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Unit 6 > Chelation therapy > Flashcards

Chelation therapy Flashcards

1
Q

Mechanism of toxicity of heavy metals

A

Bind to sulfhydryl groups in various organ systems and enzymatic processes throughout the body

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2
Q

If the mechanism of heavy metal toxicity is all the same, why do different metals have different effects?

A

Affinity for organ system toxicity is a result of the characteristics of the heavy metal and its distribution sites

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3
Q

Heavy metal acute exposure of cardiovascular system can result in __

A

Tachycardia

dysrhythmias

cardiomyopathy

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4
Q

Heavy metal acute exposure of CNS can result in __

A

altered mental status

peripheral neuropathy

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5
Q

Heavy metal acute exposure of gastrointestinal system can result in __

A

N&V

diarrhea

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6
Q

Heavy metal acute exposure of renal system can result in __

A

proteinuria

aminoaciduria

acute tubular necrosis

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7
Q

What is the difference between acute and chronic metal exposure?

A

Chronic exposure has:

  • more subtle findings.
  • increased effects at organ sites that may be less accessible acutely
  • CNS and PNS more apparent than GI effects
  • hematologic abnormalities
  • renal insufficiency
  • skin, skeleton and connective tissue abnormalities
  • neoplasm
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8
Q

Dimercaprol

A

Aka anti-lewisite

aka BAL

Chelates

  • arsenic
  • lead
  • inorganic mercury
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9
Q

Dimercaprol (BAL) - adverse effects

A
  1. Peanut allergy (BAL is always mixed with peanut oil)
  2. Dose dependent
    • nausea and vomiting
    • increases in BP and HR
    • pain at injection site (IM injection)
  3. Dissociation of BAL-metal chelate in acidic urine
    • need urinary alkalinization during or before BAL therapy to prevent metal-induced renal toxicity
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10
Q

What is needed before adminstration of dimercaprol?

A

There is dissociation of BAL-metal chelate in acidic urine

Need urinary alkalinization during or before BAL therapy to prevent metal-induced renal toxicity

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11
Q

Succimer

A

2,3-dimercaptosuccinic acid

Chelation for:

  • cadmium
  • lead
  • mercury
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12
Q

CaNa2EDTA

A

Edetate calcium disodium

Primarily used in lead poisoning

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13
Q

What is a caution that must be taken when using CaNa2EDTA?

A

Don’t accidentally confuse with Na2EDTA which can cause severe hypocalcemia

EDTA likes to chelate cations. Need to give the calcium*ized version so that it doesn’t bind up all your calcium

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14
Q

CaNa2EDTA - adverse effects

A

Renal toxicity (of proximal, distal tubules and glomeruli)

Malaise, fever, increases in ALT and AST

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15
Q

Prussian blue

A

Chelates:

  • thallium
  • cesium
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16
Q

Prussian blue - side effects

A

There is none. It is well tolerated and it is not absorbed after oral dosing

17
Q

Iron toxicity - mechanism

A
  1. Direct corrosive effect to the GI mucosa –> hematemesis, melena, periportal necrosis of the liver and intentional ulceration and edema
  2. Uncoupler of oxidative phosphorylation –> metabolic acidosis (via shunting to anaerobic metabolism and production of lactic acid)
  3. hypotension (vomitting, negative inotropic effect & vasodilator)
18
Q

How can iron cause hypotension?

A

Via 3 mechanisms

  1. vomitting –> volume depletion (remember it is direct toxin to Gi mucosa)
  2. direct negative inotropic effect –> decreased force of muscular contractions
  3. vasodilation –> hypotension
19
Q

How do you diagnose iron toxicity? (Laboratory or clinical) why?

A

Iron toxicity is a CLINICAL diagnosis.

Laboratory findings are usually not useful. Iron needs to be > 500 mg/dl (norm 60 - 170) for you to have a clear diagnosis of iron toxicity. Anything under that value is useless.

20
Q

Deferoxamine

A

Chelates iron (free iron and iron transported between transferrin and ferritin)

Does NOT chelate iron in transferrin, Hb, cytochromes or ferritin

21
Q

Deferoxamine - adverse effects

A

rate-related hypotension

anaphylactoid reactions

acute lung injury (mechanism unknown) – occurs after 24 hours of dosing

22
Q

Lead poisoning - what would you use to chelate?

What would you be concerned about with each drug?

A

dimercaprol – peanut allergy, need to alkalinize urine, dose dependent effects

succimer – well tolerated with some N&V

EDTA – renal toxicity

23
Q

Arsenic poisoning - what would you use to chelate?

What would you be concerned about with each drug?

A

dimercaprol – peanut allergy, need to alkalinize urine, dose dependent effects

24
Q

Mercury poisoning - what would you use to chelate?

What would you be concerned about with each drug?

A

same as arsenic

  • dimercaprol – peanut allergy, need to alkalinize urine, dose dependent effects
  • succimer – well tolerated with some N&V
25
Q

Cadmium poisoning - what would you use to chelate?

What would you be concerned about with each drug?

A

Succimer – generally well tolerated with some N&V

26
Q

Iron poisoning - what would you use to chelate?

What would you be concerned about with each drug?

A

Deferoxamine – rate-related hypotension, acute lung injury (if dosed for >24 hours)

27
Q

Thallium poisoning - what would you use to chelate?

What would you be concerned about with each drug?

A

Prussian blue – very well tolerated

Can chelate without being absorbed

28
Q

Cesium poisoning - what would you use to chelate?

What would you be concerned about with each drug?

A

Prussian blue – very well tolerated

Can chelate without being absorbed

29
Q

Antidotes to cyanide poisoning (CN-)

MOA

A

CN_ is metabolized in the liver to thiocynase (SCN-) which is then cleared by the kidney.

  • The limiting substrate for this conversion is the sulfur group.

Administration of sodum thiosulfate provides that sulfur donor, thereby accelerating the metabolic conversion of the poison

Can also use nitrites which will generate ferric compounds (ie methemoglobin) in situ, which will complex with CN- keeping it unreactive

30
Q

D-penicillamine

A

Chelates mercury – benefit of being able to take it orally.

Disadvantage: chelates Zn and hence is toxic

Unit 6 (10 decks)

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