PHARMACOLOGY: Management of Poisoned Patient; Occupational and Environmental toxicology

ERWIN P. CARABEO M.D., FPCP 6. Chronic serious illness

General Info 7. History of drug or alcohol abuse
All chemicals have potential to be poisons if given a large 8. Psychosis
enough dose. 9. Sense of helplessness, hopelessness
Poisoning occurs when exposure to a substance adversely
affects function of any organ system. Physical Exam

The clinical effects encountered in poisoned patients are
dependent on the dose, the length of exposure time, and the
pre-existing health of the patient.
Epidemiology
More than 2 million toxic exposures reported
over half were children < 6 yo
adolescents: 90% are girls
Poisoning third leading cause of death from 1985-1995
Incidence of toxin related deaths increase 300%
Undress pt completely for thorough exam
Check clothing for objects or substances
Assess general appearance of pt
Agitation, confusion, or obtundation
Exam skin for bruising, cyanosis, flushing
Exam eyes for pupils size, nystagmus, reactivity,
dysconjugate gaze, increased lacramaiton
Oropharynx for increase salivation or excessive dryness
CV: rhythm, rate, regularity

Modes of Exposure Lungs: bronchorrhea or wheezing

Ingestion 75 % Abd: bowel sounds, tenderness or rigidity

Dermal 7.9% Ext: fasiculations, tremor

Inhalation 6.3% Neuro: CN, reflexes, muscle tone coordination, cognition,

ability to ambulate
Ocular 5.3%
Envenomation 3.6%
Toxidromes
Resuscitation
Physiologically based abnormalities that are known to occur
First priorities are ABCs
with specific classes of substances and typically are helpful in
Vital sign including pulse ox and hypoglycemia must be diagnosis
corrected 1. Opioid: sedation, miosis, decreased bowel
Only in very rare incidences does administration of antidote sounds, decreased respirations
precede stabilizing ABCs and vital signs 2. Anticholinergic: altered mental status, sedation,
hallucinations, mydriasis, dry skin, dry mucous
Unresponsive pts treated empirically with coma cocktail membranes, decreased bowel sounds and urinary
Oxygen, naloxone, D50W, and 100mg thiamine retention

50 ml of D50W for adults and 1g/kg glucose for

3. Sedative-hypnotic: sedation, normal pupils,
decreased respirations
children (4ml/kg D25W of 10ml/kg of D10W)
1. Toxidromes
Thiamine not usually given to children
4. Sympathomimetic: agitation, mydriasis,
Glucose and thiamine should be given in timely manner tachycardia, hypertension, hyperthermia,
however thiamine does not have to precede glucose to diaphoresis
prevent Wernickes 5. Cholinergic: altered mental status, seizures,
miosis, lacrimation, diaphoresis, bronchospasm,
History
bronchorrhea, vomiting, diarrhea, bradycardia
may be unreliable
6. Serotonin Syndrome: altered mental status,
obtain as much info as possible about exposure (what, when, tachycardia, hypertension, hyperreflexia, clonus,
how much) hyperthermia

intentional or not? first time or recurrent? Toxicology Screening Tests

info from pts PCP, witness or EMT helpful In the acute care setting toxicology screen is very limited and
does not contribute significantly
check for empty bottles or containers, smells or
unusual containers Tox screens is time consuming, expensive and often
unreliable
Psychiatric Evaluation
Laboratory Tests
1. Suicide Risk Factors
2. Older solitary male
ABG

3. Suicide plan Electrolytes (Na, K, Cl, HCO3)

4. Previous attempts Renal Function Tests

5. Recent lost
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 ECG
Serum Osmolality
Gross Decontamination
Generally; achieved by; undressing patients and washing
them thoroughly with copious amounts of water
Should occur outside of ED
All towels and clothing should be put into hazardous waste
bags
Pt should initially be in isolated area
Eyes
Ocular exposures should be treated immediately by copious
irrigation
Usually 2 L NS
Use of tetracaine may be needed
Alkalies require specific considerations
Lengthy continuous irrigation until pH < 8.0
Need ophthalmologic consult
GI Decontamination
Three general methods involve removing toxin from stomach
via the mouth, binding it inside gut lumen, or mechanically
flushing it through GI tract
Each method has benefits and risks
Gastric Emptying
Emesis: achieved by using syrup of ipecac
Dosing: 15 ml for 1-12 yo and 30 ml for adults; may
repeat once if no emesis in 12 hr
90% vomit within 20 minutes of first dose and 97% vomit
with second dose
Usually 3-5 episodes of emesis and resolve in two hours; if
protracted emesis occurs consider toxin as etiology
Ipecac
induces emesis through direct irritant action on the stomach
and central action at the chemoreceptor trigger zone.
Contraindications: ingestions with potential for change in
mental status, active or prior vomiting, caustic ingestion,
toxin with more pulmonary than GI toxicity ingestion of
toxins with potential for seizures
Complications: aspiration, Boerhaave syndrome, Mallory-
Weiss tear, intractable vomiting
No evidence that it improves outcome
Current recommendations discouraged routine use of Ipecac
Gastric Lavage
Protect the airway
Large bore tube: 36-40 French (adults) and 22-24 French
(children)
LLD position
Lavage with room temperature water until it runs clear
Drug removal range from 35-56%
Indicated if w/in 1 hr of ingestion
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Contraindications: large pills, nontoxic ingestion, acid,
alkali or hydrocarbon ingestion,
Complications: laryngospasm, aspiration, esophageal or
gastric perforation, hypoxia, dysrhythmias
No evidence that it improves outcome not recommended
for routine use in the poisoned patient.
Toxin Adsorption in Gut
Activated Charcoal
Multiple-Dose Activated Charcoal
Cathartics
Whole-Bowel Irrigation
Activated Charcoal
Adsorbs toxin in gut lumen
metals, ions and alcohols do not bind to charcoal
Benefits include capability to decontaminate w/out requiring
invasive procedures
Safety proven in adults and children
Dose 1g/kg
Contraindications: suspected esophageal or gastric
perforation, caustic ingestions or emergent endoscopy
possibly needed
Complications rare; aspiration or impaction possible
Administration of activated charcoal remains a useful
decontamination technique for patients presentingwith
early, potentially severe poisoning
Multi-Dose Charcoal
One dose usually sufficient
Indications for MDAC: phenobarbital, carbamazepine,
theophylline, dapsone, quinine
Contraindications: bowel perforation, bowel obstruction,
GI hemorrhage, hemodynamic instability
Repeat dose is 0.25-0.5 g/kg
Cathartics
Osmotic cathartic usually given with activated charcoal
70% sorbitol (1 g/kg) or 10% mag citrate
Shown to decrease transit time of activated charcoal
No definitive clinical human data suggest that a cathartic
limits toxins bioavailability or changes patients outcome
Whole-Bowel Irrigation
Administration of 1-2 liters/h of (polythylene glycol) go-
lytely for first 5-6 hours following ingestion
Common indications:
Heavy metals (lead and iron)
Sustained or delayed release formulations
contraindications: ileus, bowel obstruction or perforation,
and in patients with hemodynamic instability
may be of benefit particularly in early acute poisonings,
Bowel Irrigation
End point is clear rectal effluent
 Contraindications: preceding diarrhea, expectant diarrhea, Iron: Deferoxamine
absent bowel sounds or obstruction
Isoniazid: Pyridoxine
Complications: bloating, cramping, rectal irritation
Lead: Succimer, Dimercaprol, Calcium ethylenediamine
Antiemetic frequently required tetra-acetic acid
Avoid phenergan (slows gut motility) Methanol: Fomepizole

Enhanced Elimination
Ethylene glycol: Fomepizole

Alkalinization Methemoglobinemia: Methylene blue

Acidification of urine Monomethylhydrazine Mushrooms: Pyridoxime

Forced diuresis Opioids: Naloxone

Hemodialysis/Hemoperfusion Organophosphates: Atropine Pralidoxime

Sulfonyl ureas: Glucose octreotide
Alkalinization
Beneficial in certain ingestions: 2-4-D (herbicide), Causes of Death in a Poisoned Patient
phenobarbital, chlorpropamide, salicylates, methanol CNS depression
Alkalinization achieved by IV dose of bicarb at 1-2 mEq/kg, Airway obstruction
followed by intermittent boluses or continuous bicarb drip
for urine pH 7.5-8.0 Cardiovascular toxicity
Profound hypokalemia may result, must aggressively replace Hypotension

Acidification of Urine Cellular hypoxia

Can somewhat enhance elimination of amphetamines, Seizures

phencyclidine, and some other drugs.
Traumatic injury
Risks of rhabdo far out weigh benefits
The management of the critically poisoned patient centers on
Forced Diuresis careful supportive care.
Never been shown effective for any ingestion If a poisoning is recognized early and appropriate testing and
supportive care isinitiated rapidly, the majority of patient
Technique should not be used outcomes will be good.
Occupational & Environmental Toxicology
Hemodialysis/Hemoperfusion Occupational Toxicolgy
Dialysis reserved for specific toxins: salicylates, methanol, Chemicals found in the workplace
ethylene glycol, lithium, theophylline, amanita (mushrooms) Major emphasis of occupational toxicolgy:
Benefits: removal of toxins already absorbed by gut, ability to 1. identify agents of concern
remove parent compound and active metabolite,
2. identify the diseases they cause (acute & chronic)
Less effective when toxin has large volume of distribution (>1
3. define conditions under which they could be used safely
L/kg), has large molecular weight, or highly protein bound
Dialysis rarely contraindicated
4. prevent absorption of harmful amounts of these chemicals

No dialysis for small children, exchange transfusion should Workplace Regulations

be considered PELS

Hemoperfusion permissible exposure limits

Used for decontamination of patients systemic circulation have the power of law
Involves placing a filter filled with activated charcoal into OSHA
dialysis circuit
TLV
Alleviates constraints of protein binding and molecular size
threshold limit values
Toxins must be well absorbed by charcoal and have small
volume of distribution reference points in the evaluation of potential
workplace exposures
Antidotes
Environmental Toxicology
Acetaminophen: N-acetylcysteine
deals with the potentially deleterious impact of chemicals
Benzodiazapines: Flumazenil (pollutants) on living organisms
Beta blockers: Glucagon environment: air, soil and water
Cardiac glycosides: Digoxin immune Fab
ADI
Crotalid envenomation: Crotalidae polyvalent immune Fab acceptable daily intake
Cyanide: Hydroxocobalamin
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 daily intake of chemical from food that during an entire nitrogen oxides 14%
lifetime appears to be without an appreciable risk
particulate matter 4%
FAO/WHO

Ecotoxicology Sources of Air Pollutants

toxic effects of chemical and physical agents on populations transportation
and communities of living organisms
industry
includes the transfer pathways of agents and interactions
with the environment
generation of electricity

traditional toxicology: toxic effects on individual organism space heating

refuse disposal
Toxicologic Terms
Hazard ability of the chemical to cause injury in a given Carbon Monoxide
situation or setting; assessment is based inherent toxicity of colorless, odorless, tasteless and non-irritating gas
the substance and the amounts to which individuals are
liable to be exposed by product of incomplete combustion
Risk the expected frequency of the occurrence of an average concentration in atmosphere: 0.1 ppm
undesirable effect arising from exposure to chemical or
physical agent in heavy traffic: > 100 ppm

Routes of Exposure route of entry of chemicals into the Mechanism of Action

body
industrial setting: inhalational is the major route
of entry
atmospheric pollutants: inhalation and
transdermal routes
water and soil pollutants: inhalation, ingestion and
dermal contact
Duration of Exposure length of exposure to chemicals
acute exposure: single or multiple exposures
lasting from seconds to 1 or 2 days
chronic exposure: multiple exposures continuing
over a longer period of time
combines reversibly with O2 binding sites of hemoglobin
carboxyhemoglobin failure of oxygen transport and
transfer of oxygen to tissues
affinity for hemoglobin is 220X that of O2
brain and heart are the most affected
Principal Signs of CO Intoxication:
psychomotor impairment
headache
confusion and loss of visual acuity
tachycardia, tachypnea syncope and coma

Chemical and Physical Characteristics that Determine

deep coma, convulsions, shock and respiratory failure
Environmental Impact of Toxicants: Treatment

1. degradability of the substance for acute intoxication: removal from exposure source and
maintenance of respiration
2. its mobility through air, water and soil
oxygen administration:
3. whether or not bioaccumulation occurs
4. transport and biomagnification through food chains
room air: elimination half time of CO 320 min
!!! 100% oxygen: 80 minutes
The pollutants that have the widest environmental impact hyperbaric oxygen (2-3 atm): 20 minutes
are poorly degradable
Sulfur Dioxide
are relatively mobile in air, water and soil
SO2
exhibit bioaccumulation
colorless irritant gas
exhibit biomagnification
generated by the combustion of sulfur-containing fossil fuels
Bioaccumulation accumulation of chemical within the
tissues of an organism that occurs when the intake of a long- Mechanism of Action
lasting contaminant exceeds the organisms ability to
metabolize or excrete the substance
on contact with moist membranes sulfurous acid severe
irritant effects on eyes, mucus membranes and skin
Biomagnification exponential increase in the concentration
inhalation of SO2: bronchoconstriction
of a contaminant as it passes up the food chain

Air Pollutants Clinical Effect and Treatment

5 Major Air Pollutants irritation of the eyes, nose and throat
carbon monoxide (CO) 52% reflex bronchoconstriction
sulfur oxides 14% in asthmatics: acute asthmatic attack
hydrocarbons 14%

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 no specific treatment for SO2; treatment of the irritation of
respiratory tract and asthma
Nitrogen Oxides
nitrogen dioxide (NO2)
brownish irritant gas associated with fires
Mechanism of Action
insoluble deep lung irritant capable of producing pulmonary
edema
50 ppm: moderately irritating to the eyes and nose
50 ppm for 1 hour: pulmonary edema or chronic pulmonary
lesions
100 ppm: pulmonary edema and death
Clinical Effects
acute exposure: irritation of the eyes and nose, cough,
mucoid or frothy sputum, dyspnea, chest pain
clinical signs may subside in about 2 weeks
second stage: abruptly increasing severity, recurring
pulmonary edema and fibrotic destruction of terminal
bronchioles
Treatment
no specific treatment for acute intoxication
management of deep lung irritation and pulmonary edema:
adequate oxygenation and alveolar ventilation
drugs: bronchodilators, sedatives and antibiotics
Ozone
O3
bluish irritant gas normally occurring in the atmosphere
absorbent of UV light
workplace: ozone producing devices for air and water
purification, high voltage electrical equipment
also found in polluted urban air
Clinical Effects
effects resemble that of radiation
ppm for 10-30 min: irritation and dryness of the
throat
>0.1 ppm: changes in visual acuity, substernal pain and
dyspnea
>0.8 ppm: impairment of pulmonary function
Treatment
similar to treatment of Nitrogen Oxide exposure
Solvents
Halogenated Aliphatic Hydrocarbons
used as: industrial solvents, degreasing agents, cleaning
agents
carbon tetrachloride, chloroform, trichloroethylene,
tetrachloroethylene, methyl chloroform
CCl4 and trichloroethylene have been removed from the
workplace
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Halogenated Aliphatic Hydrocarbons
Mechanism of Action & Clinical Effects
CNS depression; chloroform most potent
chronic exposure: impaired memory and peripheral
neuropathy
hepatotoxicity; CCl4 most potent
nephrotoxicity
carcinogenicity
Treatment
no specific treatment for acute intoxication
management depends on the organ system involved
Aromatic Hydrocarbons
BENZENE
component of premium gasoline
acute toxic effect: CNS depression
250-500 ppm: vertigo, drowsiness, headache
>3000 ppm: euphoria, nausea, locomotor problems, coma
7500 ppm for 30 min: fatal
chronic exposure: bone marrow toxicity aplastic anemia,
leukemia, lymphoma, myeloma
TOLUENE (Methylbenzene)
CNS depressant, skin and eye irritant,
fetotoxic
at 800 ppm: severe fatigue and ataxia
at 10,000 ppm: rapid loss of consciousness
XYLENE (Dimethylbenzene)
substitute for benzene in degreasing operations
no myelotoxic properties of benzene
CNS depressant and skin irritant
Pesticides
Organochlorine Pesticides
DDT (chlorophenotane)
benzene hexachlorides
cyclodienes
toxaphenes
Organochlorine Pesticides
Human Toxicology
interfere with activation of sodium channels and
inhibition of Calcium ion transport enhanced
excitability of neurons CNS stimulation
DDT: tremors convulsions
no specific treatment of acute intoxication
increased cancer risk exposed to halogenated
hydrocarbon pesticides: brain cancer (DDE),
testicular cancer (DDE), non-Hodgkins lymphoma
Environmental Toxicology
 considered as persistent chemicals because of slow
degradation
bioaccumulation in aquatic ecosystems
induce significant abnormalities in the endocrine
balance of sensitive animal and bird species
Organophosphorus Pesticides
used to combat a wide variety of pets
based on compounds which were developed for use as war
gases (soman, sarin and tabun)
absorbed by the skin, respiratory and GI tracts
undergoes rapid biotransformation
Human Toxicology
mechanism of action: inhibition of
acetylcholinesterase accumulation of acetyl
choline; some may have direct cholinergic activity
altered cognitive and neurologic functions
inhibition of neuropathy target esterase
progressive demyelination of neurons paralysis
Environmental Toxicology
not considered as persistent pesticides
relatively unstable and breakdown in the
environment as a result of hydrolysis and
photolysis
small impact on the environment
Carbamate Pesticides
mechanism of action: inhibition of acetylcholinesterase
possess the toxic properties associated with
organophosphorus pesticides
clinical effects are of shorter duration than those of
organophosphorus pesticides
considered to be nonpersistent pesticides
Botanical Pesticides
pesticides derived from natural sources
nicotene, rotenone, pyrethrum
Nicotene
obtained from the dried leaves of Nicotiana tabacum and
Nicotiana rustica
rapidly absorbed from mucosal surfaces
reacts with the acetylcholine receptor of the postsynaptic
membrane depolarization of the membrane
treatment directed at maintenance of vital signs and
suppression of convulsions
Rotenone
obtained from Derris elliptica, D mallaccensis, Lonchorpus
utilis, L urucu
oral ingestion: GI irritation
conjunctivitis, dermatitis, pharyngitis and rhinitis can also
occur
treatment is symptomatic
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Pyrethrum
may be absorbed after ingestion or inhalation; absorption
from skin is not significant
not highly toxic to mammals
CNS effects: excitation, convulsions, tetanic paralysis
treatment directed at management of symptoms; ivermectin,
pentobarbital, mephenesin
Herbicides
Chlorophenoxy Herbicides
2,4 Dichlorophenoxyacetic acid (2,4-D),2,4,5-
trichlorophenoxyacetic acid (2,4,5-T)
used for the destruction of weeds
toxicity ratings:
4 human lethal dose 50 500 mg/kg
3 human lethal dose 500 5000 mg/kg
large doses: coma and generalized hypotonia
confirmed link with non Hodgkins lymphoma
Glyphosate
most widely used herbicide in the world
contact herbicide: absorbed through the leaves and roots
significant eye and skin irritant
have little persistence and lower toxicity than other
herbicides
no specific treatment for glyphosate toxicity is available
Bipyridil Herbicides
Paraquat most important agent in this class
mechanism of action: reduction to free radical species
toxicity rating of 4 (human lethal dose of 50-500 mg/kg)
after oral exposure: hematemesis and bloody stools
delayed toxicity: lung edema, alveolitis and progressive
fibrosis
hepatic, renal or myocardial involvement
interval between ingestion and death may be several weeks
treatment: gastric lavage, use of cathartics, use of adsorbents
after absorption, treatment is successful in less than 50% of
cases
Environmental Pollutants
Polychlorinated Biphenyls
PCBs, coplanar biphenyls
uses: heat transfer fluids, lubricating oils, plasticizers, wax
extenders and flame retardants
industrial use and manufacture was terminated in the US in
1977
persist in the environment: highly stable, highly lipohilic,
poorly metabolized, very resistant to degradation,
bioaccumulation in food chains
foods: major source of PCB residues in humans
occupational exposure to PCBs: dermatologic problems,
hepatic involvement and elevated plasma triglycerides
 increase in various cancers: melanoma, breast, pancreas and
thyroid
deficits in childhood intellectual function was seen in
children born to mothers who had eaten large quantities of
fish contaminated with PCBs

Asbestos
has been used widely for over 100 years
has been shown to cause progressive lung disease
characterized by fibrotic process
higher levels of exposure: asbestosis
cigarette smoking increases the incidence of asbestos caused
lung cancer
other cancers: mesothelioma, colon cancer, laryngeal cancer,
stomach cancer, lymphomas
Metals
occupational and environmental poisoning with metals is a
major health problem
classic metal poisons: arsenic, lead and mercury
new occupational exposure and poisoning: beryllium,
manganese, cadmium and uranium

Beryllium
light alkaline metal; non sparking quality
uses: dental appliances, nuclear weapons, computer
components
highly toxic by inhalation
inhalation of beryllium particles progressive pulmonary
fibrosis (chronic beryllium disease) and cancer
prognosis is poor

Cadmium
uses: batteries, pigments, solder, television, plating
operations, semiconductors, plastics
toxic by inhalation and ingestion
cadmium fume fever: acute respiratory disorder common in
welders; shaking chills, cough, fever and malaise
chronic exposure: pulmonary fibrosis, severe kidney
damage

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