Chelation Therapy Flashcards
Case Presentation: Rice water diarrhea and long QT syndrome
Arsenic Poisoning
Case Presentation: Heavy chest w. radioopaque deposits in lungs & liver
Mercury Poisoning
What is the MOA of heavy metals?
they bind to sulfhydryl groups in many organ sys
What are signs of an acute exposure?
N/V/D - GI Tachycardia-->dysarrhythmias, Altered Mental status proteinuria, aminoaciduria and acute tubular necrosis "stocking glove neuropathy"
What are signs of chronic exposure?
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)
What are the big important heavy metals?
Lead, Arsenic and Mercury and Thallium
How do chelators work?
Forms complexes with heavy metals
Prevents or reverses the binding of metallic cations to reactive groups (ligands)
The chelated substance is a
Complex formed with the metal and chelator
Heterocyclic ring
5- and 6-membered rings are the most stable
The ideal chelator
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
The ideal chelate
More stable than the endogenous chelate Stable at physiologic pH Resistant to biotransformation not metablized Water soluble Readily excreted Nontoxic
Dimercaperol is also known as (BALDEE)
British Anti-Lewisite (BAL)
- mixed in peanut oil so you can have allergies
- given IM )no IV)
What is Dimercaperol/BAL useful for
*Lead poisoning w. Encephalopathy (is is lipid soluble)
Inorganic mercury poisoning
Arsenic poisoning
What are the adverse side effects of BAL/Di
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
2,3-Dimercaptosuccinic Acid is also known as
DMSA or Succimer
What is DMSA used to chelate?
LEAD
cadmium
mercury
Side effects of DMSA
Well tolerated
Nausea, vomiting, flatus, diarrhea
Mild elevations in AST & ALT
Calcium Disodium Edetate is used to chelate what metal?
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
What are the side effects of
- Renal toxicity
- Malaise, fever, Increases in ALT & AST
- Medication errors
- Hypocalcemia after inadvertent administration of Na2EDTA rather than CaNa2EDTA
Prussian Blue or Radiogardasse
used for weapons of mass destruction
CESIUM (government approved) but THALLIUM poisoning is more practical
How do you recognize Thallium poisoning?
Painful peripheral neuropathy
-Alopecia
Side Effects of Prussian Blue
doesn’t get absorbed after oral dosing so there is not side effects
LEAD POISONING (chronic)
very high lead levels would get whole bowel irrigation
EDTA, DMSA, BAL/Di
DMSA especially for?
Cadmium
Iron poisoning (Fe) results in AG met acidosis. How does lead cause local toxiciy?
direct corrosive effect on GI tract–> hematemesis, melena–> dehydration
Iron poisoning (Fe) results in AG met acidosis. How does lead cause systemic toxiciy?
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
What are the clinical stages of Iron Toxicity?
-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
What is the chelator for Iron?
Deferoxamine
MOA of Deferoxamine (IV)
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
Adverse Effects of Deferoxamine
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