Download TOXICOLOGY LECTURES

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
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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
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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
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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
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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
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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 TCA’s
• 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
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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 children’s reach
Never refer to meds as candy
Never allow kids to take meds without
supervision
Child proofing your home, cont.
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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
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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
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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 ABC’s
• 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:
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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
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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
6-12 months
12 mon. - 12 years
> 12 years
no ipecac
10 ml, do not repeat dose
15 ml, can be repeated once
30 ml, can be repeated once
Remember 15 ml = 1 tbsp. = 3 tsp. = 1/2 ounce
Syrup of Ipecac, cont.
• Contraindications - do not give
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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)
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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
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sorbitol
mannitol
magnesium sulfate
magnesium citrate
1-2 g/kg BW
1-2 g/kg BW
200 mg/kg (C);10-20g (A)
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
TCA’s, cont.
• Examples
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Amitriptyline - Elavil
Nortriptyline (Pamelor, Aventyl)
Imipramine - Tofranil
Desipramine (Norpramin)
TCA’s, 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
TCA’s, 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