Introduction to Toxicology

Introduction to Toxicology

• Toxicology studies harmful effects of chemicals/substances on people, animals, and the environment
• Study of poisons

Scope of Toxicology

• Toxicology encompasses the mechanism of action and exposure to chemicals
• It helps understand physiology and pharmacology using toxic agents
• It helps identify and quantify hazards from occupational exposure
• New drugs and pesticides are discovered through toxicology
• It develops standards and regulations to protect humans and the environment

Toxin

• Toxins are poisonous substances, often proteins
• They are produced by animals, plants, and pathogenic bacteria
• Capable of stimulating production of antitoxins

Toxicant

• Toxicants a poisonous substance, either synthetic or man-made
• often originating from industrial processes
• They possess mass tonnage, are widely distributed, and have compositional heterogeneity and ubiquity

Branches of Toxicology

• Mechanistic toxicology explains how chemicals cause toxic responses at the cellular, biochemical, and molecular levels
• Forensic toxicology focuses on the cause of death and legal aspects
• Clinical toxicology involves treatments to reverse injuries and poisonings caused by xenobiotics
• Environmental toxicology studies pollutants' effects on flora and fauna

Food and Regulatory Toxicology

• Food toxicology addresses adverse effects of processed or natural food components
• Regulatory toxicology assigns risk to substances of commercial importance

Dose-Response Curves

• Illustrate the relationship between substance exposure and effect

Therapeutic Index

• Used to compare toxicity of compounds
• Calculated via LD50/ED50 or TD50/ED50
• A larger ratio indicates greater relative safety

Assessment of Poisoned Patients: Burden of Poisoning

• Poisoning is a leading cause of injury-related death
• Most deaths are unintentional
• Over 90% of toxic exposures occur at home involving a single substance
• Most exposures occur through ingestion
• 40% of cases involve non-drug agents
• 60% involve drugs like analgesics, vitamins/topical preparations, and antihistamines

Assessment of Poisoned Patients: Approach

• Similar to trauma assessment and management (ABCDE’s of Trauma):
• Airway: Check if the patient can talk without voice changes
• Breathing: Check rate, rhythm, and symmetric chest wall rise
• Circulation: Check blood pressure and pulse
• Disability: Assess mental state and level of consciousness
• Exposure: Uncover areas, look at the abdomen and perineum

Assessment of Poisoned Patients: Physical Examination

• Targeted history and physical examination refines a differential diagnosis refined via diagnostic testing
• History:
• Determine if poisoning was intentional
• Look for witnesses
• Apply OLDCARTS for symptoms:
• Onset, Location, Duration, Character, Aggravating and Alleviating factors, Relieving factors, Timing, Associated Symptoms
• Identify any toxic syndrome
• Gather information to identify the poison and amount taken

Assessment of Poisoned Patients: Physical Examination specifics

• Includes orderly Inspection, Palpation, Percussion, and Auscultation
• Head-to-Toe or Systems-Based evaluation focuses on:
• Vital Signs
• Mental Status
• Pupils
• Nystagmus
• Skin
• Bowel sounds
• Muscle tone

Assessment of Poisoned Patients: Diagnostics

• A basic chemistry panel is necessary for all poisoned patients
• Includes electrolytes, renal function tests, and glucose measurement
• Patients with acidosis should have an anion gap calculated
• Paracetamol poisoning: check liver transaminases and INR
• Prolonged “down time” requires creatinine kinase evaluation to evaluate rhabdomyolysis

Assessable Toxins in Blood

• Blood can be tested for Salicylates, Anticonvulsants, Acetaminophen, Iron, Digoxin, Methanol, Ethanol, Lithium, Ethylene Glycol, Theophylline, Lead, and Carbon Monoxide

Abnormalities in Blood pH

• Prevented by:
  • Proteins
  • Bicarbonate buffer system (Respiratory)
  • Ammonium buffer system (Urinary)

Normal Values to maintain in ABG, arterial blood gases

• Normal arterial blood gas levels:
  • pH = 7.35-7.45
  • Carbon dioxide = 35-45 mmHg
  • Oxygen = 80-100 mmHg
  • Bicarbonate = 22-26 mmol
  • Oxygen saturation = 95-100%

Agents Causing Anion Gap Metabolic Acidosis (MUDPILES CAT)

• Methanol, metformin, uremia, diabetic ketoacidosis, propylene glycol, isoniazid, iron, massive ibuprofen, lactic acidosis, ethylene glycol, salicylates, cellular asphyxiants (CN, CO, H2S), alcoholic ketoacidosis, Tylenol

Management of the Poisoned Patient

• Supportive care
• Directed Therapy
• Decontamination
• Enhanced elimination
• Keep the patient alive and stabilize vital signs
• Only available antidote can be used while supportive care is maximized

Supportive Care

• Goal: support the patient’s vital functions until the patient can eliminate the toxin.
• Ensure adequate Airway, Breathing, and Circulation
• Patients can quickly become comatose
• Endotracheal intubation is often needed

Hypotension in Poisoned Patients

• Poisoned patients can be hypotensive while euvolemic:
• Standard bolus of 1 unit of crystalloid
• Direct acting vasopressor (norepinephrine or epinephrine)
• If with seizure: GABA potentiating medications are preferred

Decontamination

• Goal is to minimize absorption of toxic substances
• Efficacy decreases over time once exposed
• Dermal and Ocular Decontamination involves removal of contaminated clothing and particulate matter
• and flushing of the affected area with tepid water or normal saline

Flushing methods

• Alkaline corrosives: flush longer
• Lipophilic toxins: cleansing with soap is necessary
• React with water: elemental Na, P, CaO, Titanium tetrachloride should NOT be cleansed with water
• Inhalational exposure: move to fresh air and administer supplemental oxygen, if indicated

Gastrointestinal Decontamination

• Likely most effective in first 1-2 hours after ingestion
• Delayed gastrointestinal absorption of poisons:
  • Agents that slow motility (anticholinergics and opioids), massive amount of pills, sustained-release preparations, and agents that form bezoars

Methods of GI Decontamination

• Induced emesis with ipecac
• Gastric lavage
• Cathartics
• Activated charcoal
• Whole bowel irrigation

Syrup of Ipecac use

• Contains Emetine and Cephaeline (emetic alkaloids)
• Its use is CURRENTLY ABANDONED

Gastric Lavage

• Procedure: Insertion of large tube into stomach to aspirate content and flush with aliquots of fluid
• Poor clinically relevant efficacy
• Disadvantages:
• time-consuming, painful, causes bradycardia, delays administration of definitive treatment

Single-Dose Activated Charcoal

• Charcoal is activated by heating to extreme temperatures creating pores to provide ADsorptive surface area and prevent GI tract absorption
• AC does not work with charged molecules, and liquids
• Effective when given within 1 hour of ingestion
• Extended Release (with erratic absorption) preparations and salicylate poisoning are best treated with activated charcoal
• Administer 1g/kg or 50-100 grams to adolescents and adults

Cathartics

• Sorbitol, Magnesium sulfate, Magnesium citrate
• Adjuncts to activated charcoal that prevent constipation
• They accelerate evaluation of the charcoal-toxin complex

Whole Bowel Irrigation

• Instillation of large volumes of PEG-electrolyte solution via NG tube, until rectal effluent is clear
• Goal: "wash out” intestinal tract Specific Instances
• Poisoning with sustained release medications
• substances not well adsorbed by charcoal
• foreign bodies,
• Cathartics: Contraindicated in patients with, signs of ileus and compromised airway

Antidotal Therapy

• Available for few toxins, key to poison management
• Intralipid Emulsion Therapy:
  • Sequester fat-soluble drugs
  • Supply energy source
  • Increase calcium
• Indicate those with hydrophobicity

Hemodialysis

• Few drugs/toxins are removed in amounts to justify risks and difficulties
• Toxins amenable have: low volume distribution, high water solubility, low molecular weight, and low protein binding
• Can correct severe electrolyte and acid-base derangements

Multi-dose Activated Charcoal

• Interrupts enterohepatic recycling and gastrointestinal dialysis
• Activated charcoal given by mouth doses every 4-6 hours