Introduction in toxicology. Determination of toxicity. Dose-response curve. Mode of entry of toxins. Lecture 1.

Introduction in toxicology. Determination of toxicity.Dose-response curve. Mode of entry of toxins.

Lecture 1

Clinical Toxicology

-20 to 50 compounds tested-Many routine kits available-Automation possible

Analytical Toxicology

-8000 pharmaceuticals are currently used- 40000 other potentially toxic compounds exist- routine kits available for screening for some common drugs- no automation

Types of Intoxication:Known origin Unknown origin

Causes of intoxication %%Ethanol 32Benzodiazepines 60Tricyclic antidepessants 13Barbiturates 6Acetaminophen 1Salicylates 2

N

N

N R HN NH

O

OOR R

HN

OH

O

CH3

Tests to be available for oriented screen in emergency toxicology

CompoundPreferred sample Intoxication origin Preferred technique

Cyanide Whole blood (heparinized)

Fire, suicide, potassium ferrocyanide treatment

microdiffusion + colorimetry, head-space GC

Ethylene glycol (antifreeze)

Serum Abuse (with urinary excretion of oxalate)

GC

Cholinesterase activity Whole blood (heparinized)

Organophosphates (pesticides)

Photometry

Bromide, fluoride Serum Industry Selective electrode, ion chromatography

Pesticides (paraquat, diquat)

Whole blood (heparinized), random urine

Agriculture Color tests, GC, HPLC

Halogenated hydro carbons (solvents, chloral hydrate)

Whole blood, random urine, gastric fluid

Industry, abuse Color test, GC

Heavy-metals screen Whole blood (heparinized), random urine

Industry, accidental (children)

Atomic absorption, flame emission

Methaemoglobin Whole blood (heparinized)

Nitrate and nitrite exposure, abuse of certain vasodilators ("poppers")

Spectroscopy, color test, GC

Analytical techniques used in emergency toxicology

Spot tests

Immunoassays

Gas chromatography

GC-MS

HPLC and LC-MS

Thin layer chromatography

Dose-response curve

What is there that is not poison?All things are poison and nothing without poisonSolely the dose determines that a thing is not a poison

log C

Highly toxic

toxic

effective drug

dangerous drug

food

nonactive

+

-

0

Non-linear response curves

Mode of entry of toxins

Skin transport

Respiratory route

Oral route

sintravenou

oral

curveunderarea

curveunderareailitybioavailab

__

__

log C

time

log C

time

One-compartment kinetics Two-compartment kinetics

Cocaine metabolic profile. BE-benzoyllecgonine, EME-ecgonine methyl ester,CE- cocethylene