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Chapter 23
Toxicology Principles in the
Management of Acute Poisonings
Toxicology Principles in the
Management of Acute Poisonings
• The basic principles of toxicology come into
play in the rational management of individuals
that have become ill from chemicals through
either intentional or unintentional exposures.
Toxicology Principles in the
Management of Acute Poisonings
• Among the important toxicological principles that are
applied in evaluating the poisoned individual are:
– Exposure and aspects related to reducing
absorption
– Dose–response considerations
– Target tissue and systemic effects
– Chemical interactions
– Chemical antagonism as a management approach
– Acute versus chronic effects
Did You Know?
• In 2011, the top 5 substance classes most
frequently involved in all human exposures
were
– analgesics (11.7%),
– cosmetics/personal care products (8.0%),
– household cleaning substances (7.0%),
– sedatives/hypnotics/antipsychotics (6.1%), and
– foreign bodies/toys/miscellaneous (4.1%).
Management of Acute Poisoning
• In the management of an individual who may
have been acutely poisoned, the medical staff
must:
– Make a rapid assessment of the patient with
respect to the level of consciousness, ventilation,
blood pressure, and other physiological
assessments as deemed necessary
– Consider the need for a clinical chemistry
assessment for determining blood levels of certain
drugs or illicit substances
Management of Acute Poisoning,
cont.
– Consider whether it is possible or necessary to
limit further absorption of the chemical or
attempt to increase its elimination
– Consider whether an antidote is available,
appropriate, or necessary
– Consider contacting their regional poison
information center for additional advice
Management of Acute Poisoning:
Clinical Assessment for Known Chemicals
• Clinical assessment is made to determine the
need for specific treatments when the
chemical has been identified. Examples
include:
– Salicylates: to assess the severity of poisoning and
the need for alkaline diuresis or hemodialysis
– Acetaminophen: to assess the severity of
poisoning and the need for administration of Nacetylcysteine
Management of Acute Poisoning:
Clinical Assessment for Known Chemicals
– Iron: to assess the severity of poisoning and the
need for administration of deferoxamine
– Theophylline: to assess the severity of poisoning
and the need for charcoal hemoperfusion
– Lithium: to assess the severity and the need for
hemodialysis
– Barbiturates: to assess the need for charcoal
hemoperfusion
Management of Acute Poisoning:
Clinical Assessment for Known Chemicals
– Methanol: to assess the severity of poisoning and
the need for administration of ethanol or
hemodialysis
– Ethylene glycol: to assess the severity of poisoning
and the need for administration of ethanol or
hemodialysis
– Ethanol: to facilitate the monitoring of treatment
of ethylene glycol and methanol poisonings
Reducing Toxicant Absorption
• Absorption is a requirement for systemic
toxicity.
– For respiratory exposures, the only ways to reduce
absorption is by eliminating the chemical from the
breathing zone or shortening the exposure time.
– The absorption of chemicals that have been
spilled onto the skin can often be reduced, the
extent of which depends on the nature of the
chemical (e.g., lipid vs. water solubility), its
concentration, and the duration of contact time.
Reducing Toxicant Absorption
• Example: The washing of skin with soap and
water as quickly as possible after a spill of a
residential use organophosphate pesticide
formulation further reduces skin absorption.
• This is especially important for undiluted
liquids from the product container and for
solid preparations as well.
Reducing Toxicant Absorption,
cont.
• Shortened exposure time coupled with
dilution reduces the amount absorbed.
• This is commonly referred to as
“decontamination.”
Reducing Toxicant Absorption- Oral
Consumption
• For oral consumption, reduction of absorption
may be accomplished (depending on the
chemical) through gastric lavage and activated
charcoal.
– For chemicals already absorbed into the blood and
in severe cases of intoxication, charcoal
hemoperfusion may be a clinical option.
– Gastric lavage is used when a patient has ingested
life-threatening amounts of a toxic agent up to 1–
2 hours previously.
Reducing Toxicant Absorption- Oral
Consumption cont.
– It is not used for corrosive substances because of
increased risk of esophageal and gastric
perforations or petroleum compounds because of
risk of chemical pneumonitis.
– Activated charcoal is often used to limit further
absorption because it adsorbs a wide variety of
drugs and toxic agents, if given within and hour or
two of ingestion.
Reducing Toxicant Absorption- Oral
Consumption cont.
– It has been shown to be effective for many
pharmaceuticals (e.g., aspirin, paracetamol,
digoxin, phenobarbitone, and theophylline) as
well as many nonpharmaceutical chemicals.
Reducing Toxicity by the Use of an
Antidote
• An antidote can simply be defined as a clinical
treatment using a chemical(s) to counteract the
effects of another.
• An antidote for any chemical can only be developed
upon a thorough understanding of the toxicokinetics
and toxicodynamics of the offending agent.
• Because a potential antidote may have additional
risks associated with its use, the toxicological
properties must be determined as well.
Reducing Toxicity by the Use of an
Antidote
• The ultimate therapeutic goal is to reduce toxicity by
interacting with the toxicant in ways that:
– Directly inhibit its effect through modification of
its chemical properties
– Inhibit its effect by altering its physical properties
– Reduce effects at its sites of action
– Facilitate its elimination
– Provide for replacement of endogenous protective
(e.g., glutathione) or required (e.g., oxygen)
chemicals
Table 23-1 Examples of Common
Poisonings and Their Antidotes
Table 23-1 Examples of Common
Poisonings and Their Antidotes
Route of Exposure Influences
Toxicity: An Example Using Cocaine
• When cocaine is injected, the entire dose is delivered
systemically in seconds and a peak plasma level is
obtained so rapidly that the individual experiences a
“rush” or “flash” that produces increased feelings of
alertness, euphoria, well-being, energy, confidence,
and sexuality.
– The user becomes more restless and irritable and
visual, tactile, and auditory hallucinations may
occur.
Route of Exposure Influences
Toxicity: An Example Using Cocaine
• Cocaine hydrochloride (the water-soluble
form of cocaine) is snorted or injected
intravenously, whereas crack cocaine is
smoked.
• The route of exposure can profoundly
influence the level of toxicity for the same
dose.
Cocaine Example, cont.
• Topical application onto the nasal mucosa results in a
much slower absorption due to local vasoconstriction
and a lower peak plasma level.
• Smoking crack cocaine delivers the substance directly
to the pulmonary circulation, where it is delivered to
the heart and into the brain.
– Not all the cocaine that is smoked is available for
delivery, so the delivered dose is less than that for
intravenous use.
Route of Exposure Influences
Toxicity: An Example Using Cocaine
• Cocaine, like amphetamines, is
sympathomimetic:
– it produces behavioral effects
– it increases heart rate
– it increases blood pressure
– it increases muscle tension
– it increases core body temperature
• These effects are associated with its toxicity.
Cocaine Example, cont.
• The resulting tachycardia and hypertension
may result in:
– myocardial infarction
– cerebrovascular hemorrhage
– coronary vasospasms
– cardiac arrhythmias
• Many individuals have the signs and
symptoms of a myocardial infarction.
Cocaine Example, cont.
• The most potentially serious toxicity results from
intravenous use, then respiratory and then nasal
exposures.
• Overdose of cocaine is usually rapidly fatal, with
victims dying within minutes from arrhythmias,
seizures, and respiratory depression.
• In 2004 approximately 40,000 cases of illicit stimulant
and other street drug use resulted in 214 fatalities.
• The management of individuals with severe cocaine
intoxication includes measures to antagonize the
sympathetic effects of this substance
Intentional and Unintentional
Exposures in the American Population
• In 2004 approximately 84% of reported
poisonings (2 million cases) resulted from
unintentional exposures to chemicals, with
approximately 200 deaths as outcomes.
• This category of exposures includes
therapeutic error, misuse, animal bites and
stings, food poisonings, occupational and
environmental exposures, adverse reactions
and unspecified
Intentional and Unintentional
Exposures in the American Population
• Intentional exposures resulted in less than
20% of reported poisonings, however over
900 deaths occurred.
• Intentional exposure to nonclinically
important chemicals for the purpose of
obtaining a “high” continues to be a problem
of enormous public health concern.
Intentional and Unintentional
Exposures in the American Population
• Marijuana is the most commonly used illicit
drug and is used by approximately 15 million
Americans.
• Approximately 2 million persons currently use
cocaine, and there are 200,000 current heroin
users.
Intentional and Unintentional
Exposures in the American Population
• Among youngsters aged 12–17 years, inhalant
use is higher than the use of cocaine.
• Current illicit drug use is highest among young
adults 18 to 25 years old, with over 20% using
drugs.
Intentional and Unintentional Exposures in
the American Population, cont.
• The costs of illicit substance use, from the
suppliers to the users, through law
enforcement and the court system and the
associated medical costs for treatment of
acute poisonings and rehabilitation programs
are staggering.
• Intentional exposures may very well represent
the number one preventable public health
problem in the country.
Inhalant Use
• Volatile organics contained in such products as
lacquer thinners, gasoline, typing correction
fluid, lighter fluids, and glues that may be
collected in a common paper bag so that the
vapors can be concentrated and inhaled.
Inhalant Use
• Aerosols with fluorocarbons and other
propellants that can be release along with
other chemicals such as alcohols, ketones, and
n-hexane (found in such common products as
cans of spray paint) when inhaled directly
have the potential to produce significant
neurological, cardiovascular, and liver toxicity.
Inhalent use, cont.
• Anesthetic agents such as chloroform, methyl
trichloroethylene, and ether that may be
present in common products (e.g., special
cleaners, grease dissolvers).
• Nitrites such as isobutyl, butyl, and amyl
nitrite that are found in many commonly
available household products and have similar
effects to nitrites that are used clinically as
vasodilators.
Toxicities Associated with
“Street Drugs”
• The most common toxicities associated with
street drugs result from stimulants,
depressants, hallucinogens, and narcotics.
Common Stimulants
• Methamphetamine (“speed,” “crystal,” “ICE”)
• Methylenedioxymetamphetamine (ecstasy,
MDMA, XTC)
• Methylenedioxyamphetamine (MDA)
• Methylphenidate (Ritalin®, used to treat
attention deficit and hyperactivity disorders,
especially in children)
• Phenmetrazine (used to treat obesity)
• Cocaine (in all its forms)
Depressants
• Depressants (sedative hypnotics) include:
– barbiturates such as pentobarbital (yellow
jackets)
– phenobarbital (purple hearts)
– amobarbital (blue angels)
– secobarbital (red devils)
Depressents, cont.
• The benzodiazepines include:
– flurazepam (sleeping pills)
– flunitrazepam (“date rape drug”)
– diazepam (Valium®)
– alprazolam (Xanax®)
– chlordiazepoxide (Librium®)
– clonazepam (anticonvulsant)
– methaqualone (Quaalude or “downers”)
Flunitrazepam (Rohypnol®)
• An example of a clinical drug (a benzodiazepine) that
has become a popular street drug, especially among
teenagers and young adults.
• Clinically, it is used in the short-term management of
insomnia and as a sedative hypnotic and
preanesthetic medication.
• It is 10 times more potent than Valium®.
• Its effects begin within 30 minutes, peak within 1–2
hours, and, depending on the dose, may persist for 8
hours or longer.
Flunitrazepam (Rohypnol®), cont.
• It produces a marked decrease of blood pressure,
urinary retention, visual disturbances,
gastrointestinal disturbances, memory impairment,
dizziness, confusion, and excitability or aggressive
behavior in some users.
• Intoxications can result in death from respiratory
failure and cardiovascular collapse, especially in
combination with alcohol.
• On the street, the drug is referred to as rophy, circles,
Mexican Valium, roofies, etc. Being under its
influence is referred to as being “roached out.”
Gamma-hydroxybutyrate (GHB)
• The drug gamma-hydroxybutyrate (GHB) is an
increasingly abused and potentially lethal drug.
• GHB is a CNS depressant most often abused for
the purpose of feeling euphoric and uninhibited.
• In the United States GHB can be prescribed in a
very low dose as an experimental treatment for
narcolepsy.
Gamma-hydroxybutyrate (GHB),
cont.
• Those who abuse GHB (also known as “G” or “liquid
ecstasy”) may require emergency medical attention
when they overdose or experience withdrawal
symptoms.
• GHB and other “club drugs” are often abused by
young people at all-night parties and “raves.”
• In some European countries GHB is prescribed as a
treatment for alcoholism, although the medical
evidence to support its use is wanting.
Gamma-hydroxybutyrate (GHB),
cont.
• GHB, usually in combination with alcohol, has
been linked to more than 60 deaths, mostly
among young adults.
• The number of reported GHB-related deaths
may be an underestimate because GHB does
not remain in the body very long and is usually
not tested for at autopsy.
Depressants
• The general progression of effects from
depressants are:
relief from anxiety  sedation  hypnosis 
confusion, ataxia and delirium  surgical
anesthesia depression of vasomotor and
respiratory centers in the brainstem  coma 
death
Depressants, cont.
• Treatment of overdose of benzodiazepines includes
flumazenil, a benzodiazepine receptor blocker.
• A number of hallucinogens are illegally used, and
although these drugs differ in mechanisms of action,
chemical similarities, CNS target receptors, and
seriousness of toxic effects, they are often
considered together because of the common form of
intoxication that includes hallucinations, delusions,
and illusions that occasionally result in death due to
dangerous behaviors.
Common Hallucinogens
• Cannabis: marijuana, delta-9-THC
• Anticholinergics: atropine, scopolamine, mandrake
root, jimson weed
• Indolamines: lysergic acid diethylamide (LSD),
morning glory seed (LSM), psilocybin, psilocin,
ibogaine, dimethyltryptamine (DMT)
• Phenylethylamines: mescaline, bufotenin,
dimethoxymethyl-amphetamine (DOM)
• Dissociative anesthetics: ketamine, phencyclidine
(PCP)
Websites
• Agency for Toxic Substances and Disease Registry
(ATSDR): http://www.atsdr.cdc.gov/
• American Association of Poison Control Centers:
http://www.aapcc.org
• American College of Medical Toxicology:
http://www.acmt.net/main/
• Centers for Disease Control and Prevention (CDC):
http://www.cdc.gov/
Websites
• Food and Drug Administration (FDA):
http://www.fda.gov/
• MEDLINEplus: http://medlineplus.gov/
• Medwatch Homepage:
http://www.fda.gov/medwatch/report/hcp.htm
• National Institute on Drug Abuse:
http://www.nida.nih.gov/DrugPages/DrugsofAbuse.h
tml
Websites
• National Institute of Environmental Health Sciences
(NIEHS): http://www.niehs.nih.gov/
• National Institutes of Health (NIH):
http://www.nih.gov/
• Poisonous Plants Informational Database:
http://www.ansci.cornell.edu/plants/
• U.S. Department of Health and Human Services:
http://www.dhhs.gov/news/press/2003pres/200309
05.html
• World Health Organization: http://www.who.int