Chelation Therapy Flashcards
What are the signs of acute arsenic poisoning?
Long QTc and rice water diarrhea
In mercury poisoning, what is the Tx of choice?
Succimer
What is the general heavy metal mechanism of toxicty?
Bind to sulfhydryl groups in various organ systems and enzymatic processes throughout the body
On what organ systems does acute metal toxicity manifest and how?
- Cardiovascular - tach. and cardiomyopathy
- CNS - Altered mental status, peripheral neuropathy
- GI - N/V/D
- Renal - Proteinuria, aminoaciduria, ATN
What is difficult about Dx chronic heavy metal exposure?
Subtle findings
What are important steps in making a heavy metal Dx?
- PE
- Question occupation/hobbies
- Labs
- Serum metal levels
What are the top 4 heavy metal considerations?
- Lead
- Arsenic
- Mercury
- Thallium
What is a chelating agent?
Forms complexes with heavy metals and prevents/reverses binding of metallic cations to reactive groups
What is a chelate?
Complex formed with the metal and chelator; 5/6 member rings are the most stable
What ligands do lead and mercury bind best to?
Sulfur and Nitogen
What ligands does calcium bind best to?
Oxygen
What is the determinant of the chelator efficacy?
RElative affinity of the chelator for the metal and distribution of the chelator compared with the distribution of the metal
What are the characteristics of an ideal chelator?
- 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
What is another name for dimercaprol?
British Anti-Lewisite
What is BAL suspended in, and why is this a concern?
Mixed with peanut oil, which carries allergic implications
What type of metal poisoning is BAL useful for?
Arsenic, Lead, Inorganic Mercury
Adverse effects of BAL?
- Pain at injection site
- N/V
- Transient increase in BP and HR
What is an important concurrent treatment that must occur when administering BAL?
Urinie must be alkalinized because BAL-metal chelate dissociates in acidic urine!
What is another name for DMSA?
Succimer
What is Succimer used to treat?
- Lead
- Arsenic
- Mercury
- Cadmium
Adverse rxns to Succimer
Although relatively well-tolerated, N/C/Flatus/Diarrhea, Mild Elevations in AST and ALT
What is Edetate Calcium Disodium used to treat?
Primarily lead
What are the adverse reactions to edetate calcium disodium?
Principal toxicity due to the metal chelate - leading to renal toxicity, malaise, fever, AST/ALT elevatiaon
What is a medication error that occurs with Edetate calcium disodium?
Sodium EDTA is prescribed instead causing accidental hypocalcemia
How does Prussian Blue work? What metals does it chelate?
Enters GI system and binds Thallium and Cesium (Is not absorbed into body)
Side effects of Prussian BLue?
Not absorbed after oral dosing, well-tolerated
What compartment of the body is iron contained in during an iron OD?
Iron is a free cation in the blood in OD situations
After iron is absorbed, why are iron cations free in solution?
Massive amounts of iron overwhelm transferrin and therefore there is an increased circulation of free iron
What are the two major types of toxicity that occur in Fe overload?
Direct corrosive GI toxicity and systemic toxicity
Describe the pathogenesis of Fe toxicity
- 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
What direct cardiovascular effects does iron toxicity have?
- Direct negative inotropic effect
- Vasodilation and further hTN
What is an important clinical sign that someone has iron toxicity?
Multiple bouts of nausea and vomiting w/i 6 hours of poisoning
What are the most important tests to make a Dx of iron poisoning?
Assessment of acid-base balance, acute blood loss
Iron toxicity is a clinical Dx
What chelator is used to treat iron tox?
Deferoxamine
How does deferoxamine work?
Chelates ferric iron and is excreted in urine as ferrioxamine
What are the adverse SEs of Deferoxamine?
- Rate-related hTN
- Anaphylactoid rxn
- Facilitates growth of unusual organisms (Yersinia enterocolitis)
- Acute Lung Injury
