gerry's real world guide to pharmacokinetics & other - Anesthesia

188 Pages·2008·1.44 MB·English

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GERRY’S
REAL WORLD GUIDE
TO
PHARMACOKINETICS
& OTHER THINGS

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www.anesthesiaweb.org
GERRY’S
REAL WORLD GUIDE
TO
PHARMACOKINETICS
& OTHER THINGS

By

G. M. Woerlee MBBS (W. Aust), FRCA (Lond.)

Anesthesiologist

Rijnland Hospital, Leiderdorp, the Netherlands

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Copyright © 2008 G M Woerlee

ISBN 978-1-60145-650-2

All rights reserved. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted in any form or by any
means, electronic, mechanical, recording or otherwise, without the
prior written permission of the author.

Disclaimer:
This is a textbook presented in the form of a work of fiction. Accor-
dingly, the locations, characters and events in this book are ficti-
tious. Any similarities to actual locations, or real persons, either
living or dead, are coincidental and not intended by the author. As
regards the medical data and calculations, every effort has been
made to ensure the accuracy of the information presented in this
book. Furthermore, any person using data contained in this book
should realize that medical data is always subject to inter-individual
variation, as well as ensuring they have checked their own calcula-
tions before proceeding with any medical treatments. The publishers
accept no responsibility for any inaccuracies contained within this
text.

Printed in the United States of America.

Booklocker.com, Inc.
2008

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Contents
Contents ......................................................................................... i
Preface ......................................................................................... iii

1. Bob ................................................................................... 1
Concepts of half-life, recirculation and clearance / Terra
and terror / Calculating the duration of anxiety under
general anesthesia

2. Asleep in ten seconds!! ................................................... 16
Speed of anesthetic induction / The Koran and
unconsciousness / Cause of hypotension after induction /
Bombs on Pearl Harbor / Calculating effects of induction
during hypovolemia / How fast will I lose consciousness
after decompression at 10,000 meters altitude?

3. Compartmentalized & distributed .................................. 34
The unspeakable Hawley Crippen / Speed of awakening
after induction / One, two, and three compartment
pharmacokinetic models / Pharmacokinetic parameters

4. Paralyzed for hours ......................................................... 57
Renal failure and muscle relaxants / You can use any
relaxant you want! / Dual block misconceptions / “Ohhhh,
the suffering, the suffering...”

5. Blood loss, drug loss ....................................................... 69
Blood loss and loss of anesthetic drugs / Stress proteins
and anesthetic drug action / Capnography and cardiac
output / Ecclesiastes and the teaching experience

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6. Corpulentia maxima ........................................................ 82
Physiology of anesthesia in the obese / Calculating why the
induction dose must be larger, etc / Effects of oxygen
starvation at different saturation levels / Mushrooms and
anesthesia residents

7. Feeding time.................................................................... 95
Breastfeeding and anesthesia / Calculating the amount of
drug in the baby / How long can you can live without
breathing? / Effects of hypocapnia and hypercapnia

8. Short and long ............................................................... 108
Upanishads and Sevoflurane / Reasons why drugs have
short or longer durations of action / Effect compartment
and t k / Selection of drugs to administer in anticipation
1/2 e0
or reaction

9. The arterial reality of infusions ..................................... 121
Cybele - She who must be obeyed! / Physiology of drug
infusions versus theoretical calculations / Calculation of
loading doses / Context sensitive half-life / Nietzsche and
anesthetic residents

10. A foot in the door .......................................................... 140
Thrombocyte transfusion and pharmacokinetics / Bill
Pillpedler the drug salesman / Calculation of drug usage
profiles / Krishna and the epiphany of Bob

Appendix ................................................................................... 157
References ................................................................................. 167

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Preface
Anesthesiologists are regularly bombarded with pharmacoki-
netic and pharmacodynamic data about the drugs they use. Some
pay attention to these data, using these data to guide them in their
choice and use of drugs. Yet others ignore these data, simply
asking their colleagues and pharmaceutical company representa-
tives, “How can I best use this drug? How much should I adminis-
ter? How long will it work?” Both approaches have their merits.
In fact, when asked, both groups will actually use anesthetic drugs
in a similar manner. So why bother learning anything about the
pharmacokinetic and pharmacodynamic properties of drugs, when
an empirical approach works just as well? By now the reader will
have noticed I used the word pharmacokinetic three times, just as
I also used the word pharmacodynamic three times in this para-
graph. But what do these terms mean?

• Pharmacokinetics is the mathematical and qualitative de-
scription of the distribution of drugs within the body, as
well as their elimination from the body.
• Pharmacodynamics is the mathematical and qualitative
description of the effects of drugs upon the organ systems
of the body.

There are good reasons for understanding and using the
pharmacokinetic and pharmacodynamic properties of drugs. One
of the most important reasons is that a purely empirical approach
means that learning how to use any drug safely and appropriately
entails a long and inefficient period of trial and error. Indeed,
while writing this preface, I was reminded of a piece of advice in
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an old book on practical anesthesia, in which the authors advised
that because suprapubic prostatectomy is not especially painful,
all that was required for adequate anesthesia was intravenous
Thiopental, sometimes supplemented with Meperidine. Most
modern anesthesiologists would fall over backwards with asto-
nishment upon reading this. But at the time this advice was given,
the usual anesthetic intravenous induction doses of Thiopental
were very high—high enough to induce coma in nearly all people,
with the resulting unresponsiveness to pain, which is why few
patients ever reacted to the pain of the operation. Such doses of
Thiopental were also high enough to induce severe myocardial
depression, vasodilatation, and even lethal shock in some patients.
Such salutary near-lethal, and actual lethal experiences, eventually
taught anesthesiologists to use lower Thiopental doses, upon
which they discovered that suprapubic prostatectomy really was
painful. This is an example of empirical determination of drug
use.
Understanding of pharmacokinetics and pharmacodynamics
offers a better way. Known and unfamiliar drugs can be used
more efficiently and safely, and their clinical effects are readily
understood. Moreover, understanding of the pharmacokinetic and
pharmacodynamic properties of current anesthetic drugs makes it
possible to devise new ways of using these drugs. Knowledge of
the pharmacokinetic and pharmacodynamic properties of new
drugs makes it possible to calculate whether they offer more
advantages than existing drugs, as well as their initial applications
and dosage regimes—all of which considerably reduces the
amount of trial and error needed to learn to use such new drugs, or
whether it is worthwhile using them at all.
This book is written for all those wishing to learn about just
these basic principles of pharmacokinetics and pharmacokinetics
as applied to anesthetic drugs. It is intended as a light, easily read,
and hopefully entertaining guide teaching these things with a
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maximum of practical common sense and a minimum of mathe-
matical knowledge. It does not pretend to offer the nirvana of total
knowledge and control. Such knowledge and such control are
dreams. But what the interested reader will find is a path, a way of
thinking and doing—a Real World Guide to Pharmacokinetics &
Other Things. These “Other Things” are intended to give readers
some insights into the ways basic physiology, pharmacokinetics,
and pharmacodynamics can be applied to the questions and
wondrous phenomena confronting them each day during their
clinical duties. In other words, this is a book written for anesthesi-
ologists, consultant or specialist anesthesiologists, residents,
senior registrars, registrars, senior house officers, and anesthetic
nurses. For the sake of simplicity I will call the average reader a
resident, the American term for a doctor undergoing postgraduate
specialization.
Some people may say that the pharmacokinetic and pharma-
codynamic concepts in this book could all be summarized on four
pages. I fully agree, but years of experience have taught me that
very few residents ever really learn these concepts in this way. My
personal experience is that concepts are only truly learned, un-
derstood, and anchored in the minds of residents when accompa-
nied by memorable practical examples illustrating those concepts.
This is what I have attempted to do for each concept.
Purists may object to the use of the two-compartment phar-
macokinetic model throughout this book. They will almost cer-
tainly say that, “The kinetics of many anesthetic drugs are more
accurately described by a three-compartment model.” They are
quite correct—but only to a certain degree. A two-compartment
pharmacokinetic model makes it possible to perform simple, but
clinically relevant calculations in situations of intermittent intra-
venous bolus drug administration and short intravenous infu-
sions—methods of drug use in more than 95% of all general
anesthetics administered throughout the world. Furthermore, this
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