Introduction to Toxicology (Lynn R. Panganiban, MD) Flashcards
It is the science of adverse effects of chemical, physical and biological agents on living organisms.
Toxicology
What are the physical agents toxicology is concerned with?
Radiation and heat waves
What are the biological agents toxicology is concerned with?
Parasites and infectious disease etiologic agents
Define: Toxicity
Ability of a substance to cause harm in an organism
T/F: Toxicity is an innate property of the substance.
True
While we cannot control a drug’s toxicity, we can control its toxicity during (1).
Manufacture
Define: Toxicodynamics
- Mechanisms of actions of chemicals
2. Extension of definition of pharmacodynamics
Define: Toxicokinetics
ADME of substances in their toxic statess
i.e. changes from 1st order to 0 order
Define: Poison
Any agent capable of producing a deleterious effect leading to injury or death
What is the more medically acceptable term for “poison”?
Toxicant
T/F: Toxins are artificial substances.
False
They are naturally occurring substances of endogenous plant or animal origin.
What are used for substances that are synthetically manufactured?
Xenobiotics
What is the state of being overdosed on drugs, medicaments, chemicals and biological substances?
Poisoning
What is the difference between an adverse reaction and poisoning?
An adverse reaction always occurs within therapeutic doses.
Enumerate the factors affecting responses to toxic agents
- Physical & chemical properties
- Exposure situation
- Individual factors
Enumerate the important physical and chemical properties of toxic agents
- Physical state
- Solubility
- Vapor pressure
- Vapor density
- Reactivity
What physical state is most toxic to humans?
Gas
In terms of solubility, what toxicants are most harmful?
Fat-soluble, non-ionised substances
What values of vapour pressure are considered most toxic?
Greater than or equal to 1 mmHg
What values of vapour density are considered most toxic?
Greater than one (heavier than air)
Dangerous for people on the first floor!
Toxicants with (1) and (2) are more deleterious.
(1) Charged particles
(2) Reactive oxygen species
Define: Acute Exposure
- Exposure happens in less than 24 hours.
- Single dose
- Series of doses within 13hrs if administered orally
- Continuous for 4 hrs via inhalation
- Large volume of drugs
- Effects appear within 14 days
Define: Subacute Exposure
- Repeated daily exposure for 21 ways via specific route
- No need for high dosage
- SSx manifest within 21 days.
Define: Subchronic Exposure
- Repeated daily exposure for 90 days
2. Can be low dose
Define: Chronic Exposure
- Lifetime exposure
- Two years for rat and mice
- Seventy years for humans
- May result in transgenerational effects
What parameter is expressed in terms of exposures/time period?
Frequency
What parameter is critical to the concentration level of substance in biological fluids at the site?
Frequency
Enumerate the major routes by which toxic substances gain access to the body
Ingestion Inhalation Dermal/Percutaneous Parenteral Mucosal
Rank the routes of entry in terms of descending effectiveness toxicity
Parenteral Inahalational Intraperitoneal Intramuscular Subcutaneous Intradermal Oral & Dermal
What is the most critical factor determining whether the intrinsic property of a substance will be expressed?
Dosage
T/F: Dose should not be dependent on the weight of the individual.
False
It should be.
Which tenet may not necessarily apply in cases of toxicity?
The dose makes the poison
What are examples of endocrine disruptive agents?
Bisphenol A (found in plastics and can affect reproductive development of children) DDT (affects reproductive development)
What substances can induce their effects in picograms?
Dioxins
What is the mechanisms of action of carcinogenic or genotoxic substances?
Disrepair of components of the central dogma
Enumerate the individual factors that contribute to toxicity
Age
Sex (pregnant women > women reproductive age group)
Genetic Background (toxicogenomics; G6P deficiency bleeding from nitrates)
Nutritional Status (low protein/albumin)
General Health Status (liver, kidney or heart disease)
ADME
T/F: Toxic action of drug is an exaggeration of its therapeutic action.
False
What happens when a person overdoses on paracetamol?
Develops liver problems
What is the mechanism of action of isoniazid?
Attacks the ribosomes of Mycobacterium
How does isoniazid overdose manifest?
Inhibition of GABA synthesis resulting in seizures and B6 deficiency
T/F: One toxicant may exert several mechanisms of toxic actions.
True
Toxicity may also affect the (1) not just the CNS. Give an example.
blood; lead toxicity
What does lead toxicity do to the body?
- Breakdown of sulfhydryl molecules of myelin sheaths causing neuropathy
- Interference with haemoglobin production by enzyme inhibition leading to multi-organ system effects
e. g. alcohol & tobacco
T/F: Toxic action can only be brought about by the parent compound.
False
What is a metabolite of diazepam that has the same potency as its parent compound?
Oxazepam
When metabolised, what is paracetamol converted to? Is it toxic?
NAPQI; yes
T/F: The mechanism of toxic action in acute exposure is no different from those in chronic exposure.
False
e.g. seizure as a result of acute exposure and cancer as a result of chronic exposure
What substances inhibit acetylcholinesterase?
Organophosphate
Enumerate the clinical signs of cholinergic manifestation
Salivation, diarrhoea, pupil dilation, sweating and bradycardia
Intensity of the toxic effect depends primarily on what properties of the ultimate toxicant?
Concentration and persistence
T/F: The effect of a chemical is dependent solely on the dose administered.
False.
It depends more on the concentration and disposition of the chemical in the target organ.
T/F: Drugs that are normally metabolised through first-order kinetics may change to zero-order kinetics during overdose.
True
Give examples of drugs that exhibit zero-order kinetics when overdosed.
Phenobarbital, theophylline and salicylate
T/F: During overdose, some drugs may change their volume of distribution
True
Enumerate the factors affecting kinetic processes.
- Duration and concentration at the portal of entry.
- Rate and amount of chemical absorbed
- Distribution of the toxicant within the body
- Efficiency of biotransformation and nature of metabolites
- Ability of the chemical or its metabolites to pass through cell membranes and come into contact with specific cell components
- Amount and duration of storage of the chemical or its metabolites in body tissues
- Rate and site of excretion
T/F: The higher the concentration of the chemical at the portal of entry, the greater the damage
True
e.g. concentrated HCl causes greater damaged than diluted HCl
In terms of rate and amount of chemical absorbed, when will toxicity be low?
Slow absorption and small amount of absorption
T/F: Slowly released products have a wide margin of safety.
True