Metals in Medicine I - III Flashcards
What is a transition metal?
in groups 3-12 in periodic table
presence of d orbitals
What is paramagnetism?
is defined as the phenomenon whereby some materials show magnetic properties only once they are exposed to a magnetic field. Outside this magnetic field, no magnetic properties are seen. This is in contrast to ferromagnets, which show magnetic properties independent of the environment.
Define Coordination complexes?
are defined as chemical structures that consist of a central atom or metal ion, and the surrounding molecules or anions called the ligands
Why use transition metals in medicine? (4)
- DNA deformation
- Photodynamic Therapy (PDT)
- Magnetic Resonance Imaging (MRI)
- Radiopharmaceuticals for Imaging and Therapy
What group are the coinage metals and what are their features?
Group 11
Relatively inert, corrosion-resistant metals
excellent conductors of heat and electricity
How is Copper involved in a medical context?
Copper and the human body
Wilson disease
Wound healing
What can copper do in the body in excessive amounts?
Absorbed (50%) in GI tract Processed in liver transported to peripheral tissue Binding to glyco-proteines and albumin Excessive copper excreted via bile and faeces
Define cuproenzymes and some examples
Copper–dependant enzymes
e.g.
Lysyl oxidase: cross-linking collagen and elastin (formation of blood vessels and heart)
Ceruloplasim: oxidation of ferrous to ferric ion
Cytochrome c
Superoxide dismutase
What forms of copper are present in the body?
Cupric (Cu2+) dominant form in human body compared to cuprous form (Cu+)
What is Wilson Disease?
Genetic, inherited
excessive copper built in body
What is the treatment for wilson disease?
Chelation therapy: BAL, D-penicillamine
Zinc supplementation
Liver transplant
What is the role of Glycyl-L-histidyl-L-lysine - Cu(II)?
GHK-Cu(II):
Anti-inflammatory: protects tissue from oxidative injury after damage
Activator for wound healing as activates tissue remodelling
Where is GHK secreted from?
Tripeptide- Secreted by mast cells in the skin
What is Silver used for in a medical context? (3)
- Water disinfectant
- Silver nitrate (AgNO3) – wart treatment
- Silver(I) sulfadiazine- antiseptic
What % silver nitrate does wart treatment contain?
40%
What are warts caused by?
Papilomavirus
What type of burns is silver (I) sulfadiazine used on? What does it do?
2nd and 3rd degree burns
It prevents the growth of a wide array of bacteria, as well as yeast, on the damaged skin.
What is the proposed mode of action for silver based compounds?
Oliogodynamic effect:
Ag damages irreversibly key enzymes (lactate dehydrogenase and glutathione peroxidase) in the cell membranes of pathogens
Enzymes precipitation / inactivation (bacteria but not viruses)
What is the mode of action of silver dressing?
Silver ions bind to the DNA of bacteria and bacterial spores, thus reducing their ability to replicate
How are Ag+ ions released from the dressing?
released from the dressing through oxidation when the silver atoms come into contact with fluid.
What causes Argyria?
Caused by a build up of colloidal silver in the body.
bluish-gray discolouration of the skin
What is the electron configuration of Gold?
5d106s1
Whats the medical use of Gold?
Historic use
Treatment of rheumatoid arthritis
What is Chrysotherapy?
The treatment of certain diseases, especially rheumatoid arthritis, with gold compounds
What are the TWO types of groups used in Chrysotherapy?
- Au(I)thiolates
Solganol
(Di)sodium aurothiomalate
Aurothiopropanolsulphonate
Sodium gold 4-amino-2-mercaptobenzoic acid
- Auranofin
What is the main toxicity concern with sodium aurothiomalate?
Myelosuppression (bone marrow suppression)
What monitoring is required with sodium aurothiomalate?
with full blood counts (FBC) and urine tests before each dose!
What is the dose regimen with sodium aurothiomalate?
Start therapy with 10mg test dose to exclude hypersensitivity
Follow with 50mg IM weekly injections until response occurs
Benefit not expected until patient receives 300-500mg (6-10 weeks)
Once disease is controlled, interval between doses can be lengthened gradually to monthly injections and continue for up to 5 years of complete remission
At what dose should treatment with sodium aurothiomalate be discontinued if there is no response?
1g
Summary Au(I)thiolates?
Linear
Mostly two coordinated
Au compounds are water soluble => intramuscular injection as preferred way of administration (50 mg/week).
Disadvantage: required frequent visit to the doctor.
3 - 6 months before gold injections have an effect on RA symptoms.
Side effects: accumulation in organs (kidneys, liver), resulting in nephrotoxicity.
What are the side effects of gold injections? (6)
Discoloration of skin.
Nausea and vomiting.
Metallic taste
Gold injections cause mouth sores in about a third of patients
Itching and rash (can be severe in some patients).
Kidney damage and decreased white blood cell count (rare) – bone marrow damage.
What is Auranofin?
2nd gen drug
Lipophilic => administered orally (doses 3-6 mg/d
What is the dose regimen of Auranofin?
Less effective than sodium aurothiomalate
Given as 6mg/day in two doses initially, then one dose if tolerated, for 6 months
If no response, increase after 3 months to 9mg/day in three doses for a further 3 months
If there is no response with Auranofin when should it be discontinued?
After 6 months
When should gold therapy be discontinued?
in case of presence of blood disorders (sudden and fatal), GI bleeding or unexplained proteinuria (>300mg/litre)
What is the mode of action of Gold? Poorly understood (4 steps)
1) In the blood stream, Au-drugs form a complex with albumin
2) Au(I)/albumin complex arrive at the site of action => synovial cavity
3) Au(I) may enter the cell via (second) thiol exchange reaction with membrane transport proteins.
Auranofin: taken up rapidly –>Thiol-Shuttle Model:
4) Once absorbed in the cell, Au(I) might interact with mitochondria inducing cell apoptosis.
