Chelation 1 and 2

Question 1

In case 1, what were a couple indications that the patients were poisoned with arsenic?

Answer 1

Rice water diarrhea and QTc interval increased

Question 2

Mech of heavy metal toxicity; affinity for organ system toxicity is a result of :

Answer 2

binds sulfhydryl groups in various organ systems and enzymatic processes throughout the body;
characteristics of the heavy metal and its distribution sites

Question 3

What are some symptoms in heavy metal acute and chronic exposure?

Answer 3

Acute: CV (tachy and maybe dysrhythmias and cardiomyopathy), CNS (peripheral neuropathy and altered mental status), GI (N/V and diarrhea; usually seen FIRST), renal (proteinuria, aminoaciduria, ATN);
Chronic: CNS and PNS more apparent than GI effects, hematologic abnormalities, renal insufficiency, certain skin abnormalities, neoplasm

Question 4

For heavy metal diagnosis, what is the main lab to focus on? Basophilic stippling indicates

Answer 4

Radiograph analysis (metals are radioopaque);
lead poisoning (look for BLOOD lead and not urine lead)

Question 5

In general, how do you treat acute and chronic toxicity?

Answer 5

Acute: ABCs, GI decontamination (important is WHOLE BOWEL IRRIGATION), and CHELATION therapy;
Chronic: removal from source and CHELATION!!

Question 6

A chelating agent forms; a chelate is a

Answer 6

complexes with heavy metals and prevents or reverses the binding of metallic cations to reactive groups (ligands);
complex formed with the metal and chelator, leading to excretion and ideally avoiding end-organ toxicity

Question 7

Ideal chelator:

Answer 7

1. Vd of the chelator greater than Vd of chelate
2. High water solubility
3. Resistant to biotransformation
4. Ability to reach the site of where the metal is stored
5. Capacity to form nontoxic complexes (remove easily from body)
6. Stable at physiologic pH
7. Low affinity for TRACE elements (those important to us)

Question 8

Ideal chelate:

Answer 8

1. More stable than endogenous chelate
2. Stable at physiologic pH
3. Resistant to biotransformation
4. Water soluble
5. Readily excreted
6. Nontoxic

Question 9

Facts on dimercaprol:

Answer 9

Name: British Anti-Lewisite (BAL);
Application: topically (antidote for Lewisite); mixed with peanut-oil (dose IM, NO IV DOSING, allergic implications);
Uses: arsenic, lead (particularly lead ENCEPHALOPATHY), inorganic mercury poisoning or MAL
SE’s: can get pain at injection site, N/V, increases in BP and HR; also need to prevent metal-induced renal toxicity b/c of BAL-metal chelate dissociation in acidic urine

Question 10

Facts on 2,3-Dimercaptosuccinic Acid:

Answer 10

Name: DMSA/Succimer
Uses: Chelation of cadmium, lead and mercury; also for arsenic poisoning (CALM)
SE’s: well-tolerated (N/V, flatus, diarrhea; mild elevations in AST and ALT)

Question 11

Edetate Ca Disodium:

Answer 11

Use: primarily used in lead poisoning (especially if someone has lead encephalopathy, and you can combine with BAL)
SE’s: DON’T confuse with Na2EDTA (causes severe HYPOCALCEMIA!!); think renal toxicity; malaise, fever, increases in ALT and AST; MED ERRORS: inadvertently give Na2EDTA instead of CaNa2EDTA

Hall of FAMeR

Question 12

Prussian blue:

Answer 12

Uses: Thallium poisoning and Cesium poisoning

SE’s: Not absorbed after oral dosing; well-tolerated!!!

Question 13

How does iron cause toxicity?

Answer 13

If free iron is in the circulation (exogenous Fe poisoning)

Question 14

Pharmacokinetics and toxic mechanism of iron?

Answer 14

Peak serum concentrations occur 2-6 hrs after ingestion, and massive amounts of Fe absorption overwhelm transferrin and there is increasing circulating free Fe;

Local can cause hematemesis, melena, and periportal necrosis of the liver and intentional ulceration and edema, with volume depletion, while systemic can lead to high AG metabolic acidosis (ferrous Fe converted to ferric and you get liberated H ion and acidosis, and also get uncoupled oxphos if deposited in the mito; hypoperfusion can lead to lactic acid generation;
direct neg inotropic effect (hypotension), vasodilator for hypotension

HUMmELs HAILs Germany

Question 15

Clinical effects of iron toxicity:

Answer 15

1. Early: think GI with N/V (1-6 hrs)
2. Intermediate: N/V could decrease because of metabolic acidosis and sequelae (6-12 hrs)
3. Local and systemic effects (12-24 hrs)
4. Late: hepatotoxicity, ARDS, renal (2-3 days)
5. Gastric outlet obstruction (2-8 wks)

Question 16

Define iron toxicity dose:

Answer 16

Greater than 20 mg/kg of elemental iron; if serious, VOMITING occurs within 6 hrs after exposure;
focus on acid-base, blood loss, and CLINICAL DIAGNOSIS, NOT on TIBC or WBC/glucose

Question 17

Iron treatment:

Answer 17

1. ABC’s
2. Radiograph is patient is vomiting
3. CBC, electrolytes, ABG
4. GI DECONTAMINATION (whole bowel irrigation)
5. Chelation therapy

Question 18

Chelator for iron: deferoxamine:

Answer 18

Mech: chelates ferric iron and is excreted in the urine as ferrioxamine which gives reddish brown color to urine;
reaches intracytoplasmic and intramito free Fe, and chelates free Fe and Fe transported b/w transferrin and ferritin; will NOT chelate Fe in transferrin, Hg, cytochromes or ferritin
Applications: acute Fe poisoning and chronic Fe overload
SE’s: anaphylactoid rxns, rate-related hypotension; ACUTE LUNG INJURY