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TOXICOLOGY
AND THERAPY OF INTOXICATION (5.0 hr)
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Subcommittee:
Introduction
A medical pharmacology course
should be primarily concerned with three aspects of toxicology: adverse
effects of therapeutic agents, acute intoxications, and chronic
poisoning/environmental toxicology. The adverse effects of drugs should be
taught along with the pharmacology of individual drugs or groups of drugs.
The discussion of acute
intoxications should constitute a short, but important, part of the
pharmacology course and should deal with the techniques and procedures used
in dealing with the effects of exposure to acutely toxic materials.
Lectures dealing with chronic intoxications should emphasize environmental
toxicology and risk assessment.
Major recommendations
1.
Principles of Toxicology:
Many
of the mechanisms by which chemicals induce toxic effects are governed by the
same principles (e.g. pharmacodynamics, pharmacokinetics) that govern
pharmacological effects. The principles section of the pharmacology course
could cover both of these topics. The principles of toxicology section can
be presented with some additional time to cover bioactivation, cellular
defense mechanisms, and threshold concepts. Moreover, these principles
should be reinforced and reiterated later in the toxicology section of the
corse. (1 hr)
2.
Toxicology of Individual Drugs and Drug Groups:
The
toxicological effects of drugs should be included in the discussion of the
pharmacology of the specific drugs and drug groups. A discussion of the
toxicology of heroin and other opiates, cocaine, and cardiac glycosides,
for example, provides an opportunity to relate principles of toxicology to
the therapy of intoxication.
3.
Priority Toxic Chemicals:
Rather
than extensive discussions of many individual toxicants, priority should be
given to select chemicals to include acetaminophen, tricyclic
antidepressants, carbon
monoxide, cyanide, lead, iron (if not discussed elsewhere), methanol (if
not discussed along with ethanol and other alcohols in the CNS section of
the course), and organophosphate
and carbamate pesticides (if not discussed in the ANS section of the course).
This list may be expanded in some schools to satisfy perceived local or
regional needs. For example, agricultural chemicals may be given more
emphasis in rural areas and air pollutants may be emphasized in urban
areas. Finally, the therapeutic use of specific antidotes could be covered
along with the relevant priority chemicals or could be discussed in
connection with the management of intoxication. (2 hr)
4.
Management of Acute Intoxications:
The
therapeutic approach to the management of acute intoxication with either
drug or non-drug chemicals should be taught. This lecture could effectively
present a “decision-tree” approach. If the identity of the poison is known,
then the approach would be different than in the case where the identity of
the poison is not known. A discussion of the hepatotoxicity of
acetaminophen affords an opportunity to relate bioactivation mechanisms,
the protective role of glutathione, and therapy with N-acetylcysteine in a case-based
setting.
5.
Environmental Toxicology/Risk Assessment:
Because
chronic, low-dose exposures to chemicals occur more frequently than acute,
high-dose exposures, medical students should be provided with information
about risk assessment and the hazards
associated with chronic exposure to chemicals. Moreover, chronic use of
therapeutic agents at moderately high doses, compared to low dose exposure
to chemicals in the food, air and water, is now commonplace.
Lectures
in this area should deal with the neurotoxic, carcinogenic, mutagenic, and
teratogenic potential of chemicals including:
a.
Carcinogenic (e.g.,
the concept of precarcinogen, proximate and ultimate carcinogen.
b.
Metabolic
transformations of chemical carcinogens.
c.
Mechanisms of
carcinogenesis (initiation and
promotion processes, relationship with DNA binding, concept of DNA repair).
d.
Mutagenicity and
relationships with carcinogenicity, Ames test.
e.
Smoking and lung
cancer (if not covered adequately in pathology) e.g., major carcinogens in
cigarette smoke.
f.
Chemical prevention
of carcinogenicity (e.g. antioxidants).
g.
Neurotoxic
potential as a common basis for establishing exposure limits.
h.
These lectures
provide an excellent opportunity to reinforce fundamental concepts
(dose-response, variability of responses in a population, etc.) and to
train students to use these concepts in evaluating risk. The reliance on
fundamental concepts is important in an area where reliable data for the
human population is usually lacking.
6.
Sources of Information:
Because
intoxication associated with diverse types of chemicals may be encountered
in clinical practice, medical students should be aware of the information
sources available to them. A presentation by the Director of the local or
regional poison information center may be effective. Students should also
be made aware of available CD-ROM or Internet databases on toxicants. (2 hr
for 4, 5 and 6)
7.
Lecture Time:
In
the idealized curriculum, about five lectures should be devoted to
toxicology. These lectures may be held in conjunction with discussions in
clinical conferences.
Specific knowledge objectives to be considered:
1.
Describe four basic
components in the management of acute poisoning (evaluation of the poisoned
individual, supporting care, termination of exposure, and specific drug
therapy) and how to decide on their sequence of initiation.
2.
Describe a Poison
Control Center and list services a physician should expect from an ideal
center. Provide information concerning current Internet sources of
toxicology databases.
3.
Discuss the general
principles of risk assessment associated with long-term,
low dose
exposures. How can fundamental concepts (i.e. dose-response) be
used in
assessing risk?
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