Post on 17-Jan-2016
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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. COMPOSITION OF THE TOXIC AGENT
2. DOSE & CONCENTRATION
3. ROUTE OF EXPOSURE
4. METABOLISM OF THE TOXICANT
5. STATE OF HEALTH
6. AGE & MATURITY
7. NUTRITIONAL STATE
8. GENETICS
9. GENDER
10. 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 (nausea, pulmonary edema)
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 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
Ox.
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….
• G6PD deficiency…..protect RBCs from oxidative damage, may cause hemolytic anemia
Esterase (liver)
Succinic acid + choline
Principle in management of poisoned patientWhat 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 -
adrenoceptor-mediated 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
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
(Restlessness, Cyanosis, Low SpO2, Apnea, 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 axisPharyngeal axisTracheal 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