Transcript Slide 1

Lecture 1
Introduction in toxicology.
Determination of toxicity.
Dose-response curve.
Mode of entry of toxins.
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
Benzodiazepines
Tricyclic antidepessants
Barbiturates
Acetaminophen
Salicylates
%%
32
60
13
6
1
2
O
O
N
HN
N
N R
HN
NH
O
O
R R
OH
CH3
Tests to be available for oriented screen in emergency toxicology
Preferred 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 hydrocarbons (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
Compound
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 poison
Solely the dose determines that
a thing is not a poison
+
Non-linear response curves
effective drug
food
nonactive
0
log C
toxic
dangerous drug
-
Highly toxic
Mode of entry of toxins
Skin transport
Respiratory route
Oral route
area _ under_ curveoral
bioavailability 
area _ under_ curveintravenous
log C
log C
One-compartment kinetics
time
Two-compartment kinetics
time
Cocaine metabolic profile. BE-benzoyllecgonine,
EME-ecgonine methyl ester,CE- cocethylene