5+6: Intro to Toxicology + ADRs Flashcards
list 3 possible classifications for toxic agents
physical state
chemical stability/ reactivity
chemical structure
poisoning potential
biochemical MOA
target organ
use
source
T or F: most toxic agents can be classified by a single classification system
F- No single classification that is applicable to entire spectrum, combination of classification systems generally needed
to have a toxic exposure, 3 things are required
sufficient concentration
of active form
for enough time
describe the 3 characteristics of acute effects
<24hrs or immediately
usually relatively high dose
short duration/ reversible
describe the 3 characteristics of subacute effects
<1mth
from repeated doses
reversible/ irreversible
describe the 3 characteristics of subchronic effects
1-3mths
repeated doses
rev/ irrev
describe the 3 characteristics of chronic effects
> 3mths after exposure
due to lower repeated doses over months/ years
usually irreversible
defattening of the skin is a
1. local effect
2. systemic effect
3. allergic reaction
4. idiosyncratic reaction
1
combined effect of 2 substances equal to sum of the individual effects (2+2=4)
additive
toxic eff of each substance is unaffected by simultaneous exposure (2+2 = 2 and 2)
independent
combined effect is greater than the sum of the individual effects
synergistic
enhancement of one agent by another so that the combined effect is greater than the sum of the effects of each alone (0+2=7)- one drug does not elicit a response on its own
potentiation
when 2 chemicals administered together interfere with each other’s actions, or one with the other (4+6=8, 4+0=1)
antagonism
what are the 4 types of antagonism
receptor (blocker)
chemical
dispositional
functional
describe receptor antagonism
prevention of chemical receptor interaction or activation
describe chemical antagonism
direct interaction of 2 chemicals preventing receptor interaction/ activation
describe disposition antagonism
altered metabolism or CL of chemical prevents receptor interaction or activation
activated charcoal preventing absorption of toxin is an example of
1. receptor antagonism
2. chemical antagonism
3. functional antagonism
4. dispositional antagonism
4
describe functioning antagonism
opposing effects on the same physiologic system
Fall in BP caused by barbiturate (GABA4 receptor) antagonized by vasopressor norepinephrine (a-adrenergic receptor) is an example of
1. receptor antagonism
2. chemical antagonism
3. functional antagonism
4. dispositional antagonism
3
NOAEL is
no observable AE level
LOAEL
lowest observable AE level
the slope on a dose response relationship indicates
the change in % of the population responding as the dose increases (Steep vs shallow)
a steep curve on a dose response relationship indicates
some beneficial effect will be offset by toxicity, small ↑ dose = large ↑ in response
a shallow curve on a dose response relationship indicates
safer, low dose may be effective without producing toxicity
what is ED50
effective dose 50% of the population (normally ref to beneficial eff but can be used for harmful eff)
what is TD50
toxic dose 50% of the population (AEs)
what is LD50
lethal dose for 50% of pop (common for acute toxicity- not really used)
what is the threshold dose on dose response relationships
point where toxicity first occurs
therapeutic index =
TD50/ED50
Therapeutic index is used to
compare therapeutically effective dose to toxic dose of drug
a ______ TI = better safety
larger
MOS =
TD10/ED90
SI =
TD10/ED90
efficacy is
the extent a chemical can elicit a response
max on Y axis
potency is
the range of doses where the chemical produces a response
x axis (lower = more potent)
what is the difference between an ADE vs and ADR
ADE = does not necessarily have a causal relationship
ADR = a response to a drug that is unintended
medical occurrence that may present during tx with a pharmaceutical product but which does not necessarily have a causal relationship with this tx describes AD_
ADE
Occurs while taking the drug but not always attributable to it describes AD_
ADE
May be associated with inappropriate use of the drug or other confounders that occur during drug therapy- but are not necessarily caused by the pharmacology of the drug itself describes AD___
ADE
Attributed to some action of the drug and Occur despite appropriate prescribing and dosing describes AD__
ADR
a response to a drug that is noxious and unintended and occurs at doses normally used in humans for prophylaxis, diagnosis, therapy, or modification of physiologic function describes AD___
ADR
any unintended effect of a drug occuring at doses normally used in humans which is related to the pharmacological properties of the medicine
side effect
what is the difference between an ADR vs a SE
ADRs are always noxious and usually worse than SEs
SEs are only unintended effects- may not always be undesired
an AD__ is a type of AD___ is a type of _________
ADR is a type of ADE is a type of adverse event
what is a medication error
any preventable even that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the HCP, pt, or consumer
type A reactions are dose _______ and _________
dependent and predictable
type A reactions are (more/less) common than type B
more
type A reactions primarily result from ___________ and represent ______________
drug pharmacology + represent augmentation or exaggerated effect
type A reactions are problematic when there is a
narrow therapeutic window
warfarin causing bleeds is a type ____ reaction
A
malignant hyperthermia in response to anesthetics is a type ___ reaction
B
type B reactions are _____ of dose, _______ to known pharm actions
independent of dose
unrelated to known pharm actions
type B reactions are often caused by
immunological responses and pharmacogenic mechanisms
type B reactions are often _______ and affects _____ populations
idioxyncratic
small populations
type C reactions are _____ reactions that _____________________________
continuing reactions that persist for relatively long periods of time with cumulative doses
how to treat type C reaction
reduce dose or withhold meds
type A reactions are reversible by
reducing dose/ withdrawal
osteonecrosis of the jaw from chronic use of BPs is a type ___ reaction
C
what type of reaction emerges after the patient has started treatment
type D- delayed
doxorubicin used to treat cancer resulting in later cardiomyopathies is an example of type ___ reactions
d
describe a type E reaction
Occurs after pt stops tx, uncommon
how to avoid/ stop type E reaction
reintroduce then slowly withdrawal causative agent
stopping BZDs suddenly results in anxiety, insomnia, and psychosis is an example of ______
type E reaction
what is a type F reaction
unexpected failure of efficacy, common
type F may be ____ or _____
dose related or drug intx
which of the following is common
1. type B
2. type D
3. type E
4. type F
4
what is an example of a type F reaction
resistance to antibiotics
what is type 1 hypersensitivity
antibody mediated hypersensitivity due to IgE release
reexposure after sensitization triggers response in type __ hypersensitivity
1
type ___ hypersensitivity is antibody based and primarily involving IgG or IgM response
2
type 2 hypersense rxn primarily involves
IgG or IgM antibody mediated response
type 2 hypersense rxns emerge in ____ days and sx in _____
5-21 days
sx in 24-48 hrs
_____ and _____ are often targets in type 2 hypersens rxn
blood cells and platelets
type 3 hypersensitivity is
nonimmediate immune complex mediated hypersensitivity
type 3 hypersens reactions are ____ reactions involving ___
antibody reactions
IgG
what type of hypersens rxns are due to elevated levels of antigen- antibody complexes
type 3
what type of hypersensitivity rxn causes serum sickness
type 3
which type of hypersensitivity takes the longest to develop sx
type 4
type 4 hypersens is also known as
T cell mediated hypersensitivity
type 4 hypersense is a reaction involving ___________________________
drug sensitizing T cells
which hypersensitivity type doesn’t depend on antibodies
1. type 1
2. type 2
3. type 3
4. type 4
4
SJS is an example of type ___ hypersens rxn
type 4 hypersens
therapeutic agent used to counteract toxic action of a drug or toxin
antidotes
which of the following is true
1. less than 2% toxins have a known antidote
2. you should treat the patient’s specific toxin, not the sx which will go away with adequate toxin control
3. antidotes typically have low potential SEs and toxicity or a large TI
4. all of the above are true
1
activated charcoal is commonly given as a (single/ multiple), (large/ small) dose
single large dose
activated charcoal characteristics
large SA
small particle size
very porous
activated charcoal is not useful with
alcohols
cyanide
iron
lithium
arsenic
activated charcoal is CI with
caustics
4 ways antidotes can work
direct action on toxin
action on the toxin binding site
decreasing toxic metabolites
counteracting the effects
activated charcoal works by
1. direct action on toxin
2. action on the toxin binding site
3. decreasing toxic metabolites
4. counteracting the effects
direct action on toxin
NAC works by
1. direct action on toxin
2. action on the toxin binding site
3. decreasing toxic metabolites
4. counteracting the effects
3
naloxone and flumazenil work by
1. direct action on toxin
2. action on the toxin binding site
3. decreasing toxic metabolites
4. counteracting the effects
2
atropine works by
1. direct action on toxin
2. action on the toxin binding site
3. decreasing toxic metabolites
4. counteracting the effects
4
when actvated charcoal is given in multiple smaller doses, the intent is to
enhance elimination like dialysis
when activated charcoal is given as a large single dose, the intent is
to bind poison and avoid systemic absorption
