Chelation Therapy

Question 1

Case Presentation: Rice water diarrhea and long QT syndrome

Answer 1

Arsenic Poisoning

Question 2

Case Presentation: Heavy chest w. radioopaque deposits in lungs & liver

Answer 2

Mercury Poisoning

Question 3

What is the MOA of heavy metals?

Answer 3

they bind to sulfhydryl groups in many organ sys

Question 4

What are signs of an acute exposure?

Answer 4

N/V/D - GI
Tachycardia-->dysarrhythmias, 
Altered Mental status
proteinuria, aminoaciduria and acute tubular necrosis
"stocking glove neuropathy"

Question 5

What are signs of chronic exposure?

Answer 5

subtle findings, occurs over time
diagnosis of exclusion
progressive deterioration of the organs (work, hobbies, poisoned)
*Rarely have GI Sx.
[except for lead ( wrist drop, foot drop)

Question 6

What are the big important heavy metals?

Answer 6

Lead, Arsenic and Mercury and Thallium

Question 7

How do chelators work?

Answer 7

Forms complexes with heavy metals

Prevents or reverses the binding of metallic cations to reactive groups (ligands)

Question 8

The chelated substance is a

Answer 8

Complex formed with the metal and chelator
Heterocyclic ring
5- and 6-membered rings are the most stable

Question 9

The ideal chelator

Answer 9

VD of the chelator > VD of the chelate
High water solubility
Resistant to biotransformation
Ability to reach the site of where the metal is stored
Capacity to form nontoxic complexes
Stable at physiologic pH
Low affinity for trace elements

Question 10

The ideal chelate

Answer 10

More stable than the endogenous chelate
Stable at physiologic pH
Resistant to biotransformation not metablized 
Water soluble
Readily excreted
Nontoxic

Question 11

Dimercaperol is also known as (BALDEE)

Answer 11

British Anti-Lewisite (BAL)

• mixed in peanut oil so you can have allergies
• given IM )no IV)

Question 12

What is Dimercaperol/BAL useful for

Answer 12

*Lead poisoning w. Encephalopathy (is is lipid soluble)
Inorganic mercury poisoning
Arsenic poisoning

Question 13

What are the adverse side effects of BAL/Di

Answer 13

Dissociation of BAL-metal chelate in acidic urine

• Urinary ALKALINIZATION employed during BAL therapy to prevent metal-induced renal toxicity or it will worsen the renal toxicity
  
  • give Bicarb first

Pain at injection site
Nausea, vomiting
Increases in BP and HR

Question 14

2,3-Dimercaptosuccinic Acid is also known as

Answer 14

DMSA or Succimer

Question 15

What is DMSA used to chelate?

Answer 15

LEAD
cadmium
mercury

Question 16

Side effects of DMSA

Answer 16

Well tolerated
Nausea, vomiting, flatus, diarrhea
Mild elevations in AST & ALT

Question 17

Calcium Disodium Edetate is used to chelate what metal?

Answer 17

LEAD

*NOT to be confused with Na2EDTA which was used for hypercalcemia
Causes severe hypocalcemia

***If used for lead encephalopathy there is potential for lead redistribution into the brain so you have to give BAL first

Question 18

What are the side effects of

Answer 18

1. Renal toxicity
2. Malaise, fever, Increases in ALT & AST
3. Medication errors
4. Hypocalcemia after inadvertent administration of Na2EDTA rather than CaNa2EDTA

Question 19

Prussian Blue or Radiogardasse

Answer 19

used for weapons of mass destruction

CESIUM (government approved) but THALLIUM poisoning is more practical

Question 20

How do you recognize Thallium poisoning?

Answer 20

Painful peripheral neuropathy

-Alopecia

Question 21

Side Effects of Prussian Blue

Answer 21

doesn’t get absorbed after oral dosing so there is not side effects

Question 22

LEAD POISONING (chronic)

Answer 22

very high lead levels would get whole bowel irrigation

EDTA, DMSA, BAL/Di

Question 23

DMSA especially for?

Answer 23

Cadmium

Question 24

Iron poisoning (Fe) results in AG met acidosis. How does lead cause local toxiciy?

Answer 24

direct corrosive effect on GI tract–> hematemesis, melena–> dehydration

Question 25

Iron poisoning (Fe) results in AG met acidosis. How does lead cause systemic toxiciy?

Answer 25

It stops aeorobic metabolism
High anion gap metabolic acidosis
Ferrous iron is converted to ferric liberating a H+ ion resulting in acidosis
High intramitochondrial concentrations disrupt oxidative phosphorylation
–Uncoupler of oxidative phosphorylation
Hypoperfusion leading to lactic acid generation
Direct negative inotropic effect
Hypotension from this in addition to hypovolemia

Vasodilator
Hypotension

Question 26

What are the clinical stages of Iron Toxicity?

Answer 26

-Early
Local tissue effects of the Gastrointestinal tract. Nausea and vomiting as a minimum (1-6 hours)
-Intermediate
Nausea and vomiting may temporarily decrease with an increase in development of metabolic acidosis and sequelae (6-12 hours)
-Intermediate II
Severe local and systemic effects which may result in death (12-24 hours)
-Late
Hepatotoxicity, ARDS, Renal (2-3 days)
-Fifth
Gastric outlet dysfunction

Question 27

What is the chelator for Iron?

Answer 27

Deferoxamine

Question 28

MOA of Deferoxamine (IV)

Answer 28

Chelates ferric iron and is excreted in the urine as ferrioxamine which imparts a reddish brown color change to the urine
Reaches intracytoplasmic and intramitochondrial free iron
Chelates FREE IRON & iron transported between transferrin and ferritin
Does NOT chelate the iron in transferrin, hemoglobin, cytochromes or ferritin
***must be done w/in 24 hrs

Question 29

Adverse Effects of Deferoxamine

Answer 29

Acute LUNG Injury
(Occurs in patients that are treated for > 24 hours)Rate-related hypotension
Anaphylactoid reactions
*Yersinia enterocolitis
DFO-Iron Chelate facilitates growth of unusual organisms