Toxicology General Principles Flashcards
Define Toxicology
The study of poisons
Define Posion
any chemical substance which can cause harm
Define hazard
likelihood an event will occur based on how the product is packaged, formulated, or its accessibility
Define risk
the probability that an event will occur based on patient
vulnerability
Define drug Co-ingestant
Xenobiotic (foreign substance) in circulation at
the time of toxicity.
Poisoning is the ___ cause of injury deaths and the ___ cause of hospitalizaton
Fourth. fifth
The most common cause of poisoning is?
Preascription medicaitons
Approximately ___ of people taking acetaminophen in Canada overdose
10 000
WIth opioid related poisonings ___ involved opioids that were non-pharmaceutical
88%
Toxicology is the study of AE of chemicals on living systems including: (5)
*Mechanisms of action and exposure to chemicals as a cause of acute
and chronic illness.
*Understanding physiology and pharmacology by using toxic agents as
chemical probes.
*Recognition, identification, quantification of hazards from occupational
exposure to chemicals.
*Discovery of new drugs and pesticides.
*Development of standards and regulations to protect humans and the
environment from adverse effects of chemicals.
What is ED50?
dose at which 50% of population therapeutically responds. (ED50=1 mg/kg)
What is the TD50?
dose at which 50% of population experiences toxicity (TD50=10 mg/kg).
What is the LD50/
dose at which 50% of population dies (LD50=100 mg/kg).
What does ED, TD and LD stand for?
Effective dose, Toxic dose, lethal dose
What is the NOAEL score?
Highest dose at which - no observed
adverse effect level
What is the LOAEL?
Lowest dose at which - observed adverse
effect level
What is the TI?
TI is the ratio of the doses of the
toxic and the desired responses.
How is the therapeutic index calculated?
TI is used an index of ___ toxicity of two different materials
comparative
The larger the ratio of the TI?
the greater the relative safety.
Which drug is safeR?
Drug A
Example of a poisoning scale
Define Mechanistic
cellular, biochemical and molecular
mechanisms by which chemicals cause toxic
responses
Define Foresnic
cause of death, legal aspects
Define clinical
treatments for poisonings and injuries
caused by xenobiotics
Can you determine LD50 on human clinical trial?
No, unethical, we are even trying to reduce the usage of mice
Define environmental
environmental pollutants, effects
on flora and fauna
Define Food
Adverse effects of processed or natural
food components
Define regulatory
assigns risk to substances of
commercial importance (toxicology meets
regulations/policies).
What are the factors affecting toxicity?
Route and site of exposure
Duration of exposure
Elimination rate and frequency of expsorue
What are the major routes and site of exposure?
Major poisons access the body via:
* GI (77%)
* Lungs
* Skin
* Parenteral routes - most toxic and rapid response (BYPASS FIRST PASS)
* Ocular
* GU and other routes
Define acute duration of exposure?
Acute: within previous 24 h
Define subacute duration of exposure
Subacute: repeated exposure x 14 d
Define Subchronic duration of exposure
- Subchronic: repeated exposure x 3 m
Define Chronic duration of exposrue
- Chronic: repeated exposure > 6 m
Review the next slide with regards to elimination and frequency of exposure
Notice A is eliminated slow, B is = frequency of dose, C= fast elimination
Define Absorption
Rate and extent (bioavailability) of
absorption are important because they
determine concentration and ultimately,
the likelihood of toxic effect.
Describe the Flow of blood from digestive to arterial circulation
- GI: Cmax is low and Tmax is large
- IV– Drug does not undergo first pass metabolism. Cmax is larger and Tmax is
smaller. Even though the conc of the drug administered is same. - Inhalation (Lungs) – Cmax is even large and Tmax is further smaller. E.g.
anaesthetics.
Different routes of administration may cause different ___ and ___ at the same concentration of the drug
Cmax and Tmax
Review the next slide
Enterohepatic circulation drgus?
E.G.
ANTIBIOTICS, NSAID, WARFARIN, OPIOIDS, DIGOXIN
What may be the pharmacological effect of the toxicant itself?
- Gastric hypomotility or delayed gastric emptying from anticholinergic effect
- Pathophysiologic consequences: hypotension, hypothermia → hypoperfusion
Curve 3 falls faster than curve one because
ate of excretion is proportional to the current conc of the drug as the drug follows first order
kinetics.
Half-life of the drug is same regardless
of the route of administration.
Half-life is drug characteristics and not route based.
Where is absorption in oral exposure mostly?
Small intestine
Pharmacobezoars
formation of four different
extended-release formulations
Distribution can be divided into 4 categories
Blood, Extracellular fluid, fat, intracellular fluid
Volume of distribution?
How much of the drug needs to be in the body to get a certain conc. in the plasma.
What is the Vd equation
What is Kc dependant on?
Permiability of barriers
pH of compartments
Binding capacity
Drug characteristics
Equilibrium constant Kc is a number that-
Tells if the balance is in forward or backward direction.
What is distribution
Blood flow, Plasma protein binding
Vd, transporters, pH of the blood
What is the toxic effect compartment?
- May differ from therapeutic effect compartment
- Onset of toxicity depends on the rate of distribution to the toxic effect
compartment
Example of Toxic effect compartment
Lead in liver and stored in bone, Lithium to plasma and brain
What does Glucuronosyltransferases lead to
glucuronidation
What are some factors affecting metabolism (3 main ones)
Enzyme Saturation
Genetic polymorphism
Variation
What are the variation factors affecting metabolism?
Rate of blood flow, protein binding and the intrinsic ability (organ clearance)
What are the elimination mechanisms?
Kidney, liver
The renal excretion of drugs is the result of different mechanisms:
glomerular filtration, passive back diffusion, tubular secretion and
tubular reabsorption (saturable).
Things to consider for renal excretion (3)
- Passive filtration: relies on filtrate pH and blood flow rate
- Changes to blood pH: may cause ion trapping
- Saturation of active secretion: may lead to accumulation
What are the approaches to the poisoned patient?
SLIDE RESUSCITATION AND STABILIZAITON
