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Pharmacology > 36_Heavy Metals > Flashcards

36_Heavy Metals Flashcards

1
Q

What are the three heavy metals? Which one is a metalloid?

A

Lead, Mercury, Arsenic

Arsenic is the metalloid

These metals have no physiologic function in the body

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2
Q

How is Lead absorbed into the body?

A

Inhalation: Lead dust; common industrial exposure

GI Tract: Kids absorb more than adults (50% v 10-15%)

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3
Q

What increases the absorption of Lead?

A

Low dietary Ca2+
Fe Deficiency
Empty Stomach

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4
Q

What cell does Pb bind to?

A

RBCs (99% of it does) and then distributed t/o body

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5
Q

What is the Pb half-life in Blood/Soft tissue?

Bone?

A

1-2 months blood
years to decades in bone

90% of Pb in body is in bone and is slowly released so that the blood level remains constant even when exposure stops

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6
Q

Can a bullet cause Lead damage?

A

Depends on where it is.

If in soft tissue and no vital organs injured. just leave it in. no risk of poisoning

If in joints, near bone, in CSF…THEN COULD CAUSE POISONING

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7
Q

Name some of the toxic effects of Pb poisoning?

A
  1. Inhibition of Enzyme Function
  2. Interference with essential CATIONS (Ca, Fe, Zn)
  3. Generation of Oxidative Stress
  4. Changes in Gene Expression
  5. Altered Cell Signaling
  6. Disruption of Membrane Integrity
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8
Q

Who are at the highest risk of developing Pb Neurotoxicity?

A

Fetus & Young Children…the developing CNS is more susceptible

Associated with lower IQ, there is no established “threshold” where below it there is no effect. So avoid it all costs

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9
Q

What is the definition of toxic lead level?

A

10 ug/dL since 1991

Higher levels are now less common, multiple environmental measures to ensure it stays low

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10
Q

For Pb neurotoxicity in adults, what could chronic exposure lead to?

A

Chronic exposure with blood levels 10-30 ug/dL may cause subtle clinical effects

If above 30, tho…get neuro cognitive effects:
Irritability, fatigue, anorexia, sleeping issues, impaired coordination, tremor

If above 100…wowzers get encephalopathy
Ataxia, peripheral neruopathy (classic sign IS WRIST DROP), stupor, coma, seizure, death

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11
Q

What kind of anemia would be expected with Pb hemotoxicity?

A

Normocytic or Microcytic/Hypochromic

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12
Q

In Pb hemotoxicity, what steps in Heme synthesis does Pb interfere with?

A

The two enzymes inhibited are:
delta-Aminolevulinate dehydratase (build up of D-ALA)
ferrochelatase (build up of protoporphyrin)

Postulated Inhibition:
delta-Aminolevulinate synthase
coproporphyrinogen oxidase

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13
Q

What will be elevated in Pb Hematoxicity?

A

Protoporphyrin

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14
Q

What other histologic features can be seen in Pb Hematoxicity?

A

Increased RBC fragility (might get hemolysis)

Basophilic stipling (common clue on boards that there is Pb toxicity)

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15
Q

What other organs can Pb be toxic to?

A

Kidney–>Pb Nephropathy
Reproductive Organs–>Reprotoxicity
CV: HTN
GI: Lead Colic, Gingival Lead Lines

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16
Q

In Pb Nephrotoxicity, what would you expect to see?

A

Possible decrease in uric acid excretion which may lead to SATURNINE GOUT

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17
Q

Lead Poisoning much rarer now

A

Levels have fallen 90% in North America and Europe. May be obsolete now

Just an fyi slide

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18
Q

How is Pb poisoning treated?

A 
Terminate further exposure (find the source...could be paint, toys, even food)
Supportive care (hydration, urination)
Chelation
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19
Q

If there is encephalopathy due to Pb poisoning, how is it treated?

A 
For Encephalopathy
Treat cerebral edema/seizures with:
----Steroids, Mannitol, Anticonvulsants
IV CaNa2EDTA
IM dimercaprol
20
Q

When is oral chelation used for treatment of Pb poisoning?

A

When its not encephalopathic

–Use Succimer for primary agent i.e. DMSA (dimercaprosuccinic acid, or Chemet

21
Q

When is dimercaprol used?

A

Used for Encephalopathic Pb poisoning

22
Q

What is succimer and what is it used for?

A

It is a chelator used for NON encephalopathic treatment of Pb poisoning. The two kinds are DMSA or Chemet

23
Q

In adult chronic Pb toxicity, how do ppl get the blue discoloration of the gums?

A

It is a rxn of Pb with the S ions released from microbes to create PbS. This deposits PbS at the interface of teeth and gums (Burtons Line)

24
Q

Though Arsenic (As) has few therapeutic uses, what beneficial uses does it have?

A

Salvarsan: Arsenical pre PCN antibiotic

Arsenic Trioxide: Acute Promyelocytic Leukemia

25
Q

What are the symptoms of acute INORGANIC As poisoning?

A

Rapid onset gastroenteritis

then…Cardiopulmonary, Hemotoxicity & Neuro effects (ASCENDING SENSORIMOTOR peripheral neuropathy, possible encephalopathy)

Delayed: Mees Lines
- Transverse white nail lines that indicate period of decreased growth

26
Q

What are the symptoms of chronic As poisoning?

A 
Constitutional symptoms
Anemia
Sensorimotor peripheral neuropathy
Skin Lesions
Increased Cancer risk (skin, kidney, Lung)
27
Q

What is Hg still commonly used in?

A

Dental amalgum

28
Q

What are the three flavors of Hg?

A
  1. Elemental
    - Liquid (least toxic)
    - Vapor (well absorbed and DANGEROUS)
  2. Hg Salts
    - Corrosive, may cause hemorrhagic gastritis
    - Acute tubular necrosis, Renal Failure
  3. Organomercuries
    - Neurotoxicity
29
Q

What is Erethism?

A

It is neuropyschiatric effects from chronic occupational Hg poisoning. Symptoms include:

  • shyness
  • social w/drawal
  • depression
  • explosive anger
  • blushing
30
Q

What is the classic triad of chronic Hg toxicity?

A

Tremor, Neuropsychiatric disturbances, gingivostomatitis

31
Q

What is acrodynia? What demographic is it more common in?

A

It is painful extremity erythema due to Hg toxicity. It is associated with HTN, Diaphoresis, & Irritability

Found mostly in children

32
Q

What are some fish preggos should avoid due to high Hg levels?

A

Shark, swordfish, King Mackerel, Tilefish

33
Q

Chelators have multiple O, N, or S groups that do what?

A

They contribute e- pairs to complex a metallic cation ligand

34
Q

How do heavy metals inhibit enzymes?

A

They will bind to the SULFHYDRYL groups on enzymes which causes their inhibition. The metal ion complexes with e- pairs on the S atom

35
Q

How do chelators “mop up” the heavy metals?

A

They provide alternate sulfhydryl binding sites for the heavy metals to bind to. this mobilized the heavy metals and enhancing urinary excretion.

36
Q

What are some caveats of heavy metal mobilization?

A

Mobilization could redistribute heavy metal from a less dangerous to a more dangerous part of the body (i.e. from soft tissue to blood to brain)

May chelate physiological or needed metals

Difficult to mobilize metal from compartments with long half lives (i.e. bone)

37
Q

Name me some chelators gurrlll

A

DDD SED (Triple D Said)

DMPS
D-Penicillamine
Deferoxamine, Deferasirox; Prussian Blue
Succimer
Edetate Ca Disodium
Dimercaprol
38
Q

What is Dimercaprol?
What solution is it made in?
What are its indications?

A

It is 2,3 Dimercaptopropanol which is a British Anti Lewisite (BAL) that was developed as an antidote for As used in chemical warfare

10% solution in peanut oil, IM injections are painful

Indciations: As, inorganic Hg, Severe Pb poisoning (with CaNa2EDTA)

39
Q

What is succimer?
How is it administered?
Indications?
SEs?

A

Dimercaptosuccinic acid
DMSA

H20 soluble analog of dimercaprol
Given orally

Indications: kids with BLL >45 ug/dL; can use in adults too but not FDA approved. Also occasionally for As, and Hg

SEs: GI, rash, increased liver transaminases

40
Q

What is edentate Ca Disodium
How is it given?
Indications?
Deaths?

A

Calcium Na EDTA
CaNa2EDTA

Given IV

Indications: Lead, not sure about Zn, Mn, some radionuclides

Deaths: In autistic children have occurred when NaEDTA was inappropriately substituted for CaNa2EDTA (to treat Hg)
- presumably due to hypOcalcemia

41
Q

What is UNITHIOL?
How is it given?
Indications:

A

Dimercaptopropanesulfonic acid
DMPS

NOT AVAILABLE IN US

Given IV or PO

Indications: Hg, As

42
Q

What is D-Penicillamine?
How is it given?
Indications?
SEs?

A

Chelator

Given PO

Indications: Copper (Wilsons Disease)
Severe Rheumatoid Arthritis
Pb, Hg (but Succimer works better for these these two

SEs: Hypersensitivity Rxns, Nephrotoxicity

43
Q

What is Trientine?

A

It is a copper chelator for Wilson’s disease that can be used if the person is intolerant to succimer

Kayser Fleischer ring is copper deposition in Descemet’s membrane of the cornea

44
Q

What are the Iron chelators? How are they given

A

Deferoxamine

  • IV for acute Fe toxicity
  • Also for Al (with dialysis pts)

Deferasirox

  • PO Iron chelator
  • Used for Fe overload with frequent blood transfusions, thalassemia, myelodysplasia
45
Q

What is Prussian blue?
How is it given?
What does it complex with, and what is the point of this drug?

A

Dark blue pigment used in art, contains cyanide

Taken PO BUT NOT ABSORBED

Complexes with Cesium, thallium

  • used in case of radioactive cesium risk from dirty bombs
  • Prevents cesium and thallium absorption from GI tract
46
Q

What is Na Polystyrene Sulfonate?

Indications?

A

Metal binding agent thats frequently used as a binding resin that EXCHANGES Na for K

Doesn’t have multiple “teeth” so not a true chelator

Indications: Hyperkalemia, Li/Thallium toxicity (?)

Pharmacology (17 decks)

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