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Lecture 1 Introduction to Pharmacology by ltq93779

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									Introduction to Pharmacology
    and Pharmacokinetics

           Pharmacology 49.222
            Bill Diehl-Jones RN, PhD
 Faculty of Nursing and Department of Zoology
                        Agenda
   The instructor
   The course
     organization
     expectations/grading

   Introduction
       Purpose of drug therapy
   Principles of Pharmacokinetics
                    The Instructor

   Office: 333 Helen Glass
   Lab: 336 Helen Glass
   Phone: 474-7136
   Email:
       Bill_Diehl-
        Jones@umanitoba.ca
   Office Hours:
       by appointment
                 The Course

   Introductory level course designed for nursing
    students
   Lecture notes are available on my website
   Physiological and pharmacological principles
    will be integrated
                     Optional Text
   It is currently in the U
    of M bookstore

   Primary text:
       Lilly and Aucker, 2001
               Core Concepts
Introduction to Pharmacology

General Principles

Pharmacotherapeutics

The Role of the Nurse

Drug Issues in Society
           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
Why Do We Study Pharmacology?
   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
   “… 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
                     A Graphical Example:
Drug Concentration

                                                Lethal
                                                Dose


                      Peak Onset


                                            
                                            Therapeutic
                                              Range
                       Duration
                                               Sub-
                                            Therapeutic


                            Time in Hours
How Do We Study
 Pharmacology?
             General Concepts
                           Drug Dose
                          Administration

                          Disintegration
Pharmaceutical               of Drug

Pharmacokinetics       Absorption/distribution
                       metabolism/excretion

Pharmacodynamics          Drug/Receptor
                           Interaction

Pharmacotherapeutics        Drug Effect
                            or Response
How are Drugs
Administered?
        Routes of Drug Delivery
Parenteral                     Inhaled
  (IV)
                        Oral

    Transdermal
                        Parenteral
     Topical            (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

                                  4. Elimination
         Drug/metabolites
        in urine, feces, bile
                                Modified from Mycek et al. (1997)
We are now talking about …



       Pharmacokinetics
          Factors Affecting Drug
               Absorption
   Transport                 ATP
       active vs. passive
   pH
   Physical factors          ADP
       blood flow            + Pi
       surface area
       contact time
                              A-
                             BH+
    What Factors Affect Distribution?
   Blood flow                     Endothelial cells
       brain vs. fat              in liver capillary
   Capillary permeability
       differences in capillary
        structure
   Binding to proteins
       role of albumin


                                    Endothelial cells
                                    in brain capillary   Glial cell
               An Important Concept:
                BIOAVAILABIITY
   Def’n:
       Fraction of a drug that




                                       Serum Concentration
        reaches systemic circulation
        after a particular route of
        admin’n                                               Injected Dose
   Affected by:
       1st pass metabolism     (eg:
        Lidocaine, propranolol)
       Solubility
       Instability             (eg:                         Oral Dose
        Penicillin G, insulin)
                                                                Time
        Volume of Drug Distribution

   Drugs may distribute into           Plasma
    any or all of the following        (4 litres)
    compartments:
                                   Interstitial Fluid
       Plasma
                                      (10 litres)
       Interstitial Fluid
       Intracellular Fluid       Intracellular Fluid
                                      (28 litres)
                          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 can’t fit through these
                                    darn fenestrations!
                                 More “So What?”
                 It takes time for a drug to distribute in the body
                 Drug distribution is affected by elimination
Serum Concentration



                      1.5

                                                              Drug is not eliminated
                      1.0                        Elimination Phase

                      0.5
                            Distribution Phase                Drug is eliminated
                      0
                            0               Time
        Albumin Affects Distribution
                                       Albumin
   Drugs bind differentially
    to albumin
   2 drug classifications:
       Class I: dose less than
                                                        Drug X
        available binding sites (eg:
        most drugs)
       Class II: dose greater
        than binding sites      (eg:
        sulfonamide)
   The problem:
       one drug may out-
        compete the other
                                          Sulfonamide
   Drug Metabolism
(we’re still talking about
  Pharmacokinetics)
                    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
           Drug Metabolism (cont’d)
                                        Drug
   Two Phases: I and II                       Phase I
       Phase I: conversion to                 Oxidation
        lipophilic cpds                        Reduction
       Phase II: conjugation                  Hydrolysis
   Phase I involves the         Activation/Inactivation
    cytochrome P-450 system
                                               Phase II
   Ultimate effect is to                    Glucuronidation
    facilitate elimination
                                 Conjugation Products
An Example of Phase I and II
    Biotransformation:

      CH3CON-      -OC2H5     Phenacetin
            H
    PHASE I

      CH3CON-      -OH        Paracetamol
             H
    PHASE II
                  OH
    CH3CON-      -O- HO -OH   Glucuronic Acid
         H                      Conjugate
                     O COOH
An Example of Drug Metabolism
First Pass Metabolism Occurs
Primarily in the Liver and Gut
              Drug Elimination
   Most important route is the kidney

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

   What clinical scenarios may affect drug
    elimination?
Elimination of a drug is usually
   linked to renal filtration,
  secretion and reabsorption.
             Food for Thought
   What conditions might affect renal function
    (and therefore drug elimination)?

   What other organ systems are involved in drug
    clearance?
               Important Point
   The pharmacokinetic profile of a drug also
    depends on its mode of administration …
    Example: Intravenous Infusions

   Plasma concentration
    rises until elimination



                              Plasma Concentration
    = input                                                   Fast Infusion
   Faster infusions get
    more drugs on board,
    but does not change                                      Slow Infusion
    the time to achieve a
    steady state
                                                     Time
                                                         Time at which
                                                     steady state is achieved
    Example: Intravenous Injection

   Peak plasma
    concentration of the                              100 mg injected




                               Plasma Concentration
    drug is achieved at time
    =0
   There is no steady state                          50 mg injected
    concentration. Why?



                                                         Time
              Example: Oral Dose

   A single oral dose will
    give you a single peak



                                Plasma Concentration
    plasma concentration
   The drug concentration
    then continuously
    declines
   Repeated doses result
    in oscillations in plasma
    concentration                                      Time
Are We Having Fun Yet?

								
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