Clinical uses of Lanthanides Flashcards
What are lanthanides, where can you find them on periodic table and what uses do they have
Rare earth elements
15 elements with atomic numbers 57 to 71 from lanthanum to lutetium
f- block elements: filling 4f electron shell (except lutetium which is a d block lanthanide)- f shell can contain 14 in total
Variety of uses (lasers and glow in the dark materials)
What are the clinical uses of lanthanides
Most trivalent lanthanide ions have unpaired f electrons (except lanthanum and lutetium)
Magnetic moment of varying strength
Gd3+ (Gadolinium) has max number of unpaired electrons (7- half full) all electrons have a parallel spin
Important for use as contrast agents in MRI scan- blood and vascular containing regions of body
Magnetic moment of varying strength
Describe paramagnetism
Define: A form of magnetism which occurs only in the presence of an externally applied magnetic field
Paramagnetic materials are attached to magnetic fields
Unlike ferromagnets (standard bar magnet) which are attracted to magnetic fields, paramagnets do not retain any magnetisation in the absence of an externally applied magnetic field
Many elements (or ions) are paramagnetic but this doesn’t mean they are ferromagnetic, oxygen for instance
Occurs when there are electrons that are unpaired, all it means is oxygen will respond to magnetic field
1s2, 2s2, 2p4
Describe what is MRI and how it works
Magnetic Resonance Imaging
Non invasive method of examining tissues that is normally used for medical imaging to demonstrate pathological or physiological alterations of living tissue
Mechanism: relies on the relaxation properties of excited hydrogen nuclei in waters and lipids
When object is imaged, it is placed in a powerful, uniform magnetic field, the atomic nuclei show a different behaviour according to their environment
Relaxation times are different for protons in water in comparison to lipids- allowing contrast and can see difference between blood and organs
Big NMR machine essentially
Amount of blood flow to region of brain increases amount of blood to each region changes amount of iron in brain
Describe contrast agents use in MRI and give examples of them
MR image contrast can be further enhanced by administration of suitable MRI contrast agents
The presence of contrast agents causes dramatic variations of the water proton relaxation rates and allows to add physiological information to the impressive anatomical resolution commonly obtained in the uncontested images
Examples: Gd (III)- Gd3+ is ideal because of its high paramagnetism (7 unpaired electrons)
Describe the toxicity of gadolinium and its pharmacokinetic properties
Gd (III) does not have any physiological use in mammals
Administration as a free ion is extremely toxic even at low doses of 10 micromol/kg
Necessary to use ligands that form stable chelates with the lanthanide ion
Pharmacokinetic properties:
Distribution in extracellular fluid
Elimination via glomerular filtration
Give examples of products that contain gadolinium
Gadopentetic acid- most wide spread example
Gadoteric Acid
Describe what is a chelate
- Formation or presence of bonds (or other attractive interactions) between two or more separate binding sites within the same ligand and single central atom
- Molecular entity in which there is chelation (and the corresponding species) is a chelate
What are the terms bidentate, tridentate, tetradenate, multidentate used to indicate
Number of potential binding sites of the ligand, at least 2 of which must be used by the ligand to form a chelate
Give an example of a chelate and non-chelate from the platinums
Cisplatin- not a chelate
Oxaliplatin- chelate
What is the use of Gadopentetic acid and how do you administer it
Used for diagnostic use only as a paramagnetic contrast medium in cranial, spinal and whole body MRI
Administration:
- Given intravenously as meglumine gadopentetate
- Used for evaluation of renal function
- Given by intra-articular injection for arthography
- Used orally and rectally in imaging of the GI tract
Contrast enhanced MRI can begin after administration medium
What is the dosage of gadopentetic acid and pharmacokientics
Dosage:
0.2mL Magnevist per kg body weight is sufficient in provision of diagnostically adequate contrast
Pharmacokinetics:
Rapidly distributed into extracellular space after IV injection
Elimination t1/2= 1.6 hours
Not metabolised
90% of dose is excreted in urine within 24 hours
Does not appear to bind to plasma proteins
Small amount in breast milk
Removed mainly by haemodialysis (Gadopentetate)
What is the use of gadoteric acid and how is it administered
Similar to gadopentitic acid that:
distributes mainly into extracellular fluid
Does not cross BBB
Used in imaging of cranial and spinal structures and of whole body and in magnetic resonance angiography
Administration:
Given IV as meglumine salt
Solution containing meglumine gadoterate 376.9mg/mL (0.5 mmol/L)
What is the dose of gadoteric acid and pharmacokinetic properties
Dose:
Adults + child = 0.2mL/kg (0.1mmol/kg) by IV injection
Second dose up to 0.4 mL/kg (0.2mmol/kg) given within 30 minutes if necessary
Angiography: dose of 0.1 to 0.2mL/kg (0.05 to 0.1 mmol/kg) may be given, repeated if required
Pharmacokinetic: Gadoterate is distributed into the extracellular space after IV injection Not bound to plasma proteins t1/2 = 1.5 hours Not metabolised 90% excreted in urine within 24 hours
What are the adverse effects of MRI contrast media
- Nausea and vomiting- known possible adverse reactions of all extracellular MRI contrast media- should refrain from eating 2 hours prior to investigation
- Headache and dizziness
- Transient sensations of heat or cold
- Taste disturbances
- Rare: convulsions, hypotension, allergic or anaphylactoid reactions and shock
- Nephrogenic systemic fibrosis may occur rarely in patients with renal impairment
