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

B4.010 Adverse Drug Effects Flashcards

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
Q

target organs of anaphylactic shock

A

GI
skin
lung
vasculature

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26
Q

clinical manifestations of anaphylactic shock

A

GI allergy
uticaria
asthma
anaphylactic shock

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27
Q

mechanism of anaphylactic shock

A

IgE

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28
Q

target organs of cytotoxic hypersens

A

circulating blood cells

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29
Q

clinical manifestations of cytotoxic hypersens

A

leukopenia
thrombocytopenia
hemolytic anemia
granulocytopenia

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30
Q

mechanism of cytotoxic hypersens

A

IgM, IgG

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31
Q

target organs of Arthus hypersens

A

blood vessels
skin
joints
kidney

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32
Q

clinical manifestations of arthus hypersens

A

serum sickness
vasculitis
arthritis
glomerular nephritis

33
Q

mechanism of arthus hypersens

A

Ag-Ab complexes

34
Q

target organs of cell-mediated hypersens

A

skin
lungs
CNS

35
Q

clinical manifestations of cell mediated hypersens

A

contact nephritis
tuberculosis
allergic encephalitis

36
Q

mechanism of cell mediated hypersens

A

sensitized T cells

37
Q

describe the key concepts surrounding drug idiosyncrasies

A

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
Q

what is frequently a cause of drug idiosyncrasies

A

genetic abnormalities in enzymes or receptors (pharmacogenomics differences)

39
Q

what are some general mechanisms of adverse drug rxns

A 
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
Q

what are some major challenges when managing a poisoned patient?

A

no credible info on substance type, time of exposure, or dose of exposure

41
Q

general stepwise approach in management of a poisoned patient

A

clinical stabilization
clinical evaluation
prevention of further toxicant absorption
enhancement of toxicant elimination
admin of antidote (if available)
supporting care, monitoring, and followup

42
Q

ABCDTs

A 
airway
breathing
circulation
drugs
temp
43
Q

airway

A

should be cleared of vomit or any other obstruction and an airway or endotracheal tube inserted

44
Q

breathing

A

assessed by observation and by measurement of arterial gases (pulse ox), intubate and mechanically ventilate if needed

45
Q

circulation

A

monitor pulse, BP, and urinary output

start IV and draw blood for glucose and other labs

46
Q

drugs

A

dextrose for altered mental status
thiamine for alcoholic and malnourished pts to prevent Wernicke-Korsakoff
lorazepam or diazepam for seizure control

47
Q

temperature

A

tepid sponge bath and fan for cooling

48
Q

example causes of death due to drug/chemical toxicity

A 
CNS depression
airway obstruction
respiratory arrest
hypotension
cardiac arrhythmias
hypoxia
specific organ damage-necrosis
49
Q

what is a toxidrome

A

constellation of clinical symptoms, that when taken together, are likely associated with exposure to a certain toxicological class of chemical

50
Q

anion gap calculation and significant

A

gap = [Na+] - ([HCO3-]+[Cl-])
normally 12 +/- 2
INCREASED in metabolic acidosis

51
Q

AT MUD PILES for conditions that can cause an increased anion gap

A 
Alcohol
Toluene
Methanol
Uremia
DKA
paraldehyde
iron, isoniazid
lactic acid
ethylene glycol
salicylates
52
Q

osmolar gap calculation

A

osmolar gap = 2Na + (glucose/18) + (BUN/2.8)

normal = 285

53
Q

MAE DIE for conditions that alter osmolar gap

A 
methanol
acetone
ethanol
diuretics
isopropanol
ethylene glycol
54
Q

what is torsades de pointes?

A

prolonged QT intervals followed by ventricular tachycardia and a QRS that spirals around the isoelectric line

55
Q

what types of drugs cause TdP?

A 
quinidine (class IA & III antiarrhythmics)
tricyclic antidepressants
antipsychotics
non sedating antihistamines
cisapride
56
Q

what causes the prolonged QT in TdP

A

b1 stimulation and intense SYM activation

57
Q

factors that contribute to TdP

A

electrolyte imbalance
bradycardia
ischemia
hypoxia

58
Q

treatment of TdP

A

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
Q

what are 2 ways to remove/eliminate toxin

A

gastric lavage using activated charcoal

induction of emesis using ipecac syrup

60
Q

when is gastric lavage/emesis used?

A

is overdosed drug is suspected to be in stomach

downsides include aspiration (cant use with solvent chemicals)

61
Q

how to prevent an inhaled substance from absorbing further?

A

remove from toxic environment and provide ventilation

62
Q

how to prevent a topical substance from absorbing further?

A

remove contaminated clothing and wash with appropriate method

63
Q

how to prevent an ingested substance from absorbing further?

A 
much more involved
induce emesis
gastric lavage
oral admin of activated charcoal
whole-bowl irrigation (prevent further absorption via GI tract)
64
Q

what are some methods of enhancing elimination of toxicant

A 
alkalinization of urine
hemodialysis
hemoperfusion
plasma exchange
continuous hemofiltration
multiple dose activated charcoal (MDAC)
65
Q

what is ion trapping (alkalinization of urine)

A

change pH of urinate filtrate resulting in ionization of weak acids, thus trapping them in filtrate and preventing reabsorption

66
Q

what is hemodialysis

A

drug removal based on concentration gradient

67
Q

what is hemoperfusion

A

blood is passed over cartridge of adsorptive substance

68
Q

what is hemofiltration

A

blood is filtered using specific filters and plasma ultrafiltrate is removed
necessary fluids and electrolytes are replaced

69
Q

downside of antidotes

A

very limited and specific

70
Q

ethylene glycol antidote

A

fomepizole

71
Q

cyanide antidote

A

hydroxicobolamine

binds to cyanide ion and chelates it

72
Q

organophosphate/ nerve gas antidotes

A

atropine

73
Q

digoxin antidote

A

Fab fragments

74
Q

what are metal chelators

A

used for heavy metal poisoning

bind to metals and chelate them

75
Q

dimercaprol

A

arsenic, gold, mercury, acute lead

76
Q

calcium disodium EDTA

A

lead

77
Q

penicillamine

A

lead, copper

78
Q

succimer

A

oral chelator for lead

RC Test 1 (19 decks)

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