Clinical toxicology
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Jun 05, 2012
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CLINICAL CLINICAL
TOXICOLOGYTOXICOLOGY
Joseph Hanig, Ph.D.Joseph Hanig, Ph.D.
TOXICOLOGYTOXICOLOGY
Joseph Hanig, Ph.D.Joseph Hanig, Ph.D.
LEARNING OBJECTIVESLEARNING OBJECTIVES
To understand the general principles of To understand the general principles of
clinical toxicologyclinical toxicology
To know general factors that influence To know general factors that influence
toxicitytoxicity
To understand the initial approach to the To understand the initial approach to the
poisoned patient in terms of setting poisoned patient in terms of setting
immediate prioritiesimmediate priorities
To appreciate the necessity to conduct, as To appreciate the necessity to conduct, as
the first order of business, those the first order of business, those
procedures that evaluate and preserve procedures that evaluate and preserve
vital signsvital signs
To understand the general principles of To understand the general principles of
clinical toxicologyclinical toxicology
To know general factors that influence To know general factors that influence
toxicitytoxicity
To understand the initial approach to the To understand the initial approach to the
poisoned patient in terms of setting poisoned patient in terms of setting
immediate prioritiesimmediate priorities
To appreciate the necessity to conduct, as To appreciate the necessity to conduct, as
the first order of business, those the first order of business, those
procedures that evaluate and preserve procedures that evaluate and preserve
vital signsvital signs
LEARNING OBJECTIVESLEARNING OBJECTIVES
To know what aspects of the physical To know what aspects of the physical
examination and what diagnostic tests are examination and what diagnostic tests are
to be conducted to evaluate the general to be conducted to evaluate the general
type as well as the specifics of the type as well as the specifics of the
poisoningpoisoning
To understand the goals of treatment e.g. To understand the goals of treatment e.g.
to treat the patient, not the poison, to treat the patient, not the poison,
promptlypromptly
To know and understand strategies for To know and understand strategies for
treatmenttreatment
To know and understand specific To know and understand specific
approaches for reducing the body burden approaches for reducing the body burden
of various poisonsof various poisons
To know what aspects of the physical To know what aspects of the physical
examination and what diagnostic tests are examination and what diagnostic tests are
to be conducted to evaluate the general to be conducted to evaluate the general
type as well as the specifics of the type as well as the specifics of the
poisoningpoisoning
To understand the goals of treatment e.g. To understand the goals of treatment e.g.
to treat the patient, not the poison, to treat the patient, not the poison,
promptlypromptly
To know and understand strategies for To know and understand strategies for
treatmenttreatment
To know and understand specific To know and understand specific
approaches for reducing the body burden approaches for reducing the body burden
of various poisonsof various poisons
LEARNING OBJECTIVESLEARNING OBJECTIVES
To know how to counteract toxicological To know how to counteract toxicological
effects at receptor sites, if possibleeffects at receptor sites, if possible
To know and understand important To know and understand important
treatment contraindications that prevent treatment contraindications that prevent
serious injury or death of patientsserious injury or death of patients
To be aware of newer approaches and To be aware of newer approaches and
treatment modalitiestreatment modalities
To know where to rapidly obtain facts, To know where to rapidly obtain facts,
specific antidotes, or other information on specific antidotes, or other information on
poison control needed immediately to poison control needed immediately to
treat the patienttreat the patient
To know how to counteract toxicological To know how to counteract toxicological
effects at receptor sites, if possibleeffects at receptor sites, if possible
To know and understand important To know and understand important
treatment contraindications that prevent treatment contraindications that prevent
serious injury or death of patientsserious injury or death of patients
To be aware of newer approaches and To be aware of newer approaches and
treatment modalitiestreatment modalities
To know where to rapidly obtain facts, To know where to rapidly obtain facts,
specific antidotes, or other information on specific antidotes, or other information on
poison control needed immediately to poison control needed immediately to
treat the patienttreat the patient
Common Causes of Death in the Common Causes of Death in the
Acutely Poisoned PatientAcutely Poisoned Patient
Comatose patient:Comatose patient:
–Loss of protective reflexesLoss of protective reflexes
–Airway obstruction by flaccid tongueAirway obstruction by flaccid tongue
–Aspiration of gastric contents into Aspiration of gastric contents into
tracheobronchial treetracheobronchial tree
–Loss of respiratory driveLoss of respiratory drive
–Respiratory arrestRespiratory arrest
Hypotension – due to depression of Hypotension – due to depression of
cardiac contractilitycardiac contractility
Acutely Poisoned PatientAcutely Poisoned Patient
Comatose patient:Comatose patient:
–Loss of protective reflexesLoss of protective reflexes
–Airway obstruction by flaccid tongueAirway obstruction by flaccid tongue
–Aspiration of gastric contents into Aspiration of gastric contents into
tracheobronchial treetracheobronchial tree
–Loss of respiratory driveLoss of respiratory drive
–Respiratory arrestRespiratory arrest
Hypotension – due to depression of Hypotension – due to depression of
cardiac contractilitycardiac contractility
Common Causes of Death in the Common Causes of Death in the
Acutely Poisoned PatientAcutely Poisoned Patient
Shock – due to hemorrhage or internal Shock – due to hemorrhage or internal
bleedingbleeding
Hypovolemia – due to vomiting, diarrhea Hypovolemia – due to vomiting, diarrhea
or vascular collapseor vascular collapse
Hypothermia – worsened by i.v. fluids Hypothermia – worsened by i.v. fluids
administered rapidly at room temperatureadministered rapidly at room temperature
Cellular hypoxia – in spite of adequate Cellular hypoxia – in spite of adequate
ventilation and Oventilation and O
22 admin. – due to CN, CO admin. – due to CN, CO
or Hor H
22S poisoningS poisoning
Acutely Poisoned PatientAcutely Poisoned Patient
Shock – due to hemorrhage or internal Shock – due to hemorrhage or internal
bleedingbleeding
Hypovolemia – due to vomiting, diarrhea Hypovolemia – due to vomiting, diarrhea
or vascular collapseor vascular collapse
Hypothermia – worsened by i.v. fluids Hypothermia – worsened by i.v. fluids
administered rapidly at room temperatureadministered rapidly at room temperature
Cellular hypoxia – in spite of adequate Cellular hypoxia – in spite of adequate
ventilation and Oventilation and O
22 admin. – due to CN, CO admin. – due to CN, CO
or Hor H
22S poisoningS poisoning
Common Causes of Death in the Common Causes of Death in the
Acutely Poisoned PatientAcutely Poisoned Patient
Seizures – may result in pulmonary Seizures – may result in pulmonary
aspiration;asphyxiaaspiration;asphyxia
Muscular hyperactivity resulting in Muscular hyperactivity resulting in
hyperthermia, muscle breakdown, hyperthermia, muscle breakdown,
myoglobinemia, renal failure, lactic myoglobinemia, renal failure, lactic
acidosis and hyperkalemiaacidosis and hyperkalemia
Behavioral effects –traumatic injury Behavioral effects –traumatic injury
ferom fights, accidents, fall from hih ferom fights, accidents, fall from hih
places. Suicides, etcplaces. Suicides, etc
Acutely Poisoned PatientAcutely Poisoned Patient
Seizures – may result in pulmonary Seizures – may result in pulmonary
aspiration;asphyxiaaspiration;asphyxia
Muscular hyperactivity resulting in Muscular hyperactivity resulting in
hyperthermia, muscle breakdown, hyperthermia, muscle breakdown,
myoglobinemia, renal failure, lactic myoglobinemia, renal failure, lactic
acidosis and hyperkalemiaacidosis and hyperkalemia
Behavioral effects –traumatic injury Behavioral effects –traumatic injury
ferom fights, accidents, fall from hih ferom fights, accidents, fall from hih
places. Suicides, etcplaces. Suicides, etc
Common Causes of Death in the Common Causes of Death in the
Acutely Poisoned PatientAcutely Poisoned Patient
Massive damage to a specific organ Massive damage to a specific organ
system:system:
–Liver (acetaminophen; amanita Liver (acetaminophen; amanita
phylloides [poison mushroom]phylloides [poison mushroom]
–Lungs (paraquat)Lungs (paraquat)
–Brain (demoic acid)Brain (demoic acid)
–Kidney (ethylene glycol)Kidney (ethylene glycol)
–Heart (cobalt salts)Heart (cobalt salts)
Note: death may occur in 48 – 72 hrsNote: death may occur in 48 – 72 hrs
Acutely Poisoned PatientAcutely Poisoned Patient
Massive damage to a specific organ Massive damage to a specific organ
system:system:
–Liver (acetaminophen; amanita Liver (acetaminophen; amanita
phylloides [poison mushroom]phylloides [poison mushroom]
–Lungs (paraquat)Lungs (paraquat)
–Brain (demoic acid)Brain (demoic acid)
–Kidney (ethylene glycol)Kidney (ethylene glycol)
–Heart (cobalt salts)Heart (cobalt salts)
Note: death may occur in 48 – 72 hrsNote: death may occur in 48 – 72 hrs
APPROACH TO THE POISONED APPROACH TO THE POISONED
PATIENTPATIENT
History; Oral statements concerning History; Oral statements concerning
details details
Call Poison Control Center re: drug Call Poison Control Center re: drug
labeling labeling
Initial physical examinationInitial physical examination
Assessment of vital signs Assessment of vital signs
Eye examination Eye examination
CNS and mental status examinationCNS and mental status examination
PATIENTPATIENT
History; Oral statements concerning History; Oral statements concerning
details details
Call Poison Control Center re: drug Call Poison Control Center re: drug
labeling labeling
Initial physical examinationInitial physical examination
Assessment of vital signs Assessment of vital signs
Eye examination Eye examination
CNS and mental status examinationCNS and mental status examination
APPROACH TO THE POISONED APPROACH TO THE POISONED
PATIENTPATIENT
Examination of the skin Examination of the skin
Mouth examination Mouth examination
Lab (clinical chemistry and x-ray Lab (clinical chemistry and x-ray
procedures procedures
Renal function tests Renal function tests
EKG EKG
Other screening testsOther screening tests
PATIENTPATIENT
Examination of the skin Examination of the skin
Mouth examination Mouth examination
Lab (clinical chemistry and x-ray Lab (clinical chemistry and x-ray
procedures procedures
Renal function tests Renal function tests
EKG EKG
Other screening testsOther screening tests
TREATMENT OF ACUTE TREATMENT OF ACUTE
POISONINGPOISONING
Treat the patient, not the poison", Treat the patient, not the poison",
promptlypromptly
Supportive therapy essential Supportive therapy essential
Maintain respiration and circulation – Maintain respiration and circulation –
primaryprimary
Judge progress of intoxication by: Judge progress of intoxication by:
Measuring and charting vital signs and Measuring and charting vital signs and
reflexes reflexes
POISONINGPOISONING
Treat the patient, not the poison", Treat the patient, not the poison",
promptlypromptly
Supportive therapy essential Supportive therapy essential
Maintain respiration and circulation – Maintain respiration and circulation –
primaryprimary
Judge progress of intoxication by: Judge progress of intoxication by:
Measuring and charting vital signs and Measuring and charting vital signs and
reflexes reflexes
TREATMENT OF ACUTE TREATMENT OF ACUTE
POISONINGPOISONING
- 1st Goal - keep concentration of - 1st Goal - keep concentration of
poison as low as possible by poison as low as possible by
preventing absorption and increasing preventing absorption and increasing
elimination elimination
- 2nd Goal - counteract toxicological - 2nd Goal - counteract toxicological
effects at effector site, if possible effects at effector site, if possible
POISONINGPOISONING
- 1st Goal - keep concentration of - 1st Goal - keep concentration of
poison as low as possible by poison as low as possible by
preventing absorption and increasing preventing absorption and increasing
elimination elimination
- 2nd Goal - counteract toxicological - 2nd Goal - counteract toxicological
effects at effector site, if possible effects at effector site, if possible
PREVENTION OF ABSORPTION PREVENTION OF ABSORPTION
OF POISONOF POISON
Decontamination from skin surfaceDecontamination from skin surface
Emesis: indicated after oral ingestion of Emesis: indicated after oral ingestion of
most chemicals; most chemicals;
–must consider time since chemical ingestedmust consider time since chemical ingested
Contraindications:Contraindications:
ingestion of corrosives such as strong acid or alkali; ingestion of corrosives such as strong acid or alkali;
if patient is comatose or delirious; if patient is comatose or delirious;
if patient has ingested a CNS stimulant or is if patient has ingested a CNS stimulant or is
convulsing; convulsing;
if patient has ingested a petroleum distillate if patient has ingested a petroleum distillate
OF POISONOF POISON
Decontamination from skin surfaceDecontamination from skin surface
Emesis: indicated after oral ingestion of Emesis: indicated after oral ingestion of
most chemicals; most chemicals;
–must consider time since chemical ingestedmust consider time since chemical ingested
Contraindications:Contraindications:
ingestion of corrosives such as strong acid or alkali; ingestion of corrosives such as strong acid or alkali;
if patient is comatose or delirious; if patient is comatose or delirious;
if patient has ingested a CNS stimulant or is if patient has ingested a CNS stimulant or is
convulsing; convulsing;
if patient has ingested a petroleum distillate if patient has ingested a petroleum distillate
PREVENTION OF ABSORPTION PREVENTION OF ABSORPTION
OF POISONOF POISON
Induce emesis in the following Induce emesis in the following
ways: ways:
mechanically by stroking posterior mechanically by stroking posterior
pharynx; pharynx;
use of syrup of ipecac, 1 oz followed by use of syrup of ipecac, 1 oz followed by
one glass of water; one glass of water;
use of apomorphine parenterallyuse of apomorphine parenterally
OF POISONOF POISON
Induce emesis in the following Induce emesis in the following
ways: ways:
mechanically by stroking posterior mechanically by stroking posterior
pharynx; pharynx;
use of syrup of ipecac, 1 oz followed by use of syrup of ipecac, 1 oz followed by
one glass of water; one glass of water;
use of apomorphine parenterallyuse of apomorphine parenterally
PREVENTION OF ABSORPTION PREVENTION OF ABSORPTION
OF POISONOF POISON
Gastric lavage: insert tube into Gastric lavage: insert tube into
stomach and wash stomach with stomach and wash stomach with
water or ½ normal saline to remove water or ½ normal saline to remove
unabsorbed poisonunabsorbed poison
Contraindications are the same as Contraindications are the same as
for emesis except that the for emesis except that the
procedure should not be attempted procedure should not be attempted
with young childrenwith young children
OF POISONOF POISON
Gastric lavage: insert tube into Gastric lavage: insert tube into
stomach and wash stomach with stomach and wash stomach with
water or ½ normal saline to remove water or ½ normal saline to remove
unabsorbed poisonunabsorbed poison
Contraindications are the same as Contraindications are the same as
for emesis except that the for emesis except that the
procedure should not be attempted procedure should not be attempted
with young childrenwith young children
PREVENTION OF ABSORPTION PREVENTION OF ABSORPTION
OF POISONOF POISON
Chemical Adsorption Chemical Adsorption
activated charcoal will adsorb many activated charcoal will adsorb many
poisons thus preventing their absorptionpoisons thus preventing their absorption
do not use simultaneously with ipecac if do not use simultaneously with ipecac if
poison is excreted into bile in active formpoison is excreted into bile in active form
adsorbent in intestines may interrupt adsorbent in intestines may interrupt
enterohepatic circulationenterohepatic circulation
OF POISONOF POISON
Chemical Adsorption Chemical Adsorption
activated charcoal will adsorb many activated charcoal will adsorb many
poisons thus preventing their absorptionpoisons thus preventing their absorption
do not use simultaneously with ipecac if do not use simultaneously with ipecac if
poison is excreted into bile in active formpoison is excreted into bile in active form
adsorbent in intestines may interrupt adsorbent in intestines may interrupt
enterohepatic circulationenterohepatic circulation
PREVENTION OF ABSORPTION PREVENTION OF ABSORPTION
OF POISONOF POISON
Purgation Purgation
Used for ingestion of enteric coated tablets Used for ingestion of enteric coated tablets
when time after ingestion is longer than when time after ingestion is longer than
one hour one hour
Use saline cathartics such as sodium or Use saline cathartics such as sodium or
magnesium sulfatemagnesium sulfate
Chemical InactivationChemical Inactivation
Not generally done, particularly for acids or Not generally done, particularly for acids or
bases or inhalation exposure bases or inhalation exposure
For ocular and dermal exposure as well as For ocular and dermal exposure as well as
burns on skin; treat with copious water burns on skin; treat with copious water
OF POISONOF POISON
Purgation Purgation
Used for ingestion of enteric coated tablets Used for ingestion of enteric coated tablets
when time after ingestion is longer than when time after ingestion is longer than
one hour one hour
Use saline cathartics such as sodium or Use saline cathartics such as sodium or
magnesium sulfatemagnesium sulfate
Chemical InactivationChemical Inactivation
Not generally done, particularly for acids or Not generally done, particularly for acids or
bases or inhalation exposure bases or inhalation exposure
For ocular and dermal exposure as well as For ocular and dermal exposure as well as
burns on skin; treat with copious water burns on skin; treat with copious water
PREVENTION OF ABSORPTION PREVENTION OF ABSORPTION
OF POISONOF POISON
Alteration of biotransformation Alteration of biotransformation
Interfere with metabolic conversion of Interfere with metabolic conversion of
compound to toxic metabolite compound to toxic metabolite
Metabolism of some compounds Metabolism of some compounds
produces highly reactive electrophilic produces highly reactive electrophilic
intermediates; if nucleophiles present, intermediates; if nucleophiles present,
toxicity is minimal; if nucleophiles toxicity is minimal; if nucleophiles
depleted, toxicity results depleted, toxicity results
Increasing urinary excretion by Increasing urinary excretion by
acidification or alkalinization acidification or alkalinization
OF POISONOF POISON
Alteration of biotransformation Alteration of biotransformation
Interfere with metabolic conversion of Interfere with metabolic conversion of
compound to toxic metabolite compound to toxic metabolite
Metabolism of some compounds Metabolism of some compounds
produces highly reactive electrophilic produces highly reactive electrophilic
intermediates; if nucleophiles present, intermediates; if nucleophiles present,
toxicity is minimal; if nucleophiles toxicity is minimal; if nucleophiles
depleted, toxicity results depleted, toxicity results
Increasing urinary excretion by Increasing urinary excretion by
acidification or alkalinization acidification or alkalinization
PREVENTION OF ABSORPTION PREVENTION OF ABSORPTION
OF POISONOF POISON
Decreasing passive resorption from Decreasing passive resorption from
nephron lumennephron lumen
DiuresisDiuresis
CatharticsCathartics
Peritoneal dialysis Peritoneal dialysis
Hemodialysis Hemodialysis
Hemoperfusion Hemoperfusion
OF POISONOF POISON
Decreasing passive resorption from Decreasing passive resorption from
nephron lumennephron lumen
DiuresisDiuresis
CatharticsCathartics
Peritoneal dialysis Peritoneal dialysis
Hemodialysis Hemodialysis
Hemoperfusion Hemoperfusion
Antagonism of the absorbed poison Antagonism of the absorbed poison
If poisoning is due to agonist acting If poisoning is due to agonist acting
at receptors for which specific at receptors for which specific
antagonist is available; antagonist antagonist is available; antagonist
may be available may be available
Drugs that stimulate antagonistic Drugs that stimulate antagonistic
physiologic mechanisms may of little physiologic mechanisms may of little
clinical value; titration difficult clinical value; titration difficult
Use of antibodiesUse of antibodies
If poisoning is due to agonist acting If poisoning is due to agonist acting
at receptors for which specific at receptors for which specific
antagonist is available; antagonist antagonist is available; antagonist
may be available may be available
Drugs that stimulate antagonistic Drugs that stimulate antagonistic
physiologic mechanisms may of little physiologic mechanisms may of little
clinical value; titration difficult clinical value; titration difficult
Use of antibodiesUse of antibodies
Strategies for Treatment of the Strategies for Treatment of the
Poisoned PatientPoisoned Patient
Evaluate and stabilize vital signsEvaluate and stabilize vital signs
Give supportive therapy, if neededGive supportive therapy, if needed
Determine the type and specifics of Determine the type and specifics of
the poisonthe poison
Time of exposureTime of exposure
Determine the presumed current Determine the presumed current
location of the poisonlocation of the poison
Determine Volume of Distribution Determine Volume of Distribution
and Kand Ki i for the poisonfor the poison
Poisoned PatientPoisoned Patient
Evaluate and stabilize vital signsEvaluate and stabilize vital signs
Give supportive therapy, if neededGive supportive therapy, if needed
Determine the type and specifics of Determine the type and specifics of
the poisonthe poison
Time of exposureTime of exposure
Determine the presumed current Determine the presumed current
location of the poisonlocation of the poison
Determine Volume of Distribution Determine Volume of Distribution
and Kand Ki i for the poisonfor the poison
Strategies for Treatment of the Strategies for Treatment of the
Poisoned PatientPoisoned Patient
Use the drug dissociation constant, Use the drug dissociation constant,
presumed pH based on location and the presumed pH based on location and the
Henderson-Hasselbach equation to Henderson-Hasselbach equation to
determine the ratio of ionized to non-determine the ratio of ionized to non-
ionized poisonionized poison
Determine the immediate (real time) risk Determine the immediate (real time) risk
or hazard for absorptionor hazard for absorption
Intiate body burden reduction procedures Intiate body burden reduction procedures
or specific antidotes based on the above or specific antidotes based on the above
informationinformation
Poisoned PatientPoisoned Patient
Use the drug dissociation constant, Use the drug dissociation constant,
presumed pH based on location and the presumed pH based on location and the
Henderson-Hasselbach equation to Henderson-Hasselbach equation to
determine the ratio of ionized to non-determine the ratio of ionized to non-
ionized poisonionized poison
Determine the immediate (real time) risk Determine the immediate (real time) risk
or hazard for absorptionor hazard for absorption
Intiate body burden reduction procedures Intiate body burden reduction procedures
or specific antidotes based on the above or specific antidotes based on the above
informationinformation
Strategies for Treatment of the Strategies for Treatment of the
Poisoned PatientPoisoned Patient
If volume of distribution is very large; do If volume of distribution is very large; do
not waste time on any type of dialysisnot waste time on any type of dialysis
X-ray for location of enteric coated pills X-ray for location of enteric coated pills
and use cathartics if in the stomachand use cathartics if in the stomach
Use hypocholesteremics for poisons Use hypocholesteremics for poisons
trapped in enterohepatic biliary systemtrapped in enterohepatic biliary system
Poisoned PatientPoisoned Patient
If volume of distribution is very large; do If volume of distribution is very large; do
not waste time on any type of dialysisnot waste time on any type of dialysis
X-ray for location of enteric coated pills X-ray for location of enteric coated pills
and use cathartics if in the stomachand use cathartics if in the stomach
Use hypocholesteremics for poisons Use hypocholesteremics for poisons
trapped in enterohepatic biliary systemtrapped in enterohepatic biliary system
SPECIFIC ANTIDOTESSPECIFIC ANTIDOTES
PoisonPoison
AcetaminophenAcetaminophen
Acetylcholinesterases, Acetylcholinesterases,
OP’s, physostigmineOP’s, physostigmine
Iron saltsIron salts
Methanol, Ethylene Methanol, Ethylene
glycolglycol
Mercury, leadMercury, lead
Narcotic drugsNarcotic drugs
Anti/muscarinics-Anti/muscarinics-
cholinergicscholinergics
OP anticholinergicsOP anticholinergics
AntidoteAntidote
AcetylcysteineAcetylcysteine
AtropineAtropine
DeferoximeDeferoxime
EthanolEthanol
Metal ChelatorsMetal Chelators
NaloxoneNaloxone
PhysostigminePhysostigmine
Praladoxime (2-PAM)Praladoxime (2-PAM)
PoisonPoison
AcetaminophenAcetaminophen
Acetylcholinesterases, Acetylcholinesterases,
OP’s, physostigmineOP’s, physostigmine
Iron saltsIron salts
Methanol, Ethylene Methanol, Ethylene
glycolglycol
Mercury, leadMercury, lead
Narcotic drugsNarcotic drugs
Anti/muscarinics-Anti/muscarinics-
cholinergicscholinergics
OP anticholinergicsOP anticholinergics
AntidoteAntidote
AcetylcysteineAcetylcysteine
AtropineAtropine
DeferoximeDeferoxime
EthanolEthanol
Metal ChelatorsMetal Chelators
NaloxoneNaloxone
PhysostigminePhysostigmine
Praladoxime (2-PAM)Praladoxime (2-PAM)
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