Medicinal Inorganic Chemistry 2

Question 1

What is heavy metal poisoning?

Answer 1

Toxic accumulation of heavy metals in the soft tissues of the body

Question 2

What are heavy metals?

Answer 2

Chemical elements which have a specific gravity (a measure of density) at least 5 times that of water
e.g. lead, mercury, arsenic

Question 3

Name 3 heavy metals which are required in the body in small amounts

Answer 3

Zinc
Copper
Iron

Question 4

How do heavy metals cause problems in the body?

Answer 4

Compete with and displace essential minerals (e.g. zinc, copper, calcium) and interfere with organ system function

Question 5

List 3 contact sources of heavy metals

Answer 5

Industrial work
Agriculture
Children playing in contaminated soil

Question 6

List 4 symptoms of heavy metal poisoning

Answer 6

Nausea
Vomiting
Diarrhoea
Stomach pain
In severe cases patients exhibit obvious impairment of cognitive, motor and language skills

Question 7

How is heavy metal poisoning diagnosed?

Answer 7

Blood and urine tests
Hair and tissue analysis
X-ray

Question 8

How is heavy metal poisoning treated?

Answer 8

Chelation therapy

Question 9

What is chelation therapy?

Answer 9

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

Question 10

What is a chelating agent?

Answer 10

A substance whose molecules can form several bonds to a single metal ion

Question 11

Name 4 chelating agents

Answer 11

EDTA
Dimercaprol (BAL)
Penicillamine
Dimercaptosuccinic acid (DMSA)

Question 12

Explain the mode of action of chelation therapy

Answer 12

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

Question 13

Define: Chelation

Answer 13

The formation of 2 or more co-ordinate bonds between a polydentate ligand and a single atom

Question 14

Define: Polydentate ligand/chelator/chelating agent

Answer 14

A single ligand which has more than 1 atom which can bind to the central atom in a co-ordinate complex

Question 15

Define: Denticity (k)

Answer 15

The number of donor groups in a single ligand that bind to a central atom in a co-ordinate complex

Question 16

What does it mean if a ligand has a denticity of 1?

Answer 16

The ligand is monodentate and only 1 co-ordinate bond is formed from the ligand to the metal is formed

Question 17

What does it mean if a ligand has a denticity of 2?

Answer 17

The ligand is bidentate so 2 co-ordination bonds are formed from the ligand to the metal

Question 18

How does EDTA act as a chelating agent?

Answer 18

Binds to metals via 4 carboxylate (O=C-O(-))and 2 amine groups (N)

Question 19

List 3 clinical uses

Answer 19

Acute hypercalcemia
Mercury poisoning
Lead poisoning

Question 20

How is EDTA used to measure kidney function (GFR)?

Answer 20

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

Question 21

How is EDTA used to collect blood?

Answer 21

EDTA strongly and irreversibly chelates calcium to prevent blood from clotting

Question 22

How does Dimercaprol (BAL) work?

Answer 22

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

Question 23

What are the risks associated with administering Dimercaprol (BAL)?

Answer 23

Dimercaprol (BAL) is itself toxic = narrow therapeutic range
Tendency to concentrate arsenic in some organs
Administration by painful intramuscular injection
Multiple side effects

Question 24

List the 4 most common adverse effects of Penicillamine

Answer 24

Bone marrow suppression
Anorexia
Vomiting
Diarrhoea

Question 25

What is Dimercaptosuccinic acid (DMSA)?

Answer 25

Modified version of Dimercaprol (BAL)
Can cross BBB to extract heavy metals from the brain
Replaced BAL & EDTA to become 1st line treatment