Download Factors influencing Toxicity

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
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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
absorbed)
3. Route of exposure
Vs
concentrated
solution
(easily
Factors influencing Toxicity
4. Metabolism of the toxicant
 1st pass effect
• NOT ALWAYS
Ox.
• MeOH
effects
Formaldehyde + Formic acid …serious side
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, CV)….decrease detoxification, excretion,
distribution
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?
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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 sedativehypnotic 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 or hyperthermia can also produce severe hypotension
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/sedative-hypnotic
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
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A
Airway
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B
Breathing
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C
Circulation
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D
Dextrose
Airway……Ensure airway and protect cervical spine
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Airway Assessment:


Consider to breath and speak to assess air entry
Signs of obstruction
(Restlessness, Cyanosis, Low SpO2, Apnea, cyanosis, airway distress)

Management Goals:

Optimize the airway position……force the flaccid tongue
forward and maximize the airway opening
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Prevent aspiration

Permit adequate oxygenation
Airway……Ensure airway and protect cervical spine
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The following techniques are useful:.
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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
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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
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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%)
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Profound shock

GCS (Glasgow Coma Scale) ≤ 8
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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