Clinical Toxicology

“Poisons & their control”

 Toxicology
“Toxicology is the study of adverse effects of exogenous
agents on biologic systems. The term poison refers to
agents that cause harmful effects.”
 Focuses on the effects of substances in patients caused by
accidental poisonings or intentional overdoses of
medications, drugs of abuse, household products, or various
other chemicals

 Intoxication: Toxicity associated with any chemical

substance
 Poisoning. A clinical toxicity secondary to accidental
exposure
 Overdose. An intentional exposure with the intent of causing
self-injury or death
 Toxidromes. A group of signs, symptoms, and laboratory
findings that suggest a specific ingestion
Introduction
Clinical Toxicology
 This branch of toxicology deals with the harmful
effects of chemical substances on human and
animals and examines poisoning from lethal point of
view.
 Clinical toxicology deals with the assessment and
treatment of patients exposed acutely or
chronically to potentially harmful agents
 Because of the diverse nature of the substances
involved in poisonings and the wide range of clinical
manifestations and their treatment, optimal
management is achieved by an interdisciplinary
approach using the expertise of physicians,
nurses, pharmacists, and prehospital professionals.
What is a Poison ?

“A poison is any substance, including

medications, that is harmful (causing death or injury) to
your body if too much is eaten, inhaled, injected, or
absorbed through the skin. ”
(CDC. USA)
An Unintentional poisoning occurs when a person
taking or giving too much of a substance did not mean to
cause harm.
 The word poison comes from the Latin word, “potare”,
which means to drink, but the poisons can also enter
the body through other ways as well.
◦ From exposure to radiation
◦ Venom from snake bite, etc.
Poisoning
“The development of dose related
adverse effects following
exposure to chemicals, drugs or
other xenobiotics.”
A xenobiotic is a foreign chemical substance found within an
organism that is not normally naturally produced by or
expected to be present within. E.g., Antibiotics

Poisoning refers to exposure to any agent which is

capable of producing a deleterious response in a
biological system, seriously injuring functions or
producing death.
Types of poisoning
Acute Poisoning
 Acute poisoning is sudden exposure to a poison on one
occasion or during a short period of time.
 Symptoms develop in close relation to the exposure.
Absorption of a poison is necessary for systemic poisoning.
In contrast, substances that destroy tissue but do not
absorb are classified as corrosives rather than poisons.
 Onset of signs and symptoms are abrupt in case of acute
poisoning.
Chronic Poisoning
 Chronic poisoning is long-term repeated or continuous
exposure to a poison where symptoms do not occur
immediately or after each exposure.
 The patient gradually becomes ill, or becomes ill after a
long latent period. Chronic poisoning most commonly
occurs following exposure to poisons that bio accumulate
such as mercury and lead. It is produced by small doses
taken over a long period.
 Onset is usually NOT abrupt.
EPIDEMIOLOGY
 WHO (2004) - 3,46,000 deaths in a year d/t poisoning.
 In Pakistan unintentional poisoning condition was the
26th cause of mortality in 1990 but increased to the 22nd by 2010
 The NHS Pakistan 1990-1994, a nationally representative household
survey, reported an incidence of 3.3 non-fatal injuries due to poisoning
per 1,000 per year from which 3.4% recovered with handicap.
 Estimates from previous reports
◦ range from 21.5% to 77.0% for non-fatal injuries;
◦ self-inflicted poisoning ranges from 18% to 70% and
◦ homicidal poisoning from 1.8% to 5%
 Commonest cause in PAKISTAN –
◦ Insecticides > Tranquilizers > Narcotics
◦ Among medical drugs, 60% accounted for BZD.
 Reasons – Agriculture based economy
- Easy availability pesticides
- Poverty
 Relevant definitions
Fulminant poisoning
 It is produced by a massive dose of poison. Death occurs rapidly,
sometimes without preceding symptoms and patient collapse suddenly.
Sub acute Poisoning
 Some poison also show a sub acute type of poisoning which lies
somewhere between the latter two extremes mentioned above.
Toxin and Toxicant
 Chemical that can potentially produce harm is termed as toxicant.
 The term toxin is reserved for those chemicals that are produced by the
living organisms. For example rattle snake venom, poisonous
mushroom containing toxin.
Venom
 Venom is an animal poison that is produced in a poison gland or a
group of cells and is delivered to another animal or living animal or living
organism via a bite or sting. This is referred to as envenomation.
“If you bite it and you die, it's poison.
If it bites you and you die, it's venom.”
 Relevant definitions
Corrosives
 Corrosives are the substances that rapidly destroy or
decompose the body tissues at point of contact. Some examples
are hydrochloric acid, nitric acid, sulfuric acids, phenol, sodium
hydroxide and iodine etc.
Irritants:
 Substance which, while not corrosive, causes a temporary or
reversible inflammation of living tissue (such as eyes, skin, or
respiratory organs) by a chemical action at the point of contact.
The effects of an irritant may be acute (due to a single high level
exposure) or chronic (due to repeated low level exposures).
Deliriants:
 Deliriants are a class of hallucinogen. Deliriants are considered
to be true hallucinogens, because the visuals they produce are
hard or impossible to tell apart from reality; they are also known
for negative physical effects.
Biocide
 A chemical substance capable of killing living organisms.
Role of pharmacist
 Assisting medical team
◦ Correct diagnosis
◦ Assessment of severity
◦ Appropriate initial management
 Acts as advisor/consultant (Emergency pharmacist)
 Availability of antidotes
 Maintenance of inventory
 Pharmacist in emergency care unit
 Preventing unintentional drug poisoning (awareness &
education)
 Plan of therapy (management)
 Classification of toxic agents on the basis of treatment
by pharmacist
Role of pharmacist
 Plan of therapy
◦ Decrease the absorption of toxin.
 a) Inducing emesis.
 b) Performing gastric lavage.
 c) Using chemical adsorbent.
◦ Enhances the elimination of toxin.
 It includes the study of;
 a) Urinary alkalization/acidification.
 b) Dialysis.
 c) Whole bowel irrigation
◦ Chemical inactivation.
 Antidotes can change the chemical nature of the poison
by
 a) Rendering it less toxic.
 b) Preventing its absorption.
◦ General treatment of local exposure.
Classification of poisons
 According to the chief symptoms produced
 Corrosives .
 Systemic
 Irritants
 Miscellaneous

1. Corrosives
a) Strong acids- H2SO4 , HNO3 , HCl
b) Strong alkalis- Hydrates & Carbonates of Na+ , K+ &
NH3
c) Metallic salts – Zinc chloride, Ferric chloride, KCN ,
Silver nitrate, Copper sulphate.
Classification continued….

2. Irritants
a) Inorganic –i) Nonmetallic – Phosphorus, Iodine
Chlorine.
ii) Metallic – Arsenic, Antimony, Lead.
iii) Mechanical – Powdered glass, hair

b) Organic
Vegetable – Abrus precatorius, Castor, Croton,
Calotropis.
Animal – Snake & insect venom,
Cantharides
Classification continued…….

3. Systemic
a) Cerebral
 CNS depressants – Alcohol, opioids, hypnotics, general
anesthetics.
 CNS stimulants – Amphetamines, Caffeine
 Deliriant – Datura (Angel’s trumpets),
Cannabis, Cocaine
b) Spinal – Nux vomica
c) Peripheral – Conium (hemlock), Curare
d) CVS - Aconite (wolf’s bane), Quinine, HCN
e) Asphyxiantes – CO, CO2 , H2S

4) Miscellaneous – Food poisoning, Botulism

Botulism is a rare and potentially fatal illness caused by a toxin
produced by the bacterium Clostridium botulinum. The
disease begins with weakness, blurred vision, feeling tired,
and trouble speaking.
.
 Biochemical investigations
 Hematologic
 CBC, Platelet count, Coagulation profile
◦ Hemolytic anemia- lead, NSAIDS, Quinidine
◦ Thrombocytopenia- Aspirin, Phenytoin, Procanamide
◦ Coagulopathy- snake venoms, warfarin

 Liver function tests

 S. bilirubin , enzymes – AST,ALT , ALP, coagulation profile
◦ Acetaaminophen, sulfonamides, rifampicin, TCA, INH,

 Renal functions tests

◦ Aspirin, lead, barbiturates, alcohol, amphetamines,
copper sulphate
Principles of Management
 Initial ABC assessment if necessary (ABC stands for
airway, breathing, circulatory resuscitation)
 A secondary survey for infection or trauma of the
head or cervical spine, if the patient mental or
metabolic activities are abnormal.
 Supportive care with continuous assessment and
monitoring
 Case specific management such as preventing
further absorption using antidotes or enhanced the
elimination of poison
 Rapid evaluation of poison from blood, vomitus or
from other body fluids or parts
 In case of extensive poisoning, early treatment and supportive
care should be provided to the patient prior to extensive
investigations or apparent diagnosis
 Attention must be given to maintain patient vital signs and
providing immediate treatment of life threatening conditions
such as hypotension, hypertension, bradycardia, tachycardia,
cardiac arrhythmias, hyperthermia, hypothermia, respiratory
depression.
 Cardiac monitoring and immediate treatment is needed for
arrhythmias and conduction defects.
Initial Steps to stabilizing patients
Get Help

Prioritize this patient over not sick patients

Rapidly assess the patient

Simultaneously stabilize the patient

Expedite diagnostic workup and management

 Initial assessment of acutely ill
patient

Identify and treat immediate life

threats

Perform A-B-C-D
Say “OMI” Oxygen, Monitor, IV
 ABCs of assessment

AIRWAY BREATHING CIRCULATION

Talking = good Look: work of Look: mental status,

breathing, respiratory color
rate
Look: edema, blood,
vomitus, foreign body Feel: Peripheral pulses
Listen: Breath sounds
Listen: Noisy = Check: Heart rate,
obstructed Check: Pulse oximetry cardiac rhythm, blood
pressure
 Supportive Management
 ABCD principle
A for airway
B for breathing
C for circulation
D for diagnosis and drugs
Airway
 Airway obstruction can cause death
 First evaluate mental status and cough reflex to check if the patient is
conscious or unconscious.
 In the unconscious patient, the priority is airway management, to avoid a
preventable cause of hypoxia. Common problems with the airway of patient
with a seriously reduced level of consciousness involve blockage of
the pharynx by the tongue, a foreign body, or vomit.
 At a basic level, opening of the airway is achieved through manual movement
of the head using various techniques, with the most widely taught and used
being the "head tilt — chin lift", although other methods such as the
"modified jaw thrust" can be used, especially where spinal injury is
suspected, although in some countries, its use is not recommended for lay
rescuers for safety reasons.
 Interventions which can be used to facilitate airways are:
◦ Sniffing position
◦ Jaw thrust
◦ Head-down, left-sided position
◦ Examine the oropharynx
◦ Clear secretions
◦ Use of Airway devices
 Before considering Intubation…
 Breathing
 Determine if respirations are adequate
 Give supplemental oxygen
 Assist with bag-valve-mask.
 In the unconscious patient, after the airway is opened the next area to
assess is the patient's breathing, primarily to find if the patient is
making normal respiratory efforts. Normal breathing rates are between
12 and 20 breaths per minute, and if a patient is breathing below the
minimum rate, then CPR should be considered, although professional
rescuers may have their own protocols to follow, such as artificial
respiration.
 Auscultate lung fields
◦ For Bronchospasm: Albuterol nebulizer
◦ For Bronchorrhea/rales: Atropine
◦ For Stridor: Determine need for immediate intubation
 Respirations – are they breathing 14 times a minutes or 4
 Bag/mask – to support inadequate respirations, as you prepare for
intubation
 Stridor – Gama hydroxybutyric acid is sometimes made with lye, can
cause airway burns and edema
If Airway/Breathing are impaired
Begin high-flow Prepare to manage the
oxygen airway
• To reduce hypoxemia • Remove obstacles
• Or intubation in severe cases

Stabilizing
A&B

Auscultate lungs Obtain STAT chest X-

carefully ray
• Checking lung sounds • To get an idea about what’s
going on physiologically
Circulation
 Once oxygen can be delivered to the lungs by a clear airway and
efficient breathing, there needs to be a circulation to deliver it to
the rest of the body.
 For an appropriate circulation, we should have normal blood
pressure (120/70 mmHg) and a normal rhythmic pulse/heart rate
(between 60-80 beats per minute).
 Interventions which can be done to secure circulation:
◦ Secure the IV access for fluid replacement in states of shock.
◦ Obtain blood work/laboratory tests
◦ Measure & monitor blood pressure, & pulse
◦ Hypotension treatment:
 Normal saline fluid challenge, 20 mL/kg
 Vasopressors (adrenaline, noradrenaline, isoproterenol) if still
hypotensive
 Packed Reb Blood Cells (PRBC) /Blood transfusion if bleeding or
anemic
◦ Hypertension treatment:
 Nitroprusside, beta blocker, or nitroglycerin
◦ Continuous ECG monitoring
 To assess for arrhythmias, & treat accordingly
Vital signs related to Circulation

Pulse/Heart Cardiac Blood

rate rhythm pressure
If Circulation is impaired
Establish two large-bore IVs Identify cardiac rhythm
• For backup incritically ill patients • Differentiate from sinus to non-
sinus arhythmias

Stabilizing
circulation

Consider treating non-sinus Consider IV fluids

rhythms • Not all patients require fluids
but majority benefits from fluid
optimization.
• Fluid wont help in valvular
disease
Clinical presentation & diagnosis
Substance. Pertinent information includes the quantity of each ingredient
in the product. The history may be unreliable or unavailable in
suicidal patients or substance abusers; patients with altered mental
status or those exposed to a substance in an unmarked container or
who ingest an unidentified plant may be unable to provide a history.

Amount. If an accurate determination of the amount ingested is not

possible and the substance is toxic, a potentially toxic dose should be
assumed. For intentional exposures, the patient's report of the dose is
suspect.

Time since exposure. This information coupled with information on the

onset and duration of action of the substance, allows assessment of
whether clinical manifestations are consistent with the history of dose
and time since exposure. Whether to institute some therapeutic options,
including GI decontamination, is determined by time since ingestion.

Clinical manifestations. Evaluate if clinical effects are consistent

with the substance(s); if not, evaluate for other substances and/or medical
conditions. Severe effects (respiratory and cardiovascular depression)
necessitate immediate treatment.

Patient's age and weight. Determine the toxicity of the substance, dosing
of antidotes, and likely reason for the exposure based on this information.
ANTIDOTAL THERAPY
 NON-SPECIFIC
 SPECIFIC
NON SPECIFIC ANTIDOTES
 Activated Charcoal
 Activated charcoal by virtue of its large surface
area adsorbs many drugs and toxins. It is used
orally to limit the drug or toxin absorption.
 Initial dose
 1.0g /kg orally or via gastric tube
 Repeat dose
 15-30 g every 2-4 hours. Administer small dose of
cathartic with every 2nd or 3rd charcoal dose
 Patients showing nausea and vomiting require
antiemetic drugs also.
SPECIFIC ANTIDOTES
1 N-AcetylCysteine Paracetamol Poisoning

2 Flumazenil BDZ Poisoning

3 Atropine/pralidoxime Pesticide Poisoning

4 Oxygen Carbon Monoxide

Poisoning
5 Pencillamine Heavy metal Poisoning

6 Deferoxamine Iron poisoning

 Common Emergency Treatments for
Poisoning
poisoning
Antidote/Treatment Mechanism
Paracetamol N-acetyl cysteine Act as –SH group donor,
(acetaminophen) increasing glutathione
production.
Morphine, Codeine, Naloxone Competitive antagonism
Heroine, Methadone,
Iron Deferoxamine Chelation
Copper (in Wilson’s Penicillamine Chelation
disease)
Salicylates Charcoal, Alkalization Decreased Absorption
(NaHCO3) Increased elimination
Petroleum distillates & Activated charcoal, Decreased Absorption
Solvents (insecticides). Supportive treatment
Methanol (wood alcohol) gastric lavage. Decreased Absorption
Hemodialysis
folic acid, thiamine, breakdown of toxic
and pyridoxine metabolites
BZD Flumezanil Competitive antagonism
Activated Charcoal
 It contains the extremely small particles and have pores
that’s why it absorbs the toxins. The particle surface area
may exceed from 3000 m2. A substance that is absorbed
to activated charcoal cannot be absorbed from GIT.
 Activated Charcoal is a highly absorbent gritty black
material that is commonly found in air and water filters.

Therapeutic Uses for Activated Charcoal

 1. Universal antidote for drugs, chemicals and poisons.
 2. Systemic clearance of drugs and intoxicants.
 3. General detoxification.
 4. Anti-aging and life extension.
 5. Reducing cholesterol, coronary disease and
arteriosclerosis.
 6. Counteracting pathogens.
 7. Intestinal complaints.
Factors affecting charcoal activity:
 1. The type of toxicant (its chemical structure
and physical properties).
 2. The amount and type of charcoal ingested.
 3. The length of time from toxin ingestion to
Activated Charcoal ingestion.
 4. The contents of your intestinal fluids and
intestinal transport efficiency

Dose
 Child Dose under 12 years (1g/kg body
weight) Adult Dose 50grams
N-Acetyl Cysteine
 It is an antidote for paracetamol poisoning
Mechanism of action
 It acts as a sulfhydral group donor, substituting
glutathione. It rapidly binds with the reactive
metabolites. The toxic metabolites N-acetyl Para
benzo quinine imines in the liver. The glutathione
conjugates these toxic metabolites and prevent
hepatotoxicity.
Naloxone
 It is indicated in the patients with opiate drugs such as
Morphine, Codeine, Heroine, Methadone
 These drugs tend to produce extreme drowsiness
associated with respiratory compromise and hypoxia

Mechanism Of Action
 It acts as competitive antagonist