Heavy Metals Flashcards
1
Q
Background
A
- Metals accumulate
- Not metabolized
- Bind to target proteins, enzymes via S, O, N
- Chelators used for detoxification
2
Q
Properties of an Ideal Chelating Agent
A
- Chelator-heavy metal complex less toxic than metal
- Enhances excretion of metal
- Chelate metal at physiologic pH
- Not readily metabolized
- Hydrophilic
- Has greater affinity for metals than calcium or iron in body
3
Q
Calcium Disodium EDTA
A
- Metal displaces calcium in center of molecule
- IV/IM administration
- Tx: Lead and cadmium
- Metal-EDTA complex excreted in urine: contraindicated in renal disease
4
Q
Succimer
A
- DMSA
- Sulfhydryl groups bind to metal and excreted in urine
- Administered orally
- Lead toxicity
- Low compliance due to nausea and bad taste
5
Q
Dimercaprol (BAL)
A
- SH groups bind to metal
- Tx: Lead, Arsenic, and inorganic mercury poisoning
- IM Administration (in peanut oil)
- Metal-BAL complex excreted in urine and bile: dissociates in acidic urine
- Contraindicated in liver disease
6
Q
Penicillamine
A
- Sulfhydryl containing agent
- Complex excreted in urine: contraindicated in renal disease
- Oral administration
- DOC in Wilson’s disease
- Agranulocytosis is major adverse effect
7
Q
Lead
A
- Exposed by ingestion (water, soil, paint chips, pottery made outside US) or inhalation
8
Q
Absorption and Distribution of Lead
A
- Children absorb it >5 times higher than adults
- Distributes first to liver, kidney, RBC
- RBC have >95% of lead in blood bound to hemoglobin
- Redistributes to bone replacing calcium to form tertiary lead phosphate
9
Q
Lead Poisoning
A
- Blood, microcytic anemia, basophilic stipling and hemolysis (acute)
- GI, lead colic (chronic)
- Nerve, muscle weakness, memory loss, lead palsy (chronic)
- Lead encephalopathy: most serious condition, convulsions, cerebral edema, death
10
Q
Neurological Target Tissues for Lead
A
- Peripheral, axon degeneration
- Brain, lead interferes with calcium dependent reactions in brain
- Brain is most sensitive organ
11
Q
Hematologic Target Tissues for Lead
A
- Most sensitive indicator of toxicity
- Lead inhibits heme synthesis
- Basophilic stipling due to ppt of RNA
- Anemia due to decreased life span and heme synthesis
12
Q
Blood and Urinary Indicators of Lead
A
- Inhibits 2 Sulfhydryl dependent enzymes
- Cause increase urinary levels of delta-aminolevulinic acid
- Lead levels in whole blood sensitive indicator of toxicity
13
Q
Chelation Therapy
A
- Low levels, asymptomatic (succimer PO, Penicillamine PO: not FDA approved)
- Aggressive Therapy (Calcium Disodium EDTA IV, Dimercaprol IM)
14
Q
Mercury
A
- 3 forms: elemental, inorganic, and organomercurial
- Bind to Sulfhydryl groups, inactivate proteins and enzymes
15
Q
Elemental Mercury
A
- Inhalation: respiratory and neurological damage
- Not toxic orally
- Unionized so crosses BBB
- In RBC, converted from 0 valence to +2
- Toxicity tremor, irritability, erethism,
16
Q
Inorganic Mercury
A
- Oral exposure binds to SH-proteins in mouth and esophagus causing a gray color
- GI, vomiting, hematochezia
- Renal: PCT, chronic tubular and glomerular damage
- Photophobia and acrodynia
17
Q
Organomercurials
A
- Most toxic form
- Target is nervous system, readily enters the brain: muscle tremor, visual field constriction, ataxia
18
Q
Tx of Mercury Toxicity
A
- Elemental and Inorganic mercury use Penicillamine and Dimercaprol
- Methyl mercury: Penicillamine shows moderate success, Dimercaprol contraindicated because in increases brain levels
19
Q
Arsenic
A
- Forms: inorganic (As3+ and As5+), organoarsenical, and arsine gas
20
Q
Arsenic MOA
A
- As3+ — binds SH groups
- As5+ — replaces P in ATP production causing uncoupling of oxidative phosphorylation
- Ash3 hemolysis
21
Q
Arsenic Toxicity
A
- Vascular: VD, increases capillary permeability, arrhythmia
- GI: increased blood flow, loss of albumin into SI coagulates giving a gelatinous diarrhea called rice water diarrhea
- Skin: cancer and hyperkeratosis
- Arsine gas: hemolysis
- Kidney: PCT and glomerular
22
Q
Chronic Arsenic Toxicity
A
- Muscle weakness
- Hyperkeratosis
- Arrhythmia
- Enlarged liver
- Garlic odor to breath and sweat
- Mee’s line on fingernails
23
Q
Tx for Arsenic Toxicity
A
- Penicillamine
- Dimercaprol
- Arsine gas chelation therapy ineffective so Tx symptoms
24
Q
Cadmium
A
- Ingestion: target is kidney
- Inhalation: target kidney and lung, kidney: PCT necrosis, lung: pulmonary edema, irritation and chronic exposure causes emphysema
25
Q
Cadmium Toxicity and Metallothionein
A
- Metallothionein is an Inducible protein: induced by cadmium, mercury, and arsenic exposure
- Cadmium accumulates in liver and kidney bound to Metallothionein
26
Q
Tx for Cadmium Toxicity
A
- Chelation Therapy: Disodium EDTA, BAL contraindicated in renal toxicity
- Monitor urinary B2-microglobulin
27
Q
Wilson’s Disease
A
- Inappropriately high copper levels
- Defect in ATP7B protein: impacts biliary copper excretion, diminished copper incorporation with ceruloplasmin
- First line of therapy is Penicillamine
- Trientine alternate choice chelator when Penicillamine not tolerated
