Table Of ContentActivated
Charcoal
in
Medical
Applications
DAVID O. COONEY
University of Wyoming
Laramie, Wyoming
informa
healthcare
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To Eric and Jon
FOREWORD
Because there are few specific antagonists for ingested toxic substances, medical treat
ment consists primarily of supportive measures and attempts to decrease systemic ab
sorption by a variety of gastrointestinal decontamination measures. Over the past several
years it has become increasingly clear that, at least for drug ingestions treated in emer
gency departments, stomach-emptying techniques such as induced emesis and gastric
aspiration/lavage result in little benefit in terms of improved clinical outcome. These
measures also result in delayed administration of activated charcoal, whose clinical
efficacy has been well demonstrated. Current clinical practice for most cases of drug
ingestion treated in the hospital is to forego gastric emptying in favor of early adminis
tration of activated charcoal. Repeated doses of activated charcoal constitute an active
therapy for removing a number of systemically absorbed substances.
In this extensive and comprehensive review, Professor Cooney explores the history
of activated charcoal in medical practice, describes its chemistry and pharmacology,
details its past and current clinical applications for poisoning treatment, and elucidates
the need for studies of its potential clinical application in gastroenterology and other
medical fields. Health care professionals who treat poisoned patients, as well as phar
macology and toxicology researchers, will find a wealth of information about activated
charcoal in this volume, which lays a firm foundation for the rational use of activated
charcoal in medical therapy.
Barry H. Rumack, M.D.
Director Emeritus
Rocky Mountain Poison and Drug Center
Clinical Professor of Pediatrics
University of Colorado Health Sciences Center
Denver, Colorado
Alan H. Hall, M.D., F.A.C.E.P.
Senior Consultant
Rocky Mountain Poison and Drug Center
Clinical Assistant Professor of Preventive Medicine
and Biometrics
University of Colorado Health Sciences Center
Denver, Colorado
V
PREFACE
Activated charcoal, long known to the ancients as a substance of therapeutic value in a
variety of maladies, has been relatively recently "rediscovered" to be of great general
use as an oral antidote for drug overdoses and poisonings. Over the past several decades,
orally administered activated charcoal has been proven to be highly effective in reducing
the systemic absorption of analgesics and antipyretics, sedatives and hypnotics, alkaloids,
tricyclic antidepressants, cardiac glycosides, and a wide variety of other kinds of drugs
and chemicals. The efficacy of activated charcoal in binding drugs and poisons, especially
nonpolar or lipophilic ones, has been demonstrated emphatically by a host of in vitro
studies and in vivo tests with humans, dogs, rabbits, pigs, cattle, sheep, rats, and mice.
It is rather surprising that prior to about the mid-1960s activated charcoal was
essentially neglected, considering that its therapeutic effects had already been extensively
reported in the medical literature. This neglect perhaps resulted from the fact that many
medical personnel were never really aware of how and why activated charcoal really
works (i.e., the physical chemistry of adsorption by charcoal in various biological media).
Such a lack of knowledge would explain the origin of the absurd notion, prevalent in
the 1950s, that burnt toast be used in place of activated charcoal. "Universal antidote"
is another example of an antidote that, on a chemical basis, can be shown to be decidedly
inferior to plain activated charcoal as a general antidote. The promotion and acceptance
of such ill-founded notions undoubtedly did considerable harm to the reputation of
activated charcoal and deterred people from Rising it.
Fortunately, the virtues of activated charcoal have finally been recognized by large
numbers of people in the medical community. Nevertheless, very few private homes
today have activated charcoal on hand as a ready antidote. One reason may be that
charcoal in water makes a rather gritty, tasteless mixture that is difficult to swallow.
With the relatively recent development of ways in which to add lubricants and flavors
to charcoal slurries without interfering with their efficacy, palatable formulations are
now possible. Even "flavors" such as chocolate syrup and ice cream, which do decrease
the adsorption capacity of charcoal to some extent, are useful, since one can overcome
this drawback by simply giving a larger charcoal dose. However, as of this writing, no
palatable formulations are being commercially marketed to the general public. (Formu
lations containing the sweetener/cathartic sorbitol are marketed commercially, but only
vii
viii Preface
to hospitals.) Again we must speculate: perhaps the sale of such formulations to the
general public is not a financially attractive venture, considering that most people might
never need to use such an antidote. (Thus, repeat sales would be small.) And so there
continues to be a wide gap between the appreciation of charcoal by medical researchers
and the acceptance and utilization of charcoal by the general public.
This book represents an attempt to gather in one volume most of what has been
reported to date on the use of activated charcoal for medical purposes. A successor to
Activated Charcoal: Antidotal and Other Medical Uses (Cooney, D. O., New York:
Marcel Dekker, 1980), it incorporates nearly all significant studies on the use of activated
charcoal for antidotal purposes that have appeared between about 1979 and early 1994.
In addition to reviewing most of the research on the in vitro and in vivo adsorption of
a wide variety of drugs and poisons over the past several decades, I review what was
known about charcoal by our ancestors, beginning at about 1500 B.C.
The coverage has been expanded to include a wide variety of medical uses of
activated charcoal other than as an antidote for drug overdoses and poisonings, e.g., the
use of activated charcoal for treating pruritus, neonatal jaundice, porphyria, hyperlipid-
emia, and wounds. A wide range of studies involving activated charcoal as an adsorbent
for viruses, bacteria, vitamins, hormones, endogenous and exogenous toxins, etc., are
also reviewed.
Some rather intriguing uses of activated charcoal in other biological contexts, e.g.,
to promote plant growth, in assays for hormones, and even in the removal of "congeners"
from whiskeys, have been included to demonstrate the breadth of activated charcoal
applications.
New chapters have been added that will provide a basis for understanding the large
numbers of clinical studies discussed. These include chapters on: general methods for
treating overdoses and poisonings, basic gastrointestinal tract physiology, the design of
clinical studies and the statistical analysis of data, and basic pharmacokinetic modeling.
New chapters also have been added on various hazards of using antidotal charcoal,
on currently available charcoal formulations, and on interactions between ipecac/cathar
tics and charcoal. There is an expanded discussion of multiple-dose charcoal therapy.
Detailed comparisons are given of the effects of induced emesis alone, gastric lavage
alone, and other types of treatments versus activated charcoal alone.
In the writing of this book, several policies have been established that should be
mentioned and explained:
1. Activated charcoal is referred to as an "antidote" throughout this volume. To many
readers, the word antidote connotes a specific chemical agent that has the ability to
inhibit or block the mechanisms of toxicity of drugs, poisons, or toxins (e.g., diphen
hydramine is an antidote for bee-sting toxin). Activated charcoal is thus not an
antidote in this sense but a simple nonspecific adsorbent. However, dictionaries
generally define antidote as any remedy or agent used to counteract the effects of
a poison. In this sense, activated charcoal is an antidote. Additionally, reference to
activated charcoal as an antidote by the medical community is so common and so
established that there is more than sufficient justification for referring to it as such.
2. Reference is made thousands of times to charcoal. Including the adjective activated
in every instance seems unnecessary, and furthermore would increase the text by
roughly 2%! Thus, except in a brief part of Chapter 2 involving a discussion of
Preface ix
early charcoals (those made prior to about 1900), the term charcoal, if used without
activated, should be taken to mean "activated charcoal."
3. Many commercially marketed brands of charcoals (e.g., Norit), charcoal formulations
(e.g., InstaChar), and drugs (e.g., Theo-Dur) are mentioned. It seems unnecessary
to superscript these names with the trademark symbol (™) or the registered trademark
symbol (®) in every instance, or even just at the first reference to each product (this
latter policy would lead to sections of text where some products are "tagged" and
others are not, which would appear awkward). Thus, these symbols are omitted. The
reader will have no difficulty discerning product names, as they always carry initial
capital letters and are quite obviously brand names.
4. Researchers often use many different units for concentrations, such as mg/L, Hg/mL,
ng/L, mg%, mg/100 mL, mg/dL, and g/L. Some of these are equivalent (e.g., mg/L
and fig/mL, mg/100 mL and mg/dL). To provide for a degree of consistency in this
volume, most concentrations are expressed on a "per liter" basis. Thus, the reader
will typically find mg/L, |J,g/L, or ng/L for concentrations. Exceptions are cases in
which amounts per mL or per 100 mL (or "per dL") seem more appropriate.
5. It is assumed that the reader is reasonably familiar with medical terminology com
mon to the field involved (e.g., anatomical terms, names for various medical con
ditions, and parameters such as t , AUC, LD , etc.). However, because this volume
m 50
may be read by persons having significantly different backgrounds (e.g., clinical
MDs, emergency medical technicians, pharmacists), the text often explains medical
terms and concepts in language approaching that of a pure layman, particularly the
first time these terms or concepts are encountered. Readers who are familiar with
more formal scientific terminology are implored to be tolerant of this, and not take
offense. Such writing is not intended to insult the reader. One very important specific
point regarding terminology that must continually be kept in mind is the great
difference in the two similar nouns adsorption and absorption. They are used very
frequently in this work.
6. There is no consistent pattern among researchers when reference is made to the
adsorption of a substance by, to, on, or onto charcoal. In this volume, all four
prepositions are used, with no consistent pattern, and should be construed to mean
the same thing.
7. The medical community's practice of using the adjectives maximal and minimal
rather than maximum and minimum has generally been followed. With respect to
the practice of referring to certain drugs in the sodium salt form as phenobarbital
sodium rather than sodium phenobarbital, usage in the medical community is not
consistent (chemists generally use the latter form). Thus, both forms are used in this
volume. The choice of form often follows that used in the journal paper being
discussed, and at other times is simply arbitrary.
8. While this volume is concerned primarily with activated charcoal, it should be
recognized that other sorbents are sometimes used for similar purposes (sorbent is
a general term for substances that bind molecules by physical adsorption, chemical
adsorption, ion exchange, absorption, etc.). Specifically, anion- and cation-exchange
resins and clays have a substantial history of use in treating intoxications. Many of
the in vitro and in vivo studies discussed in this book have employed one or more
of these alternative sorbents in addition to activated charcoal. In such cases, the
results obtained with these other sorbents are generally presented and compared to
X Preface
those obtained with charcoal, since there are situations in which these other sorbents
are more effective than charcoal, and readers may wish to learn about them. Also,
one chapter (Chapter 22) is devoted to studies in which these alternative adsorbents
alone have been used.
Thanks are due to all those researchers who have cited the first edition of this work.
It was those citations that provided the inspiration for this new volume. As with any
work, the coverage and interpretations offered here reflect the personal decisions of the
writer. The field being addressed has now grown to the point where it is clearly im
possible to cover everything, or to cover many excellent research studies in the depth
they deserve.
David O. Cooney
CONTENTS
Foreword Hi
Preface v
1 Introduction 1
I. DATA ON POISONING INCIDENTS IN THE USA 1
II. INITIAL APPROACHES TO THE TREATMENT OF POISONING 3
III. THE GROWING USE OF ACTIVATED CHARCOAL 5
IV. GENERAL REVIEW PAPERS 7
V. REFERENCES 7
2 Historical Background of Activated Charcoal 9
I. TERMINOLOGY 9
II. EARLY HISTORY 10
III. EVOLUTION OF METHODS FOR TESTING MEDICINAL CHARCOALS 12
IV. REFERENCES 16
3 Fundamentals of Activated Charcoal and the Adsorption Process 18
I. THE MANUFACTURE OF ACTIVATED CHARCOAL 18
A. Carbonization 19
B. Activation with Oxidizing Gases 19
II. THE PROPERTIES OF ACTIVATED CHARCOAL 20
A. Densities 22
B. Pore Volume and Pore-Size Distribution 22
C. Surface Area 24
D. Nature of the Charcoal Surface 25
III. THE NATURE OF THE ADSORPTION PROCESS 28
A. Effect of Temperature 28
B. Nature of the Solvent 28
C. Surface Area of the Charcoal 28
D. Pore Structure of the Charcoal 29
E. Nature of the Solute 29
F. pH of the Solution 31
G. Presence of Inorganic Salts 35
xi
xii
H. Competing Solutes 36
IV. DETERMINING ADSORPTION ISOTHERMS 37
A. The Langmuir Isotherm Equation 38
B. The Freundlich Isotherm Equation 41
C. Least-Squares Fitting of Data to Determine Isotherm Constants 43
D. Theoretical Aspects of Isotherm Equations 45
V. SUMMARY 46
VI. REFERENCES 47
4 Properties of Antidotal Charcoal 50
I. REQUIREMENTS OF THE U. S. PHARMACOPEIA 50
II. "SUPERACTIVE" CHARCOAL 53
III. CURRENTLY AVAILABLE USP CHARCOALS IN THE USA 55
IV. CURRENTLY AVAILABLE CHARCOAL PRODUCTS IN THE USA 56
V. OTHER CURRENTLY AVAILABLE CHARCOAL PRODUCTS 61
VI. THE "CONTAINER RESIDUE" ISSUE 64
VII. COMPARATIVE STUDIES OF ANTIDOTAL CHARCOALS 66
VIII. SUMMARY 70
IX. REFERENCES 71
5 The Nature of Drug Absorption, Distribution, and Elimination 73
I. THE EFFECT OF DRUG DOSAGE FORM 73
II. ROUTES OF DRUG ADMINISTRATION 75
III. THE ROLE OF pH IN DRUG ABSORPTION 75
IV. MECHANICAL ASPECTS OF GASTROINTESTINAL PHYSIOLOGY 77
V. ABSORPTION IN THE GASTROINTESTINAL TRACT 79
VI. DRUG FATE AFTER ABSORPTION 82
VII. GASTROINTESTINAL DIALYSIS AND INTERRUPTION OF THE
ENTEROHEPATIC CYCLE 85
VIII. SUMMARY 88
IX. REFERENCES 89
6 Basic Details of Pharmacokinetic Modeling 91
I. INTRODUCTION 91
II. THE PHARMACOKINETICS OF INTRAVENOUSLY ADMINISTERED
DRUGS 96
A. The One Compartment Open Model 98
B. The Two Compartment Open Model 103
III. MODELS WITH FIRST-ORDER DRUG ABSORPTION 105
A. One Compartment Open Model 105
B. Two Compartment Open Model 106
IV. EXAMPLES OF PHARMACOKINETIC CALCULATIONS 106
A. Area Under the Curve 107
B. Elimination Half-life 107
C. Estimating U for Drug Absorption 107
A
D. Mean Residence Time 107
V. SUMMARY 108
VI. REFERENCES 108
7 Methods for Treating Poisoning and Drug Overdose 110
I. GENERAL CHARACTERISTICS OF POISONED PATIENTS 110
