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