Introduction to Toxicology

Chapter 1
 INTRODUCTION
• Historically, 15th century, the “science of
poisons”
• physician Paracelsus, one of the early “fathers
of toxicology,”
• “all substances are poisons, there is none
which is not a poison . . . The right dose
differentiates a poison from a remedy”
(Paracelsus, 1493–1541).
 BASIC DEFINITIONS
• The classic definition of toxicology has
traditionally been understood as the
• study of xenobiotics, or, simply stated, as the
science of poisons—that is, the
• interaction of exogenous agents with
mammalian physiological compartments.
 Clinical Toxicology
• field of toxicology concerned with the toxic
effects of agents whose intent is to treat,
modify, or prevent disease states.
• These compounds would fall under the
classification of therapeutic agents
• clinical toxicologist is interested in
identification, diagnosis, and treatment of a
condition, pathology, or disease resulting from
environmental, therapeutic, or illicit exposure
to chemicals or drugs
 Mechanistic Toxicology
• the identification of the cause of toxicity of a
chemical at the cellular or tissue level.
• The classification of toxicity of a chemical,
therefore, may be expressed in terms of its
mechanism of toxicity (mechanism of action).
• Mechanistic toxicologists are interested in
researching the mechanism of action of toxins
for research purposes.
 Regulatory Toxicology
• Regulatory toxicology defines, directs, and
dictates the rate at which an individual may
encounter a synthetic or naturally occurring
toxin, and establishes guidelines for its
maintenance in the environment or within the
therapeutic market.
• Regulatory toxicologists role is to sanction,
approve, and monitor the use of chemicals by
enforcing rules and guidelines.
 Descriptive Toxicology
• explaining the toxic agents and their
applications.
• Descriptive toxicology developed principally as
a method of bridging the vacuum between
science and the public’s understanding
 Forensic Toxicology
• Is the use of toxicology and other disciplines
such as analytical chemistry, pharmacology
and clinical chemistry to aid medical or legal
investigation of death, poisoning, and drug
use.
• Forensic toxicologists integrated different
techniques (e.g. ELISA, LC/MS) to identify
compounds from mixtures of sometimes
unrelated poisons as a result of incidental or
deliberate exposure.
 General management of
poisoned patients
+
Toxidroms and Vital signs
Chapter 2
Chapter 3
General Information
 All chemicals have potential to be
poisons if given a large enough dose
 Poisoning occurs when exposure to a
substance adversely affects function of
any organ system
 Paracelsus (1493-1541)
‘Grandfather of Toxicology’

"All things are poison and

nothing is without poison,
only the dose permits
something not to be
poisonous."

“The dose makes the poison”

therapeutic toxic
increasing dose effect
effect
3
Toxicology

 the study of the effect of poisons on the

function of living systems.
 Toxicokinetic:denotes the absorption,
distribution, excrection,and metabolism
of toxines, toxic doses of therapeutic
agents, and their metabolits.
 Toxicodynamics: is used to denote the
injurious effects of toxic substances on
vital function.
Toxicokinetics
 Overdose of a drug can alter the usual
pharmacokinetic processes, and this
must be considered when applying
kinetics to poisened patients,
 For example, dissolution of tablets or
gastric emptying time may be slowed so
that absorption and peak toxic effects
are delayed.
Toxicokinetics
 Drugs may injure the epithelial barrier
of the Gastrointestinal Tract (GIT) and
thereby increase absorption.
 With a dramatic increase the
concentration of drug in the blood,
protein binding capasity may be
exceeded, resulting in an increased
fraction of free drug and grater toxic
effect.
Toxicokinetics
 If the plasma concentration is very high
and normal metabolism is saturated,
the rate of elimination may become
fixed. This change in kinetics may
markedly prolong the apperent serum
half-life and increase the toxicity.
The poisoned
or overdosed patient

 Poisonings and drug overdoses can cause

quick physical and mental changes in a
person.
Bystanders usually are the ones who must
initiate care and call a poison control center
or emergency number.
 The most common routes of exposure in
poisoning are inhalation, ingestion, and
injection. 9
Chemical agents that cause toxicity
include:

 Drugs
 Insecticides/herbicides
 Plant toxins, Animal toxins
 Chemical weapons,
 Radioactive elements
 Drugs
 Poisoning can occur in the health care
environment when a medication
normally given only by the
subcutaneous or intramuscular route is
given intravenously, or when the
incorrect medication is injected.
 Poisoning by injection can also occur in
the setting of substance abuse, as when
a heroin addict inadvertently (without
knowledge or intention) injects too much
heroin.
 Household cleaning products
 Poisoning may result from the improper
mixing of household cleaning products.
 The ingestion of poisons and toxins
occurs in various settings and in
different age groups.
 Poisoning in the home usually occurs
when children ingest household
cleaners or medicines. Improper
storage of these items contributes to
such accidents.
Household cleaning products
 Plants, pesticides, and paint products
are also potential household poisons.
 Because of mental or visual impairment,
illiteracy, or a language barrier, older
adults may ingest incorrect amounts of
medications.
Toxic fumes
 Most exposures to toxic fumes occur in
the home. Burning wood, gas, oil, coal,
or kerosene produces carbon monoxide
(CO).
 CO gas is colorless, odorless, tasteless,
and nonirritating, which makes it
especially dangerous.
 Cellular hypoxia may occur in spite of
adequate ventilation and oxygen
administration when poising is due to carbon
monoxide, cyanide, hydrogen sulfide, and
other poisons that interfere with transport or
utilization of oxygen.
 In such patients, cellular hypoxia is
evident by the development of tachiycardia,
hypotension, severe lactic asidosis, and
ischemia
Substance Abuse
and Overdose
 Admission of most poisoned patients to a critical
care unit is for an intentional or suspected suicidal
overdose. As part of their histories, these patients
frequently have mental illness, substance abuse
problems, or both.
 Often, withdrawal symptoms complicate the
assessment of potential toxidromes.
 A toxidrome is a group of signs and symptoms
(syndrome) associated with overdose or exposure
to a particular category of drugs and toxins.
16
 Commonly observed poisonings or drug
overdoses are caused by (but certainly not
limited to) carbon monoxide, salicylates,
acetaminophen, nicotine, alcohol, heroin,
marijuana, narcotic analgesics,
benzodiazepines, tricyclic antidepressants,
amphetamines, and cocaine.

17
Approach to
the poisened patient
 How does the poisoned patient die?
 Many toxins depress the Central
Nervous System(CNS), resulting in
coma.
 Patients under the influence of
hallucinogens such as LSD may die in
fights or falls from high places.
 Comatose patients frequently lose their
airway protective reflexes and their
respiratory drive. Thus they may die as
a result of airway obstruction by the
flaccid tongue, aspiration of gastric
contents into the tracheobronchial tree,
or respiratory arrest .
 These are the most common causes of
death due to overdose of narcotics and
sedative-hypnotic drugs.
 Cardiovascular toxicity is also frequently
encountered in poising. Hypotension
may be due to depression of cardiac
contractility; peripheral vascular collaps
due to blockade of alpha adrenoceptor-
mediated vascular tone or cardiac
arrhythmias.
 Hypothermia or hyperthermia due to
exposure as well as the temperature
dysregulating effects of many drugs can
also produce hypotension.
 Hyperthermia may result from sustained
muscular hyperreactivity and can lead
to muscle breakdown and
myoglobinuria, renal failure, lactic
asidosis, and hyperkalemia.
 Lethal arrhythmias such as ventricular
tachycardia and fibrillation can occur
with overdoses of many cardioactive
drugs such as epinephrine,
amphetamines, cocaine, digitalis and
theophylline; and drugs not usually
concidered cardioactive, such as
tricyclic antidepressants, antihistamines,
and some opioid analogs.
 Seizures, muscular hyperactivity, and
rigidity may result in death.
 Seizures may cause pulmonary
aspiration,hypoxia, and brain damage.
 Drugs and poisons that often cause
seizures include antidepressants,
isoniazid, diphenhydramine, cocain, and
amphetamines.
 Some organ system damage may occur
after poisoning and is sometimes
delayed in onset.
 Pulmonary fibrosis may begin sevral
days after ingestion.
 Massive hepatic necrosis due to
poisoning by acetaminophen or certain
mushrooms result in hepatic
encephalopathy and death 48-72 hours
or longer ingestion.
ASSESSMENT

 A health care facility’s systematic

approach to the assessment of the
poisoned or overdosed patient includes
performing triage,
 A) Obtaining the patient’s history,
 B) Performing a physical examination, and
 C) Conducting laboratory studies.
25
 Triage

 Triage is always the first step performed in

the emergency department.
 Two essential questions to be considered in the

triage evaluation are:

1. Is the patient’s life in immediate danger?
2. Is the patient’s life in potential danger?

26
 Initial management of the
poisoned patient
 If the patient’s life is in immediate danger, the
goals of immediate treatment are patient
stabilization and evaluation and management of
airway, breathing, circulation and dextrose
(ABCDs).

27
 Stabilization;First the airway should be
cleared of vomitus or any other obstruction
and an oral airway or nasotracheal or
endotracheal intubation may be necessary
to adequately maintain and protect the
patient’s airway.For many patients is
sufficient to move the flaccid tongue out of
the airway.
28
 Breathing

Breathing should be assesed by

measuring arterial blood gases.
Mechanical ventilation may be necessary
to support the patient.
Many drugs and toxins, such as heroin,
depress the respiratory drive. Patients
therefore may require ventilatory
assistance until the drugs or toxins are
eliminated from the body.
Circulation

 should be assesed by continious

monitoring of pulse rate, blood
pressure, urinary output and evaluation
of peripheral perfusion
 Some toxic drug ingestions impair
myocardial contractility, cause cardiac
conduction delays and arrhythmias and
fluid overload may result because of the
heart’s inability to pump effectively.
 In these cases, fluid balance needs to be
carefully controlled.
 Invasive monitoring (e.g., central venous
pressure, pulmonary artery catheter, Foley
catheter with urometer) and drug therapy
may be necessary to prevent or minimize
complications such as pulmonary edema

31
 Every patients with altered mental
status should receive a concentrated
Dextrose. Adults are given 25g/Kg
(50ml of 50% dextrose solution) i.v.
Children 0.5g/kg(2ml/kg of 25%
dextrose).
 Hypoglycemic patients may appear
to be intoxicated , and there is no
rapid and reliable way to distinguish
them from poisened patients.
 Supportive Care

• Coma cocktail
– Thiamine: 100 mg IV, before dextrose
– Dextrose: 50 grams IV
– Naloxone: 0.01 mg/kg IV
 Supportive Care

• Treat Seizures
– Lorazepam 2 mg IV, may repeat as
needed
– Dilantin 10 mg/kg IV
• Control agitation (restlessness)
– Haldol 5-10 mg IM
– Ativan 2-4 mg IM or IV
– Geodon 20 mg IM
REASSESS
. . . frequently
A. History and Physical
examination
 Once the essantial initial ABCD
interventions have been instituted ,
 one can begin a more detailed
evaluation to make a spesific
diagnosis.This includes gathering any
available history and performing a
toxicologically oriented physical
examination.
 The history of the drug(s) or toxin(s)
involved may not be reliable or even
known, especially when patients are found
unconscious or have attempted suicide

37
 History
 A history of the patient’s exposure provides a
framework for managing the poisoning or
overdose.Need to obtain as much info as
possible about exposure
 Key points include identifying the drug(s) or

toxin(s), type of exposure, the time and

duration of the exposure, amount or dose,
empty bottles or containers, houshold
products, over the counter drug (OCD),
smells or suicide note.
History
 First aid treatment given before arrival at the
hospital, allergies, and any underlying
disease processes or related injuries.
This information may be obtained from the
patient, family members, friends, rescuers, or
bystanders.
 In some cases, family or police may need to
search the patient’s home for clues.
 Number of exposed persons may supply
additional information.
B. Physical Examination
 Check clothing for objects or substances
 A quick but thorough physical
examination is essential.These include
vital signs and temperature, eyes and
mouth, skin, abdomen and nervous
system.
Toxidrome
 A toxidrome is a group of signs and
symptoms associated with overdose or
exposure to a particular category of
drugs and toxins.
 Recognizing the presence of a
toxidrome may help identify the toxin(s)
or drug(s) to which the patent was
exposed, and the crucial body systems
that may be involved.
1.Vital signs

 Careful evaluation of vital signs (blood

pressure, pulse, respirations, and
temperature) is essential in all
toxicologic emergencies. The critical or
potentially critical patient’s vital signs
and temperature are measured
frequently to track changes indicating
additional problems.
 Lungs

 Wheezing?
 Rapid respirations are typical of
salicylates, CO,and other toxines that
produce metabolic acidosis or cellular
asphyxia.
CV system
 rhythm, rate, regularity
 Hypertension and tachycardia are
typical with amphetamines, cocain and
anticholinergic drugs. Hypotension
and bradycardia are characteristic
features of overdose with calcium
channel blockers, beta blockers,
clonidine, and sedative hipnotics.
 Hypotension with tachycardia is
common with tricyclic antidepressants,
vasodilators and beta agonists.
2.Eyes
 The eyes are a valuable source of
toxicologic information.
 Exam eyes for pupils size, nystagmus,
reactivity, increased lacramaiton
 Miosis is typical of opioids,
cholinesterase inhibitors (e.g.
Organophosphate insecticides), and
deep coma due to sedative drugs.
 Mydriasis is common with
amphetamines, cocaine,
LSD, atropine and other
anticholinergic drugs.
 Horizontal nystagmus is
characteristic of
intoxication with alcohol
and other sedative drugs.
The presence of both
vertical and horizontal
nystagmus is strongly
suggestive of
phencyclidine poising.
3. Mouth
 The mouth may show signs of burns
due to corrosive substances, or soot
from smoke inhalation.
 Typical odors of alcohol or ammonia
may be noted.
 4.Skin
 Exam skin for hot, and dry,
flushing, bruising, cyanosis,
 Cyanosis may be caused by
hypoxemia or by
methemoglobinemia.
 Icterus may suggest
hepatic necrosis.
 Excessive sweeting occurs
with organophosphates,
nicotine and sympathomimetic
drugs.
Methemoglobinemia
 5. Abdomen

 Hyperactive bowel sounds, tenderness

abdominal cramping and diarrhea are
common in poisoning with
organophosphatase, iron, arsenic,
teophylline, Amanita muscaria and
phalloides.
6. Nervous
system
 A careful neurologic examination is essantial
 Assess general appearance
 Agitation or confusion

 reflexes, muscle tone coordination, cognition

 Focal seizures or motor deficits suggest a
structural lesions.
 Extremities: fasciculation, tremor
 muscular rigidity can be
caused by anti-psychotic
agents, serotonin
syndrome and by
strychnine.
 Nystagmus and ataxia
are typical of phenytoin,
alcohol or other sedative
intoxication.
 CNS Examination
 Physiologic excitation – anticholinergic,
sympathomimetic, or central hallucinogenic
agents, drug withdrawal
 Physiologic depression – cholinergic
(parasympathomimetic), sympatholytic,
opiate, or sedative-hypnotic agents, or
alcohols
 Mixed state – polydrugs, hypoglycemic
agents, tricyclic antidepressants, salicylates,
cyanide
 Mentation
 Many factors can affect the patient’s
mental status.
 Hypoglycemia and hypoxemia; that can
be life-threatening but easily addressed
by administering oxygen and IV
dextrose until laboratory results are
available.
C.Laboratory Studies

 Relevant clinical laboratory data are

vital to the assessment of the poisoned
or overdosed patient.
 Tests that provide clues to the agent(s)
taken by the patient include arterial
blood gases (ABGs), electrolytes,
serum osmolality tests, urinalysis,
complete blood count,
electrocardiography , imaging findings
and hepatic function.
Acid–base balance and
electrolyte homeostasis
 Electrolyte abnormalities and metabolic
acidosis frequently occur and may
require serial measurements of
electrolytes and arterial blood gases
(ABGs), and other specific laboratory
tests.
1.Arterial Blood Gases (ABGs)
 Hypoventilation will result in an elevated
PCO2 (hypercapnia) and a low PO2(hypoxia).
 The PO2 may also be low with aspiration
pneumonia or drug induced pulmonary
edema.
 Signs of inadequate ventilation or
oxygenation include cyanosis, tachycardia,
hypoventilation, intercostal muscle retractions,
and altered mental status.
 2. Electrolytes
 Acute poisoning can cause an
imbalance in a patient’s electrolyte
levels, including sodium, potassium,
chloride, bicarbonate, carbon dioxide,
magnesium, and calcium.
 Serum level measurements are also
available for carbamazepine, iron,
ethanol, lithium, aspirin, and valproic
acid and may be obtained if these
agents are suspected in an overdose.
 The anion (A negatively charged
ion) gap represents the difference
between unmeasured anions and
cations (An ion or group of ions
having a positive charge ) in the
blood.
 Anion gap = (Na + K) - (HCO3 + Cl)

 The normal value in urine for the anion

gap
is approximately 8 to 16 mEq/L.
 An anion gap that exceeds the upper normal
value can indicate metabolic acidosis caused
by an accumulation of acids in the blood.
 Drugs, toxins, or medical conditions that can
produce an elevated anion gap include iron,
isoniazid (INH), lithium, lactate, carbon
monoxide, cyanide, methanol, ethanol,
metformin, ethylene glycol, salicylates,
hydrogen sulfide, diabetic ketoacidosis,
uremia, seizures, and starvation.

60
 3. Serum osmolality
 The osmolal gap is the difference
between the measured osmolality and
the calculated osmolality.
 The calculated osmolality is derived
using laboratory values for the major
osmotically active substances in the
serum, such as sodium, glucose, and
blood urea nitrogen (BUN).
 Like the anion gap, it is a simple, cost-
effective tool for evaluating the
poisoned patient for certain drugs or
toxins
Diagnostic tools-continue

4. Electrocardiography

can provide evidence of drugs causing

arrhythmias or conduction delays (e.g.,
tricyclic antidepressants).
 5.Radiology
Many substances are radiopaque, or can be
visualized using a contrast-enhanced
computed tomography (CT) scan (e.g.,
heavy metals, button, batteries, some
modified-release tablets or capsules,
aspirin concretions, cocaine or heroin
containers).
Chest radiographs provide evidence of
aspiration and pulmonary edema.
6. Renal function tests
 Some toxines have direct nephrotoxic,
in other cases renal failure is due to
shock or myoglobinuria.
 BUN and creatinine levels should be
measured and urinanalysis performed.
7.Toxicology screens
A toxicology screen is a laboratory
analysis of a body fluid or tissue to
identify drugs or toxins. Saliva, spinal
fluid, and hair may be analyzed, blood
or urine samples are used more
frequently.Each screen tests for specific
drugs or agents.
 The sample must also be properly collected,
and there must be a laboratory near enough
to obtain results quickly.
 The test sample must be collected while the
drug or toxin is in the body fluid or tissue
used for testing.

 For example, cocaine is a rapidly

metabolized drug; however, its metabolite,
benzoylecgonine, can be detected in the
urine for several hours after cocaine use.
67
MANAGEMENT
 Management of the poisoned or overdosed
patient seeks to prevent absorption of and
further exposure to the agent.
 Treatment begins with first aid at the scene
and continues in the emergency department
and often the intensive care unit (ICU).
 Advanced general management involves
further steps to prevent absorption and
enhance elimination of the agent. For
instance, antidotes, antivenins (the
treatment of venomous bites or stings) or
antitoxins may be administered.
68
General- management
I. provision of supportive care
II. prevention of poison absorption
III. enhancement of elimination of poison
IV. administration of antidotes
I. Supportive care

 Vital signs, mental status, and pupil size

 Cardiac monitoring, ECG
 Protect airway
 Intravenous access
 Cervical immobilization if suspect
trauma
 Rule out hypoglycaemia
 II.Preventing absorption
Decontamination;
A) dermal
B) ocular
C) inhalation
D) ingestion exposures follow
A) DERMAL EXPOSURE
 Generally; achieved by; undressing
patients and washing them thoroughly
with copious amounts of lukewarm
water for 15 to 30 minute
 All towels and clothing should be put
into hazardous waste bags
 Some toxins may require further
decontamination. For example, three
separate soap and water washings or
showers are recommended to
decontaminate organophosphate
pesticides (e.g., Malathion or Diazinon).
 Protective clothing should be worn to
reduce the risk for toxicity while handling
contaminated clothing or assisting with
skin decontamination. 73
 B) Eyes
 Many substances can accidentally
splash into the eyes. When this
happens, the eyes must be flushed to
remove the agent.
 Immediate irrigation with lukewarm
water or normal saline is recommended.
 Continuous flooding of the eyes with a
large glass of water or low-pressure
shower should be done for 15 minutes.
 The patient should blink the eyes open
and closed during the irrigation.
 If necessary, the pH of the eyes can be
tested. If the pH is abnormal, irrigation
should continue until the pH normalizes.
 An ophthalmologic examination is
needed when ocular irritation or visual
disturbance persists after irrigation.
 C) INHALATION EXPOSURE
 A victim of an inhalation exposure
should be moved to fresh air as quickly
as possible.
 The responder must also protect himself
or herself from the airborne toxin.
 Further evaluation is needed if the
patient experiences respiratory irritation
or shortness of breath.
D) 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
 Milk or water dilutes ingested irritants
such as bleach or caustics such as
drain cleaner.
 Further evaluation is necessary after
dilution if there is mucosal irritation or
burns.
 Because of the risk of aspiration,
ingestions should not be diluted when
they are accompanied by seizures,
depressed mental status, or loss of the
gag reflex.
 Again, neutralization is not used
because of the risk of thermal burn.
Gastrointestinal Decontamination

1. Vomiting
2. Gastric lavage
3. adsorbents (is the adhesion of
molecules of gas, liquid, or
dissolved solids to a surface)
4. cathartics
5. whole-bowel irrigation
are used to prevent absorption
toxins
1. Induced Vomiting
Ipecac

 Risk of aspiration Emesis: achieved by

using syrup of ipecac
 Dosing: 15 ml for 1-12 years old and

30 ml for adults; may repeat once if

no emesis in 12 hr
 Usually 3-5 episodes of emesis and
resolve in two hours; if protracted
emesis occurs consider toxin as etiology
 Use of Ipecac very limited
 Contraindications: ingestions with
potential for change in mental status,
active or prior vomiting, caustic
ingestion, toxin with more pulmonary
than GI toxicity (hydrocarbons),
ingestion of toxins with potential for
seizures
 The American Academy of Pediatrics no
longer recommends the use of emetics
(such as syrup of ipecac) for GI
decontamination.
2.GASTRIC LAVAGE

 Fluid (usually normal saline) is

introduced into the stomach through a
large-bore orogastric tube and then
drained in an attempt to reclaim part of
the ingested agent before it is absorbed.
 A small-bore nasogastric tube is
ineffective for lavage because
particulate matter such as tablets or
capsules are too large to pass through
the tube.
 Contraindications: Not in unconscious
patient unless intubated (risk
aspiration)
 caustic ingestion or hydrocarbons with a
high aspiration potential, airway
integrity not secured, more toxic to lung
than GI
 gastric lavage should be used only if the
patient has ingested a life-threatening
amount of a substance and the
procedure is undertaken within an hour
of the ingestion.
 Complications: insertion into trachea,
esophageal or gastric perforation,
decreased O2, pulmonary aspiration,
electrolyte imbalance, tension
pneumothorax, and hypothermia (when
cold lavage solutions are used).
 Charcoal should be used before
withdrawal of tube
 The contents of the stomach can then
be collected for drug or toxin
identification.
 Drug removal range from 35-56%.
 Indicated if in 1 hr of ingestion.
 For the lavage, the patient is positioned
in the left. lateral decubitus position,
with the head lower than the feet.
3. ADSORBENTS

 An adsorbent is a solid substance that

has the ability to attract and hold
another substance to its surface (“to
adsorb”).
 Activated charcoal is an effective
nonspecific adsorbent of many drugs
and toxins.
 Activated charcoal adsorbs, or traps the
drug or toxin to its large surface area
and prevents absorption from the GI
tract.
 Activated charcoal is a fine, black powder
that is given as a slurry with water, either
orally or by nasogastric or orogastric tube, as
soon as possible after the ingestion.
 Commercially available activated charcoal
products may be mixed with 70% sorbitol to
decrease grittiness (composed of or covered
with relatively large particles, increase
palatability (Acceptable to the taste) , and
serve as a cathartic. The usual dose that is
given is one 50-g bottle (1g/kg).

88
Drugs/Toxins Well
Adsorbed
by Activated Drugs/Toxins Not Well
Charcoal Adsorbed
■ Acetaminophen by Activated Charcoal
■ Amphetamines ■ Acids
■ Antihistamines ■ caustic alkalis
■ Aspirin ■ Alcohols
■ Barbiturates ■ Iron
■ Benzodiazepines ■ Lithium
■ Beta blockers ■ Metals cyanide
■ Calcium channel blockers
mineral acids,
■ Cocaine
organic solvents,
■ Opioids
■ Phenytoin
■ Theophylline
■ Valproic acid 89
 4. CATHARTICS

 A cathartic is a substance that causes or

promotes bowel movements.
 In theory, cathartics decrease the absorption
of drugs and toxins by speeding their
passage through the GI tract, thereby limiting
their contact with mucosal surfaces.
 70% sorbitol (1 g/kg) or 10% Mg citrate
90
5. WHOLE-BOWEL IRRIGATION

 The goal of whole-bowel irrigation is to

give large volumes of a balanced
electrolyte solution rapidly (1 to 2
L/hour) to flush the patient’s bowel
mechanically without creating
electrolyte disturbances.
 Commercial products used in whole-
bowel irrigation include GoLYTELY and
Colyte.
 Whole-bowel irrigation is
contraindicated in the patient with
bowel obstruction or perforation.
III.Enhanced Elimination of the
Drug or Toxin

 The absorption rate, body distribution,

metabolism, and elimination must be
considered when choosing methods to
eliminate the drug or toxin from the
body.
There are six methods of
enhanced elimination:

1. Multiple-dose activated charcoal

2. Alteration of urine pH
3. Chelation
4. Hemodialysis (for water soluble
drugs)
5. Hemoperfusion
6. Hyperbaric oxygenation (HBO)
therapy
1. Multi-Dose Charcoal
 One dose usually sufficient
 Indications for multi-dose activated
charcoal:
ingestion of large doses, substances
that slow release toxins, toxins that
slow gut function, toxins with
enterohepatic circulation,
repetitive doses useful to enhance the
elimination of certain drugs (eg,
theophylline, phenobarbital,
carbamazepine, valproic acide, aspirin)
2. ALTERATION OF URINE pH

 Alkalinization:Alkalinizing the patient’s

urine enhances excretion of drugs that
are weak acids by increasing the
amount of ionized drug in the urine.
 This form of enhanced elimination is
also termed ion trapping.
Alkalinization achieved by IV dose of
bicarb at 1-2 mEq/kg, followed by
intermittent boluses or continuous
bicarb drip for urine pH 7.5-8.0
 Used to eliminate acidic drug that
mainly excreted by the kidney
e.g.salicylates overdose.
 Complications of alkalinization include
cerebral or pulmonary edema and
electrolyte imbalances.
 Need expert monitoring
Acidification of Urine
 Urine acidification is no longer
recommended because of low drug
clearance and the risk of
complications such as
rhabdomyolysis. Rhabdomyolysis
is the breakdown of muscle fibers
resulting in the release of muscle
fiber contents into the circulation.
Some of these are toxic to the
kidney and frequently result in
kidney damage.
 Can enhance elimination of
amphetamines, and phencyclidine.
3. CHELATION

Chelation involves the use

of binding agents to remove
toxic levels of metals from
the body, such as mercury,
lead, iron, and arsenic.
Examples of chelating agents
are dimercaprol (BAL in oil),
calcium disodium edetate
(EDTA), and deferoxamine.
 4.HEMODIALYSIS

 Hemodialysis is the process of altering

the solute composition of blood by
removing it from an artery, diffusing it
across a semipermeable membrane
(between the blood and a salt solution),
then returning it into a vein.
Hemodialysis
 It is used in moderate to severe
intoxications to remove a drug or toxin
rapidly when more conservative
methods (e.g., gastric lavage, activated
charcoal, antidotes) have failed or in
patients with decreased renal function.
 Hemodialysis requires consultation with
a nephrologist and specially trained
nurses to perform the procedure and
monitor the patient.
 Drug should be dialyzable. Low
molecular weight, low protein
binding, and water solubility are
factors that make a drug or
toxin suitable for hemodialysis.
 may also be used temporarily or
as long term if the kidneys are
damaged due to the overdose.
 Dialysis reserved for
specific toxins: salicylates,
methanol, lithium, theophylline,
amanita (mushrooms)
Dialysis con’t
 Benefits: removal of toxins already absorbed
by gut, ability to remove parent compound
and active metabolite,
 Dialysis rarely contraindicated
 No dialysis for small children, exchange
transfusion should be considered
5.HEMOPERFUSION
 Hemoperfusion removes drugs and toxins
from the patient’s blood by pumping the
blood through a cartridge of adsorbent
material, such as activated charcoal.
 An advantage of hemoperfusion over
hemodialysis is that the total surface
area of the dialyzing membrane is much
greater with the hemoperfusion cartridges.
As in hemodialysis, drugs that have high
tissue-binding characteristics and a large
volume distributed outside the circulation
are not good candidates for
hemoperfusion because little drug is
found in the blood.
 Although rarely used in the poisoned and
overdosed population, hemoperfusion
has been used successfully in patients
experiencing a theophylline overdose
 6.HYPERBARIC OXYGENATION
THERAPY (HBO)

In HBO therapy, oxygen is

administered to a patient in an
enclosed chamber at a pressure
greater than the pressure at sea
level (e.g., 1 atmosphere absolute).
This therapy has been used in carbon
monoxide and methylene chloride
poisonings (methylene chloride is
metabolized to carbon monoxide
in the body).
 Complications of HBO
therapy include pressure-
related otalgia (ear pain),
sinus pain, tooth pain, and
tympanic membrane rupture.
 anxiety, convulsions, and
tension pneumothorax also
have been observed in
patients receiving HBO
therapy.
 IV. Antidotes (Antitoxins) and
Antagonists),

 In pharmacology, an antagonist is a
substance that counteracts the action of
another drug.
 Although the general public often
believes there is an antidote for every
drug or toxin, the opposite is closer to
the truth.
 There are, in fact, very few antidotes.
Antitoxins neutralize a toxin.
For instance, botulism (food poisoning
from ingesting botulin)(potent
bacterial toxin) produced by the
Clostridium botulinum that causes
botulism; can be used as a
bioweapon)
 Antivenins are antitoxins that neutralize the
venom of the offending snake or spider.
 Antitoxin trivalent (equine) A,B, and E is
available through the Centers for Disease
Control and Prevention to counteract the
effects of botulism.
 There are several antitoxins; each is active
against a specific venom.
 Continuous Patient Monitoring
 Seriously poisoned or overdosed
patients may require continued
monitoring for hours or days after
exposure.
 Physical examination, the use of
diagnostic tools, and careful
assessment of clinical signs and
symptoms provide information about the
patient’s
 Antidotes
 Acetaminophen N-acetylcysteine
 Organophosphates Atropine, pralidoxime
 Anticholinergic physostigmine
 Arsenic, mercury, gold dimercaprol
 Benzodiazepines flumazenil
 Beta blockers glucagon
 Calcium channel block calcium
 Carboxyhemoglobin 100% O2
 Cyanide nitrite, Na thiosulfate
 Digoxin digoxin antibodies
 Antidotes
 Ethylene glycol fomepizole, HD
 Heparin protamine
 Iron deferoxamine
 Isoniazid pyridoxime
 Methanol fomepizole, HD
 Methemoglobin methylene blue
 Opioids naloxone
 Salicylate alkalinization, HD
 TCA’s sodium bicarbonate
 Warfarin FFP, vitamin K