Pharmacology for Anesthesia I

Introduction

What is a Drug?

Pharmacokinetics (PK)

What the body does to the drug

• Absorption

• Distribution

• Metabolism

• Excretion

Absorption

Skipped by administering drugs parenterallyInhaled agents require special considerations

The process of diffusion or transport of a drug from the site of administration to the plasma

Fick’s Law

concentration gradient x surface area x diffusion coefficient

membrane thicknessRate of Diffusion =

Diffusion coefficient =Permeability

Size

Ionization StateHenderson – Hasselbalch Equation

log concentration (protonated)concentration (unprotonated) = pKa - pH

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

First Order Kinetics• Single compartment model• Double compartment model• Three compartment model• Etc.

Distribution and Clearance

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 ABSORPTION PATTERN SPECIAL UTILITY LIMITATIONS AND PRECAUTIONS

Intravenous 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-weight protein and peptide drugs

Not suitable for oily solutions or poorly soluble substances

Subcutaneous Prompt, from aqueous solutionSuitable for some poorly soluble suspensions and for instillation of slow-release implants

Not suitable for large volumes

 Slow and sustained, from repository preparations

 Possible pain or necrosis from irritating substances

Intramuscular Prompt, from aqueous solutionSuitable 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)

Oral ingestionVariable, depends on many factors (see text)

Most convenient and economical; 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