TOXICOLOGY

School of Biomedical and Laboratory Sciences

Department of Clinical Chemistry

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 CHAPTER ONE

INTRODUCTION TO
TOXICOLOGY

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 Objectives

At the end of this chapter, students will be able to:

 Define toxicology and discuss the historical aspects and

classification of toxicology

 Discuss the principles of toxicology

 Discuss the nature of toxic responses, routes of poisoning

 Discuss the Potential causes of toxicity

 Discuss the diagnosis and management of poisoning
 Discuss the analytical and other methods of toxicology

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 Outline

 Definition, classification and principles of toxicology

 Nature of toxic responses, routes of poisoning

 Potential causes of toxicity

 Factors influencing toxicity

 Diagnosis and management of poisoning

 Analytical and other methods of toxicology

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 Definitions
Toxicology

 Is the science dealing with

property,
action,
toxicity,
fatal dose,
detection ,
estimation of poisons &
interpretation of the result of toxicological
analysis

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 Definitions cont’d
• Derived from Greek word, toxikon and logos
• Toxicology is the study of the adverse effects of xenobiotics
 It also deals with foods and cosmetics for public consumption both
in alive or dead victims

 Toxicology is the qualitative and quantitative study of the adverse or

toxic effect of chemicals and other anthropogenic materials or
xenobiotics on organisms

 It has many dimension: the social, the moral & legal aspects of
exposure of populations to chemicals of unknown or uncertain
hazard
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 Historical Aspects of Toxicology
 In the past it was mainly a practical art utilized by murderers &
assassins
 In Ancient time (1500 BC) earliest collection of medical records
contains many references and guidelines about poisons

 Dioscorides (50 AD) a Greek physician, classify poisons as animal,

plant or mineral & recognizing the value of emetics

 Maimmonides (1135-1204 AD), wrote poisons and their antidote

which detailed some of the treatments consideration to be effective

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 Historical aspects of toxicology cont’d
 Paracelsus (1493 AD), summarized his concept in the following
famous phrase ;
 “All substances are poisons; there is none that is not a poison. The
right dose differentiates a poison from a remedy”

 Orifila (1787-1853 AD), Spanish physician who contributed to

forensic toxicology by devising means of detecting poisonous
substances

 From then on toxicology began in a more scientific manner & began

to include the study of the mechanism of action of poisons

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 Historical aspects of toxicology cont’d
 The 20th century- toxicology has now become much more than the
use of poisons

 There are marked improvements in toxicological diagnosis, &

management (production of antidote for them)

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 Toxicological terms and definitions
 Toxin- a poison of natural (biological) origin

 Poison- a chemical that may harm or kill an organism

 Toxic-having the characteristic of producing an undesirable or

adverse health effect

 Toxicity-any toxic (adverse) effect that a chemical or physical agent

might produce within a living organism

 Hazard - is the likelihood that injury will occur in a given situation

or setting: the conditions of use and exposure are primary
considerations
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 Toxicological terms and definitions cont’d
 Risk - is defined as the expected frequency of the occurrence of an
undesirable effect arising from exposure to a chemical or physical
agent RISK= HAZARD + EXPOSURE

Acute poisoning
– is caused by an excessive single dose, or several dose of
a poison taken over a short interval of time.
e.g. Strychnine, potassium cyanide
Chronic Poisoning
– is caused by smaller doses over a period of time, resulting in
gradual worsening
e.g. arsenic, phosphorus, antimony and opium

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 Toxicological terms and definitions cont’d
Sub acute poisoning
– shows features of both acute and chronic poisoning
Fulminant poisoning
– is produced by a massive dose
– in this death occur rapidly, sometimes without preceding
symptoms

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 Classification
Toxicology is broadly divided into different classes
Depending on:

 Research methodology

 Socio-medical

 Organ/specific effects

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 Classification cont’d
I. Based on research methodology

Descriptive toxicology
– Descriptive toxicology deals with toxicity tests on chemicals
exposed to human beings and environment as a whole

Mechanistic toxicology
– Mechanistic toxicology this deals with the mechanism of toxic
effects of chemicals on living organisms
– This is important for rational treatment
– Facilitation of search for safer drugs (e.g. Instead of
organophosphates, drugs which reversibly bind to cholinesterase
would be preferable in therapeutics

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 Classification cont’d
Regulatory toxicology :
 studies whether the chemical substances has low risk to be used in
living systems, Examples:
 encompasses the collection, processing and evaluation of
epidemiological and experimental toxicology data to permit
toxicologically based decisions

 Food and drug administration regulates drugs, food,

cosmetics medical devices & supplies in USA

Environmental protection agency regulates pesticides, toxic

chemicals, hazardous wastes and toxic pollutants in USA

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 Classification cont’d
 Occupational safety and health administration regulates the safe
conditions for employees in USA authority

 DACA (now FMHACA)- regulates drugs, food, cosmetics and

medical devices & supplies in Ethiopia

Predictive toxicology

 Predictive toxicology studies about the potential and actual risks of

chemicals /drugs

 This is important for licensing a new drug/chemical for use

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 Classification cont’d
II. Based on specific socio-medical issues

Occupational toxicology

– It deals with chemical found in the workplace

– E.g. – Industrial workers may be exposed to these agents during

the synthesis, manufacturing or packaging of substances

– Agricultural workers may be exposed to harmful amounts of

pesticides during the application in the field

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 Classification cont’d

Environmental toxicology

– This deals with the potentially deleterious impact of chemicals,

present as pollutants of the environment, to living organisms

Ecotoxicology

– Ecotoxicology has evolved as an extension of environmental

toxicology

– It is concerned with the toxic effects of chemical and physical

agents on living organisms, especially in populations and
communities with defined ecosystems
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 Classification cont’d
Clinical toxicology
– Clinical toxicology deals with diagnosis and treatment of the
normal diseases or effects caused by toxic substances of
exogenous origin.

Forensic toxicology
– Forensic toxicology closely related to clinical toxicology
– It deals with the medical and legal aspects of the harmful effects
of chemicals on man, often in post mortem material, for instance,
where there is a suspicion of murder, attempted murder or suicide
by poisoning
Animal and plant toxicology
– deals with the diagnosis and treatment of harmful effects of
animals and plants
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 Classification cont’d

III. Based on the organ/system effect

– Cardiovascular toxicology

– Renal toxicology

– Central nervous system toxicology

– Gastrointestinal toxicology

– Respiratory toxicology, etc

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 Principles of toxicology
Paracelsus (1493-1541) once said

– "All substances are poisons; there is none which is not a poison

The right dose differentiates a poison from a treatment’’

– It is not easy to distinguish toxic from non toxic substances

– A key principle in toxicology is the

 The chemical form
 routes and sites of exposure
 duration and frequency of exposure(acute, sub-acute, sub-
chronic,chronic)
 Dose-response effects

 There is a graded dose-response relationship in individuals, and

 organophosphate Vs esterase enzyme inhibition in the brain
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 A quantal dose-response relationship in the population
Diagram of a quantal dose–response relationship

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 “All things are poison and nothing is without poison, only the
dose permits something not to be poisonous
The dose makes the poison”

therapeutic toxic
effect increasing dose effect

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 Principles of toxicology cont’d
• There are a number of assumptions that should be
considered before D- R r/n ships are used
appropriately
o The response is due the chemical administered
o The magnitude of the response is related to dose
-There is a molecular target site(s) with which the
chemical interacts to initiate the response
-The production of a response and the degree of response
are related to the concentration of the chemical at the
target site
-The concentration at the target site is related to the dose
administered
o There exists both a quantifiable method of
measuring and a precise means of expressing the
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Principles of toxicology cont’d

 Dose is the amount, usually per unit body mass, of a toxicant to

which an organism is exposed

 Response is the effect on an organism resulting from exposure to

a toxicant

 In order to define a dose–response relationship, it is necessary to

specify a particular response, such as:

• Death of the organism, as well as

• The conditions under which the response is obtained, such as

the length of time from administration of the dose

• Consider a specific response for a population of the same kinds

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of organisms
Principles of toxicology cont’d

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 Principles of toxicology cont’d
Thresholds
 An important concept pertinent to the dose–response relationship is
that of threshold dose, below which there is no response

 Threshold doses apply especially to acute effects and are very hard
to determine, despite their crucial importance in determining safe
levels of exposures to chemicals

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 Nature of toxic responses

The resulting biologic effect of combined exposure to several agents

can be characterized as:
 Synergism
when the effect of two chemicals is greater than the effect of
individual chemicals 1) Example: 2 + 2 = 20
e .g carbontetrachloride + alcohol= more toxic to the liver than the
sum of the individual drugs.
 Additive effect-
when the total pharmacological action of two or more chemicals
taken together is equivalent to the summation of their individual
pharmacological action
Example: 2 + 3 = 5
Organophosphorus pesticides ⇒ Cholinesterase inhibiters
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 Nature of toxic responses cont’d
 Potentiation effect
when the net effect of two chemicals used together is greater than the
sum of individual effects (the capacity of a chemical to increase the
effect of another chemical without having the effect alone) Example:
0 + 2 = 10
Isopropanol is not hepatoxic, but enhance carbon tetrachloride
induced hepatoxicity
 Antagonism - is the phenomenon of opposing actions of two
chemicals on the same system
Example: 4 + 0 = 1
Dimercaprol (BAL) chalets with metal ions, As, Pb….

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 Nature of toxic responses cont’d
RELATIVE TOXICITIES

 Standard toxicity ratings that are used to describe estimated

toxicities of various substances to humans

 Their values range from one (practically nontoxic) to six

(supertoxic)

 In terms of fatal doses to an adult human of average size, a “taste” of

a supertoxic substances (just a few drops or less) is fatal

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 Parameters
 Median lethal dose (LD50) – is the dose which is expected
to kill 50% of the population in the particular group.

Median effective dose (ED50) –is the dose that produces a

desired response in 50% of the test population when
pharmacological effects are plotted against dosage.

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 Median toxic dose (TD50) – is the dose which is expected to
bring toxic effect in 50% of the population in the particular group
• TI = LD50 (or TD50)/ED50

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 Nature of toxic responses cont’d
REVERSIBILITY AND SENSITIVITY
a) Reversibility Vs. Irreversible
 Sub lethal doses of most toxic substances are eventually eliminated
from an organ system. If there is no lasting effect from the exposure,
it is said to be reversible
 However, if the effect is permanent, it is termed irreversible

 Irreversible effects of exposure remain after the toxic substance is

eliminated from the organism

 For various chemicals and different subjects, toxic effects may range
from the totally reversible to the totally irreversible

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 Nature of toxic responses cont’d

b)Hypersensitivity vs. Hyposensitivity

 In some cases hypersensitivity is induced

 After one or more doses of a chemical, a subject may develop an

extreme reaction to it

 This occurs with penicillin, for example, in cases where people

develop such a severe allergic response to the antibiotic that

exposure results in death if countermeasures are not taken

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 Nature of toxic responses cont’d

 hyposensitivity is induced by repeated exposures to a toxic

substance leading to tolerance and reduced toxicities from later
exposures

 Tolerance can be due to a less toxic substance reaching a receptor or

to tissue building up a resistance to the effects of the toxic substance

example, with repeated doses of toxic heavy metal cadmium

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 Routes of poisoning
 Oral route – the GIT is the most important route of absorption, as
most acute poisonings involve ingestions

 Dermal route – lipid solubility of a substance is an important factor

affecting the degree of absorption through the skin

 Inhalational route – toxic fumes, particulate and noxious gases may

be absorbed through the lungs

 Intramuscular route – unreliable and varied from patient to patient

 Intravenous route – is the most reliable and provides the most rapid
clinical response

 Rectal route – is generally considered to produce erratic absorption

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 Route of Administration/absorption cont’d

 Oral (commonest)

 Inhalation: gas poison

 Parenteral (IM, IV, Sub-Cutaneous, Intra-Dermal)

 Natural Orifices other than mouth (Nasal, Rectal, Vaginal, Urethral),

 Ulcers, wounds and intact skin

The decreasing order of effectiveness in different routes is:
Intravenous, inhalation, intra-peritoneal, subcutaneous, intramuscular,
intra-dermal, oral, and dermal

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 Potential causes of toxicity
The potential causes of toxicities include:
 Therapeutic agents

 Industrial & house hold chemicals

 Environmental contaminants

 Animal & plant toxins

 Drugs of abuse

 Food preservatives

 Traditional drugs

 Fumes …..
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 Sources of Poison
 Domestic or household sources

 Agricultural and horticultural sources

 Industrial sources

 Commercial sources

 From uses as drugs and medicines

 Food and drink

 Miscellaneous sources - snakes bite poisoning, city smoke, sewer

gas poisoning etc.

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 Sources of Poison cont’d
 Domestic or household sources - detergents, disinfectants, cleaning

agents, antiseptics, insecticides, rodenticides etc.

 Agricultural and horticultural sources- different insecticides,

pesticides, fungicides and weedicide

 Industrial sources- In factories, where poisons are manufactured or

poisons are produced as by products

 Commercial sources- From store-houses, distribution centres and

selling shops 40
 Sources of Poison cont’d

 From uses as drugs and medicines – Due to wrong medication,

overmedication and abuse of drugs

 Food and drink – contamination in way of use of preservatives of

food grains or other food material, additives like colouring and

odouring agents or other ways of accidental contamination of food

and drink

 Miscellaneous sources- snakes bite poisoning, city smoke, sewer

gas poisoning etc. 41

 Common poisons and drugs
 Corrosive poisons

 Irritant poisons

 Analgesic, Hypnotic, Tranquilizer, and Narcotic poisons

 Stimulants, Excitants, and Convulsants poisons

 Paralytic, Anticholinesterase and Antihistamine poisons

 Gaseous and Volatile poisons

 Industrial gaseous and Volatile poisons

 Poisons by Plants, flora, and fungi

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 Factors influencing toxicity

• Discus 4 five minute to what condition

may influence toxicity
????

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 Factors influencing toxicity

1. Quantity:
 A high dose of poison acts quickly and often resulting in  fatal
consequences.

 A moderate dose causes  acute poisoning

 A low dose may have sub-clinical effects and causes  chronic

poisoning on repeated exposure

 Very large dose of Arsenic may produce  death by shock without

dose irritant symptoms,

 While smaller dose than lethal dose produces its  therapeutic

effects 44
 Factors influencing toxicity cont’d
2. Physical form:
 Gaseous or volatile poisons are very quickly absorbed and are thus
most rapidly effective

 Liquid poisons are more rapid than solid poisons

 Some poisonous vegetable seeds may pass through the intestinal

canal ineffective when taken intact due to their impermeable pericarp

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 Factors influencing toxicity cont’d
3. Chemical form:

 Chemically pure arsenic and mercury are not poisonous because

these are insoluble and are not absorbed

 But white arsenic (arsenic oxide) and mercuric chloride are deadly

poisonous

 Barium sulphide is deadly toxic but barium sulphate is non-toxic

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 Factors influencing toxicity cont’d

4. Concentration (or dilution):

 Concentrated form of poison are absorbed more rapidly and are also
more fatal but there are some exceptions too

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 Factors influencing toxicity cont’d
5. Condition of the stomach:

 Food content presence of food-stuff acts as diluent of the poison and

hence protects the stomach wall

 Dilution also delays absorption of poison.

 Empty stomach absorbs poison most rapidly

 In cases of achlorohydria, KCN and NaCN is ineffective due to lack

of hydrochloric acid, which is required for the conversion of KCN
and NaCN to HCN before absorption

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 Factors influencing toxicity cont’d
6. Route of administration:

 absorption rate is different for different routes. Decreasing order

IV, inhalation, intra-peritoneal, subcutaneous, intramuscular,
intra-dermal, oral, and dermal
7. Age:

 some poisons are better tolerated in some age groups

 Opium and its alkaloids are tolerated better by elderly subjects but
badly by children and infants.

 Belladonna group of drugs are better tolerated by children than by

adults
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 Factors influencing toxicity cont’d
8. State of body health:

 A well built person with good health can tolerate the action of poison
better than a weak person.

9. Presence of disease:

 In certain diseased conditions some drugs are tolerated exceptionally

well

 e.g.: sedatives and tranquilizers are tolerated in very high dose by

manic and deliriant patients

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 Factors influencing toxicity cont’d

10. Intoxication arid poisoning states

 In certain poisoning cases some drugs are well tolerated, like, in case
of strychnine poisoning, barbiturates and sedatives are better
tolerated.

 Whereas in case of barbiturate poisoning any sedative or tranquilizer

will accentuate the process of death

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 Factors influencing toxicity cont’d
11. Sleep

 Due to slow metabolic process and depression of other body

functions during sleep, usually the absorption and action of the
poison is also slow

 But depressant drugs may cause, more harm during the state of sleep.

12. Exercise

 Action of alcohol on C.N.S. is slowed during exercise because more

blood is drawn to the muscles during exercise

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 Factors influencing toxicity cont’d

13. Cumulative action of poisons:

 Preparations of cumulative poisons (poisons which are not readily

excreted from the body and are retained in different organs of the
body for a long time) like lead may not cause any toxic effect when
enters the body in low dose

 But when such poisons enter over a long period of time, may cause
harm when their concentration in different tissue reaches high level
due to their cumulative property

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 GENERAL MANAGEMENT PRINCIPLES
Initial Approach to the Poisoned Patient
 Focus on six major areas:
o Resuscitation and stabilization
o History and physical examination, including evaluation
for a specific toxidrome
o Appropriate decontamination of the gastrointestinal
tract, skin, and eyes
o Judicious use of laboratory tests, electrocardiograms,
and radiographic studies
o Administration of specific antidotes, if indicated
o Utilization of enhanced elimination techniques for
selected toxins

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55
 Resuscitation and Stabilization
 The first priorities in the management of seriously
poisoned patients are the same as with all patients

 Maintain patency of airway followed by assistance

of breathing and support of circulation

 Establish cardiac monitoring, pulse oximetry, and

intravenous access

 In patients with altered mental status,

administration of naloxone, dextrose, and thiamine
should be considered 56
 History and Physical Examination
 The history provides critical information in the assessment
of the patient with suspected overdose
 Medications potentially available to a patient or a
history of chronic medical illnesses in members of the
household …… a clue
 As far as possible history should be sought for toxicant
 The P/E gives important clues to both the severity and
cause of poisoning
 Vital sign and mental status abnormalities ….tells
severity
 Characteristic “toxidromes” indicate the presence of
agents with cholinergic, anticholinergic,
sympathomimetic, and opioid effects.
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 The clinical features associated with some common
poisons may be specific
 For example, the combination of pin-point pupils,
hyper salivation, incontinence and respiratory
depression
 suggests poisoning with a cholinesterase inhibitor
such as an organophosphorus pesticide.
 Characteristic odors suggest the presence of toxins,
such as cyanide (almond odor) or ethchlorvynol (vinyl
odor)
 Provide physiologic clues to the toxicologic etiology and
severity of an illness
 Valuable parameter with which to assess and monitor a
patient’s response to supportive treatment and antidotal
therapy
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• Temperature
– Exposure to various toxins can result in hyperthermia
or hypothermia
• Pulse
– Drug-Induced Tachycardia/Bradycardia
• Blood Pressure
– Drug induced hypertension/hypotension
Respiratory Rate
– Drug- and Toxin-Induced Hyperventilation
(Tachypnea or Hyperpnea)/Bradypnea

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• Neurologic manifestation of toxins:
– Agitation & delirium, sedation & coma, seizures,
pupils size (miosis, mydriais), Nystagmus,
Movement Disorders(Toxin-induced
parkinsonism)

• Dermatologic manifestations of toxins:

– Cyanosis, Erythema, Ecchymosis, Diaphoresis,
Skin Necrosis, Alopecia, …
• Gastrointestinal manifestations of toxins
– Oral Cavity (hyper salivation), Breath Odors,
Vomiting/Hematemesis, Altered Intestinal Activity
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 TOXIDROMES
• Are groups of signs and symptoms that consistently
result from particular toxins
• These syndromes are usually best described by a
– combination of the vital signs and clinically obvious
end-organ manifestations
• The signs that prove most clinically useful are:
– Those involving the central nervous system (mental
status); ophthalmic system (pupil size)
– Gastrointestinal system (peristalsis)
– dermatologic system: skin (dryness vs. diaphoresis)
and
– mucous membranes (moistness vs. dryness) and
– Genitourinary system (urinary retention vs.
incontinence) 61
• Anticholinergic Syndrome
– “hot as a hare, blind as a bat, dry as a bone, red as a
beet, mad as a hatter, bloated as a bladder,”

• Sympathomimetic Syndrome
– hypertension, diaphoresis, tachycardia, tachypnea,
hyperthermia, and mydriasis
– Restlessness, agitation, excessive speech, tremors,
and insomnia also occur

• Opioid Syndrome
– mental status depression, respiratory depression, and
pinpoint pupils, Bradycardia, hypotension (rare),
hypothermia, hyporeflexia, and needle marks
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• Anticholinesterase Syndrome
– Organophosphates are commonly available as
insecticides
– DUMBELS is a mnemonic used: defecation,
urination, miosis, bronchorrhea, bronchospasm,
bradycardia, emesis, lacrimation, and salivation.
– Clinical findings suggestive of acute
anticholinesterase intoxication.

• Sedative-Hypnotic Syndrome
– Hypotension, bradypnea, hypothermia, mental status
depression, slurred speech, ataxia, and hyporeflexia

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 Gastrointestinal Decontamination
 Preventing drug absorption
 To decontaminate the entire GI tract not just the
stomach while reducing the risk of iatrogenic harm
 Common Methods of Gastrointestinal (GI)
Decontamination
 Activated charcoal
 Gastric lavage
 Syrup of ipecac
 Cathartics, e.g. Sorbitol, Magnesium sulfate/citrate
 Whole bowel irrigation
 for patients who have ingested iron, other metals
and radiopaque material, and substances not
adsorbed to charcoal or for body packers or body
stuffers 65
Extracorporeal Removal of Drugs and Toxins
• Are principles and techniques applied to enhance
elimination of toxins from the blood

• Is a logical step after GI decontamination are initiated or

can not be used

• The extracorporeal techniques most commonly employed

for the removal of toxins are :
– Hemodialysis and Charcoal hemoperfusion, Peritoneal
Dialysis
– Plasmapheresis, exchange transfusion, and
continuous ultrafiltration techniques

• Extracorporeal therapies because xenobiotic removal

66
occurs in a blood circuit outside the body
 Toxins and Drugs Removed by Hemodialysis
/Hemoperfusion

Common Uncommon
Barbiturates Aminoglycosides
• Ethylene glycol Atenolol
• Lithium Boric acid
• Methanol Bromide
• Salicylates Carbamazepine
• Theophylline Chloral hydrate (trichloroethanol)
Diethylene glycol
Ethanol Isopropanol
Magnesium
Metformin
Methotrexate (high flux)
Paraquat (very early)
Procainamide/N-acetylprocainamide
Sotalol Thallium Valproic acid
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 DIAGNOSTIC TESTING
• Serum concentrations of specific drugs are useful in guiding
management
– Acetaminophen, theophylline, lithium, salicylates, digoxin

• Other tests:
– such as serum electrolytes, calculated anion gap,
glucose, arterial blood gases, serum creatinine, and liver
function tests, can assist in the indirect evaluation of the
end organ effects of a toxin

• also aid in the diagnosis of specific agents

• Electrocardiograms should be obtained in patients
ingesting toxins known to produce cardiac
dysrhythmias or conduction delays
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Clinical toxicology laboratory

• The toxicology laboratory provide appropriate

testing in three general areas:
– Identification of agents responsible for acute
or chronic poisoning
– Detection of drugs of abuse; and
– Therapeutic drug monitoring

• Know that
– The majority of toxicological diagnoses and
therapeutic decisions are made on a clinical
basis 69
 Situations in which qualitative toxicology
tests or screens have utility
• When the differential diagnosis is sufficiently narrowed to
a drug cause vs. a disease cause (e.g., psychosis—
functional vs. amphetamines)

• Documentation that the working diagnosis was correct

(post facto)

• After admission if the diagnosis is still unclear

70
 Role: Toxicology Lab
• The most important role for the toxicology laboratory to
be the quantitation of drug concentrations to determine
the need for dangerous or expensive treatment
• Therapeutic Drug monitoring
– For instance,
• Drugs that require:
– hemoperfusion (e.g., theophylline,
phenobarbital)
– hemodialysis (e.g., salicylate, methanol,
lithium) to avoid life-threatening concentrations
• To shorten coma, and to evaluate the efficacy of
extracorporeal elimination
• When deciding to treat a digoxin overdose with
Fab fragments (Digibind) and for the appropriate
use of chelators in metal poisoning 71
Serum quantitation of overdosed drugs: TDM

• Rationale and Uses

– Quantitative drug levels in overdose can monitor
• the course of the patient, predict whether toxicity is
occurring but not yet clinically apparent, or predict
that toxicity will occur in the future

• Two criteria need to be satisfied for blood levels to be

useful
– should be an absence of reliable clinical indicators
that reveal the status or condition of the patient
– the existence of a concentration-effect relationship

72
Assay methods…
• The techniques for detecting the presence
of drugs include
– a variety of chromatographic methods,
immunoassays, and chemical and
spectrometric techniques
• can be adapted to detect a wide number of drugs
and chemicals, or focused to detect and quantitate
certain drugs
– Immunoassays are most widely used for
discrete analysis, and gas chromatographic
techniques are used for broad screens

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 Serum conc…..cont’d
• Availability and Reliability
– Measurements should be available on an immediate,
24-hour basis and should be precise (not
semiquantitative)
– Increasing use of quantitative IAs on rapid chemistry
analyzers
– Serum quantitations require adequate precision to
recognize change from time point to time point and
should also be accurate so that management
decisions can be made correctly

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 Consideration in serum measurement
• Serum drug quantitation's must be evaluated
with respect to each patient’s clinical condition

• Interpretation of serum concentration should

consider:
– variation in pharmacology from person to
person
– the interactions of diseases and medications
– the altered pharmacodynamics and
pharmacokinetics with overdose
– potential interferences in assays
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 Administration of specific antidotes
• Specific antidotes exist for a few toxins
• Are definite treatment available
• There are different types:
• Pharmacodynamic antidotes
• Pharmacokinetic antidotes
• Chemical antidotes
• Physiological antidotes

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 References and Suggested Reading
 Phillip L. Williams, Robert C.James, and,Stephen M.
Roberts,eds.,Principles of toxicology: environmental and industrial
applications, 2nd ed ., A Wiley-Interscience,New York, 2000.
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 Quiz
1. List four factors that influence toxicity (2pt)
2. Write the initial approaches for a poisoned
individual (2pt)
3. Which chromatographic technique(method) has the
highest resolution power (1pt)

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