Clinical Chemistry Blog Notes 19F

TOXICOLOGY…

Toxicology is the study of substances toxic to the body. It is the study of the adverse effects of chemicals on living organisms. It is the study of symptoms, mechanisms, treatments and detection of poisoning, especially the poisoning of people.

Absorption of toxins in the gastrointestinal tract is by passive diffusion – this process requires that the substance cross cellular barriers. Toxins that are not absorbed from the gastrointestinal tract do not produce systemic effects but may produce local effects –diarrhea, bleeding and malabsorption of nutrients.

In cases of drug overdose, CBC, serum electrolytes, BUN, glucose, urinalysis and blood gas must be determined.

Common substances causing acute toxicity: Alcohol, acetaminophen, salicylate and carbon monoxide.

Routes of exposure:

Ingestion
Inhalation
Trans dermal absorption

TERMINOLOGIES

· Acute toxicity- single, short term exposure to a substance

· Chronic toxicity- repeated exposure for extended period of time

· TD₅₀- is the dose that would be predicted to produce a toxic response in 50% of the population.

· LD₅₀-is the dose that would predict death in 50% of the population

· ED₅₀- is the dose that would be predicted to be effective of have a therapeutic benefit in 50% of the population.

I. TOXIC AGENTS

A. Alcohols

- Common depressants.

- Cause disorientation, euphoria, confusion and may progress to unconsciousness, paralysis and even death.

- Symptoms of alcohol intoxication begin when the concentration is >0.05%w/v (>50 mg/dl blood alcohol)

1.    Ethanol (grain alcohol)
-      most common abused drug
-      it is converted to acetic acid
-      ethanol abuse causes acidosis through accumulation of ketones and lactates and also through direct generation of hydrogen ions as alcohol is oxidized
-      causes diuresis by inhibiting ADH
-      “hangover symptoms” due to the effects of acetaldehyde
-      Major metabolic pathway: conversion to acetaldehyde by alcohol dehydrogenase (AD)
-      Detection limit: 12 hrs
-      Fatal dose: 300-400 ml of pure alcohol consumed in less than one hour
-      Toxic blood levels: 250-400 mg/dl

2.    Methanol (wood alcohol)
-      Commonly used solvent and a contaminant of homemade liquors.
-      Converted first into formaldehyde, then finally formic acid in the liver
-      Fatal dose: 60-250 ml

3.    Isopropanol (rubbing alcohol)
-      Metabolized to hepatic ADH to acetone
-      Fatal dose: 250 ml

4.    Ethylene glycol (1,2-ethanediol)
-      Common constituent of hydraulic fluid and antifreeze
-      Converted to oxalic acid and glycolic acid
-      Production of final product leads to deposition of calcium oxalate crystals in renal tubules
-      Fatal dose: 100 mL for adults (70 kg)

B.   Carbon Monoxide
-      Colorless, odorless, tasteless gas
-      Very toxic substance
-      Incomplete combustion of carbon-containing substances like gasoline engines, organic materials in fire and cigarette smoke.
-      Toxic levels: 20% CO
-      Indicator of toxicity: “cherry red” color of the face
-      Sample for testing: EDTA whole blood
-      Method of testing: co-oximetry

C. Cyanide
-      Can exist as solid, gas or in solution;
-      Super toxic substance
-      Component of insecticides and rodenticides
-      Common suicide agent
-      Pyrolysis product- burning of plastics
-      Characteristic: odor of bitted almonds
-      Antidote: sodium thiosulfate, amyl and sodium nitrite
-      Toxic symptoms: tachypnea, convulsions, coma
-      Toxic levels: >2µg/ml

A.   Metals
-      All metals can be toxic if ingested in large quantities and absorbed in their ionized forms.

1.    Arsenic
-      Component of rodenticides, paints and metal alloys
-      Acute fatal dosage: 120 mg

2. Lead
-      Component of household paints
-      Significant environment pollutant
-      Exposure to this metal results to encephalopathy, birth defects and compromised immunity
-      Toxicity dose: >0.5mg/day
-      Toxic blood levels: >70µg/dl (definitive lead poisoning)

3.    Mercury
-      Binds with proteins
-      Small drops of mercury on bench tops and floors can poison the environment in a poorly ventilated room.
-      Significant exposure: >50µg/dl (whole blood)

II.             Drug Abuse