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PHAR 324 > Decontamination, Elimination, Antidotes > Flashcards

Decontamination, Elimination, Antidotes Flashcards

1
Q

What is decontamination?
Why it is used? (3 total)

A
  1. Stop ongoing exposure - no longer in direct contact with the patient
  2. To prevent absorption
  3. Decrease the possiblity of transfer of the toxic substance to health care workers
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2
Q

What are 3 principles of GI decontamination to know?

A
  1. If a patient is already symptomatic, it means absorption has occurred and decontamination is unlikely to be of benefit- its efficacy decreases with time.
  2. Prioritize airway protection and provide symptomatic and supportive care (ABCs).
  3. Risk vs. benefit of GI decontamination is largely dependent on severity of potential toxicity.
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3
Q

Is activated charcoal absorptive or adsorptive?

A

ADsorptive

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4
Q

How does SDAC work? (3)

A
  1. Toxicant must come in direct contact with AC.
  2. Toxicant-AC complex is not systemically absorbed; toxicant therefore removed with AC upon bowel movement.
  3. Allows for the adsorption of drugs and toxins through weak intermolecular forces
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5
Q

Can ethanol be adsorbed by SDAC?

A

No

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6
Q

Can digoxin be adsorbed by SDAC?

A

Yes

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7
Q

Can amitriptyline be adsorbed by SDAC?

A

Yes

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8
Q

Can acetaminophen be adsorbed by SDAC?

A

Yes

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9
Q

Can lithium be adsorbed by SDAC?

A

No

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10
Q

Can iron be adsorbed by SDAC?

A

No

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11
Q

Can cyanide be adsorbed by SDAC?

A

No

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12
Q

Can amphetamines be adsorbed by SDAC?

A

Yes

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13
Q

Can cimetidine be adsorbed by SDAC?

A

Yes

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14
Q

Can boric acid be adsorbed by SDAC?

A

No

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15
Q

Can petroleum distillates be adsorbed by SDAC?

A

No

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16
Q

Can methanol be adsorbed by SDAC?

A

No

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17
Q

Can codeine be adsorbed by SDAC?

A

Yes

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18
Q

Can chlordiazepoxide be adsorbed by SDAC?

A

Yes

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19
Q

Can salicylates be adsorbed by SDAC?

A

Yes

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20
Q

Can diazepam be adsorbed by SDAC?

A

Yes

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21
Q

Can ethylene glycol be adsorbed by SDAC?

A

No

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22
Q

Can malathion be adsorbed by SDAC?

A

No

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23
Q

Can chlorpromazine be adsorbed by SDAC?

A

Yes

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24
Q

When dosing SDAC - if the amount of toxicant ingested is know, we use __-__x the dose of the toxicant

A

10-40

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25
Q

Yay or nay? SDAC use more than 1 hour after toxicant ingestion?

A

No evidence to support or exclude the use of AC when more than 1 hour has passed since ingestion

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26
Q

We should start AC method within 1 hours of ingestion (if feasible), BUT we should consider these 4 things:

A
  1. Bezoar (clump of ingested pills)
  2. Modified release product
  3. Toxicant or co-ingestants that reduce GI motility/gastric emptying rate
  4. Effect of volume ingested on gastric emptying rate
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27
Q

When does SDAC see benefits well beyond 1 hour of toxicant ingestion? (3)

A
  1. Extended-release formulation
  2. Drugs that form bezoars
  3. Very large ingestions
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28
Q

What are 5 contraindications to using SDAC?

A
  1. Toxicant known not to adsorb to AC
  2. Unprotected airway (unconscious or trauma)
  3. Ingestion of hydrocarbons- risk of aspiration (destroy
    surfactant, airway epithelium, alveolar septae, and pulmonary capillaries, leading to inflammation, atelectasis, and fever )
  4. Risk of GI perforation (has ulcer, surgery, took caustic
    agent)
  5. Endoscopy will be required (ex. corrosives)
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29
Q

Gastric lavage (pumping stomach) should not be considered unless…

A

Patient has ingested a potentially life-threatening amount of a poison and the procedure can be undertaken within 60 minutes of ingestion

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30
Q

What are some practical indications to gastric lavage? (6)

A
  1. Toxicant likely to be life-threatening
  2. Obvious signs and symptoms of life-threatening toxicity
  3. Reason to believe significant amount in stomach
  4. AC not an option (not adsorbed, dose required is unreasonable)
  5. No spontaenous emesis
  6. No highly effective antidote or alternative therapies pose high risk
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31
Q

What is whole bowel irrigation (WBI)?

A

Introduction of large amounts of fluid into the GIT to expel intraluminary contents

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32
Q

What is the rationale behind using WBI?

A

Cleanses bowel with large amounts of PEG (polyethylene glycol electrolyte) solution to minimize drug absorption and expel intraluminal contents out of the GIT; does not cause net change in ions, therefore no electrolyte imbalances.

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33
Q

WBI is an option for possibly doing what? (remember body packers)

A

Expediting the gastrointestinal luminal clearance of sustained-release preparations, toxic heavy metals, or packets of illicit drugs smuggled within the body (“body packers”).

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34
Q

What is used to perform WBI?

A

PEG-ES

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35
Q

What are the contraindications to doing WBI? (6)

A
  1. Unprotected or compromised airways
  2. GI compromise/GI hemorrhage
  3. Hemodynamically unstable
    - Low BP: gut poorly perfused –> defective motility and cannot handle the high volume of PEG-ES in a coordinated manner –> abdominal distention and vomiting
  4. Persistent vomiting
  5. Suspected leakage from drug packets or Bowel obstruction or perforation
  6. Expecting patients to drink adequate amounts of WBI fluid is unrealistic.
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36
Q

What are the complications associated with PEG-ES? (5)

A
  1. Nausea/vomiting
  2. Abdominal cramping / bloating
  3. Aspiration/ARDS (acute respiratory distress syndrome) –> because of misplacement of the NG tube
  4. Hypo-/hypernatremia (leading to altered consciousness, seizures, cerebral edema, and death)
  5. Interference with AC
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37
Q

What is the significance of Vd > 1 L/kg?

A

It is considered large because it indicates that only a small portion of the total dose (<5-10%) is in the plasma

38
Q

What is the big intracorporeal elimination method?

A

Multiple dose activated charcoal (MDAC)

39
Q

What are the 3 major extracorporeal elimination methods?

A
  1. Hemodialysis
  2. Hemofiltration
  3. Hemoperfusion
40
Q

How does MDAC work?

A

Multiple-dose activated charcoal (MDAC) therapy involves the repeated administration of oral-activated charcoal to enhance elimination of drugs already absorbed into the body by functioning as an adsorbent “sink” at several sites in the gut

41
Q

Dose and administration interval of MDAC is tailored to? (5)

A
  1. The amount and dosage form of xenobiotic ingested
  2. Severity of the overdose
  3. Whether the patient is vomiting
  4. Potential lethality of xenobiotic
  5. Tolerability
42
Q

MDAC enhances elimination of these drugs the most (5)

A
  1. Carbamazepine
  2. Dapsone
  3. Phenobarbital
  4. Quinine
  5. Theophylline
43
Q

What are the contraindications to using MDAC? (7)

A
  1. Patients with an unprotected airway (in other words, a depressed level of consciousness) without endotracheal intubation
  2. If activated charcoal use is likely to increase the risk and severity of aspiration of a toxin (hydrocarbons with high aspiration potentials)
  3. When the threat of GI perforation or hemorrhage is high secondary to medical conditions or recent surgery
  4. When endoscopy is likely to be attempted as activated charcoal may obscure endoscopic visualization
  5. In the presence of an intestinal obstruction
  6. When activated charcoal is known to not meaningfully adsorb the ingested toxin such as metals, acids, alkalis, electrolytes, or alcohols
  7. If decreased peristalsis is likely to occur from the substance ingested (opioids or anticholinergics)
44
Q

What are some complications associated with MDAC? (5)

A
  1. Constipation
  2. Bowel obstruction- could require intervention
  3. Emesis/aspiration
  4. Rectal ulcer/hemorrhage
  5. Reduction of therapeutically used xenobiotics as the therapeutic xenobiotic may bind to the AC
45
Q

Which drugs will have increased elimination to a clinically significant degree by MDAC? (Not specific drugs, but 3 specific properties)

A
  1. Long t1/2
  2. Small Vd (<1 L/kg)
  3. Undergo enterohepatic recirculation
    (Assuming they are adsorbed)
46
Q

Define hemodialysis

A

Uses diffusion through a conc gradient

47
Q

Define hemofiltration

A

Uses convection through a pressure gradient
- Removes larger molecules

48
Q

Define hemoperfusion

A

Blood passes through adsorbent substance
- Even larger molecules
- Plasma removed, treated, and returned to body

49
Q

Define hemodiafiltration

A

Combines hemodialysis and hemofiltration

50
Q

What is the MOA of urine alkalinzation?

A

Ion trapping - Ionized drugs cannot cross lipid bilayer. They are polar and water soluble and lipid insoluble - gets eliminated by the kidneys

51
Q

What is the major prerequisite to using urine alkalinization?

A

Major route of elimination must be kidneys

52
Q

Alkaline urine favors the ionization of ______ compounds
Acidic urine favors the ionization of ________ compounds

A

acidic
alkaline

53
Q

What are some examples of drugs that can be eliminated with urine alkalinization? (8)

A
  1. Salicylates
  2. Phenobarbital
  3. Chlorpropamide
  4. Formate
  5. Diflunisal
  6. Fluoride
  7. Methotrexate
  8. 2,4-dichlorophenoxyacetic acid
54
Q

In urine alkalinization alkalinization is done by _______ ___________ whereas acidification is done by ________ ____

A

sodium bicarbonate
ascorbic acid

55
Q

What are the 2 contraindications to using urine alkalinization?

A
  1. Established/incipient renal failure
  2. Pre-existing heart failure: Heart failure; can’t withstand the fluid and sodium, therefore would likely be better suited for hemodialysis
56
Q

Urine alkalinization should be considered as first line treatment in patients with…

A

moderately severe salicylate poisoning who do not meet the criteria for hemodialysis (first line)

57
Q

What are antidotes?
How do they work?
(What’s the deal with antidotes? haha)

A
  1. Neutralize or counteract the toxin.
  2. Prevents the development of, or reverses the signs and symptoms of toxicity
  3. Specifically counteracts the poison beyond a more general
    decontamination/ elimination strategy
58
Q

What are 4 types of antidotes?

A
  1. Receptor antagonists
    - e.g., Atropine, vitamin K
  2. Chemical/chelator
    - Forms compounds of lesser toxicity that is removed
    - e.g., Deferoxamine, digoxin-specific antibody fragments, idarucizumab
  3. Dispositional
    - Alters toxicant’s ADME
    - e.g., Ethanol, fomepizole
  4. Unclassified
    - e.g., Intralipid
59
Q

What is atropine used against? (in general - no need for specific names) (4)

A
  1. Acetyl-cholinesterase inhibitors
  2. Pesticides
  3. Clitocybe or inocybe mushrooms
  4. Sometimes for digitalis although indirect MOA
60
Q

What is the MOA of atropine? (2)

A
  1. Competitive antagonist of acetylcholine
  2. Common binding site on muscarinic receptors but not nicotinic receptors
61
Q

Why is atropine used in surgery?

A

To reduce saliva and fluid in the respiratory tract

62
Q

Atropine inhibits the PNS or the SNS?

63
Q

Atropine is reversed by what drug?

A

Physostigmine

64
Q

What is the MOA of deferoxamine?

A

Acts as a chelator and binds free Fe3+ to form ferrioxamine, which is renally excreted (brown urine results)

65
Q

Severe iron toxicity is defined as serum levels >__micromol/L

66
Q

Deferoxamine should be accompanied by? (2)

A
  1. GI decontamination (gastric lavage if warranted) AND
  2. Supportive measures (ABC)
67
Q

What are 3 complications of deferoxamine?

A
  1. Rapid IV administration can cause:
    - Flushing, urticaria, hypotension, shock
  2. Fe3+ - Ferrioxamine complex:
    - Hypotension
    - Accumulation if there is renal disease
    - Reddish urine
  3. May need hemodialysis to remove ferrioxamine complex because it may accumulate in renal impairment
68
Q

What is the MOA of digiFAB antibody?

A

Binds to digoxin and complex is excreted renally

69
Q

Each vial of digiFAB binds approximately how much digoxin (in mg)?

70
Q

DigiFAB
1. Average # of vials needed for chronic toxicity: up to _ per adult
2. Average # of vials needed for acute toxicity = __

71
Q

True or false? DigiFAB has no contraindications

72
Q

What antidote is used for reversing dabigatran-induced anticoagulation?

A

Praxbind (Idarucizumab)

73
Q

What are 3 precautions for using idarucizumab?

A
  1. Thrombosis
  2. Hypersensitivity
  3. Hereditary fructose intolerane
74
Q

What is the MOA of ethanol and fomepizole as an antidote in toxic alcohol ingestion?

A

Blocks the formation of toxic metabolites by having a higher affinity for the enzyme Alcohol Dehydrogenase (ADH)

75
Q

What are the 2 antidotes for toxic alcohol ingestion (thinking methanol and ethylene glycol ingestion)

A

1st line = fomepizole
2nd line = ethanol

76
Q

Ethanol has __._x more affinity for alcohol dehydrogenase than methanol, and __x more affinity than ethylene glycol

77
Q

The relative affinity of fomepizole for human alcohol dehydrogenase is _____ times greater than that of methanol and ethylene glycol, and ____ times greater than that of ethanol

A

80,000
8,000

78
Q

What is the antidote for local anesthetic systemic toxicity?

A

Intravenous lipid emulsion (ILE) (Intralipid)

79
Q

What is the MOA of intralipid? (3)

A
  1. Modulation of intracellular metabolism
  2. Lipid sink
  3. Activation of ion channels
80
Q

What are 3 complications associated with intralipid?

A
  1. Pancreatitis
  2. Fat emboli syndrome
  3. Lipemic serum (high lipid content in the serum)
81
Q

What are the contraindications for using whole-bowel irrigation?
A. Large volume of toxicants
B. Hemodynamically unstable
C. Perforated GI lining
D. Answers B and C are correct

82
Q

What is the main difference between hemodialysis and hemofiltration?
A. Hemodialysis uses an adsorbant substance (contained in a cartridge) to filter the toxicant out of the plasma before returning to body
B. Hemofiltration uses diffusion through a concentration gradient
C. Hemodialysis uses convection to move smaller-sized molecules
D. Hemofiltration uses convection through a pressure gradient to filter larger-sized molecules (but no larger than that of hemoperfusion)

83
Q

Which of the following “antidotes” (not all are antidotes) has the largest binding affinity for alcohol dehydrogenase?
A. Ethanol
B. Furosemide
C. Acetone
D. Fomepizole

84
Q

What is the mechanism of action for atropine in anticholinesterase toxicity?
A. Competition for acetylcholine receptors
B. Negatively modulates acetylcholine receptors
C. Competitive antagonist at adrenergic receptors
D. Chelates to acetylcholine to form a larger complex that can be
excreted

85
Q

The antibody-antigen complex formed between dabigatran and
Idarucizumab is excreted via:
A. Kidneys
B. Induced vomit
C. Feces
D. Perspiration

86
Q

Which one of the following is correct regarding the administration of the antidote for ethylene glycol or methanol?
A. Loading dose over 1 hour followed by maintenance dosages based on ethanol levels
B. Duration is 24 hours for methanol, unless dialysis is used, then the duration is 2 hours
C. There is no antidote, dialysis is required
D. Must be administered as a 20% v/v IV infusion

87
Q

Frankie, aged 6, drank a bottle of Floradix iron solution, because he thought it “tasted like blood” and he wanted to be a vampire. He has been throwing up, and he is not very cognitively responsive. His blood pressure is also low and continues to drop. Gastric lavage was already performed. What is the antidote?
A. Deferoxamine
B. Ferrioxamine
C. Milk
D. Sodium bicarbonate

88
Q

Activated charcoal method of decontamination should be used within 1 h of ingestion (if feasible). However, it can be used even up to 6 hours if:
A. The number of pills is three only
B. The ingested product is an immediate release product.
C. Toxicant or coingestants reduce gastrointestinal motility/gastric emptying rate
D. Toxicant does not affect the gastric emptying rate and also does not adsorb to the activated charcoal

89
Q

Urine alkalinization is carried out by the compound:
A. Sodium bicarbonate
B. Calcium carbonate
C. Calcium bicarbonate
D. Sodium carbonate

90
Q

Atropine is reversed by
A. Physostigmine
B. Deferoxamine
C. Hemodialysis
D. Fomipezole

PHAR 324 (9 decks)

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