Download Toxicology

References
1. Casarett & Doull’s: Essentials of Toxicology, 2nd Ed.,
2010 by Curtis Klaassen and John Watkins III
2. Poisoning and Drug Overdose, 6th Ed., 2012 by
Kent R. Olson
3. Goldfrank's Toxicologic Emergencies, 10th Ed. 2014
by Lewis R. Goldfrank
4. Emergency Toxicology, 2nd Ed., 1998 by Peter
Viccellio
Toxicology (1203562)
(2 credit hours)
Dr. Khawla Abu Hamour
Department of Biopharmaceutics & Clinical Pharmacy
University of Jordan
Introduction:
TOXICOLOGY IN PERSPECTIVE
DEFINITIONS & TERMINOLOGY
• Toxicology: (toxicum) & (logia)….the Study of Poisons
(The science of poisons, including their source, chemical
composition, action, tests, and antidotes).
• Poisons: are drugs that have almost exclusively harmful effects
• However, Paracelsus (1493–1541) famously stated that “THE DOSE
MAKES THE POISON”
• a substance that, on ingestion, inhalation, absorption,
application, injection, or development within the body, in
relatively small amounts, may cause structural or functional
disturbance. Called also toxin
• biologic origin, ie, synthesized by plants or animals, in contrast to
inorganic poisons (lead and iron)
• Toxicology: is the branch of pharmacology that deals with the
undesirable effects of chemicals on living systems
Disciplines of Toxicology
TOXICOLOGY DISCIPLINES
Applied Toxicology.
 Environmental toxicology:
• study the effects of chemicals that are contaminants of
food, water, soil, or the atmosphere
 Industrial (occupational) toxicology:
• Toxic exposure in the work place or during product
testing
 Clinical (medical) toxicology: focus on the diagnosis,
management and prevention of poisoning or ADEs due to
medications, occupational and environmental toxins, and
biological agents
TOXICOLOGY DISCIPLINES
 Veterinary toxicology**
 Forensic toxicology: is the use of toxicology to aid medical
and legal investigation of death
 Nanotoxicology: is the study of the toxicity of nanoparticles
(<100 nm diameter). Because of large surface area to volume
ratio, (nanomaterials have unique properties compared with
their larger counterparts)
What is a Poison??
• “What is there that is not poison?
All things are poison and nothing without
poison. Solely, the dose determines that a
thing is nota poison”
Paracelsus (1493-1541)
Water Intoxication?
 Water poisoning….fatal disturbance in brain functions
when the normal balance of electrolytes in the body is
pushed outside of safe limits (e.g., hyponatremia) by
overhydration
 Water, just like any other substance, can be considered
a poison when over-consumed in a specific period of
time
 Intravenous LD50 of distilled water in mouse is 44ml/kg
 Intravenous LD50 of isotonic saline in mouse is 68ml/kg
What is a Poison??
 Poisoning or exposure??
 Many people consider that poisoning start the moment
exposure occurs
 In reality, we are exposed to a wide variety of toxic
substances each day from food and water that we
ingest, and air that we breath
 We do not display toxic symptoms, we are not actually
poisoned
• Exposure is defined as:
• Actual or suspected contact with any substance
which has been ingested, inhaled, absorbed,
applied to, or injected into the body, regardless
of toxicity or clinical manifestation.
• Poisonings happen when the exposure results in
an adverse health reaction; when a substance
interferes with normal body functions after it is
swallowed, inhaled, injected, or absorbed.
What is Response?
Change from normal state – could be molecular, cellular,
organ, or organism level……the symptoms
 The degree and spectra of responses depend upon the
dose and the organism
 Immediate vs. Delayed (carcinogenic)
 Reversible vs. Irreversible (liver vs. brain, teratogenic
effect)
 Local vs. Systemic
 Graded vs. Quantal……degrees of the same damage vs.
all or none
 Allergic Reactions & Idiosyncratic Reactions….ADRs
Dose
 The amount of chemical entering the body
 This is usually given as:
mg of chemical
/ kg of body weight = mg/kg
 The dose is dependent upon:
 The environmental concentration
 The exposure pathway
 The length of exposure
 The frequency of exposure
 The properties of the toxicant
Exposure: Pathways
 Routes and Sites of Exposure:
 Ingestion (GIT), (first pass effect)

Ex. Lidocaine and Verapamil (antiarrhythmic drugs)
 Inhalation (Lungs): rapid absorption, because of large alveolar
surface area
 Dermal/Topical (Skin), absorption varies with area of
application and drug formulation, but usually absorption is
slower than other routes
 Injection

Intravenous, intramuscular, intraperitoneal
 Typical response of Routes and Sites of Exposure:
i.v > inhalation > i.p > i.m > oral > topical
Exposure: Duration

Toxicologists usually divide the exposure of experimental
animals to chemicals into 4 categories……:
Acute
< 24hr
Usually 1 exposure
Sub-acute
1 month
Repeated exposure
Sub-chronic
1-3 months
Repeated exposure
Chronic
> 3 months
Repeated exposure
 Over time, the amount of chemical in the body can build up, it
can redistribute, or it can overcome repair and removal
mechanisms
 Lethal injection by capital punishment…..
The other time-related factor that is important in the temporal
characterization of repeated exposures is the frequency of exposure
Exposure = Intensity x Frequency x Duration
Exposure = How much x How often x How long
Dose Response Relationship
 The magnitude of drug effect depends on the drug
concentration at the receptor site, which is in turn
determined by the dose of drug administered and by
factors of the drug pharmacokinetic profile
 There is a graded dose-response relationship in each
individual and a quantal dose-response relationship in a
population
Graded-dose response relationship
 The response to a drug is a graded effect, meaning that
the measured effect is continuous over a range of doses
 Graded dose response curves are constructed by plotting
the magnitude of the response against increasing doses of
a drug (or log dose)
Dose-Response Relationship
 As the dose of a toxicant increases, so does the response
Steep
curve….relative
small dose changes
cause large
response changes
Graded-dose response relationship
 Two important properties of drugs can be determined by
the graded dose response curves:
 Potency
 Maximal toxicity
‘U’ Shape of the Dose-Response Curve
Quantal-dose response relationship
 The quantal (all or none) dose-effect curve often
characterizes the distribution of responses to different
doses in a population of individual organisms
 Median toxic dose(TD50): the dose at which 50% of
individuals/population exhibit a particular toxic effect
 If the toxic effect is death of the animal, a median lethal
dose (LD50) may be experimentally defined
 Median effective dose (ED50) is the dose that produces a
quantal effect (all or nothing) in 50% of the population
that takes it
LD50
 The dose of chemical required to produce death in
50% of the organism exposed to it
 LD50 is not an absolute description of the
compound toxicity in all individuals…..Variations
 it’s possible to take more than the lethal dose and live,
and take less of the lethal dose and die.
 the LDLo (Lethal Dose Low) is the lowest dose known
to have resulted in fatality in testing, whilst the LD100
(Lethal Dose 100%) is the dose at which 100% of the
test subjects are killed.
No. of individuals
Quantal-dose response relationship
Hyper
susceptible
Resistant
Majority
Sever Response
Mild Response
Dose or log dose
Toxicity rating chart
Rating
Oral Lethal Dose
Partially non toxic
>15 g/kg
Slightly toxic
5-15 g/kg
Moderately toxic
0.5-5 g/kg
Very toxic
50-500 mg/kg
Extremely toxic
5-50 mg/kg
Super toxic
<5 mg/kg
Assumptions in Deriving the DoseResponse Relationship
1. Confirms that a chemical is responsible for a
particular effect
2. Establishes the lowest dose for which an effect
occurs – threshold effect (µg’s….g’s)
3. Individuals vary in their response to a certain dose
of xenobiotic
4. The magnitude of the response is related to the
dose………!!!!!
!!!……Molecular Target Concept
Agonist
Antagonist
Toxicodynamics & Kinetics
Toxicodynamics
Toxicodynamics refers to the molecular,
biochemical, and physiological effects of
toxicants or their metabolites in biological
systems
These effects are result of the interaction of the
biologically effective dose of the ultimate (active)
form of the toxicant with a molecular target
Toxicokinetics: Disposition (ADME)
• Toxicokinetics is the quantitation of the time course of
toxicants in the body during the processes of absorption,
distribution, biotransformation, and excretion or clearance
of toxicants
• In other words, toxicokinetics is a reflection of how the
body handles toxicants as indicated by the plasma
concentration of that xenobiotic at various time points
• The end result of these toxicokinetic processes is a
biologically toxic concentration of the toxicant/s
Absorption
 Ability of a chemical to enter the blood stream (GI tract, skin,
lungs)
 Absorption: RATE & EXTENT
 The rate is of toxicological importance coz is the main
determinant of the peak plasma concentration
 The extent determine the total body exposure or internal
dose
 The fraction absorbed…..bioavailability(F)
 Comparing to i.v (1 or 100%)
Absorption
 Route of exposure
 Inhalation: readily absorb gases into the blood via the
alveoli (large alveolar surface, high blood flow)
 Particle size is the main determinant, ≤ 1μm penetrate the
alveolar sacs of the lungs (nanoparticles!!)
 Enteral administration: particle size, surface area, blood
flow rate, pKa, Pgp, intestinal motility??
Factors influencing Toxicity
Oral is related to:
• Solid forms? Tendency to
clump together
• Presence of food:
• protein and fat delay absorption,
• carbohydrate beverages increase
absorption
Absorption
 Dermal: fortunately not very permeable
 Absorption through epidermis by passive diffusion (stratum
corneum thickness, condition of skin, blood flow, small size)
 …..then dermis by diffusion….systemic circulation
 Parenteral: I.V, I.P, I.M, S.C
 Physicochemical properties of the toxicant..
Distribution
 The process in which a chemical agent translocates
throughout the body
 Blood carries the agent to and from its site of action, storage
depots, organ of transformation, and organs of elimination
 Storage in adipose tissue: very lipophilic compounds (DDT)
will store in fat
 Rapid mobilization of the fat (starvation) can rapidly
increase blood concentration
 Liver and kidney: high binding capacity for several chemicals
 Storage in bone: chemicals analogues to calcium, fluoride,
lead, strontium
Distribution: storage & binding
 Rate of distribution dependent upon
 Blood flow
 Characteristics of toxicant (affinity for the tissue, and the partition
coefficient)
 Binding plasma proteins: in equilibrium with the free portion,
displacement by another agent
 Distribution may change over time
 BBB……tight capillary endothelial cells, P-gp (not fully developed
at birth)
ELIMINATION =
EXCRETION + METABOLISM
Elimination
 Toxicants are eliminated from the body by several routes
 Urinary excretion
 Water soluble products are filtered out of the blood by the
kidney and excreted into the urine
 Exhalation
 Volatile compound are exhaled by breathing
 Biliary excretion via fecal excretion
 Compounds can be extracted by the liver and excreted into
the bile. The bile drains into the small intestine and is
eliminated in the feces
 Milk, Sweat, Saliva
Metabolism (biotransformation)
 Toxicity depends on the concentration of active compound
at the target site over time
 The process by which the administered chemical (parent
compound) are modified by the organsim by enzymatic
reactions
 1st objective – make chemical agents more water soluble
and easier to excrete
 Increase solubility ---- decrease amount at target
 Increase ionization ---- increase excretion rate ---- decrease toxicity
 Bioactivation/toxication ---- biotransformation can result in
the formation of reactive metabolites
Metabolism (biotransformation)
 Can drastically affect the rate of clearance of compounds
 Can occur at any point during the compound’s journey from
absorption to excretion
 Key organs in biotrasnformation
 Liver (principal)
 Intestine,
 Lung, kidney
 Biotransformation pathways
o Phase I: make the toxicant more water soluble
o Phase II: links with a soluble endogenous agent
Factors influencing Toxicity

Poisoning do not always follow the “text-book” descriptions
commonly listed for them

S&S that are often stated as being pathognomonic for a particular
toxic episode may or may not be evident with each case of poisoning

An experimentally determined acute oral toxicity expression, such as
LD50 value, is not an absolute description of the compound’s
toxicity in all individuals

Imp. principle to be always kept in mind when evaluating a victim’s
response to a toxic chemical is that there are numerous factors that
may modify the patient’s response to the toxic agent

Those factors are the same as those which determine a drug’s
pharmacologic action
Factors influencing Toxicity
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
COMPOSITION OF THE TOXIC AGENT
DOSE & CONCENTRATION
ROUTE OF EXPOSURE
METABOLISM OF THE TOXICANT
STATE OF HEALTH
AGE & MATURITY
NUTRITIONAL STATE
GENETICS
GENDER
ENVIRONMENTAL FACTORS
Factors influencing Toxicity
1. Composition of the toxic agent:
 A basic fallacy: responsible toxicant is the pure substance
 Physiochemical composition of toxicant: solubility,
charge, hydrophobicity, powder/dust
• Solid vs Liquid
• Poisoning is more with liquid and small particles (particle
size)
Factors influencing Toxicity
1. Composition of the toxic agent:
 E.g: Cr3+ relatively non-toxic, Cr6+ causes skin and nasal
corrosion and lung cancer
 PH: strong acids or bases vs mild acids and basics
 Stability:
paraldehyde…..acetaldehyde
pulmonary edema)
(nausea,
Factors influencing Toxicity
2. Dose and concentration:
 Most important factor: e.g. acute ethanol exposure
causes CNS depression, chronic exposure liver cirrhosis
 Diluted solutions Vs concentrated solution (easily
absorbed)
3. Route of exposure
Factors influencing Toxicity
4. Metabolism of the toxicant
 1st pass effect
• NOT ALWAYS
• MeOH Ox. Formaldehyde + Formic acid …serious side
effects
5. State of health:
• Hepatic, renal insufficiency
• Diarrhea or constipation may decrease or increase the
time of contact between chemical and absorptive site
• Hypertension may exacerbate response to chemical with
sympathomimetic activity
Factors influencing Toxicity
6. Age and maturity
• Chloramphenicol….grey baby syndrome
• Geriatric….generalized decrease in blood supply to
tissue…..decrease in toxicity….(not always)
• P.O drugs….absorption decrease
• Diseases (hepatic, renal,
excretion, distribution
CV)….decrease
detoxification,
Factors influencing Toxicity
7. Nutritional state
• Empty stomach or food contents (pH, high fat,….)
 Ca2+ in milk and tetracycline
 Fatty food increase absorption of griseofulvin
 Tyramine rich food and MAO inhibitors
 Hypoalbuminemia: greater amount of free drug
Factors influencing Toxicity
9. Gender
• Difference in absorption…..
• Difference in metabolism rate….
• Differences in quantities of muscle mass and fat
tissue….in i.m injection
Factors influencing Toxicity
8. Genetics: (Genetic toxicology….normal Gaussian curve)
• Species, strain variation, inter-individual variations
• Succinylcholine metabolized by pseudocholisterenase into
succinylmonocholine + choline then….
Esterase (liver)
Succinic acid + choline
• G6PD deficiency…..protect RBCs from oxidative damage,
may cause hemolytic anemia
Principle in management of poisoned
patient
What to do, and in what order to do it?!
“The surest poison is
time”
Ralph Waldo Emerson (1803-1882)
Poisoning in Jordan
• Period during 2006-2008 at the National Drug and Poison
Information Center (NDPIC) (poisoning emergency no. 109)
• The problem is underestimated and sometimes unreported
• The most common reason of poisoning was unintentional
(49.39%), followed by suicidal attempts (23.94%)
• The highest incidence was in children less or equal to 5 years
(34.9%), then 20-29 years (~23%)
Poisoning in Jordan
 The major cause of poisoning was due to drugs (42%) of all
exposures, where acetaminophen products were responsible
for most of the cases within this category (13.4%) then
benzodiazepines, NSAID and then antihistamines
 Bites and stings were relatively highly prevalent (23.7% of
exposures), which is justified by the geographical nature of
Jordan
 Then household products, hydrocarbons and pesticides
How Does the Poisoned Patient
Die?
 Many toxins depress the central nervous system
(CNS)…coma
 A comatose patients frequently lose their airway protective
reflexes and their respiratory drive
 ………may die as a result of airway obstruction by the
 flaccid tongue,
 aspiration of gastric contents in the tracheobronchial tree,
or
 respiratory arrest
 ......most commonly due to overdoses of narcotics and
sedative-hypnotic drugs (eg, barbiturates and alcohol)
How Does the Poisoned Patient
Die?
 Cardiovascular toxicity……Hypotension may be due to depression
of cardiac contractility
 Hypovolemia resulting from vomiting, diarrhea
 Peripheral vascular collapse due to blockade of -adrenoceptormediated vascular tone
 Lethal
cardiac
arrhythmias…….overdose
of
ephedrine,
amphetamines, cocaine, digitalis, and theophylline
 Hypothermia
hypotension
or
hyperthermia
can
also
produce
severe
How Does the Poisoned Patient
Die?
 Seizures may cause pulmonary aspiration, hypoxia, brain damage
 Cellular hypoxia may occur in spite of adequate ventilation (poisons
that interfere with transport or utilization of oxygen cyanide, HS,
CO..)
 Other organ system damage may be delayed in onset…..
acetaminophen or certain mushrooms / paraquat
 Finally some patients may die because the behavioral effects of the
ingested drug may result in traumatic injury (alcohol/sedativehypnotic drugs)
• A 62-year-old woman with a history of depression is found in
her apartment in a lethargic state. An empty bottle of
bupropion is on the bedside table. In the emergency
department, she is unresponsive to verbal and painful
stimuli. She has a brief generalized seizure, followed by a
respiratory arrest. The emergency physician performs
endotracheal intubation and administers a drug
intravenously, followed by another substance via a
nasogastric tube. The patient is admitted to the intensive
care unit for continued supportive care and recovers the next
morning. What drug might be used intravenously to prevent
further seizures? What substance is commonly used to
adsorb drugs still present in the gastrointestinal tract?
Principle in management of poisoned
patient
 While the majority of poisoned patients are awake and
have stable vital signs, some may present unconscious or in
shock…..so….:
1. Always assess the condition of the patients “ABCD”…clinical
evaluation
2. Decide what must be done and in what order
3. Once the patient is stabilized, and only then, try to identify
the poison, the quantity involved and how much time has
been elapsed since exposure
4. Then, proceed with decontaminating / antidoting the
poison
ABCD
 A
Airway
 B
Breathing
 C
Circulation
 D
Dextrose
Airway……Ensure airway and protect cervical spine
 Airway Assessment:
 Consider to breath and speak to assess air entry
 Signs of obstruction (flaccid tongue, vomitus….)
 Apnea, dysphonia, cyanosis, airway distress
 Management Goals:
 Optimize the airway position……force the flaccid tongue
forward and maximize the airway opening
 Prevent aspiration
 Permit adequate oxygenation
Airway……Ensure airway and protect cervical spine
• The following techniques are useful:.
• Caution: Do not perform neck manipulation if you suspect a
neck injury.
• Place the neck and head in the “sniffing” position, with the neck
flexed forward and the head extended….(chin lift to open the
airway)
• Apply the “jaw thrust” maneuver to create forward movement of
the tongue without flexing or extending the neck.
• https://www.youtube.com/watch?v=r3ckgEQEE_o
• Place the patient in a head-down, left-sided position…..allows the
tongue to fall forward and secretions or vomitus to drain out of the
mouth….(lateral decupitus position)
Oral axis
Pharyngeal axis
Tracheal axis
Airway
 The airway can also be maintained with artificial
oropharyngeal or nasopharyngeal airway devices
 Placed in the mouth or nose to lift the tongue and push it
forward.
Airway
 Endotracheal intubation: attempted only by those with training
 Complications: vomiting with pulmonary aspiration; local trauma
to the oropharynx, nasopharynx, and larynx; inadvertent
intubation of the esophagus or a main-stem bronchus; and failure
to intubate the patient after respiratory arrest has been induced
by a neuromuscular blocker
 Indications:
 Unable to protect airway
 Inadequate spontaneous ventilation
 Arterial blood gases (pCO2 > 60%)
 Profound shock
 GCS (Glasgow Coma Scale) ≤ 8
Orotracheal or nasotracheal
intubation
Two routes for endotracheal intubation.
A: Nasotracheal intubation. B: Orotracheal intubation.
13-15 mild injury, 9-12 moderate injury, 8 or less severe injury
Breathing
Pulse Oximetry
 By observation and oximetry (monitor the saturation of pt’s Hb)
 Ventilatory failure…..most common cause of death in poisoned
patients:
 Hypoxia……brain damage, cardiac arrhythmias, and cardiac arrest
 Hypercarbia…...acidosis (may contribute to arrhythmias)
 LOOK for mental status, chest movement, respiratory rate
 LISTEN for air escaping during exhalation, sound of obstruction
 FEEL for the flow of air, chest wall for crepitus
 ASSESS tracheal position, auscultation of all lung fields
Circulation
Check skin color, temperature, capillary refill
Check blood pressure and pulse rate and rhythm
Management: stop major external bleeding
Begin continuous ECG monitoring
Altered mental status
 A decreased level of consciousness is the most common
serious complication of drug overdose or poisoning
• Coma sometimes represents a postictal phenomenon after
a drug- or toxin-induced seizure
• Coma may also be caused by brain injury associated with
infarction or intracranial bleeding
 Coma frequently is accompanied by
depression, which is a major cause of death
respiratory
 May be complicated by hypotension, hypothermia,
hyperthermia, and rhabdomyolysis
Disability
Assess level of consciousness by AVPU method
A…..ALERT
V…..responds to VERBAL stimuli
P…..responds to PAINFUL stimuli
U…..UNRESPONSIVE
Size and reactivity of pupils
Movement of upper and lower extremities
The DONT Cocktail
 Administer supplemental oxygen
 Dextrose: All patients with depressed consciousness should
receive concentrated dextrose unless hypoglycemia is ruled
out
 Adults: 50% dextrose, 50 mL (25 g) IV.
 Children: 25% dextrose, 2 mL/kg IV
 Thiamine: is a cofactor in a number of metabolic pathways
allowing aerobic metabolism to produce ATP and,
 Important in normal neuronal conduction
The DONT Cocktail
• Given to prevent or treat Wernicke's syndrome resulting from
thiamine deficiency in alcoholic patients (poor diet) and others
with suspected vitamin deficiencies (100 mg, in the IV bottle or
intramuscularly)
• Naloxone: All patients with CNS depression and respiratory
depression should receive naloxone!
• If artificially ventilated…..not immediately necessary
• Caution: may precipitate abrupt opioid withdrawal
The DONT Cocktail
• DOSE:
• 0.4 mg IV (may also be given intramuscularly)
• If there is no response within 1–2 minutes, give naloxone, 2
mg IV
• If there is still no response and opioid overdose is highly
suspected give naloxone, 10–20 mg IV
Exposure
Remove clothes and other items that interferes
with a full evaluation
1. History
 Historical data should include the type of toxin
 Route of exposure
intravenous)
(e.g.
ingestion,
inhalation,
 Also ask about prior suicide attempts or psychiatric
history
 If the patient is a female in reproductive years, ask
about pregnancy and obtain pregnancy test
Identify the toxicant
SAMPLE
 S: substance, amount, time, correlate symptom
 A: allergies, age, gender, wt
 M: medication (including prescription drugs, OTC
medication, vitamins, and herbal preparation)
 P: past diseases, substance abuse or intentional
ingestion
 L: last meal….influence absorption
 E: events leading to current condition
ODORS
Acetone
Garlic
• Isopropyl alcohol
• Ethanol
• Arsenic
• Organophosphates
Bitter almonds
Rotten eggs
• Cyanide
• Sulfide
 Not absolute… the odor may be subtle and may be obscured by the
smell of emesis or by other ambient odors. In addition, the ability
to smell an odor may vary
Blood Pressure
HYPERTENSION
Sympathomimetics
Amphetamines
Cocaine
MAOI
Nicotine
HYPOTENSION
 Antipsychotic

Nitrates
 Beta blockers

Opioids
 Calcium channel blockers

Sedative-hypnotics
 Ethanol

Tricyclic antidepressants
(with tachycardia)
Pulse
TACHYCARDIA
Amphetamines
Atropine
Antihistamines
Caffeine
Cyanide
Nitrates
BRADYCARDIA
 Beta blockers
 Calcium channel blockers
 Clonidine
 Digitalis
 Mushrooms
 Organophosphates
 Sedative hypnotics
RESPIRATION
HYPERVENTILATION
 Rapid respirations are typical of toxins that produce
metabolic acidosis or cellular asphyxia..
Salicylates
Carbon monoxide
Ethylene glycol
Hydrocarbons
HYPOVENTILATION
Anesthetics
Cyanide
Ethanol
Sedative hypnotics
Opioids
TEMPERATURE
 HYPERTHERMIA (>40°C):
 Sympathomimetics
 Amphetamines
 MAOI
 Anticholinergic
 Drugs producing seizures or muscular rigidity
TEMPERATURE
 HYPOTHERMIA (<32°C):
 CNS depressants (barbiturates, opioids, ethanol)
 Hypoglycemic agents
 Drugs that cause vasodilation
 …..(especially if accompanied by cold environment)
 N.B: commonly accompanied by hypotension and
bradycardia
EYE FINDINGS
Miosis:
 Cholinergic
 Clonidine
 Insecticides
 Narcotics
 Phenothiazines
EYE FINDINGS
Mydriasis:
 Anticholinergic
 Sympathomimetic
 Withdrawal states
Nystagmus:
 Horizontal……phenytoin, alcohol, barbiturates
 Both vertical & horizontal: strongly suggest
phencyclidine poisoning
OTHERS
• Absent bowel sounds: paralytic ileus……anticholinergic
intoxication or perforation coz of acid ingestion
• Hyperactive bowel sounds, abdominal cramping and
diarrhea….organophosphates, A muscaria
• Determine if bladder distention and urinary retention
exist…..anticholinergic intoxication
• Skin appearance: red, white, blue, warm, cool, dry, moist,
piloerection (opioid withdrawal)
Inhalation exposure
• Irritant gases exposure!! mainly in industry, but also after
mixing cleansing agents at home, or smoke inhalation in
structural fires
• Health care providers should protect themselves from
contamination
• Eg.: “organophosphate, fumes of H2S, cyanide, ammonia,
formaldehyde”
Inhalation exposure
Treatment:
 Immediate removal from hazardous environment
 100% humidified O2
 Assisted ventilation
 Bronchodilators
 Observe for noncardiogenic pulmonary edema. Early signs
and symptoms include “dyspnea, tachypnea, hypoxemia”
 Monitor arterial blood gases or oximetry, chest x-ray, and
pulmonary function