While I was in the middle of creating this blog, I remembered
a film I watched, where a woman was trying to kill herself due to her failed romance,
she decided to kill herself by having drug overdose, eventually after ingesting
all the drugs, she changed her mind and called her neighbor. The neighbor came
in her house and was in time to save her, or so he thought. Later on, in the hospital, the doctor
told them that she is very far from danger and the neighbors were astounded to
hear that she survived despite the length of time they spent before they sent her to the hospital
and the amount of drugs she took. The doctor then explained that, He never
heard of anyone that dies of drinking excess Ascorbic acid.
“All substances are poisons;
there is none which is not a poison. The right dose differentiates a poison
from a remedy.” (Paracelsus, 1493-1541)
Nevertheless, Excess
amounts of drugs could still kill you, despite the factors like what additive it contains and how impotent it
is, because, everything foreign to the body can produce adverse effects at a
certain amount and at a certain time. Due to that mere fact, a substance can be defined as a POISON by
knowing its toxicity to the body. This is elucidated by the branch of science
which is Toxicology.
Toxicology is
the study of poisons. Within the organizational scheme of a typical medical
laboratory, toxicology is usually considered part of the chemistry section;
this is because the methods used to evaluate toxins in a qualitative or
quantitative way are best suited to this area. However, appropriate diagnosis
and management of poisoning victims, in many instances; require an integrated
approach from all sections of the clinical laboratory.
Four
Divisions of Toxicology;
a.
Mechanistic
Toxicology – studies the cellular and biochemical effects of toxins. These studies
provide a basis for rational therapy design and the development of tests to
assess the degree of exposure of poisoned individuals.
b.
Descriptive
Toxicology – utilizes the method of risk assessment or it makes use of the
results of animal experimentation to predict what level of exposure could be
hazardous to humans.
c.
Forensic
Toxicology – primarily concerned with the medicolegal cases of toxin exposure.
A major focus of this area is establishing and validating the analytic
performance of the methods used to generate evidence in legal situations,
including cause of death.
d.
Clinical
Toxicology – study of interrelationships between toxin exposure and states.
This area emphasizes not only diagnostic testing but also therapeutic
interventions.
Early
history: Romans, Greeks, Chinese
- Knew of human and animal poisons.
- Categorized and studied poisons.
- Royal "tasters”
II. Socrates (470-399 B.C.):
- Most celebrated poisoning victim.
- Executed by poison hemlock.
- Active principle: coniine.
III. 15th
Century Europe: Italians developed poisoning into an art form
poisoning became a normal hazard of
life.....
1. Venice's "Council of
Ten" (City Council)
- Put out poisoning contracts on political enemies.
- Council transactions: detailed records with name
of victim, contractor, type and amount of poison given, results…
2. Borgia: prominent family
who practiced "applied toxicology"
- Cesare, Lucretia and others.
- Killed husbands, wives, lovers, political
opponents, churchmen….
3. Catherine de Medici
(1519-1589)
- Wife of Henry II of France, mother of three
French kings, ruler of France.
- Early "experimental toxicologist".
- Poisoned poor and sick street people under guise
of "feeding" and assistance".
- Killed political enemies for hire....
- Documented signs and symptoms.
IV. Paracelsus full name: Philipus Aurelius Theophastrus Bombastus
von Hohenheim-Paracelsus (1493-1514)
- Instrumental in logical development of toxicology
as science.
- Developed concept of "dose".
- Action a result of chemical entity -- toxicon.
V. Orfila (1787-1853) Spaniard--personal physician to Louis
XVIII
"The
Father of Modern Toxicology"
- Developed toxicology into a science.
- Compiled chemical and biological information on
most known poisons.
- Proposed the necessity of chemical analysis to
prove cause-and-effect.
VI. Mid 1800s:
- Analytical methods developed for As, Hg and
miscellaneous alkaloids.
Scope of Toxicology
Exposure
Exposure to toxic agents can occur for
various reasons. According to Thorne and Russell about 50% of poisoning cases are
intentional suicide attempts while accidental exposure occurs at 30% and the
remaining is for homicide and occupational exposure. Suicide, among all of the given reasons has
the highest mortality rate, accidental exposure happens frequently on children
and occupational exposure happens primarily in industrial and agricultural
setting.
Dose
response relationship
A poison can be defined as any
substance that causes a harmful effect upon exposure, but still there are
factors to consider for a poison to be lethal. Among these factors, Dose is the
most important, because a substance given at the correct dosage will elicit
harmful effect to the human body, even water. Therefore, there is a need to
establish an index of relative toxicity of substances to allow assessment of
their potential to cause pathological effect.
Acute
and Chronic Toxicity
Acute toxicity is usually single,
short term exposure to a substance, the dose of which is sufficient to cause
immediate toxic effects. Chronic Toxicity, on the other hand, usually occurs in
repeated frequent exposure to extended periods, at doses that are insufficient
to cause an immediate acute response.
Toxicology
of specific agents
· Alcohol – exposure to alcohol,
like exposure to most volatile organic solvents, it initially causes
disorientation, confusion, and euphoria, which can lead to unconsciousness,
paralysis, and with high level exposure can lead to even death.
· Carbon Monoxide – produced by incomplete
combustion of carbon containing substances, primary source of it will be
gasoline, furnaces and wood and plastic fires.
-
Carbon
monoxide expresses its toxic effects by causing a leftward shift in the
oxygen-hemoglobin dissociation, resulting in decreased oxygen delivery to
tissue.
·
Caustic agents – commonly found in many
household products and occupational settings. Exposure to this substance is
caused by injury, aspiration and ingestion.
· Cyanide – a supertoxic substance
that can exist as a gas, solid or solution. It expresses toxicity by binding to
heme iron. Binding to mitochondrial cytochrome oxidase causes an uncoupling of
oxidative phosphorylation. this results in rapid depletion of cellular ATP as a
result of the inability of Oxygen to
accept electrons.
·
Metals and Metalloids – example are Arsenic,
Cadmium, Mercury and Lead, most common action is blocking of enzymes.
·
Therapeutic Drugs
o
Aspirin – excessive intakes can
cause acidosis.
·
Inhibits
Krebs cycle
·
Excess
in ketone body formation
·
Drugs of Abuse
o
MDMA – its adverse effects
include headaches, nausea, vomiting, anxiety agitation, impaired memory,
violent behaviour, tachycardia, hypetension, Respiratory distress, seizures,
hyperthermia, cardiac toxicity, liver toxicity and renal failure.
o
Anabolic Steroids - Toxic hepatitis, accelerated
arthrosclerosis and abnormal aggregation of platelets, predisposition to stroke
and myocardial infarction.
o
Cocaine – Hypertension, arrhythmia,
seizure and myocardial infarction.
o
Opiates– Respiratory acidosis,
myoglobinuria, cardiac damage and can lead to cardiopulmonary failure.
o
Phencyclidine – coma and stupor.
o
Sedative – Hypnotics – Lethargy and slurred
speech, coma. Respiratory depression is the most toxic effect of these agents.
Analysis
of toxic agents
-
Two
step procedure
o
Screening
and confirmatory
·
Screening – first step
§ rapid, simple, qualitative
procedure intended to detect specific substances or classes of toxicants.
§ Have good analytic
sensitivity but lacks specificity.
§ Immunoassay
·
Confirmatory
o
Gas
Chromatography – the reference method for the qualitative and quantitative
determination of volatile substances and most organic compounds, it uses
spectrophotometer as the detector.
Bishop, M, (2010), Clinical
Chemistry, Techniques, Principles, Correlations, 6th Edition,
Lippincott Williams and Willkins
