Medicinal Inorganic Chemistry 2 Flashcards
What is heavy metal poisoning?
Toxic accumulation of heavy metals in the soft tissues of the body
What are heavy metals?
Chemical elements which have a specific gravity (a measure of density) at least 5 times that of water
e.g. lead, mercury, arsenic
Name 3 heavy metals which are required in the body in small amounts
Zinc
Copper
Iron
How do heavy metals cause problems in the body?
Compete with and displace essential minerals (e.g. zinc, copper, calcium) and interfere with organ system function
List 3 contact sources of heavy metals
Industrial work
Agriculture
Children playing in contaminated soil
List 4 symptoms of heavy metal poisoning
Nausea Vomiting Diarrhoea Stomach pain In severe cases patients exhibit obvious impairment of cognitive, motor and language skills
How is heavy metal poisoning diagnosed?
Blood and urine tests
Hair and tissue analysis
X-ray
How is heavy metal poisoning treated?
Chelation therapy
What is chelation therapy?
Chelating agent specific to the metal
Can be administered orally, intramuscularly or IV
Agent binds to metal ion so it can be excreted in urine
Effective for lead, mercury and arsenic but not for cadmium
What is a chelating agent?
A substance whose molecules can form several bonds to a single metal ion
Name 4 chelating agents
EDTA
Dimercaprol (BAL)
Penicillamine
Dimercaptosuccinic acid (DMSA)
Explain the mode of action of chelation therapy
Chelating agents surrounds and binds to the metal in the body’s tissues
Formation of a complex
Complex is then released from the tissue to travel in the bloodstream
Complex is filtered out of the body via the kidneys and excreted in the urine
Define: Chelation
The formation of 2 or more co-ordinate bonds between a polydentate ligand and a single atom
Define: Polydentate ligand/chelator/chelating agent
A single ligand which has more than 1 atom which can bind to the central atom in a co-ordinate complex
Define: Denticity (k)
The number of donor groups in a single ligand that bind to a central atom in a co-ordinate complex
What does it mean if a ligand has a denticity of 1?
The ligand is monodentate and only 1 co-ordinate bond is formed from the ligand to the metal is formed
What does it mean if a ligand has a denticity of 2?
The ligand is bidentate so 2 co-ordination bonds are formed from the ligand to the metal
How does EDTA act as a chelating agent?
Binds to metals via 4 carboxylate (O=C-O(-))and 2 amine groups (N)
List 3 clinical uses
Acute hypercalcemia
Mercury poisoning
Lead poisoning
How is EDTA used to measure kidney function (GFR)?
In combination with chromium
Administered via IV
Its filtration into urine is monitored
Cr-EDTA’s sole way out of the body is via glomerular filtration as it is not secreted or metabolised in any other way
How is EDTA used to collect blood?
EDTA strongly and irreversibly chelates calcium to prevent blood from clotting
How does Dimercaprol (BAL) work?
Heavy metals act by chemically reacting with adjacent sulfhydryl residues on metabolic enzymes - creates a chelate complex that inhibits the affected enzyme’s activity
Dimercaprol (BAL) competes with sulfhydryl groups for binding the metal ion, which is then excreted in the urine
What are the risks associated with administering Dimercaprol (BAL)?
Dimercaprol (BAL) is itself toxic = narrow therapeutic range
Tendency to concentrate arsenic in some organs
Administration by painful intramuscular injection
Multiple side effects
List the 4 most common adverse effects of Penicillamine
Bone marrow suppression
Anorexia
Vomiting
Diarrhoea
What is Dimercaptosuccinic acid (DMSA)?
Modified version of Dimercaprol (BAL)
Can cross BBB to extract heavy metals from the brain
Replaced BAL & EDTA to become 1st line treatment
