Toxicology Flashcards
Toxicology
Toxicology is the qualitative and quantitative study of the adverse or toxic effect of chemicals and other anthropogenic materials or xenobiotics on organisms.
Medical toxicology
Medical toxicology, is a medical subspecialty focusing on the diagnosis, management and prevention of poisoning and other adverse health effects due to medications, occupational and environmental toxicants, and biological agents.
Toxicology
Toxicology is the study of poisons
What are Poisons?
Poisons are chemical/physical agents that produce adverse responses in biological organisms
Any substance can be toxic if introduced in a dose capable of disturbing the normal physiological homeostatsis of the exposed body.
What are Toxins?
Toxins: are poisonous substance produced within living cells or organism (a poison of natural origin) e.g. venom
What is Poison (Toxicant)?
Poison (Toxicant) - a chemical that may harm or kill an organism
What is Toxicity?
Toxicity – is the ability of a chemical agent to cause injury
What Hazard?
Hazard – is the likelihood that injury will occur in a given situation or setting
What is a Risk?
Risk – is defined as the expected frequency of the occurrence of an undesirable effect arising from exposure to a chemical or physical agent.
What is a Synergism?
Synergism: combined effect is greater than the sum of individual effect
What is Additive effect?
combined effect is equal to the sum of their individual effect
What is Potentiation effect?
When one substance enhances the effect of another
What is Antagonism?
When one substance decreases the effect of another
What are Phase I: Biotransformation of poisons?
the drug is converted into more polar compound e .g oxidation, reduction, &hydrolysis
What are Phase II (conjugation): Biotransformation of poisons?
a drug or its metabolite is conjugated with an endogenous substance e .g glucuronide conjugate
What is Enzyme inhibition: Biotransformation of poisons?
by this the biotransformation of drugs is delayed & is a cause of increased toxicity
What is Enzyme induction: Biotransformation of poisons?
by this the biotransformation of drugs is accelerated & is a cause of therapeutic failure
Basic Classification of Toxicology
Descriptive toxicology: Descriptive toxicology deals with toxicity tests on chemicals exposed to human beings and environment as a whole.
Mechanistic toxicology : Mechanistic toxicology deals with the mechanism of toxic effects of chemicals on living organisms
Regulatory toxicology
Occupational toxicology
Environmental toxicology
Clinical toxicology: intentional consumption of poison
Forensic toxicology
Basis for Grouping Toxicology
- sources of poison
- properties of poison
- mechanism of toxicity
- detection
- clinical manifestations
- Management
Sources of Toxins
Chemical source: the commonest sources are drugs corrosives
Plant source : cocaine, cannabis
Animal source : the list but most serious source e.g. venomouse animals (snakes, scorpions, spiders, wasps)
Venomous and Poisonous Animals
Venomous animals deliver or inject venom into other organisms, using a specialized apparatus such as fangs or a stinger
The venom is produced in a gland attached to this apparatus
Poisonous animals do not deliver their toxins directly.
The entire body or large parts of it may contain the poisonous substance.
The organism may be harmful when eaten or touched.
What are Site of Toxic Actions?
Local (Non-specific): Wherever the poison contacts the biological system it starts its harmful effects. It does not require specific site or receptor to elicit its effects such as toxicity by acids or alkalis
Remote (systemic): The poison affects a system far from its portal of entry
Local and Remote: The poison has the capacity of acting locally and systemically.
Duration and Frequency of Exposure
Acute: application of a single or short-term (less than a day) dosing of a substance to cause toxicity
Sub-acute: toxicity is expressed after repeated applications for a duration less than half-life expectancy of the substance
Chronic : Expression of toxic symptoms only after repeated exposure to a chemical in doses regularly applied to the organism for a time greater than half of its life expectancy
Mechanisms of Toxicity
Direct : The poison itself can cause toxic effects as in corrosives
Indirect : toxicity results from the interactions of the poison with the biological activity within biological system
Binding to cell membrane to change in their function or structure thus affecting their normal activities
Interference with enzymatic actions
Formation of metabolites which are more toxic than the parent poison
Effect on DNA
Classification of Toxic Agents
According to the target organ e.g. hepatotoxic, nephrotoxic
According to their use e.g. food additives, pesticide, drug
According to their source e.g. animal, plant
According to their effects e.g. carcinogen, mutagen
According to their physical state e.g. gas, liquid, solid
According to their chemistry e.g. amine, hydrocarbon
According to their poisoning potentiality e.g. extremely toxic, slight toxic
According to their biochemical mechanism of action e.g. alkylating agent, acetyl cholinesterase inhibitor
Factors Affecting Action of Poison
- Factors related to the poison:
Dose : a basic principle in toxicology
Dose is the amount of chemical that comes into contact with the body or gets inside the body
The increase in dose will increase the toxicity
Physical status : gaseous state is more toxic than liquid state than the solid state
Purity: this depends on the impurity of the poison
If the impurities are more toxic than the poison, the toxicity will be more and vice versa. - Factors related to the individual :
Age
Health
Sensitivity
Sex - Factors related to mode of exposure
Inhalation —> IM —> Ingestion —> Skin Contact - Factors related to environment
Temperature, pressure . humidity,
Factors affecting Delivery
Absorption:
* Distribution towards the target of action
* Reabsorption
* Toxicity
Presystemic elimination :
* Distribution away from the target
* Excretion
* Detoxication
General Principles of Poison Management
The poison or class of poison involved.
The clinical features associated with some common poisons may be specific
Diagnoses other than poisoning must also be considered
N.B General Physical examination should include
– Vital signs
– Evaluation of specific parts of the body
Supportive measures:.
- Maintain air way, adequate ventilation & oxygenation, provide tracheal intubation if required
- If comatose, administer glucose, thiamine, &oxygen
- For seizures, administer anticonvulsants
Principles of toxin eliminations
Inhalation , Skin, Oral sources ,
Force diuresis
Dialysis
Some Antidotes &Protective Agents used in the Treatment of acute Poisoning
Antidote: Atropine
Poison: Organophosphate
Antidote: Deferoxamine
Poison: Iron
Antidote: Methylene blue
Poison: Nitrates
Antidote: Physiostigmine
Poison: Atropine
Antidote: Naloxone
Poison: Opioids
Pyridoxine
Poison: Isoniazid
Analytical Toxicology
Detection, identification and quantification of poisons
The roles of clinical toxicology laboratory
If the diagnosis is in doubt,
The administration of antidotes or protective agents is contemplated, or
The use of active elimination therapy is being considered.
Drug monitoring
Basic Information Required in toxicology laboratory
Suspected agent(s)
Suspected dose
Time of ingestion and sampling
Clinical presentation:
Location of the victim
Samples Required for Toxicological Analysis from Autopsy
Blood
The best place at autopsy is from femoral and iliac veins, then axillary veins in consequence
No samples from
Jugular vein: may be contaminated by reflux from upper thorax
General body cavity: highly contaminated by intestinal contents
Heart or great vessels in chest: postmortem diffusion of drugs and alcohol from the stomach or aspirated vomit can contaminate these sites
Urine
20-30 mls of urine in sterile container without preservatives
Faeces
Used in heavy metals as arsenic, lead, mercury
Vomit and Stomach contents
Forensic Toxicology
Forensic toxicology is concerned with the detection and estimation of poisons for legal purposes
Tissues and body fluids obtained at autopsy
Blood, urine, or gastric material obtained from a living person
Poison as a cause of death can be proven only with toxicological analyses that demonstrate the presence of the poison in the tissues or body fluids of the deceased
Presence of poisons can be demonstrated only by the chemical methods of isolation and identification.
If toxicological analyses are avoided, death may be ascribed to poisoning without definite proof
Methods of Analysis (Qualitative)
Colour test
Rapid easily performed, qualitative , screening test but not specific
Can be used as bed side rapid test
Examples
Ferric Chloride test for salicylate: It gives pink colour
Zwikker test for barbiturates: it gives purple color
Formaldehyde-Sulfuric acid test for Benzodiazepines : It gives orange colour
Mandalin test for opoid : It gives brown colour
Immunoassays
Chromatography
