Toxicity Introduction Flashcards
Most exposure of humans to chemicals is from what source
Food plants containing naturally occuring compounds
What makes the poison
Dose
Toxicity
Ability of a chemical to cause injury or harm
Dose
How much chemical gains access to the body
Dose-Response curve
Reaction to a dose with increasing concentration
True or False: All individuals respond similar to drugs or toxins
False
Therapeutic range or window
Margin in which response increases with dose to show efficacy can also have side effects
What is the rule of toxicology
Exposure before risk
Magnitude of risk is proportional to potency and extent of exposure
The dose makes the poison
Routes and sites of exposure
Ingestion: GI
Inhalation: Lungs
Dermal/Topical: Skin
Injection: IV, IM, IP
Typical effectiveness with route of administration
IV > Inhale > IP > IM > Ingest > Topical
What route of exposure is the norm in pharmacy
Oral
What route of exposure is mostly seen in hospitals and drug abuse
IV
What are important components of exposure and dose
Duration and frequency
What is meant
T. Y acute exposure
24-28 hours or single exposure
What are the three classification of repeated exposure
Sub-acute
Sub-Chronic
Chronic
Up to 30 days exposure
Sub-acute
30-90 days exposure
Sub-chronic
Greater than 90 days exposure
Chronic
What is LD50
50% percent of the dose that causes mortality
Pharmacokinetics is concerned with
ADME
Pharmacodynamics is concerned with
DME
Efficacy
Toxicity
Ability of a chemical to enter the blood
Absorption
The kinetics of absorption is altered by what factor
Drug concentration
Therapeutic dose follow what order
First
Toxic dose follow what order
Zero
Can increasing the half life increase toxicity
Yes
Process in which a chemical agent translocate throughout order
Distribution
Rate of distribution is dependent on what factors
Blood flow
Toxin characteristics
Can higher toxic dose alter distribution
Yes
What metal can rapid mobilization of fat increase is blood concentration
Mercury
What element/metal is distributed in the bone
Fluoride
Lead
Strontium
What can happen to endogenous compounds of toxins bind to plasma protein
They can be displaced
True or false: A toxin deposited in fat or bone cannot be removed by hemodialysis or chelation
True
True or false: Only free drugs are available for adverse effect or excretion
True
What does adverse reaction depend on
Concentration of active compound at the target site overtime
What is the primary objective to preventing accumulation of active metabolite at Target tissue
Make agents more water soluble and easier to excrete
Bioactivation
Biotransformation that can result in the formation of reactive metabolite
How can toxic doses induce bioactivation
By saturating primary metabolic pathway (CYP450)the metabolism of a drug can occur via a new pathway that can bioactivate instead of detoxify
What is an example of a drug that can bioactivate by a new pathway
Acetaminophen
What are the two normal pathway for acetaminophen metabolism
Phase I reaction of conjugation to form a glucuronide or sulfate to form non-toxic moiety
What happens to acetaminophen when CYP450 2E1 is activated as a new pathway
Formation of toxic n-acetyl-p-benzo-quinine- mine (NAPQI) a toxic metabolite
What is the importance of glutathione in acetaminophen toxicity
It binds to NAPQI and converts it to cysteine and mercapturic and which are non-toxic
What two things can deplete glutathione causing increasing NAPQI levels
Alcohol and overdose
What are routes by which toxicants can be eliminated
Urine
Exhalation
Billary excretion via feces
Milks, sweat, saliva
Hoar can elimination be enhanced with some toxicants
Changing ph of urine
Increasing urine flow
Increasing blood volume
Where do You find toxicity info
Drug cards
MSDS
