Toxicology Basics Quiz

Biochemical Toxicology

• The study of the adverse effects of chemicals on the body
• Approximately 80% of ER visits involve 24 common drugs or toxins
• Each lab has its own drug-testing menu
• Drug testing is important for workplace, competitive sports, pregnancy, and toxicity diagnosis

Diagnosis of Poisoning

• Diagnosis is often based on clinical findings rather than lab results
• Important data includes date/time of exposure and patient's physical condition/symptoms
• Each substance produces a specific toxic syndrome (toxidrome)
• Symptoms of different poisonings may overlap
• Common biochemical tests include serum urea, electrolytes, liver function tests (LFTS), blood glucose, and blood gases

Routes of Exposure

• Chemical's physical state and route of exposure affect toxicity
• Common toxic effects often occur at the site of absorption
• Toxins enter the body through skin, gastrointestinal tract, lungs, inhalation, injections, and eyes
• Concentration and solubility of a gas are important factors
• Gastrointestinal tract, metabolism, and distribution are involved in the process

Tests for Confirmation of Poisoning

• Signs and symptoms help identify the type of poisoning (e.g., anticholinergics, ethanol)
• Qualitative drug levels determine the presence/absence of a drug
• Examples include non-accidental poisoning and brain death confirmation
• Quantitative drug levels measure drug concentration, providing information for treatment, and indication of severity
• Serial measures (repeated measurements) can be beneficial

Dose-Response Relationship

• Any chemical can be toxic
• Most chemicals and drugs exhibit a dose-response curve unique to each substance
• A threshold is the minimum dose required to induce a response
• Some chemicals have no safe levels, and they are considered poisons.

Acute and Chronic Toxicity

• Toxic dose (TD) and lethal dose (LD) are relevant measures
• Acute toxicity occurs in a short time frame, such as single or multiple exposures
• Chronic toxicity develops over prolonged periods and often involves repeated or continuous exposure

Metal Poisoning

• Essential vs. toxic metals
• Metal poisoning is a significant and historical toxicity concern
• Chronic exposure to metals frequently causes tissue damage
• Toxic metals include lead, mercury, aluminum, arsenic, and cadmium
• Metal poisoning can influence toxicity; affecting the renal tubular system, gastrointestinal tract, and neurological systems.

Metal Poisoning - Lead

• Lead is an environmental toxin, frequently found in lead-based paint and soil
• Exposure occurs through ingestion, inhalation, and industrial pollutants
• Lead exposure can disrupt heme production, impact neuronal connection, and affect childhood mental development.
• Levels above 3.5 µg/dL are a cause for concern

Metal Poisoning - Mercury

• Mercury is a dense liquid that vaporizes at room temperature
• It is found in dental amalgams and old thermometers
• The most toxic form is methylmercury
• Exposure routes include inhalation, skin absorption, and ingestion of fish and shellfish
• Mercury concentrates in the kidneys before excretion; long-term exposure causes CNS toxicity

Metal Poisoning - Arsenic

• Arsenic is found in insecticides, pesticides and some paints
• Acute ingestion causes violent gastrointestinal pain, vomiting, shock and circulatory failure
• Chronic ingestion may cause difficult to diagnose illness including; diarrhea, dermatitis, renal symptoms and polyneuropathy
• Hair analysis >0.5 µg/g hair indicates significant exposure

Metal Poisoning - Diagnosis and Treatment

• Common clinical methods involve biochemical measurements
• Plasma, serum, and blood levels; urine and hair analysis are commonly used for diagnosis
• Common treatments include source removal, use of chelating agents (e.g., dimercaprol), and excretion

Alcohol Poisoning

Alcohols - Methanol

• Methanol (Methyl alcohol or wood alcohol) is commonly found in antifreeze
• Exposure routes involve ingestion, inhalation, and skin absorption
• Methanol is metabolized to formaldehyde and then formic acid, leading to metabolic acidosis and potentially blindness
• Lab considerations include anion gap, serum osmolality, and serum methanol levels

Alcohols - Ethanol

• Ethanol is a common cause of overdose
• Ethanol's mechanism of action affects cells and organs
• All trauma patients have ethanol measured; 0.08% - 80 mg/dL is the legal limit for driving in Ontario
• Acute ethanol poisoning is directly related to blood concentration and can include coma, other drugs, and head injuries
• Diagnosis includes blood ethanol measurement, plasma osmolality, and osmol gap
• Factors include health renal and hepatic functions

Alcohols - Ethanol (Chronic)

• Chronic ethanol abuse has toxic effects including acetaldehyde toxicity, liver failure from a disruption of homeostasis and synthetic mechanisms
• Early signs include hepatomegaly
• Sequelae (after-effects) include impaired glucose tolerance, diabetes mellitus, hypertriglyceridemia, cirrhosis, and coagulation defects.
• Diagnosis of chronic ethanol ingestion includes patient history, blood markers - gamma-glutamyl peptidase (GGT), Serum triglyceride, MCV (poor diet), and hyperuricemia

Alcohols - Isopropanol

• Isopropanol is a common solvent and disinfectant
• Exposure routes include ingestion and inhalation
• Isopropanol is metabolized in the liver to acetone; acetone is eliminated slowly by the body
• Consquences include CNS effects (2x ethanol effect) and rare cases of death.
• Diagnosis includes plasma isopropanol and urine acetone levels.

Alcohols - Ethylene Glycol

• Ethylene glycol is commonly used in antifreeze
• Exposure routes include ingestion
• Ethylene glycol (toxic metabolite) is metabolized to glycolic acid and oxalic acid, causing high anion gap and metabolic acidosis
• Ethylene glycol correlates to mortality rates; it is also a result of CNS intoxication
• Symptoms include nausea, vomiting, depressed reflexes, and coma

Anion Gap and Osmol Gap Usefulness in Toxicology

• The anion gap test is crucial in investigating toxidromes
• An increased anion gap indicates an increase in unmeasured anions (e.g., methanol, ethylene glycol, or salicylates)
• An increased osmol gap suggests the presence of other osmotically active substances (e.g., ethylene glycol, methanol, isopropanol, or acetone).
• These tests are useful in diagnosing poisoning cases.

Toxicity of Common Medications

• Drugs can have therapeutic effects and side effects.
• Drugs can also become toxic
• Common examples of toxic medications include salicylate and acetaminophen (paracetamol).

Toxicity of Common Medications - Salicylate Poisoning

• Acetylsalicylic acid (aspirin) can lead to salicylate poisoning
• The initial effects of salicylate poisoning are typically fast absorption and hydrolysis into salicylic acid
• Severe metabolic acidosis and respiratory alkalosis (stimulation of respiratory centre in the brain) can occurs.
• Hyperventilation can contribute to anion gap
• Symptoms can include tinnitus and acid-base abnormalities.

###Toxicity of Common Medications - Acetaminophen Poisoning

• Acetaminophen (paracetamol) poisoning involves a triphasic clinical corse
• Initially, the first 24 hours of acetaminophen poisoning may include nausea, vomiting, diaphoresis, and anorexia.
• Then, a period of apparent improvement will occur after 24-48 hours.
• The final stage may include serious hepatocellular damage, and possible liver failure
• A course of N-acetylcysteine is a recommended treatment

Chronic Poisoning

• Chronic poisoning involves a gradual buildup of drug concentration over time
• Ingestion of usual medications, plasma drug concentration and dose decrement, are good approaches to identify chronic poisoning.
• Consider synergistic effects, such as ethanol and benzodiazepines, which can have increased toxicity.

Role of the Laboratory in Poisoning

• Confirming diagnosis and providing information for patient management are prime roles of the laboratory
• Include further investigation, provision of antidotes, conducting hemodialysis, and aiding in diagnosis of brain death
• Laboratory testing is essential in forensic cases