6.2: Heavy Metals And Chelators Flashcards
Heavy Metals
• Lead
• Arsenic
• Mercury
What are the 9 Chelator/Chelating Agent?
- Dimercaprol
- Succimer
- Edetate Calcium Disodium
- Unithiol
- Penicillamine
- Deferoxamine
- Deferasirox and Deferiprone
- Prussian Blue
• Storage batteries, ammunition,
• metal alloys, solder, glass,
• plastics, pigments and
• ceramics
• No useful purpose in the human body
Lead
Absorbed slowly but consistently via respiratory and gastrointestinal tract
Pharmacokinetics
Identify the heavy metal based on its pharmacokinetics:
Low dietary calcium, iron deficiency and ingestion on an empty stomach increases absorption
Lead
Identify the heavy metal based on its pharmacokinetics:
Poor absorption in the skin
Lead
Up to what % absorbed in children in lead
50%
Up to what % in adults is absorbed in lead?
10-15%
Lead (pharmacokinetics):
What exposure is seen in respiratory tract?
industrial exposure
Lead (pharmacokinetics):
What exposure is seen in intestinal tract?
nonindustrial exposure
Lead [pharmacokinetics]
What % bound to RBCs, what % free in plasma
99% : 1%
Identify the heavy metal based on its pharmacokinetics:
Distributed to bone marrow, brain, kidney, liver, muscle and gonads; then bones
Lead
Identify the heavy metal based on its pharmacokinetics:
Crosses the placenta
Lead
What is the half-life of Lead?
1-2 mos
What is the half-life of Lead in bones?
years to decades
Lead [pharmacokinetics]
What % excreted in the urine
70%
Identify the heavy metal based on its pharmacodynamics:
- Multiple mechanisms of action
- Inhibition of enzymatic function
- Interference with action of essential cations (calcium, zinc, iron)
- Oxidative stress generation
- Gene expression changes
- Cell signaling alteration
- Disruption of membrane integrity
Lead
Major Forms of Lead Intoxication
- Inorganic Lead Poisoning
- Organolead Poisoning
What is the treatment for Lead?
Immediate termination of exposure, supportive care and rational use of chelation therapy
Identify the heavy metal based on its treatment:
Retained lead objects require gastrointestinal decontamination
Lead
Lead [Treatment]
Intravenous edetate calcium disodium (CaNa2EDTA) at a dosage of ___ mg/kg/d by continuous infusion for up to __ days only
30-50 mg/kg/d : 5
Treatment for Lead:
Oral Succimer (DMSA) after __ days
5
Identify this heavy metal:
Semiconductors, wood preservatives, nonferrous alloys, glass and turf herbicide monosodium methane arsonate (MSMA)
Arsenic
Groundwater may contain high amounts of arsenic
Arsenic
Identify this heavy metal:
Historically, used as a pharmaceutical agent but now limited in use
Arsenic
Identify the heavy metal based on its pharmacokinetics:
Well-absorbed via respiratory and GI tract
Arsenic
True or False:
In the pharmacokinetics of Arsenic, percutaneous absorption is limited.
True
In the pharmacokinetic of Arsenic, it is metabolized by the liver via?
methylation reactions
Arsenic [Pharmacokinetics] is excreted in the?
Urine (major), sweat and feces
Identify the heavy metal based on its pharmacodynamics:
Multiple mechanism of actions:
* Inhibition of enzyme functions
* Oxidative stress generation
* Gene expression changes
* Cell signaling alteration
Arsenic
Identify this heavy metal:
- Hyperpigmentation and hyperkeratosis involving hands and feet
- Chronic inorganic arsenic poisoning
Raindrop pattern
• Immediate termination of exposure, supportive care and chelation therapy
• Gut decontamination if appropriate
Arsenic [Treatment]
Arsenic [Treatment]
Acute Poisoning: Chelation with Unithiol __mg/kg every __ hours or Dimercaprol every __ hours
3-5mg/kg : 4-6 hours
Quicksilver or liquid metal
Mercury
Mined predominantly as HgS in cinnabar ores
Mercury
Electrolytic production of chlorine and caustic soda; electrical equipment, thermometer, instruments, fluorescent lamps; dental amalgams; artisanal gold production
Mercury
True or False:
Thimerosal, an organomercurial preservative, are kept in almost all vaccines in mercury.
False
They are removed from almost all vaccines.
Environmental release of mercury from burning of fossil fuels contributes to bioaccumulation in fishes
Mercury
Absorption varies depending on chemical form
Mercury [Pharmacokinetics]
Mercury [Pharmacokinetics]
Absorbed from the??
Lungs, GI tract, and percutaneous route
In the pharmacokinetics of Mercury, it is well-distributed into tissues and most concentrated in __?
Kidneys
Mercury [Pharmacokinetics]
Excreted via?
urine and feces
immediate removal from source, supportive care and chelation therapy
Mercury [Treatment]
Mercury [Treatment]
Acute
Unithiol, dimercaprol or succimer
True or False.
Dimecaprol should never be used for elemental or organic mercury intoxication.
True
Pharmacology of Chelators
Metallic ion + chelating agent —> metallic chelate
Drugs used to prevent or reverse the toxic effects of heavy metals on an enzyme or other cellular target, or to accelerate the elimination of metal from the body
Chelators or Chelating Agents
The metal-mobilizing effects of a therapeutic chelating agent may also redistribute some of the metal to vital organs
Chelators or Chelating Agents
They may also enhance excretion of essential cations (Zinc, Copper)
Chelators or Chelating Agents
True or False:
The longer the half-life of a metal in a particular organ, the more effectively they can be removed by chelation.
False
It will be less effective.
What are the chelators or chelating agents?
- Dimercaprol
- Succimer
- Edetate Calcium Disodium (EDTA)
- Unithiol
- Penicillamine
- Deferoxamine
- Deferasirox
- Deferiprone
- Prussian Blue
What is the antidote to a warfare agent of Dimercaprol?
Lewesite
Adverse effects: hypertension, tachycardia, nausea, vomiting, lacrimation, salivation, fever, pain at injection site, thrombocytopenia, increase Prothrombin time
Dimercaprol
[ 2,3-Dimercaptopropanolol, BAL]
Dimercaprol [ 2,3-Dimercaptopropanolol, BAL]
As single-agent: arsenic and inorganic mercury
acute poisoning
Dimercaprol [ 2,3-Dimercaptopropanolol, BAL]
As conjunction with EDTA
severe lead poisoning
[ T or F ]
Dimercaprol [ 2,3-Dimercaptopropanolol, BAL]
It prevents and reverses metal-induced inhibition ofsulfhydryl-containing enzyme
True
Dimercaprol [ 2,3-Dimercaptopropanolol, BAL]
Increases rate of excretion of ?
arsenic and lead
Dimercaprol [ 2,3-Dimercaptopropanolol, BAL]
Is given via __, excreted via __
IM : kidneys
Redistributes arsenic and mercury to CNS
Dimercaprol [ 2,3-Dimercaptopropanolol, BAL]
Identify this chelating agent:
Water-soluble analog of dimercaprol
Succimer
Dimercaptosuccinic Acid, DMSA
It prevents and reverses metal-induced inhibition of sulfhydryl-containing enzyme
Succimer [Dimercaptosuccinic Acid, DMSA]
Succimer [Dimercaptosuccinic Acid, DMSA]
Treatment of children with blood lead concentration of?
> 45mcg/dL
Identify this chelating agent:
- Increase rate of excretion of lead
- It decreases mercury content in kidney
Succimer
Dimercaptosuccinic Acid, DMSA
Identify this chelating agent:
Has protective effect against arsenic as well
Succimer
Dimercaptosuccinic Acid, DMSA
Succimer (Dimercaptosuccinic Acid, DMSA)
is given in what route?
Oral, IV
Succimer [Dimercaptosuccinic Acid, DMSA]
Adverse effects
GI disturbances are the most common
Succimer [Dimercaptosuccinic Acid, DMSA]
Associated with increase in?
ALT, AST, mild neutropenia
Calcium disodium salt form of EDTA
Edetate Calcium Disodium
[Ethylenediaminetetraacetic Acid, EDTA]
Indicated mainly for chelation of lead
Edetate Calcium Disodium
[Ethylenediaminetetraacetic Acid, EDTA]
Identify this chelating agent:
Chelator of zinc, manganese and certain heavy radionucleotide poisoning
Edetate Calcium Disodium
Ethylenediaminetetraacetic Acid, EDTA
Identify the chelating agents:
Chelates extracellular metals ions much more effectively compared to intracellular metal ions
Edetate Calcium Disodium
Ethylenediaminetetraacetic Acid, EDTA
[T or F ]
Edetate Calcium Disodium [Ethylenediaminetetraacetic Acid, EDTA]
Limited oral absorption
True
Edetate Calcium Disodium [Ethylenediaminetetraacetic Acid, EDTA]
Given __; Excreted via the __
IV infusion : kidney
Water-soluble analog of dimercaprol
Unithiol [Dimercaptopropanesulfonic Acid, DMPS]
Identify this chelating agent:
Protective effects against mercury and arsenic
Unithiol
Dimercaptopropanesulfonic Acid, DMPS
[ T or F ]
Unithiol has FDA approved indications.
FALSE
Wala!!!!
True or False:
In Unithiol, it decreases urinary excretion of mercury, arsenic and lead.
False
Increases.
True or False:
Unithiol [Dimercaptopropanesulfonic Acid, DMPS]
* Given Orally and IV (slow infusion)
* Excreted via kidneys
True
What are the adverse effects of Unithiol?
- Dermatologic reactions
- Urticaria
- Exanthems; isolated cases of SJS
- Erythema multiforme
Identify this chelating agent:
White, crystalline, derivative of Penicillin
Penicillamine
D-Dimethylcysteine
Identify this chelating agent:
Also used in Severe Rheumatoid Arthritis
Penicillamine
D-Dimethylcysteine
Identify the chelating agent:
Used primarily to treat or prevent Copper poisoning (i.e. Wilson’s Disease)
Penicillamine
D-Dimethylcysteine
[ T or F ]
Penicillamine [D-Dimethylcysteine]
L-isomer form is less toxic than the D-Penicillamine
False. Should be D-Penicillamine is less toxic than the L-isomer form
Penicillamine [D-Dimethylcysteine]
Adverse effects:
Hypersensitivity, nephrotoxicity with proteinuria, pancytopenia, pyridoxine insufficiency
[ T or F ]
Penicillamine [D-Dimethylcysteine]
Absorbed via oral route
True
Isolated from Streptomyces pilosus
Deferoxamine
Identify what chelating agent:
The parenteral chelator of choice for iron poisoning.
Deferoxamine
Identify this chelating agent:
This chelating agent is useful in treatment of aluminum toxicity with hemodialysis.
Deferoxamine
What is the adverse effects of Deferoxamine?
- Hypotension
- Flushing
- Abdominal discomfort
- Rashes
- Pulmonary complications
[Deferoxamine]
Excreted in the __
Urine
The given route of Deferoxamine is through:
IM or IV
Identify this chelating agent:
Indicated for treatment of contamination with radioactive Cesium and intoxication with thallium salts
Prussian Blue
Ferric Hexacyanoferrate
Identify this chelating agent:
Ion exchange and mechanical trapping or adsorption
Prussian Blue
Ferric Hexacyanoferrate
Prussian Blue [Ferric Hexacyanoferrate]
Adverse effects:
Constipation
[ T or F ]
Prussian Blue [Ferric Hexacyanoferrate]
Given orally, minimal GI absorption (<2%), excreted via feces
False. (<1%)