Toxicology (LAB)

1-26 Intro, 27-51 Alcohols, 52-67 Metals, 68- 77 Caustic Agents and TDA

Toxicology

Study of poisonous substance

Mechanistic Toxicology

Toxicology where they examine dose-response relationships between xenobiotics and adverse effects.

Descriptive Toxicology

Toxicology where they predict harmful levels using animal experiments

Regulatory Toxicology

Toxicology where they Interpret mechanistic/descriptive studies to establish safe exposure levels.

Forensic

Toxicology Field where Medicolegal consequences of chemical/drug exposure

Environmental

Toxicology field where it evaluates chemical pollutants and human health.

Clinical

Toxicology field where it examines links between xenobiotics and disease states

Xenobiotics

Exogenous agents with adverse effects on living organisms.

Poisons

Agents causing harm to biological systems

Toxins

Biologically synthesized substances (living cells/microorganisms).

Toxicants

Toxic environmental chemicals.

Ingestion

Most common route of exposure in clinical settings

Systemic effects

If the poison is absorbed in the GIT what effect will happen?

Local effect

If the poison is not absorbed in the GIT what effect will happen?

Ingestion
Inhalation
Transdermal absorption

Routes of exposure on Toxicology

Liberation

Parameters Determining Serum Drug Concentration by its drug release

Absorption

Parameters Determining Serum Drug Concentration by transport to blood

Distribution

Parameters Determining Serum Drug Concentration by its delivery to tissues

Metabolism

Parameters Determining Serum Drug Concentration by its chemical modification

Excretion

Parameters Determining Serum Drug Concentration by its elimination of drugs/metabolites.

ED50

Dose which is effective or have therapeutic benefit in

50% of the population

TD50

Dose which produce a toxic response in 50% of the

population

LD50

Dose which predict death in 50% of the population

High Therapeutic Index

Low toxicity at therapeutic doses means?

Individual

Term for health effects based on xenobiotic exposure in a single organism.

Quantal

Term for Population-level health effects from exposure changes.

Alcohol

Common CNS depressant. Causes disorientation, euphoria, confusion, and may progress to unconsciousness, paralysis, and even death

Ethanol (Grain Alcohol)

Readily absorbed in the GIT and diffuses easily in tissues. Causes diuresis by inhibiting ADH.

Ketones and Lactates

Ethanol can cause acidosis due to accumulation of this substance. Increases blood osmolality.

Acetaldehyde

Hangover symptoms is due to the effects of

Capped

Serum specimen for Ethanol should be

Alcohol dehydrogenase

Major metabolic pathway of Ethanol

Enzymatic

Preferred lab method for Ethanol

300 to 400mL in 1 hour

Fatal dose of ethanol occurs at what mL and in what time

Methanol (Wood Alcohol)

Symptoms of intoxication is frank blindness and acidosis.

Osmolal gap

Screening test for Methanol

GC-MS

Preferred method for Methanol

60 to 250 mL

Fatal dose of Methanol

Isopropanol (Rubbing Alcohol)

This alcohol is rapidly absorbed by the GIT

Gas chromatography

Preferred method for Isopropanol

Activated charcoal

Antidote for Isopropanol

250 mL

Fatal dose of Isopropanol

Ethylene Glycol

Common constituent of hydraulic brake fluid. Causes anuria and necrosis.

Alcohol dehydrogenase

Treatment for Ethylene Glycol is to inhibit the action of this enzyme

Calcium oxalate crystals

Indication of toxicity of Ethylene Glycol that is seen in the renal tubules

Glycolic Acid

Major metabolite of Ethylene Glycol

HPLC

Preferred method for Ethylene Glycol

100 grams

Fatal dose of Ethylene Glycol

Gas-Liquid Chromatography

Assays for Blood Alcohol that Provides quantitation + qualitative identification of alcohol and some metabolites

Enzymatic Assay

Assays for Blood Alcohol that uses alcohol dehydrogenase as a reagent and quantitates the sum of all alcohols present

Blood, urine, and exhaled breath

Specimen of Alcohol

Arsenic

Sources: Ant poisons, rodenticides, paints, metal alloys

Arsenic trioxide

Arsenic group that gives acute toxicity

Inorganic form

Arsenic group that Inhibits sulfhydryl enzymes and crosses placenta. 10 hours of half life.

Hair and nails (Mees’ lines)

Specimen for Arsenic but long term exposure.

Odor of garlic breath

Indication of toxicity of Arsenic

British anti-lewisite

Antidote for Arsenic

Cadmium

Used in Electroplating, galvanizing and pigment in paints and plastics. Binds to organic matter in soil enters plants and crops.

Itai-Itai disease

Severe osteomalacia and osteoporosis. Caused by long-term cadmium-contaminated rice consumption.

10–30 years

Half-life of cadmium

GGT

Cadmium toxic renal indicator can be seen in urine.

Lead

This metal is a potent enzyme inhibitor of ALA synthetase. Inhibits pyrimidine-5'-nucleotidase and Na-K-ATPase.

Lead

Toxic affects includes Interferes with Vitamin D and heme synthesis, Damages RBC membrane integrity, Deposits in bone matrix, Peripheral neuropathy ("wrist drop or foot drop")

ALAD test

Most sensitive test for lead

Mercury

This metal binds to sulfhydryl proteins and disrupts structure/function. Potent inhibitor of catecholamine methyltransferase.

Elemental mercury

Form of mercury that gives pink disease and erethism

Organic mercury

Form of mercury that gives Minamata disease.

Carbon Monoxide

Produced by incomplete combustion of carbon-containing substances

Cherry red skin

Indication of acute toxicity of carbon monoxide

 EDTA whole blood

Specimen for carbon monoxide

Co-oximetry

Definitive testing method for carbon monoxide

Dilution

Corrective therapy for caustic agents are

Cyanide

Found in solid, gas, or solution forms. Components of insecticides and rodenticides. Binds to iron (ferric and ferrous) and causes hypoxia.

Odor of bitter almonds

Indication of toxicity in Cyanide poisoning

Pesticides

Includes organophosphates and carbamates. It’s mechanism is it inhibit acetylcholinesterase → acetylcholine accumulation at neuromuscular junction.

Salicylates

Uses: Analgesic, antipyretic, anti-inflammatory. Cyclooxygenase inhibitor → blocks thromboxane/prostaglandin formation. Fatal in children.

Acetaminophen

Uses: Analgesic, antipyretic. Prostaglandin inhibitor.