Introduction to Toxicology

Introduction to Toxicology

Toxicology:
It is the qualitative and quantitative study of the adverse or toxic effect of chemicals and other anthropogenic materials or xenobiotics on living organisms.
or
It is the study of symptoms, mechanisms, treatment and detection of poisoning

A Poison:

Any substance capable of inducing deleterious response in a biological system leading to:
-seriously injuring function
-or causing death.

Toxicant:

It is a type of poison that is made by humans or introduced into the environment by human activity.

This is in contrast to a

Toxin: which is a poison produced naturally by an organism (e.g. plant, animal, insectetc.)

An Antidote is a substance which can counteract a form of poisoning. e.g Naloxone blocks or reverses the effects of opioid medication.


Type of exposures:
Acute exposure is a single exposure or multiple exposures occurring over 1 or 2 days.
Chronic exposure is multiple exposures continuing over a longer period of time.

Basic classification of toxicology

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

B. Mechanistic toxicology

deals with the mechanism of toxic effects of chemicals on living organisms. e.g. organophosphate poisoning → leads to accumulation of Ach →activate muscarinic and nicotinic receptors → respiratory failure.

C. Regulatory toxicology:

It studies whether the chemical substances have low risk to be used in living systems.
e.g - Food and drug administration (FDA) regulates drugs, food, cosmetics, medical devices and supplies in USA.

D. Predictive toxicology

It concerns with the development of new non-animal tests which provide a new scientific basis for safety testing. This is important for licensing a new drug or chemical for use.

E. Occupational toxicology

It deals with chemical found in the workplace.


F. Clinical toxicology
It deals with diagnosis and treatment of the normal diseases or effects caused by toxic substances of exogenous origin i.e. xenobiotics.

G. Forensic toxicology:

It deals with the medical and legal aspects of the harmful effects of chemicals on man, often in post mortem material, e.g, if there is a suspicion of murder, attempted murder or suicide by poisoning.

Classification of toxicology based on the organ/system effect

1. Cardiovascular toxicology
2. Renal toxicology
3. Central nervous system toxicology
4. Gastrointestinal toxicology

Common effects of chemicals to cause symptoms

Chemicals can cause symptoms through the following mechanisms:
Interfere with the transport or tissue utilization of oxygen (carbon monoxide, cyanide), resulting in hypoxia or a decrease in an essential substrate such as glucose
Depress or stimulate the CNS, producing coma (sedative-hypnotics) or convulsions (Sympathomimetics such as cocaine, amphetamines)
Affect the autonomic nervous system, producing cholinergic action (organophosphate insecticide)
Affect the lungs by aspiration (hydrocarbon)
Affect the heart and vasculature producing myocardial dysfunction, dysrrhythmias (antiarrhythmic agents) and hypertension or hypotension
Produce local damage (caustics and corrosives)
Delayed effects on the liver (acetaminophen) or kidneys (heavy metals).


Potential sources of toxicities
1. Therapeutic agents
drug toxicity can be due to:
over doses
unusual adverse effects
frequent administrations of therapeutic doses
drug interactions
2. Industrial chemicals -- hazard in the work place in which they are used.
3. House-hold chemicals -- cleaning agents &cosmetics.
4. Environmental contaminants -- pesticides, smokes from factories & vehicles.
5. Natural toxicants -- accidental ingestions of poisonous plants or animals & by stinging & biting.
6. Food additives -- change the nature of the food stuff.
7. Drugs of abuse
Excessive or improper use of drugs for non-medical purposes, usually for altering consciousness and for body building is known as abuse of drug. (e.g alcohol, nicotine, etc).

HOW DOES THE POISONED PATIENT DIE? - The major causes of death

1. Respiratory failure
CNS depressants (opioids, sedative-hypnotics, antipsychotics, antidepressants, alcohol) → Respiratory center depression
2. Circulatory failure
Cardiac arrest: due to asystole, or lethal arrythmias (e.g., digitalis, tricyclic AD, amphetamine)
Vascular collapse: due to VMC depression, e.g., phenothiazines, sedative-hypnotics, theophylline all cause hypotension
Hypovolemia: due to
- bleeding (e.g., from gastrointestinal ulceration in acute iron intoxication), or
- excessive fluid loss (e.g. "rice water diarrhea" in acute arsenic intoxication)
3. Systemic hypoxemia caused by:
Impaired O2 transport by hemoglobin: CO (binds to Fe++ in Hb),
Impaired O2 use by mitochondria: cyanide (bind to Fe+++ in cytochrome oxidase)
4. Seizures, which may cause death by inducing:
respiratory failure (by convulsion of respiratory muscles)
pulmonary aspiration
hyperthermia, lactic acidosis, rhabdomyolysis → hyperkalemia, myoglobinuria → renal failure


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