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Pharmacology > Chelators And Heavy Metal Toxicity > Flashcards

Chelators And Heavy Metal Toxicity Flashcards

1
Q

Which metals are good for the body

A

Iron

Copper

Zinc

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2
Q

Found in hemoglobin, myoglobin, CYP450-heme containing

A

Iron

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3
Q

Found in enzymes, hair, elastic tissue, bone

A

Copper

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4
Q

Found in over 300 enzymes including those for gene expression

A

Zinc

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5
Q

Found among mitochondrial enzymes

A

Manganese

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6
Q

What are bad metals

A

Deficiency or overdose of good metals

Exposure to:

Lead

Mercury

Arsenic

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7
Q

What are general toxicity of metals

A

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

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8
Q

Which metal induce reactive oxygen species

A

Iron

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9
Q

Where does lead act in the body

A

Blood

Nervous system

Kidneys

Reproductive organs

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10
Q

Where does arsenic act in the body

A

Lung

Skin

Liver

Kidney

Bladder

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11
Q

Where does mercury act in the body

A

CNS

GI

Kidney

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12
Q

What are the symptoms of lead toxicity

A

Headache

Fatigue

Cramps

Flulike symptoms

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13
Q

What are the symptoms of arsenic

A

GI nausea

Vomiting

Cramping

Acute shock

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14
Q

What are the symptoms of mercury

A

Chemical pneumonia is

Pulmonary edema

Acute neurological

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15
Q

What is the kinetics and dynamics of lead

A

Slow oral with slow clearance

Goes to the bone

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16
Q

What is the kinetics and dynamics of arsenic

A

Good GI absorption

Goes to hair and nails

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17
Q

What is the kinetics and dynamics of mercury

A

Variable absorption based on chemical

Widely distributed

Goes to fatty tissues

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18
Q

What is the treatment of metal toxicity

A

Chelators

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19
Q

By what general mechanism does chelators arrest metals

A

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

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20
Q

Efficiency of chelators is dependent on what factor?

A

Number of ligand binding sites (the more the better)

Can be mono, bi, or polyadenylate

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21
Q

Which functional groups can bind metals

A

SH

OH

NH

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22
Q

What is unique about these functional groups

A

They prevent metals from binding to similar functional groups of proteins

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23
Q

What is a major draw back of chelators

A

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

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24
Q

What should you keep in mind when considering choosing chelators

A

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

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25
Q

Metals for EDTA

A

Lead

Calcium

Zinc, manganese and cations of radionucloetides

26
Q

Where is EDTA application more effective

A

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

27
Q

What are the kinetics of EDTA

A

Less oral absorption

Rapid excretion = 50% in 1 hour

28
Q

What does more EDTA in the urine indicate

A

More lead in urine

29
Q

EDTA toxicity

A

Nephrotoxicity ( prevented with maintenance of urine flow)

Zn depletion

30
Q

Metals of Dimercaprol

A

Acute poisoning with

Arsenic

Mercury

Can be used in conjunction with EDTA to address lead poisoning

31
Q

How is dimercaprol administered

32
Q

What is the characteristics of dimercaprol

A

Oily colorless with strong merchantman smell

Rapidly oxidized in liquids

33
Q

How is rapid oxidation of dimercaprol in liquid addressed

A

Resuspend in 10% peanut oil

34
Q

Why is dimercaprol essentially good for acute arsenic poisoning

A

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

35
Q

Dimercaprol toxicity

A

Hypertension Tachycardia

Vomiting Salivation

Lacrimation

Fever in kids

Pain at injection site

36
Q

Why is dimercaprol not used as much

A

Low solubility replaced by Succimer a more soluble agents

37
Q

Metals of Succimer

A

Antimony

Arsenic

Lead

Mercury in kidney

38
Q

What is this Succimer

A

Water soluble analog of dimercaprol

39
Q

What does Succimer work to prevent

A

Metal induced inhibition of SH containing enzymes

40
Q

What is the dosage of Succimer

A

10 mg/kg by mouth TID

41
Q

What is the peak blood level and half life of Succimer

A

Peak blood levels is 3 hrs

T1/2 is 2 hrs

42
Q

What are the 10% toxicity effect of succimer

A

GI: VAND

Rash (5%)

43
Q

What is penicillamine

A

D-Methylcysteine

44
Q

Metals of penicillamine

A

Copper

Lead

Mercury

45
Q

Which is better for lead and mercury: penicillamine or succimer

46
Q

What disease state can penicillamine be used for

A

Wilson’s disease

RA

47
Q

What are the physical properties of penicillamine

A

White crystalline

Water soluble

48
Q

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

A

D is more therapeutic

L is toxic

49
Q

Which patient should avoid D-penicillamine

A

Penicillin allergy patient

50
Q

Toxicity of Penicillamine

A

Hypersensitivity

Rash

Itch

Fever

Nephrotoxicity with proteinuria

51
Q

Metals of Trientine

52
Q

What is the other therapy use of Trientine

A

Wilson’s disease

53
Q

What is the toxicity of Trientine compared to penicillamine

A

Less toxic

54
Q

What toxicity was found in rats with Trientine

A

Teratogenicity

55
Q

Metal of Defroxamine

A

Iron

Do not interact with trace metals

56
Q

From what organism is deferoxamine found

A

Steptomyces pilosus

57
Q

Deferoxamine kinetics

A

Poor oral absorption

58
Q

What are deferoxamine route of administration

A

Oral

IM

IV

59
Q

What is oral deferoxamine

A

Deferasirox

60
Q

Why is urine orange after deferoxamine use

A

Iron complex excreted renally

61
Q

Deferoxamine Toxicity

A

Skin: Flushing
Blotchy erythema
Hives

Heart: hypotension

GI: irritation

Lungs: pulmonary complications rare

Pharmacology (4 decks)

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