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 Pharmacokinetics for Nursing Pharmacology:  General Principles-Lecture I, slide 1

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  • Absorption

    • Fick's Law

  • Routes of Administration

  • First-Pass Effect

  • Pulmonary Effects

  • Pharmacokinetics

    • Volume of distribution

    • Clearance

      • Renal clearance: clearance of unchanged drug and metabolites

        • Other Factors Affecting Renal Clearance

      • Factors Affecting Hepatic Clearance

      • Capacity-Limited Elimination

      • Half-life

      • Drug Accumulation

    • Bioavailablity

      • Extent of Absorption

      • First-Pass Elimination

      • Rate of Aborption

    • Placental Transfer

    • Redistribution

    • Drug-Plasma Protein Binding

    • Renal Clearance

  • Drug Metabolism

    • Introduction

    • Phase I and Phase II Reaction Overview:

    • Phase I characteristics

    • Phase II characteristics

    • Conjugates

    • Principal organs for biotransformation

      • Sequence I

      • Sequence II

    • Bioavailability

    • Microsomal Mixed Function Oxidase System and Phase I Reactions

      • The Reaction

      • flavoprotein--NADPH cytochrome P450 reductase

      • Cytochrome P450: -- terminal oxidase

      • P450 Enzyme Induction

      • P450 Enzyme Inhibition

      • Human Cytochrome P450

    • Phase II Reactions

      • Toxicities

  • Individual Variation in Drug Responses

  • Genetic Factors in Biotransformation

  • Effects of Age on Drug Responses

  • Drug-Drug Interactions

Pharmacokinetics and some IV Anesthetics Agents

  • Barbiturates

    • Thiopental

  • Benzodiazepines

  • Ketamine and Etomidate

  • Propofol

  • Opioids

    • Membrane Bilayer Structure



Absorption Principles:

  • I. Aqueous diffusion 

    • Within large aqueous components (e.g.,interstitial space, cytosol)

    • Across epithelial membrane tight junctions

    • Across endothelial blood vessel lining

      • through aqueous pores: allows diffusion of molecules with molecular weights up to 20,000 -- 30,000.

    • Driving force: drug concentration gradient (described by Fick's Law ). 

      • The driving force represents a tendency for molecules to move in the direction of higher concentration to lower concentration in accord with random molecular motion. A traditional way of thinking about this is to imagine a fluid-filled container which is two sections divided by an imaginary plane.  The solution on one side is more concentrated in terms of some dissolved substance that is the solution on the other side of the boundary plane.

      • Recall that the molecules move randomly, suggesting that sometimes a molecule initially in the "low concentration" section can move to the "high concentration" section.  However, on balance.  It is more likely that based on probability molecules will tend to move from the higher concentrations side to the lower concentrations side.  Suppose that initially there are 2,000 molecules on side A and 1,000 molecules on side B. After a while we look again and find that there now are 1750 molecules on side A and 1250 molecules on side B-- a new ratio is been established, but the process continues until the ratio is approximately 1:1.


Fick's Law
  •  Fick's Law describes passive movement molecules down its concentration gradient.
  • Flux  (J) (molecules per unit time) =  (C1 - C2) · (Area ·Permeability coefficient) / Thickness
  • where C1 is the higher concentration and C2 is the lower concentration

  • area = area across which diffusion occurs

  • permeability coefficient: drug mobility in the diffusion path

    • for lipid diffusion, lipid: aqueous partition coefficient -- major determinant of drug mobility

      • partition coefficient reflects how easily the drug enters the lipid phase from the aqueous medium.

  • thickness: length of the diffusion path

Katzung, B. G. Basic Principles-Introduction , in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, p 5.
  • Plasma protein-bound drugs cannot permeate through aqueous pores

  • Charged drugs will be influenced by electric field potentials {membrane potentials, important in renal, trans-tubular transport}


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