Chelators And Heavy Metal Toxicity

Question 1

Which metals are good for the body

Answer 1

Iron

Copper

Zinc

Question 2

Found in hemoglobin, myoglobin, CYP450-heme containing

Answer 2

Iron

Question 3

Found in enzymes, hair, elastic tissue, bone

Answer 3

Copper

Question 4

Found in over 300 enzymes including those for gene expression

Answer 4

Zinc

Question 5

Found among mitochondrial enzymes

Answer 5

Manganese

Question 6

What are bad metals

Answer 6

Deficiency or overdose of good metals

Exposure to:

Lead

Mercury

Arsenic

Question 7

What are general toxicity of metals

Answer 7

Inhibit enzyme activity by binding to SH groups

Interfere with essential cations such as Ca2+, Fe3+, Zn2+

Alter the structure of plasma membrane and receptors

Question 8

Which metal induce reactive oxygen species

Answer 8

Iron

Question 9

Where does lead act in the body

Answer 9

Blood

Nervous system

Kidneys

Reproductive organs

Question 10

Where does arsenic act in the body

Answer 10

Lung

Skin

Liver

Kidney

Bladder

Question 11

Where does mercury act in the body

Answer 11

CNS

GI

Kidney

Question 12

What are the symptoms of lead toxicity

Answer 12

Headache

Fatigue

Cramps

Flulike symptoms

Question 13

What are the symptoms of arsenic

Answer 13

GI nausea

Vomiting

Cramping

Acute shock

Question 14

What are the symptoms of mercury

Answer 14

Chemical pneumonia is

Pulmonary edema

Acute neurological

Question 15

What is the kinetics and dynamics of lead

Answer 15

Slow oral with slow clearance

Goes to the bone

Question 16

What is the kinetics and dynamics of arsenic

Answer 16

Good GI absorption

Goes to hair and nails

Question 17

What is the kinetics and dynamics of mercury

Answer 17

Variable absorption based on chemical

Widely distributed

Goes to fatty tissues

Question 18

What is the treatment of metal toxicity

Answer 18

Chelators

Question 19

By what general mechanism does chelators arrest metals

Answer 19

Formation of stable covalent bonds with cation metals using two or more electronegative groups

Question 20

Efficiency of chelators is dependent on what factor?

Answer 20

Number of ligand binding sites (the more the better)

Can be mono, bi, or polyadenylate

Question 21

Which functional groups can bind metals

Answer 21

SH

OH

NH

Question 22

What is unique about these functional groups

Answer 22

They prevent metals from binding to similar functional groups of proteins

Question 23

What is a major draw back of chelators

Answer 23

It is non-specific and can chelate good metals making it the main cause for toxicity

Question 24

What should you keep in mind when considering choosing chelators

Answer 24

It is easier to chelate when metals are in blood vessels than in less vascularized tissue such as bone matrix (lead)

Question 25

Metals for EDTA

Answer 25

Lead Calcium Zinc, manganese and cations of radionucloetides

Question 26

Where is EDTA application more effective

Answer 26

If it is used for extracellular chelation. Does not penetrate plasma membrane well

Question 27

What are the kinetics of EDTA

Answer 27

Less oral absorption Rapid excretion = 50% in 1 hour

Question 28

What does more EDTA in the urine indicate

Answer 28

More lead in urine

Question 29

EDTA toxicity

Answer 29

Nephrotoxicity ( prevented with maintenance of urine flow) Zn depletion

Question 30

Metals of Dimercaprol

Answer 30

Acute poisoning with Arsenic Mercury Can be used in conjunction with EDTA to address lead poisoning

Question 31

How is dimercaprol administered

Answer 31

IM

Question 32

What is the characteristics of dimercaprol

Answer 32

Oily colorless with strong merchantman smell Rapidly oxidized in liquids

Question 33

How is rapid oxidation of dimercaprol in liquid addressed

Answer 33

Resuspend in 10% peanut oil

Question 34

Why is dimercaprol essentially good for acute arsenic poisoning

Answer 34

Arsenic loves SH groups of proteins therefore the binding of arsenic to SH groups of dimercaprol prevents that from occuring

Question 35

Dimercaprol toxicity

Answer 35

Hypertension Tachycardia Vomiting Salivation Lacrimation Fever in kids Pain at injection site

Question 36

Why is dimercaprol not used as much

Answer 36

Low solubility replaced by Succimer a more soluble agents

Question 37

Metals of Succimer

Answer 37

Antimony Arsenic Lead Mercury in kidney

Question 38

What is this Succimer

Answer 38

Water soluble analog of dimercaprol

Question 39

What does Succimer work to prevent

Answer 39

Metal induced inhibition of SH containing enzymes

Question 40

What is the dosage of Succimer

Answer 40

10 mg/kg by mouth TID

Question 41

What is the peak blood level and half life of Succimer

Answer 41

Peak blood levels is 3 hrs T1/2 is 2 hrs

Question 42

What are the 10% toxicity effect of succimer

Answer 42

GI: VAND Rash (5%)

Question 43

What is penicillamine

Answer 43

D-Methylcysteine

Question 44

Metals of penicillamine

Answer 44

Copper Lead Mercury

Question 45

Which is better for lead and mercury: penicillamine or succimer

Answer 45

Succimer

Question 46

What disease state can penicillamine be used for

Answer 46

Wilson’s disease RA

Question 47

What are the physical properties of penicillamine

Answer 47

White crystalline Water soluble

Question 48

Which configuration is preferred for penicillamine and why. L or D

Answer 48

D is more therapeutic L is toxic

Question 49

Which patient should avoid D-penicillamine

Answer 49

Penicillin allergy patient

Question 50

Toxicity of Penicillamine

Answer 50

Hypersensitivity Rash Itch Fever Nephrotoxicity with proteinuria

Question 51

Metals of Trientine

Answer 51

Copper

Question 52

What is the other therapy use of Trientine

Answer 52

Wilson’s disease

Question 53

What is the toxicity of Trientine compared to penicillamine

Answer 53

Less toxic

Question 54

What toxicity was found in rats with Trientine

Answer 54

Teratogenicity

Question 55

Metal of Defroxamine

Answer 55

Iron Do not interact with trace metals

Question 56

From what organism is deferoxamine found

Answer 56

Steptomyces pilosus

Question 57

Deferoxamine kinetics

Answer 57

Poor oral absorption

Question 58

What are deferoxamine route of administration

Answer 58

Oral IM IV

Question 59

What is oral deferoxamine

Answer 59

Deferasirox

Question 60

Why is urine orange after deferoxamine use

Answer 60

Iron complex excreted renally

Question 61

Deferoxamine Toxicity

Answer 61

Skin: Flushing Blotchy erythema Hives Heart: hypotension GI: irritation Lungs: pulmonary complications rare