Part 1: L3, Angiographic Contrast Agents II

Question 1

Define hydrophilicity and lipophilicity:

Answer 1

• Hydrophilicity: Preference for aqueous solvents
• Lipophilicity: The preference for fat-like (lipid) organic solvents

Question 2

Partition coefficient

Answer 2

Partition coefficient = conc. of drug in organic phase / conc. of drug in aqueous phase
* Often used to produce logP value

Question 3

How is toxicity typically derived?

Answer 3

• Protein-binding
• Histamine release (allergic response)
• Hydrophilicity and lipophilicity

Question 4

How do non-ionic contrast media typically behave in solution?

Answer 4

• Seem to be too hydrophilic to make differences in partition coefficient
• hydrogen bonding causes problems with biological molecules and membranes

Question 5

Cholegraphic media and protein binding:

Answer 5

• Cholegraphic media derive their ability to be excreted and concentrated in the bile rather than to be rapidly eliminated in the kidneys, because of their very high degree of protein-binding
• Cholegraphic agents (which are also ionic) have a higher chemotoxicity than the urographic contrast media

Question 6

LD50

Answer 6

Amount of contrast medium that will kill 50% of a group of treated animals (usually expressed as g of iodine/kg of body weight)
-> modern contrast media typically have a very high LD50, making them relatively safe

Question 7

Types of adverse reactions:

Answer 7

• Dose dependent - mostly due to physiochemical effects of the contrast medium such as osmolality (include heat, pain, vasodilation, cardiac depression and hypotension)
• Dose-independent - nausea, vomiting, allergy-like etc

Question 8

Issues with more viscous agents:

Answer 8

• Force required limits rate at which the agent can be injected -> slow flow can lead to inadequate visualisation of a vessel by reducing the concentration
• Warming the contrast medium can help but is inconvenient
• A mechanical pump to inject the contrast medium also helps; high injection pressures may lead to unacceptable stress on catheters, connecting-tubes or connectors etc

Question 9

How is iso-osmolality to plasma achieved?

Answer 9

• Saline is added to achieve correct iodine concentration -> low toxicity * Non-ionic dimeric agents also have a low partition coefficient due to large number of hydroxyl groups (also contributes to low toxicity)

Question 10

How may choice of contrast medium be made by clinicians?

Answer 10

• Often based on high-risk patients (25%
• Infants, elderly have problem of fluid balance
• Diabetics
• Patients with cardiac or renal impairments
• Asthmatics
• History of allergy and adverse reaction
• Clinicians can thus decided on agent using values of osmolality and viscosity