Laboratory Principles And
Toxicological Screening
Hasan Alhaddad, MSc
Department of Pharmacology and Toxicology
College of Pharmacy/ University of Baghdad
2014
Introduction to Clinical Toxicology
Objectives
To learn applications of the principles of the
drugs and chemicals-induced toxicity in
humans, and gain experience in evaluation
steps and treatment measures based on
sample analyses and interpretation of
toxicity sings and symptoms
Introduction to Clinical Toxicology
A 33 year old woman came to the ED
• She found “down”
• She took something, as reports from scene
• No pill bottles on scene
• No family with her
• Person that found her are long gone
What should I do with her? How to treat her? Do I give her an
antidote?.....?
Introduction to Clinical Toxicology
• The discipline within toxicology concerned with the toxic
effect of
• Agents whose intent is to treat, ameliorate, modify, or prevent
disease states, or the effect of drugs which, at one time, were
intended to be used as such
• Agents used with non-therapeutic intent—for example, alcohol and
drugs of misuse and chemical byproducts of industrial development
• Clinical toxicology is focused on the diseases associated with
short-term and long-term exposure to various toxic chemicals
Introduction to Clinical Toxicology
• Clinical toxicologists are Individuals who specialize in clinical
toxicology
• Their work focuses around the identification, diagnosis, and
treatment of conditions resulting from exposure to harmful agents
• They usually study the toxic effects of various drugs in the body, and
are also concerned with the treatment and prevention of drug toxicity
in the population
Introduction to Clinical Toxicology
• Clinical toxicology is focused on the diseases associated with
short-term and long-term exposure to various toxic
chemicals. It typically coincides with other sciences such as
biochemistry, pharmacology, and pathology
• It focus on:
• Molecular responses to xenobiotics and the impact on the body
• Processes that determine the disposition of xenobiotics within the body
• Mechanisms responsible for the toxic effects of xenobiotics and their
metabolites
• Types of Toxicological testing include:
• Forensic toxicological analysis is conducted by laboratories for medical-legal
purposes, which include death and criminal investigations
• Workplace drug testing is conducted by laboratories for administrative
purposes, detecting misuses of drugs
• Diagnostic or hospital drug testing is conducted in laboratories to assist in
medical treatment
Laboratory of Clinical Toxicology
• A health care facilities have a systematic approach for the
assessment of the poisoned or overdosed patient
• Toxicological testing involves:
• History and physical examination
• Toxicological screening and lab. tests
History and Toxicology laboratory: Lab
Victim Triage
physical exam. tests, Toxicological screening
Treatments: terminate exposure,
prevent absorption,…etc.
Triage, history and physical examination
Triage
A process for sorting injured people into groups based on their
need for or likely benefit from immediate medical treatment
• Is always the first step performed
in the emergency department
• immediate danger VS potential
danger
• Immediate danger, the goals of
immediate treatment are patient
stabilization and evaluation and
management of airway,
breathing, and circulation (ABCs)
Triage, history and physical examination
History
• Taking a good history is possibly
more important for drug overdose
than for other medical problems, it
includes:
• Determine the mode of exposure
(inhalation, ingestion, etc.)
• State of the toxin (solid, liquid, gas)
• Quantity
• Time of exposure, and other
circumstances
• Age/weight, symptoms, reason for
exposure, previous therapy
Triage, history and physical examination
Physical Examination
• A quick but thorough physical examination is essential
• Toxidrome, is a group of signs and symptoms associated
with overdose or exposure to a particular category of
drugs and toxins
• Focus on poison specific symptoms
• Rule out other medical conditions/trauma
• Are signs/symptoms consistent with history
• Vital signs: BP, HR, RR, T, O2 saturation
• Mouth: odors, mucous membranes
• Pupils
• Breath sounds
• Bowel sounds
• Skin
• Urination/defecation
• Neurologic exam
Triage, history and physical examination
• Cholinergic Toxidrome
• SLUDGE
• Salivation, Lacrimation, Urination, Defecation, GI upset, Emesis
• Opioids Toxidrome
• Respiratory depression
• Miosis
• Hypoactive bowel sounds
• Sympathomimetics Toxidrome
• Hypertension
• Tachycardia
• Hyperpyrexia
• Mydriasis
• Anxiety, delirium
Toxicology Screen
• A toxicology screen refers to various tests to determine the
type and approximate amount of legal and illegal drugs a
person has taken
• This test is often done in emergency medical situations. It can
be used to evaluate possible accidental or intentional
overdose or poisoning
• Toxicology screening is most often done using a blood or urine
sample. However, it may be done soon after swallowing the
medication, using stomach contents that are obtained
through gastric lavage or after vomiting
• If the test is used as a drug screen, it must be done during a
certain time period after the drug has been taken or while
forms of the drug can still be detected in the body. Examples:
Amphetamines: 24 to 48 hour, and Barbiturates: up to 6
weeks
Toxicology Screen
• Basic testing typically screens for the following, commonly-
abused drugs
• Amphetamines
• Cannabinoids (marijuana, hashish)
• Cocaine
• Opiates (heroin, morphine, opium, codeine)
• Phencyclidine (PCP)
• Extended testing might also screen for some or all of the
following, but basic testing is the most common
• Barbiturates (phenobarbital, secobarbital)
• Benzodiazepines (tranquilizers like Valium, Librium, Xanax)
• Ethanol
• Hallucinogens (mushrooms, mescaline)
• Inhalants (paint, glue, hair spray)
• Anabolic Steroids (synthesized, muscle-building hormones)
Other Lab Tests
• Other essential Lab tests may include:
• Routine labs Electrolytes
• Glucose
• BUN and creatinine
• Urinalysis, urine drug screen
• Serum osmolality
• Acetaminophen, salicylates
• Specific drug levels
• Pregnancy test
• Carboxyhemoglobin, Methemoglobin
• Radiographic Examination, for visualizing toxins like
iron, lead
Other Lab Tests
Anion Gap
• Na – (HCO3 + Cl)
• Normal: 8-12 mEq/L (8-16)
• Causes: Methanol, Uremia, Iron, isoniazid, ibuprofen, Lithium, lactic
acidosis,…
Osmolar Gap
• Measured osmolality – Calculated osmolality
• Calculated osmolality = 2(Na) + glucose/18 + BUN/2.8 + Ethanol / 4.6
• Normal = 285-290 mOsm/L
• Gap > 10 mOsm/L suggests the presence of extra solutes:
• Alcohols: ethanol, mathanol
• Sugars, mannitol
• Lipids
• Proteins
• Clinical Pearl: Anion gap acidosis with an osmolar gap should
suggest methanol or ethylene glycol poisoning
General Treatments
• Treatment begins with first aid at the scene and continues
in the emergency department and often the intensive care
unit (ICU)
• Terminate exposure
• Prevent absorption
• Enhance elimination
• Medications, antidotes
General Treatments
• Terminate exposure
• Depends on route of exposure:
• Eye exposures – immediately flush eyes with
water/saline for 15-20 minutes
• Dermal – Remove jewelry, clothing. Brush off
powders. Immediately flush with water for 15
minutes (longer for caustics)
• Inhalation – Move to fresh air
• Injection/Bites and Stings – Remove clothing, jewelry
that might constrict the extremity. Do not excise and
apply suction to bites/stings
• Ingestion – Give a glass of water to dilute chemicals
such as caustics
General Treatments
o Prevent absorption:
• Indicated for recent ingestion, toxic substance, toxic amount.
• Syrup of Ipecac
• Ipecac may be used to induce emesis to treat unintentional
ingestions
• Can be used at home if there are no contraindications
• Should be administered within 30-60 minutes of ingestion
• Use has declined markedly; limited role for management of
poisonings in children
• Mechanism: direct irritant effect on GI mucosa and central emetic
effect
• Emesis occurs in 95% of patients within 30 minutes.
• Contraindications: Lethargy, Seizures, Hydrocarbons, Caustics,
foreign objects, and agents that produce rapid onset of CNS
depression or seizures (e.g. cyclic antidepressants, camphor,..)
• Side effects include drowsiness , diarrhea, and aspiration
pneumonitis
General Treatments
o Prevent absorption:
• Orogastric Lavage
• Removes stomach contents through a large bore tube until the
return is clear
• Little or no benefit over activated charcoal; consider for substances
not adsorbed by activated charcoal
• Lumen size is a limitation, especially in children.
• Adverse effects: aspiration, cyanosis, epistaxis, esophageal
perforation, hypothermia, fluid and electrolyte imbalances
• Activated charcoal is usually instilled following gastric lavage
General Treatments
o Prevent absorption:
• Activated Charcoal
• First line of therapy in the emergency department, the most commonly
used method of gastric decontamination
• Adsorbs substances to prevent systemic absorption
• More effective than ipecac
• Prevents absorption of toxins beyond the stomach (unlike ipecac and lavage)
General Treatments
o Prevent absorption:
• Activated Charcoal
• Dosage: 1 gram/kg administered orally or by nasogastric tube
• Adverse effects: aspiration pneumonitis, GI obstruction
• Cathartics: activated charcoal may be given with a cathartic
(usually sorbitol or magnesium citrate) to hasten the
elimination of the charcoal/toxin complex
• Second dose may be administered for single acute overdoses of
drugs for which delayed or continued absorption occurs (e.g.,
carbamazepine, salicylates, valproic acid, sustained release or
enteric coated preparations)
• Contraindicated if ileus is present or foreign bodies ingested
• Does not adsorb:
• Iron, lithium, sodium, lead, cyanide, Hydrocarbons,
Caustics, and alcohols
General Treatments
o Prevent absorption:
• Whole Bowel Irrigation
• Flushes the GI tract
• Uses large volumes of isotonic polyethylene glycol electrolyte
lavage solutions (Golytely, CoLyte)
• Reduces the absorption of iron, lead, and sustained-release
drugs
General Treatments
o Enhancing elimination
• Multiple dose activated charcoal
• Multiple-dose activated charcoal therapy involves the
repeated administration (more than 2 doses) of oral
activated charcoal to enhance the elimination of drugs
already absorbed into the body
• Increases gastrointestinal clearance of substances
• Dosing: 20-50 g activated charcoal every 4 hours
• Indications: Consider for overdoses of dapsone (acute or
chronic), phenobarbital (acute or chronic), phenytoin (acute
only), theophylline (acute or chronic)
• Complications include aspiration and bowel obstruction
General Treatments
o Enhancing elimination
• Hemodialysis/Hemoperfusion
• Indication: progressive deterioration despite intensive supportive
care
• Examples:
• Hemodialysis: phenobarbital, salicylates, alcohols, lithium.
• Hemoperfusion: meprobamate, theophylline, phenobarbital
• Chelation
• Involves the use of binding agents to remove toxic levels of metals
from the body, such as mercury, lead, iron, and arsenic
• Examples: dimercaprol (BAL in oil), calcium disodium edetate
(EDTA), succimer (DMSA), and deferoxamine
• Concerns about the toxicity of the chelators; their tissue
distribution characteristics; and the stability, distribution, and
elimination of the chelator–metal complex make chelation a
complicated procedure
General Treatments
o Enhancing elimination
• Hyperbaric Oxygen Therapy (HOT)
• 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
• The small number of HBO chambers and lack of around-the-clock
staffing limits the wide use of this therapy
General Treatments
o Antidotes
• Chemical agents, which attack or combine with the
poison in such a way as to render it insoluble, and so inert
• Counter-poisons
• No one antidote is suited to all emergencies. The antidote
is required to be adapted to the poison
General Treatments
o Antidotes
General Treatments
o Continuous Patient Monitoring
• Seriously poisoned or overdosed patients may
require continued monitoring for hours or days
after exposure
o Patient Teaching
• One of the interventions the nurse can perform in
the emergency department or intensive care unit is
preventive teaching
• All patients (and parents of pediatric patients) who
have survived a toxic encounter should be taught
how to prevent such an incident from recurring.
• Practice
1. A dad calls about his 1-year-old, 8 kg child who was found with an open bottle
of Extra strength Tylenol. The bottle looks almost as full as it did yesterday but
dad isn’t sure if any are missing.
2. A 27-year-old man is in the ED following a suicide attempt with a methanol
containing gas additive. His obtunded, responsive to pain with a respiratory
rate of 28/min. Physical exam is normal. ECG, chest and abdominal x-rays are
normal.
Serum chemistries: Na, 140 mEq/L, K, 3.0 mEq/L, Cl, 94 mEq/L, HCO3, 8
mEq/L, BUN, 12 mg/dL. ABGs: pH, 7.20, PCO2, 20 mmHg, PO2, 98 mmHg.
Serum methanol concentration = 67 mg/dL.
3. Mom calls to find out if amitriptyline is toxic. Her 12 year old is on
amitriptyline and left the container out on the bathroom counter. The 2-year-
old opened the safety closure and may have ingested some tablets.
