Exam 3: Heavy Metal Toxicities Flashcards
Describe the 4 ways that metals can produce toxicity in humans
- Disrupt enzymatic and transport processes
- Loss of energy production
- Loss of ion regulation
- Potential carcinogenesis
Arsenic naturally occurs as what compound?
- Arsenopyrite
- Most common arsenic containing material
What is the use for Arsenic?
- Used therapeutically to kill amoebas and parasites (in developing countries)
- Used for homicides and suicides
Local effect of Arsenic:
Dermatological
Name the systemic effects that Arsenic can have
- Vasodilation of capillaries
- GI effects (vomiting leads to fluid loss and CV collapse)
- CNS effects (peripheral neuropathies, organic encephalopathy)
- Headache
- Coma
- “Garlic Breath”
- Teratogenic
- Carcinogenic
How might one diagnose arsenic poisoning easily?
- Garlic breath
Able to diagnose due to smell of breath
Describe the mechanism behind Arsenic causing vasodilation of capillaries
Arsenic binds to contractile mechanism so cannot contract
The vasodilation effect of Arsenic is evident in what symptoms
- Rosy complexion
- Edema
- No wrinkles
What drug is used to treat Arsenic Poisoning
- Dimercaprol
* *other names: BAL (British Anti-Lewisite); dithioglycerol
What is the mechanism of action for Dimercaprol
Sulfhydryl group combines with ions of various heavy metals to form relatively stable, nontoxic, soluble chelates which are excreted in urine
T or F, Antimony resembles a metal and reacts as such
- False, It resembles a metal but does not react chemically as one.
- Highly toxic
Antimony can be used pharmacologically how?
Used for treatment of protozoan infections
Explain the small doses vs large dose response when exposed to Antimony
- Small: Headache, dizziness, depression
- Large: violent and frequent vomiting, diarrhea, muscle pain; death within a few days
What is the antidote to Antimony?
Dimercaprol
Describe Argyria and the symptoms associated with it
- Definition: Silver and silver-containing compounds become absorbed into the circulatory system and deposited into body tissues
- Symptoms
○ Bluish-grayish pigmentation of skin and mucous membranes - Permanent but not harmful
Argyria is often mistaken for what other toxicity?
Cyanosis
T or F, Argyria is permanent and can be harmful
False, Not harmful
Gold is used in what way pharmacologically
- Used in dentistry
- Used for treatment of rheumatoid arthritis
- Enhances collagen cross-linking
T or F, Pure gold is not toxic
True
Can Gold salts be toxic?
Yes, toxic to the liver and kidneys
Name the symptoms of Gold toxicity
- Dermatitis
- Metallic taste in mouth
- Proteinuria
- GI symptoms
- Aplastic anemia
What is the antidote to Gold toxicity?
- Dimercaprol
- penicillamine
Mercury was used in the 1800’s to help infants in what?
It was in teething powders for infants and to treat toothaches
What is Thiomersal
- Preservative found in vaccines
- It degrades to ethyl mercury
- Many thought this was link to autism with vaccines. No evidence to support this
Thiomersal has been removed from all vaccines or only in trace amounts for children under 6 years except one vaccine, what is the vaccine?
Inactivated influenza vaccine
Mercury can still be found in what OTC medicines?
- Topical antiseptics
- Stimulant laxatives
- Some dipaer rash ointments
- Eye drops
- Nasal sprays
With continuing exposure to mercury, a fine tremor develops. Describe the initial tremor:
Tremor initially involves the hands and later spreads to the eyelids, lips and tongue.
Effects experience from elemental mercury exposure:
- Neurotoxicity with neuropsychiatric effects
- Acute poisoning = pneumonitis
Effects of Inorganic mercury exposure:
- Corrosive to oral cavity and gut
- Kidney damage
What are the antidotes to mercury toxicity
- N-acetyl-D,L penicillamine
- Dimercaprol
- penicillamine
What biochemical effect does lead poisoning have on the body
- Enzyme inhibitor in the production of heme
○ Inhibits protoporphyrin IX
Accumulation of aminolevulonic acid = diagnostic
What symptoms and effects occur in individuals with lead poisoning?
- Accumulates in CNS
- GI, CV effects
- Lead lines are visible in teeth in children
What are the antidotes to lead poisoning
- Combination: calcium EDTA and dimercaprol
* The combo is better than either alone
What might be some effects on the body long-term exposure to lead
- Nephropathy
- Abdominal pain
- Delayed puberty in girls
- Reduced cognitive capacity
- schizophrenia
T or F, There is no evidence linking Cadmium to cancer
False, cadmium is known to cause cancer
Cadmium poisoning is similar to what other heavy metal toxicity
- Lead poisoning
- Inhibits same processes as lead
Acute problems from cadmium poisoning
Pulmonary problems
Chronic problems from cadmium poisoning
- Emphysema, COPD
- Also goes into bones = reasonably non-toxic here
Antidote to cadmium poisoning
Dimercaprol and calcium EDTA
What is the risk of the antidote used to treat cadmium poisoning
Treatment mobilizes cadmium to the kidneys = possible renal toxicity
What is the exposure to iron from?
From ferrous sulfate tablets used in the treatment of iron-deficiency anemia
Name the symptoms of iron exposure
- GI irritation
- Pneumonitis
- Convulsions
- Coma
- Liver damage
Name the antidote to iron exposure
Deferoxamine
Mechanism of Deferoxamine
- Complexes with trivalent ions (Ferric ions) to form ferrioxamine, which is removed by the kidneys
Symptoms to Aluminum exposure
- Pots and pans senility
- Concern for assoc. with Alzheimer’s disease
- End stage renal failure
Antidote for aluminum exposure
- Deferoxamine
- Aluminum chelating agents are given to reduce amount
How might one get nickel exposure:
Exposure from electronic, steel and mining industries
Symptoms of nickel exposure
- Dermatitis
- Nasal and respiratory cancer
Antidote for nickel exposure:
Diethylthiocarbamate trihydrate
Requirements for Heavy Metal Antagonists used as antidotes
- Water solubility
- Resistant to metabolic degradation
- Small size (so excreted by kidney)
- Chelate is stable at physiological pH
- Chelate is less toxic than the ion
- Bind the toxic metal better than it binds Ca+
- *If not, risk for calcium deficiency
Dimercaprol is an antidote used in what toxicities?
- Arsenic
- Antimony
- Gold
- Mercury
Calcium disodium edelate (EDTA) is an antidote used in what toxicities?
- Lead
- Cadmium
Penicillamine has what function and is used as an antidote to what toxicities?
- Used long term to clear bone, skin and keratinized tissues of arsenic, antimony
- Gold
- Mercury
Deferoxamine is an antidote used for what toxicities?
- Iron
- Aluminum
