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RC Test 1 > B4.010 Adverse Drug Effects > Flashcards

B4.010 Adverse Drug Effects Flashcards

(78 cards)

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1
Q

toxicology

A

science that related hazardous effects of chemicals, including drugs to biological systems

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2
Q

acute toxicity

A

1 to 2 days; single or multiple exposures

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3
Q

subacute toxicity

A

repeated exposure; less than 3 months

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4
Q

chronic toxicity

A

repeated exposure; greater than 3 months

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5
Q

what is the individual dose response

A

dose response for each ‘toxic effect’ or molecular interaction’ will be different

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6
Q

what is the quantal (population) dose response

A

at a given dose there are responders or non-responders in a population
needs many doses and very large sample size

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7
Q

how is therapeutic index calculated

A

animals- TI=LD50/ED50

humans- TI=TD50/ED50

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8
Q

how is margin of safety calculated

A

animals- MS=LD1/ED99

humans- MS-TD1/ED99

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9
Q

how is risk defined

A

probability that injury will result from exposure to a substance under specified conditions of dose and route of admin

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10
Q

what is hormesis?

A

unusual dose response

lower doses have protective effects and higher doses have adverse effects

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11
Q

what are some substances that exhibit hormesis

A

vitamins
alcohol
radiation
oxidative stress

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12
Q

what are 3 types of adverse drug effects

A

toxicity
hypersensitivity
idiosyncrasies

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13
Q

toxicity

A

dose related toxicity due to non-immune mechanism

generally an overextension of the pharmalogical response

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14
Q

hypersensitivity

A

allergic reactions involving immune system

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15
Q

idiosyncrasies

A

abnormal responses not linked to immune system (mechanisms unclear)

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16
Q

what types of toxicities are typically dose limiting?

A

organ directed
aspirin induced GI tox
acetaminophen induced hep tox
doxorubicin induced cardio tox

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17
Q

benefit to risk ratio

A

expression of adverse effects that is more useful clinically than therapeutic index

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18
Q

what is the difference between direct fetal toxicity and teratogenicity

A

fetal toxicity acts on fetus directly

teratogenicity- physical defects in developing fetus due to drug exposure to the MOTHER during gestation

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19
Q

when are teratogenic effects most pronounced

A

during organogenesis

day 20 of gestation to the end of the first trimester

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20
Q

what are some examples of teratogens

A

thalidomide
alcohol
lithium
antifolates

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21
Q

what is the mechanism of a drug allergy

A

abnormal response resulting from previous sensitizing exposure activating immunologic mechanism

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22
Q

how do allergies differ from drug toxicity

A
  • altered reactions occur in only a fraction of the pop
  • dose-response is unusual (small amts can elicit severe rxn)
  • manifestations of rxn are different from usual pharmacological and toxicological effects of drug
  • primary sensitization
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23
Q

are most drugs immunogenic alone?

A

no

must bind covalently to self-macromolecule or alter structure of self-macromolecule to become immunogenic

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24
Q

4 types of drug induced hypersensitivities

A

anaphylactic (immediate)
cytotoxic (autoimmune)
arthus (immune complex)
cell mediated (delayed)

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25
target organs of anaphylactic shock
GI skin lung vasculature
26
clinical manifestations of anaphylactic shock
GI allergy uticaria asthma anaphylactic shock
27
mechanism of anaphylactic shock
IgE
28
target organs of cytotoxic hypersens
circulating blood cells
29
clinical manifestations of cytotoxic hypersens
leukopenia thrombocytopenia hemolytic anemia granulocytopenia
30
mechanism of cytotoxic hypersens
IgM, IgG
31
target organs of Arthus hypersens
blood vessels skin joints kidney
32
clinical manifestations of arthus hypersens
serum sickness vasculitis arthritis glomerular nephritis
33
mechanism of arthus hypersens
Ag-Ab complexes
34
target organs of cell-mediated hypersens
skin lungs CNS
35
clinical manifestations of cell mediated hypersens
contact nephritis tuberculosis allergic encephalitis
36
mechanism of cell mediated hypersens
sensitized T cells
37
describe the key concepts surrounding drug idiosyncrasies
untoward reactions to drugs that occur in a small fraction of patients and have no obvious relationship to dose or duration of therapy does not involve immune rxn
38
what is frequently a cause of drug idiosyncrasies
genetic abnormalities in enzymes or receptors (pharmacogenomics differences)
39
what are some general mechanisms of adverse drug rxns
``` receptor-ligand interactions membrane functions cellular energy covalent binding to biomolecules calcium homeostasis non-lethal alterations in somatic cells ligand-activated transcription factors programmed cell death (apoptosis) GSH depletion and ROS ```
40
what are some major challenges when managing a poisoned patient?
no credible info on substance type, time of exposure, or dose of exposure
41
general stepwise approach in management of a poisoned patient
clinical stabilization clinical evaluation prevention of further toxicant absorption enhancement of toxicant elimination admin of antidote (if available) supporting care, monitoring, and followup
42
ABCDTs
``` airway breathing circulation drugs temp ```
43
airway
should be cleared of vomit or any other obstruction and an airway or endotracheal tube inserted
44
breathing
assessed by observation and by measurement of arterial gases (pulse ox), intubate and mechanically ventilate if needed
45
circulation
monitor pulse, BP, and urinary output | start IV and draw blood for glucose and other labs
46
drugs
dextrose for altered mental status thiamine for alcoholic and malnourished pts to prevent Wernicke-Korsakoff lorazepam or diazepam for seizure control
47
temperature
tepid sponge bath and fan for cooling
48
example causes of death due to drug/chemical toxicity
``` CNS depression airway obstruction respiratory arrest hypotension cardiac arrhythmias hypoxia specific organ damage-necrosis ```
49
what is a toxidrome
constellation of clinical symptoms, that when taken together, are likely associated with exposure to a certain toxicological class of chemical
50
anion gap calculation and significant
gap = [Na+] - ([HCO3-]+[Cl-]) normally 12 +/- 2 INCREASED in metabolic acidosis
51
AT MUD PILES for conditions that can cause an increased anion gap
``` Alcohol Toluene Methanol Uremia DKA paraldehyde iron, isoniazid lactic acid ethylene glycol salicylates ```
52
osmolar gap calculation
osmolar gap = 2Na + (glucose/18) + (BUN/2.8) | normal = 285
53
MAE DIE for conditions that alter osmolar gap
``` methanol acetone ethanol diuretics isopropanol ethylene glycol ```
54
what is torsades de pointes?
prolonged QT intervals followed by ventricular tachycardia and a QRS that spirals around the isoelectric line
55
what types of drugs cause TdP?
``` quinidine (class IA & III antiarrhythmics) tricyclic antidepressants antipsychotics non sedating antihistamines cisapride ```
56
what causes the prolonged QT in TdP
b1 stimulation and intense SYM activation
57
factors that contribute to TdP
electrolyte imbalance bradycardia ischemia hypoxia
58
treatment of TdP
magnesium sulfate- works by suppressing early afterdepolarizations (EADs) and terminating the arrhythmia magnesium achieves this by decreasing the influx of calcium and lowering the amplitude of EADs
59
what are 2 ways to remove/eliminate toxin
gastric lavage using activated charcoal | induction of emesis using ipecac syrup
60
when is gastric lavage/emesis used?
is overdosed drug is suspected to be in stomach | downsides include aspiration (cant use with solvent chemicals)
61
how to prevent an inhaled substance from absorbing further?
remove from toxic environment and provide ventilation
62
how to prevent a topical substance from absorbing further?
remove contaminated clothing and wash with appropriate method
63
how to prevent an ingested substance from absorbing further?
``` much more involved induce emesis gastric lavage oral admin of activated charcoal whole-bowl irrigation (prevent further absorption via GI tract) ```
64
what are some methods of enhancing elimination of toxicant
``` alkalinization of urine hemodialysis hemoperfusion plasma exchange continuous hemofiltration multiple dose activated charcoal (MDAC) ```
65
what is ion trapping (alkalinization of urine)
change pH of urinate filtrate resulting in ionization of weak acids, thus trapping them in filtrate and preventing reabsorption
66
what is hemodialysis
drug removal based on concentration gradient
67
what is hemoperfusion
blood is passed over cartridge of adsorptive substance
68
what is hemofiltration
blood is filtered using specific filters and plasma ultrafiltrate is removed necessary fluids and electrolytes are replaced
69
downside of antidotes
very limited and specific
70
ethylene glycol antidote
fomepizole
71
cyanide antidote
hydroxicobolamine | binds to cyanide ion and chelates it
72
organophosphate/ nerve gas antidotes
atropine
73
digoxin antidote
Fab fragments
74
what are metal chelators
used for heavy metal poisoning | bind to metals and chelate them
75
dimercaprol
arsenic, gold, mercury, acute lead
76
calcium disodium EDTA
lead
77
penicillamine
lead, copper
78
succimer
oral chelator for lead

RC Test 1 (19 decks)

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