharmacokinetics

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The Instructor

• Office 333 Helen Glass
• Lab 336 Helen Glass
• Phone [phone]
• Email
• Bill_Diehl-Jones_at_umanitoba.ca
• Office Hours
• by appointment

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The Course

• Introductory level course designed for nursing
  students
• Lecture notes are available on my website
• Physiological and pharmacological principles will
  be integrated

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Optional Text

• It is currently in the U of M bookstore
• Primary text
• Lilly and Aucker, 2001

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Core Concepts

• Introduction to Pharmacology
• General Principles
• Pharmacotherapeutics
• The Role of the Nurse
• Drug Issues in Society

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Evaluation Methods

• Mid Term Test - 25
• Final Exam - 35
• Patient Information Pamphlet - 20
• Pop Quizzes (x 4) - 10
• Test/exam will be multiple choice, true false and
  matching

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Why Do We Study Pharmacology?

• A. Its 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

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Purpose of Drug Therapy

• 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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A Graphical Example
Lethal Dose
Drug Concentration
Peak Onset
Therapeutic Range
?
Duration
Sub- Therapeutic
Time in Hours
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How Do We Study Pharmacology?
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General Concepts
Pharmaceutical
Pharmacokinetics
Pharmacodynamics
Pharmacotherapeutics
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How are Drugs Administered?
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Routes of Drug Delivery
Parenteral (IV)
Inhaled
Oral
Transdermal
Parenteral (SC, IM)
Topical
Rectal
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What Happens After Drug Administration?
Drug at site of administration
1. Absorption
Drug in plasma
2. Distribution
Drug/metabolites in tissues
3. Metabolism
4. Elimination
Drug/metabolites in urine, feces, bile
Modified from Mycek et al. (1997)
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We are now talking about
Pharmacokinetics
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Factors Affecting Drug Absorption

• Transport
• active vs. passive
• pH
• Physical factors
• blood flow
• surface area
• contact time

ATP
ADP Pi
A- BH
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What Factors Affect Distribution?

• Blood flow
• brain vs. fat
• Capillary permeability
• differences in capillary structure
• Binding to proteins
• role of albumin

Endothelial cells in liver capillary
Endothelial cells in brain capillary
Glial cell
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An Important ConceptBIOAVAILABIITY

• Defn
• Fraction of a drug that reaches systemic
  circulation after a particular route of adminn
• Affected by
• 1st pass metabolism (eg Lidocaine,
  propranolol)
• Solubility
• Instability (eg
  Penicillin G, insulin)

Injected Dose
Serum Concentration
Oral Dose
Time
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Volume of Drug Distribution

• Drugs may distribute into any or all of the
  following compartments
• Plasma
• Interstitial Fluid
• Intracellular Fluid

Plasma (4 litres) Interstitial Fluid (10
litres) Intracellular Fluid (28 litres)
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So What?

• Most drugs distribute into several compartments
  however
• Some drugs distribute into only one or two
  compartments
• Eg Aminoglycoside antibiotics
• Streptomycin
• Gentamycin

Arggh! I cant fit through these darn
fenestrations!
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More So What?

• It takes time for a drug to distribute in the
  body
• Drug distribution is affected by elimination

1.5
Drug is not eliminated
Serum Concentration
1.0
Elimination Phase
0.5
Distribution Phase
Drug is eliminated
0
Time
0
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Albumin Affects Distribution
Albumin

• Drugs bind differentially to albumin
• 2 drug classifications
• Class I dose less than available binding sites
  (eg most drugs)
• Class II dose greater than binding sites
  (eg sulfonamide)
• The problem
• one drug may out-compete the other

Drug X
Sulfonamide
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Drug Metabolism(were still talking about
Pharmacokinetics)
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Drug Metabolism

• First pass
• metabolism of drugs may occur as they cross the
  intestine or transit the liver
• eg nitroglycerin
• Other drugs may be destroyed before absorption
• eg penicillin
• Such reactions decrease delivery to the target
  tissues

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Drug Metabolism (contd)
Drug

• Two Phases I and II
• 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
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An Example of Phase I and IIBiotransformation
Phenacetin
-OC2H5
CH3CON- H
PHASE I
Paracetamol
-OH
CH3CON- H
PHASE II
OH
Glucuronic Acid Conjugate
-O-
-OH
HO
CH3CON- H
O
COOH
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An Example of Drug Metabolism
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First Pass Metabolism Occurs Primarily in the
Liver and Gut
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Drug Elimination

• Most important route is the kidney
• May also involve bile, intestine, lung, breast
  milk
• What clinical scenarios may affect drug
  elimination?

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Elimination of a drug is usually linked to renal
filtration, secretion and reabsorption.
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Food for Thought

• What conditions might affect renal function (and
  therefore drug elimination)?
• What other organ systems are involved in drug
  clearance?

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Important Point

• The pharmacokinetic profile of a drug also
  depends on its mode of administration

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Example Intravenous Infusions

• Plasma concentration rises until elimination
  input
• Faster infusions get more drugs on board, but
  does not change the time to achieve a steady state

Fast Infusion
Slow Infusion
Time at which steady state is achieved
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Example Intravenous Injection

• Peak plasma concentration of the drug is achieved
  at time 0
• There is no steady state concentration. Why?

100 mg injected
50 mg injected
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Example Oral Dose

• 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

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Are We Having Fun Yet?