Transcript Introduction, PK and PD-1 Slides

Pharmacology for Anesthesia I
Introduction
What is a Drug?
Pharmacokinetics (PK)
What the body does to the drug
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Absorption
Distribution
Metabolism
Excretion
Absorption
The process of diffusion or transport of a drug from the site of administration to
the plasma
Skipped by administering drugs parenterally
Inhaled agents require special considerations
Fick’s Law
concentration gradient x surface area x diffusion coefficient
Rate of Diffusion =
membrane thickness
Diffusion coefficient =
Permeability
Size
Ionization State
Henderson – Hasselbalch Equation
log concentration (protonated) = pKa - pH
concentration (unprotonated)
Trapping
Distribution
The process of diffusion of
a drug throughout the body
Generally governed by the
same characteristics as
absorption
Vd = volume of distribution
Protein Binding
Metabolism
• The enzymatic modification of the drug
molecule by the body
– Often occurs in liver
– May occur elsewhere
Hepatic Metabolism
Example of Phase II prior to Phase I
CYP Enzymes
Pharmacogenetics of Drug Metabolism
Examples of Drug-Drug Interactions
Elimination
• The removal of the drug from the body
– Renal
– Hepatic
– Respiratory
– Cutaneous
Clearance
• Used to describe our ability to eliminate the active
ingredient
– Combination of metabolism and excretion
Example of Zero order kinetics
Distribution and Clearance
First Order Kinetics
• Single compartment model
• Double compartment model
• Three compartment model
• Etc.
Absorption and Clearance
Effect Not Always Governed by
Plasma Concentration
Dosing Regimens
Can speed accumulation
time by administering a
loading dose
Routes of Administration
ROUTE
Intravenous
Subcutaneous
ABSORPTION PATTERN
SPECIAL UTILITY
Absorption circumvented
Valuable for emergency use
Increased risk of adverse effects
Potentially immediate effects
Permits titration of dosage
Must inject solutions slowly as a rule
Suitable for large volumes and for
irritating substances, or complex
mixtures, when diluted
Usually required for high-molecular- Not suitable for oily solutions or poorly
weight protein and peptide drugs
soluble substances
Prompt, from aqueous solution
Suitable for some poorly soluble
suspensions and for instillation of
slow-release implants
Slow and sustained, from repository
preparations
Intramuscular
Oral ingestion
LIMITATIONS AND PRECAUTIONS
Not suitable for large volumes
Possible pain or necrosis from irritating
substances
Prompt, from aqueous solution
Suitable for moderate volumes, oily
vehicles, and some irritating
substances
Precluded during anticoagulant therapy
Slow and sustained, from repository
preparations
Appropriate for self-administration
(e.g., insulin)
May interfere with interpretation of certain
diagnostic tests (e.g., creatine kinase)
Variable, depends on many factors (see Most convenient and economical;
text)
usually more safe
Requires patient compliance
Bioavailability potentially erratic and
incomplete
Pharmacodynamics
• What the drug does to the body
– Typically receptor mediated
What factors affect the ability of a drug to interact with a receptor?
Drug size
• Large enough to be specific
• Not so large as to be unable to interact with the receptor
Drug Shape
Some drugs do not appear to fit into these categories
• Osmotic agents
• Transport regulators
Agonists
Antagonists
Competitive
Noncompetitive
Allosteric Activators
Potentiators
Partial agonists
Inverse agonists
Antagonists
Noncompetitive Antagonist and Spare Receptors
Full and Partial Agonists
Cellular Receptors
Different Drugs Similar Effects
Potency vs. Efficacy
Population Variation and
Therapeutic Window