Chelation Therapy

Question 1

mechanism of toxicity for heavy metals

Answer 1

bind to sulfhydryl groups in various organ systems and enzymatic processes throughout the body. affinity for organ system toxicity is a result of the characteristics of the heavy metal and its distribution sites

Question 2

chelating agent

Answer 2

forms complexes with heavy metals. prevents or reverses the binding of metallic cations to reactive groups.

Question 3

chelate

Answer 3

complex formed with the metal and chelator. heterocyclic ring, 5 and 6 membered rings are the most stable

Question 4

efficacy of chelating agents

Answer 4

relative affinity of the chelator for the heavy metal. distribution of the chelator compared with the distribution of the metal.

Question 5

ideal chelator qualities

Answer 5

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 physiological pH. low affinity for trace elements.

Question 6

ideal chelate qualities

Answer 6

more stable than the endogenous chelate. stable at body pH. resistant to biotransformation. water soluble. readily excreted. nontoxic.

Question 7

british anti-lewisite (BAL)

Answer 7

dimercaprol. mixed with peanut oil. Intramuscular dosing, not IV. useful in arsenic poisoning, lead poisoning (encephalopathy), inorganic mercury poisoning.

Question 8

adverse effects of BAL

Answer 8

dose dependent. pain at injection site, nausea, vomiting, increases in BP and HR. Need to keep urine alkaline so BAL-metal dissociation doesn’t occur.

Question 9

2,3-dimercaptosuccinic acid

Answer 9

Succimer. Useful in lead, arsenic, mercury, cadmium. Well tolerated. Nausea, vomiting, flatus, diarrhea, mild elevations in AST and ALT.

Question 10

CaNaEDTA (edetate calcium disodium)

Answer 10

mainly used in lead poisoning. can be mistaken for NaEDTA.

Question 11

CaNaEDTA adverse events

Answer 11

principal toxicity due to the metal chelate. Renal toxicity, malaise, fever, increased ALT and AST.

Question 12

Prussian blue

Answer 12

useful in thallium and cesium poisoning. adverse events: not absorbed after oral dosing and well tolerated.

Question 13

clinical effects of lead

Answer 13

lower levels associated with IQ changes. colic, abdominal pain. altered mental status. footdrop and wrist drop. anemia (microcytic). nephrotox. HTN (most common symptom in adults)

Question 14

workup for lead poisoning

Answer 14

capillary/venous blood. hair and urine are not helpful. CBC, BMP, LFTs, erythrocyte protoporphyrin. abdominal radiograph.

Question 15

lead poisoning treatment

Answer 15

removal from source. whole bowel irrigation if lead in bowel. succimer. if encephalopathic, CaNaEDTA plus BAL

Question 16

iron pharmacokinetics

Answer 16

peak serum concentrations occur 2-6 hours after ingestion. massive amounts of iron absorption overwhelm transferrin and there is an increase in circulating free iron

Question 17

toxicologic mechanism of iron

Answer 17

direct corrosive effect to GI mucosa. leads to volume depletion. high anion gap metabolic acidosis. Direct negative inotropic effect (hypotension). Vasodilator (hypotension)

Question 18

clinical effects of iron

Answer 18

early: local tissue effects of GI tract. N/V.
intermediate: N/V decrease and increase in metabolic acidosis and sequelae.
Intermediate II: severe local and systemic effects which may result in death.
Late: hepatotoxicity, ARDS, renal
Fifth stage: gastric outlet obstruction

Question 19

deferoxamine

Answer 19

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 ONLY!

Question 20

adverse events with deferoxamine

Answer 20

rate-related hypotension, anaphylactoid reactions, yersinia enterocolitis, acute lung injury (in patients treated over 24 hours)