Toxicology P2

Question 1

Discuss pharmacokinetics of chelators. Also discuss goals to using chelators and possible problems.

Answer 1

The purpose of a chelator is to bind metals, forming a coordinate covalent bond.
However, certain parameters must be considered to ensure that chelation and excretion of the metal occurs:
- The chelator must have a greater affinity for the metal than it does for an endogenous ligand (ca, Zn, other essential metals)
- chelator cannot be excreted faster than it is able to bind to the metal
- chelator is able to enter the compartment where the metal is stored (ex, chelation of lead in bone isn’t possible, chelator cannot enter bone)
-Must have a high enough concentration of the chelator
- the later the initiation of therapy, the less successful chelator will be at binding to and excreting metal

Question 2

What is the structural components of chelators?

Answer 2

Chelators are molecules with two or more electronegative groups (-OH, -SH, and -NH) that form covalent bonds with cationic metal atoms.

Question 3

Describe ideal characteristics of a chelator:

Answer 3

• high water solubility
• distribute to sites of metal absorption
• chelating activity at physiological pH
• resistant to biotransformation
• readily excreted once bound to metal
• form non-toxic complexes with metal

Question 4

List chelators and what they’re used to chelate:

Answer 4

EDTA- Lead
Defoeroxamine- Iron
Penicillamine/deferoxamine- copper
Dimercaprol/succimer- arsenic, mercury, lead

Question 5

Describe mechanism of EDTA use for lead

Answer 5

Lead displaces the Ca found in EDTA; however, lead can only be given IM or IV because it has poor oral absorption (highly polar)