Chelation Therapy

Question 1

Buzzwords: rice water diarrhea, long QT/torsades

Answer 1

arsenic

Question 2

What is the mechanism of toxicity of heavy metals?

Answer 2

bind to sulfhydryl groups in proteins, which inhibit function and cause multisystem organ toxicity

Question 3

What are common affects of acute exposure to heavy metals?

Answer 3

CV: tacycardia, dysrrhythmias, cardiomyopathy
CNS: altered mental status, peripheral neuropathy
GI: N/V/D
Renal: proteinura, aminoaciduria, ATN

Question 4

What are common affects of chronic exposure to heavy metals?

Answer 4

Less obvious than acute exposure! 
CNS: AMS, peripheral neuropathy
Hematologic: anemias and cytopenias
Renal: insufficiency
Skin, skeleton, connective tissue: rashes, colored lines (Mees/Burton lines) on nails and gums

Question 5

Describe the ideal chelator

Answer 5

• volume of distribution should be greater than that of the chelate
• high water solubility
• resistant to biotransformation
• able to reach site where metal is stored
• capacity for nontoxic complexes
• stable at physiological pH
• low affinity for trace elements

Question 6

What is the general mechanism of chelators?

Answer 6

• form complexes with heavy metals to prevent or reverse binding to sulfhydryl groups

Question 7

What is BAL (British Anti Lewisite)/Dimercaprol used for?

Answer 7

• early treatment of mercury, lead, or arsenic toxicity

Question 8

What should always be given in the treatment of lead encephalopathy?

Answer 8

BAL given prior to CaNa2EDTA to prevent redistribution of lead to the brain

Question 9

Why do you supplement BAL with NaHCO3?

Answer 9

Acidic urine destabilizes the BAL-metal chelate and decreases renal excretion. Alkalinizing the urine prevents this.

Question 10

What is 2,3-Dimercaptosuccinic acid used for?

Answer 10

Chelation of cadmium, lead, mercury, and arsenic

Well tolerated (SE: N/V/D, metallic taste in mouth, elevation of AST and ALT)

Question 11

What is edetate calcium disodium/CaNa2EDTA used for?

Answer 11

primarily used in lead poisoning

Question 12

What are the side effects of CaNa2EDTA?

Answer 12

Renal toxicity from the chelate

Question 13

What is prussian blue used for? What is unique about it that makes it a well tolerated drug?

Answer 13

thallium and cesium poisoning

• insoluble and not absorbed from GI tract (this creates concentration gradient and heavy metal is mobilized from body stores)

Question 14

What are the effects of iron toxicity?

Answer 14

• direct corrosive effect to GI mucosa and resulting volume depletion
• high anion gap metabolic acidosis (ferrous to ferric)
• uncouples oxidative phosphorylation
• negative inotropic effect
• vasodilator (hypotension)

Question 15

What is the use of deferoxamine?

Answer 15

• derived from Streptomyces pilosus
• high affinity iron chelator of free iron and iron transported between transferrin ferritin
• does NOT chelate the iron in tranferrin, hemoglobin, cytochromes, or ferritin

Question 16

How is deferoxamine excreted and what is an important adverse event?

Answer 16

• excreted in urine as ferrioxamine

- May cause acute lung injury with prolonged administration

Question 17

What is the use of Na2EDTA in heavy metal poisoning?

Answer 17

THERE IS NONE!
- don’t confuse this for CaNa2EDTA. If you forget the Ca component, the patient will become severely hypocalcemic and bad things will happen