Chelation Therapy

Question 1

What are the signs of acute arsenic poisoning?

Answer 1

Long QTc and rice water diarrhea

Question 2

In mercury poisoning, what is the Tx of choice?

Answer 2

Succimer

Question 3

What is the general heavy metal mechanism of toxicty?

Answer 3

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

Question 4

On what organ systems does acute metal toxicity manifest and how?

Answer 4

• Cardiovascular - tach. and cardiomyopathy
• CNS - Altered mental status, peripheral neuropathy
• GI - N/V/D
• Renal - Proteinuria, aminoaciduria, ATN

Question 5

What is difficult about Dx chronic heavy metal exposure?

Answer 5

Subtle findings

Question 6

What are important steps in making a heavy metal Dx?

Answer 6

• PE
• Question occupation/hobbies
• Labs
• Serum metal levels

Question 7

What are the top 4 heavy metal considerations?

Answer 7

• Lead
• Arsenic
• Mercury
• Thallium

Question 8

What is a chelating agent?

Answer 8

Forms complexes with heavy metals and prevents/reverses binding of metallic cations to reactive groups

Question 9

What is a chelate?

Answer 9

Complex formed with the metal and chelator; 5/6 member rings are the most stable

Question 10

What ligands do lead and mercury bind best to?

Answer 10

Sulfur and Nitogen

Question 11

What ligands does calcium bind best to?

Answer 11

Oxygen

Question 12

What is the determinant of the chelator efficacy?

Answer 12

RElative affinity of the chelator for the metal and distribution of the chelator compared with the distribution of the metal

Question 13

What are the characteristics of an ideal chelator?

Answer 13

• Chelator has a greater volume of distribution than the chelate
• High water solubility
• Resistant to biotransformation
• Ability to reach site where metal is stored
• Capacity to form non-toxic complexes
• Stable at physiologic pH
• Low affinity for trace elements
• More stable than the endogenous chelate
• Stable at physiologic pH
• Resistant to biotransformation
• Water soluble
• Readily excreted
• Nontoxic

Question 14

What is another name for dimercaprol?

Answer 14

British Anti-Lewisite

Question 15

What is BAL suspended in, and why is this a concern?

Answer 15

Mixed with peanut oil, which carries allergic implications

Question 16

What type of metal poisoning is BAL useful for?

Answer 16

Arsenic, Lead, Inorganic Mercury

Question 17

Adverse effects of BAL?

Answer 17

• Pain at injection site
• N/V
• Transient increase in BP and HR

Question 18

What is an important concurrent treatment that must occur when administering BAL?

Answer 18

Urinie must be alkalinized because BAL-metal chelate dissociates in acidic urine!

Question 19

What is another name for DMSA?

Answer 19

Succimer

Question 20

What is Succimer used to treat?

Answer 20

• Lead
• Arsenic
• Mercury
• Cadmium

Question 21

Adverse rxns to Succimer

Answer 21

Although relatively well-tolerated, N/C/Flatus/Diarrhea, Mild Elevations in AST and ALT

Question 22

What is Edetate Calcium Disodium used to treat?

Answer 22

Primarily lead

Question 23

What are the adverse reactions to edetate calcium disodium?

Answer 23

Principal toxicity due to the metal chelate - leading to renal toxicity, malaise, fever, AST/ALT elevatiaon

Question 24

What is a medication error that occurs with Edetate calcium disodium?

Answer 24

Sodium EDTA is prescribed instead causing accidental hypocalcemia

Question 25

How does Prussian Blue work? What metals does it chelate?

Answer 25

Enters GI system and binds Thallium and Cesium (Is not absorbed into body)

Question 26

Side effects of Prussian BLue?

Answer 26

Not absorbed after oral dosing, well-tolerated

Question 27

What compartment of the body is iron contained in during an iron OD?

Answer 27

Iron is a free cation in the blood in OD situations

Question 28

After iron is absorbed, why are iron cations free in solution?

Answer 28

Massive amounts of iron overwhelm **transferrin** and therefore there is an increased circulation of free iron

Question 29

What are the two major types of toxicity that occur in Fe overload?

Answer 29

Direct corrosive GI toxicity and systemic toxicity

Question 30

Describe the pathogenesis of Fe toxicity

Answer 30

* Ferrous oxidized to ferric resulting in H+ liberation and acidosis * High concentrations of Fe in mitochondria uncouple ox phos resulting in lactic acid and AG acidosis

Question 31

What direct cardiovascular effects does iron toxicity have?

Answer 31

* Direct negative inotropic effect * Vasodilation and further hTN

Question 32

What is an important clinical sign that someone has iron toxicity?

Answer 32

Multiple bouts of nausea and vomiting w/i 6 hours of poisoning

Question 33

What are the most important tests to make a Dx of iron poisoning?

Answer 33

Assessment of acid-base balance, acute blood loss Iron toxicity is a clinical Dx

Question 34

What chelator is used to treat iron tox?

Answer 34

Deferoxamine

Question 35

How does deferoxamine work?

Answer 35

Chelates ferric iron and is excreted in urine as **ferrioxamine**

Question 36

What are the adverse SEs of Deferoxamine?

Answer 36

* Rate-related hTN * Anaphylactoid rxn * Facilitates growth of unusual organisms (**Yersinia enterocolitis**) * **Acute Lung Injury**