TOXICOLOGY LECTURES

Introduction
2.1 million cases of human exposures reported in 2000
92% of the exposures occurred at home
14% occurred in a health care facility
2% occurred at work
Children > 3 years were involved in 40% of the cases
52.7% occurred in children > 6 years
Male predominance is found among poison exposures
younger than 13 years
Children > 6 comprised 2.2% of the fatalities
59% of fatalities occur in the 20-49 year age group
 Introduction, cont.
85.9% of poison exposure were unintentional
suicide intent was present in 7.5% of the cases
therapeutic errors comprised 7% of exposures
920 fatalities reported
94% of adolescent and 79% of adults were intentional
Automatic capital offense to poison someone
Most poisonings occur at home just before meal time
Most poisonings enter the body orally - 76.2%
More people die in the US from suicides than from
homicides
 Substances most frequently
involved in Human Exposures
Analgesics - 10%
Cleaning substances - 9.5%
Cosmetics and personal care products - 9.4%
Foreign bodies - 5.0%
Plants - 4.9%
Cough and cold preparations - 4.5%
Bites and envenomations - 4.2%
 Substances most frequently
involved in Pediatric poisonings
Cosmetics and personal care products - 13.3%
Cleaning substances - 10.5%
Analgesics - 7.2%
Foreign bodies - 6.8%
Plants - 6.6%
Topicals - 6.3%
Cough and cold preparations - 5.3%
 Substances most frequently
involved in Adult Exposures

Analgesics - 13.3%
Sedatives/hypnotics/antipsychotics - 9.8%
Cleaning substances - 9.5%
Antidepressants - 8%
Bites/envenomations - 7.9%
Alcohols - 5.4%
 Frequency of Plant exposure by
Plant type

Capsicum annuum - pepper plant

Spathiphyllum spp. - peace lilly
Philodendron
Ilex spp. - holy
Euphorbia spp. - poinsettia
Phytolacca sp. - poke week, ink berry
 Categories with largest number
of deaths
Analgesics
involved in 30% of fatalities
acetaminophen, aspirin and other salicylates = 72%
84% of the fatalities were intentional
Antidepressants
69% involved TCAs
Sedatives/hypnotics/antipsychotics
benzodiazepines account for 36%
Cardiovascular drugs
Alcohols
 Deaths associated with street
drug exposure

Highest proportion of exposures result in fatalities

Amphetamines and cocaine - account for 61% of
street drug deaths (39 in 2000)
Ecstasy - involved in 23 fatalities
all occurred in persons 17-24 years of age
Heroin - 29% of deaths
 Pediatric fatalities
20 of the 920 cases involved children > 6yrs
10 involved substances found around the home
3 were intentional
6 deaths in 6-12 year olds
4 were suicides
1 was a murder
66 deaths in 13-19 year olds
38% were suicides
47% due to substance abuse
 Other deaths

Carbon monoxide - 25 deaths

3 deaths from envenomations
2 rattlesnake and one scorpion
5 plant ingestion related deaths
3 due to Jimson Weed
 Definition of terms
Toxicology - the study of poisons
Toxicologist - one who studies poisons
Hazard - likelihood an event will occur based on how
the product is packaged, formulated, or its accessibility
Risk - the probability that an event will occur based on
patient vulnerability
Toxic substance - poisons
Poison - any chemical substance which can cause harm
Drug overdose - taking a harmful amount of a drug
 Definition of terms
Antidotes: from the Greek anti - against and didonai - to give
the remedy for counteracting a poison
3 types:
chemical - reacts chemically with the poison to form a
harmless compound, ie. chelators and heavy metals
mechanical - prevents absorption, ie. activated charcoal
physiologic - counteracts the effects of the poison by
producing opposite physiologic effects, ie. atropine and
organophosphate poisoning
Universal antidote - 2 parts activated charcoal, 1 part
magnesium oxide and 1 part tannic acid
 Historical perspective

Poisonings date to antiquity

Deuteronomy 14:9-10, Moses said do not
eat fish which do not have fins or scales
cause it is unclean
Job 6:4 mentions poisoned arrows
1500 BC the Ebers papyrus
King of Pontus first to develop antidotes in
the first century before Christ
 Historical perspective, cont.
Plato reported the death of Socrates by
hemlock (Conium maculatum)
13th century Peter of Abanos reviewed the
literature and divided poisons into those of
plant, animal and mineral origin
Paracelsus, 1493-1541 said that all
substances are poisons, there is none which
is not poisonous. Solely the dose determines
that which is poisonous or not.
 Historical perspective, cont.

Middle ages poisoning was considered a

hazard of living much like dying in an auto
crash is today
Orfila, 1787-1853, attending physician for
Louis 18th of France, wrote the first book
on General Toxicology and is considered
the father of modern toxicology
 Diversity of Toxicology

Occupational Toxicology - OSHA - The

Occupational Safety and Health Act of 1970
grew out of the need to protect workers in the work place
Environmental Toxicology - EPA - study of
chemicals that contaminate food, water, soil and the atm.
Forensic Toxicology - medicolegal aspects of
poisons
Clinical Toxicology - deals with the pathophysiologic
aspects clinical presentation of intoxication
Most Poisonings are Preventable
 Child proofing your home
Do not keep meds in purse or pockets
Always put meds away after use
Never take or administer meds in the dark
Store all poisons in locked containers
Store all meds out of childrens reach
Never refer to meds as candy
Never allow kids to take meds without
supervision
 Child proofing your home, cont.

Do not keep poisonous plants in the house

Never leave meds on tables, nightstands, etc.
Do not store poisons under sinks
Always rinse out med bottle before disposal
Keep meds and poisons in original containers
Use child proof caps on all meds
Never borrow or loan meds
 Child proofing your home, cont.

Never administer more than the prescribed

amount of a med
Never keep outdated meds
Always give or take the whole prescription
Never allow kids to play in garage unattended
Never allow kids to play around running cars
Use Mr. Yuk stickers
 Child proofing your home, cont.

Educate your children about poisons

Formulate a plan of action in case a
poisoning occurs
Stock and keep activated charcoal and syrup
of Ipecac in your home
Keep poison control number by phone:
1-800-POISON1
Symptoms of poisoning in a child

Children may not be able to tell you they

have ingested a poison
Err on the side of being conservative if in
doubt
Call poison control if you even suspect
anything
 Symptoms of poisoning in a child
blistering of the mouth or lips
bad odor from mouth
burning of the mouth
breathing problems
dizziness
confusion or unconsciousness
vomiting or diarrhea
convulsions
 Household Poison Safety

Kitchen
Bathroom
Garage
Common sense approach to medicines
How to handle pesticides
Know your plants
 Emergency Actions for non
specific poisons
Call poison control if you suspect poisoning
has occurred
If a patient is symptomatic call 911 or
transport immediately
Maintain airway
Check and monitor vital signs
Supportive care
 The Food and Drug
Administration
Report problems with foods, drugs, cosmetics, medical
devices, etc.
Did the product cause injury?
Was it improperly labeled?
Was it unsanitary?
Before you report a problem ask was the product used
for other than its intended purpose, were instructions
followed carefully, was the product out dated?
FDA; 5600 Fishers Lane (HFC-160); Rockville, MD
20857; phone (301) 443-1240
Principles of Toxin Elimination
and preventing absorption
 General approach
Call poison control center
1-800-222-1222
Remember the ABCs
Decontaminate the gut, clothing, skin and
environment
Monitor vital signs
If patient is symptomatic call 911
If patient is unconscious - maintain airway
 General approach, cont.

If patient is convulsing:
do not stick fingers in mouth
get them to the middle of the floor
remove constrictive clothing, etc.
keep stimuli to a minimum
call 911
 General approach, cont.

Try to determine how much they have

swallowed
child 1 swallow = 1 tsp.
adult 1 swallow = 1 tbsp.
50% of histories are incorrect
Try to ID the poison
send original container with patient if possible
 Gut decontamination
Once toxic agent is ingested it must be
absorbed (unless a local GIT irritant - iron
or corrosives)
Prevent absorption
gastric evacuation
administration of an adsorbent
catharsis
 Gut decontamination, cont.
Gastric emptying
must be done soon after ingestion
emesis
emetics
copper sulfate
mustard water
zinc sulfate
tartar emetics
apomorphine
soapy water
 Emetics, cont.

Syrup of Ipecac
first discovered in Latin America in 1648
used first in the treatment of dysentery up until
about 1900
prepared from the dried roots of Cephaelis
ipecacuanha plant
contains two alkaloids - emetine and cephaline
Use has declined since 1983
 Syrup of Ipecac, cont.
Emetine - potent emetic - works
systemically and locally. Long half life, has
a cumulative toxic effect on the heart.
Cephaline - twice as potent as emetine and
is a direct gastrointestinal irritant
Syrup of Ipecac is very effect emetic
Efficacy is not affected by concomitant
administration of activated charcoal
 Syrup of Ipecac, cont.

Give only to alert awake patients with an

intact gag reflex over 6 months of age
Never repeat dose more than once 20
minutes after first administration
Vomiting usually occurs within 20 minutes
of administration and continues for 30 to
120 minutes
 Syrup of Ipecac, cont.

Dosing guidelines
0-6 months no ipecac
6-12 months 10 ml, do not repeat dose
12 mon. - 12 years 15 ml, can be repeated once
> 12 years 30 ml, can be repeated once

Remember 15 ml = 1 tbsp. = 3 tsp. = 1/2 ounce

 Syrup of Ipecac, cont.

Contraindications - do not give

if corrosive agents have been ingested
if low viscosity hydrocarbons are ingested
if patient is having a seizure
if patient is comatose
if patient has ingested an agent which can cause
a seizure or coma
if patient does not have intact airway reflexes
 Gut decontamination, cont.

Gastric lavage - pumping the stomach

done in a hospital setting
Administration of an adsorbent
any agent capable of binding to the toxic agent
in the GIT and preventing the agents absorption
once the agent is bound, the toxin-adsorbent
complex is excreted in the feces
 Adsorbents, cont.
Activated Charcoal
first used by Hippocrates to bond toxic agents
part of the universal antidote
burnt toast and tea
activated - by micropulverizing and exposing it
to steam and acid (compare activated with a
surface binding area of 1000m2/gm verses
unactivated carbonaceous material at 3 m2/gm)
Use has increased since 1983
 Activated Charcoal, cont.
One 50 gram dose has the binding surface
area of 10 football fields
Available in tablets, capsules, powder and
suspension (most useful)
Substances not well adsorbed:
alcohols
hydrocarbons
heavy metals and inorganic minerals
corrosives
 Activated Charcoal, cont.
Dosing
try to achieve a 10:1 charcoal to toxin ratio, give 10
times as much charcoal as the toxin ingested
1 gm/kg BW also works well
children must usually have a nasogastric tube instilled
because they usually will not drink the gritty black
slurry
Administered to about 7% of patients
aspiration of AC partially responsible for 8 deaths,
given to patients who ingested CNS depressants
 Gut decontamination, cont.
Cathartics - purgatives, laxatives
drugs which promote evacuation of the bowel
facilitate the expulsion of the toxin
Commonly used cathartics
sorbitol 1-2 g/kg BW
mannitol 1-2 g/kg BW
magnesium sulfate 200 mg/kg (C);10-20g (A)
magnesium citrate 225mg/kg (C);17.5 g (A)
 Cathartics, cont.

Mechanism of action
osmotic agents
stimulate GIT motility
Scientific efficacy is uncertain
Contraindications: do not use in patients
with absent bowel sounds
with cardiovascular or renal disease or
electrolyte imbalance
Drugs used to treat Depression
 Tricyclic antidepressants
Most common cause of death due to
prescription drug overdose;
Reasons:
wide spread availability to suicide prone
patients (patients with depression)
severity of CV and CNS effects
limited efficacy of aval. treatments for OD
Mechanism of action
inhibit re-uptake of catecholamines and
serotonin neurotransmitters
 TCAs, cont.

Examples
Amitriptyline - Elavil
Nortriptyline (Pamelor, Aventyl)
Imipramine - Tofranil
Desipramine (Norpramin)
 TCAs, cont.
Clinical presentation
Life threatening OD is usually associated with
ingestion of > 1 gram
Cardiovascular - sinus tachycardia, prolonged
QRS interval, ventricular arrhythmias,
hypotension
CNS - seizures, coma
hyperthermia
ileus
Urinary retention
 TCAs, cont.

Treatment
give activated charcoal (may require repeated
doses due to pharmacologic bezoar formation)
give sorbitol (a cathartic)
do not induce vomiting - because of possibility
of rapid onset of seizures and risk of aspiration
 Lithium carbonate

Used in the treatment of depressive and bipolar

disorders, therefore it is used in a population at
relatively high risk for overdose
Narrow therapeutic index and intoxication is a
relatively frequent complication of therapy
Gradual onset of intoxication is far more common that
acute toxicity
Acute overdose carries a 25% mortality
 Lithium carbonate
Once used as a salt substitute and was an
ingredient of 7-Up
10,000 toxic exposures occur each year with 2000
being considered moderate to severe toxicities
There has been a gradual increase in toxicities
over the past 10 years
10% of exposures are in children > 19 years of age
 Lithium, cont.

Mechanism of action:
CNS is major organ system affected
competes for sodium, potassium, magnesium
and calcium and displaces them from
intracellular sites
numerous biochemical mechanisms that affect
receptor sensitivity and bring about changes in
neurotransmission
 Lithium, cont.
Clinical presentation:
CNS - fine hand tremors, hyperirritability,
spastic movements memory impairment,
anxiety, delirium
GI tract - severe gastroenteritis
CVS - arrhythmias, hypotension, circulatory
failure
should not be taken during pregnancy as it is
teratogenic causing cardiac anomalies in the
fetus (esp. of the tricuspid valve)
 Lithium, cont.

Treatment
induce vomiting
activated charcoal
transport to a medical facility