Iodinated
Contrast Media
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POSITIVE CONTRAST MATERIAL: IODINATED
- diatrizoate, iothalamate, metrizoate
- monomeric salts of tri-iodinated benzoic acid with substituted
side-chains at positions 3 and 5; iodine atoms at 2,4 and 6;
cation at position 1.
- anion is the radiopaque portion but both the anion and cation
are osmotically active therefore the solution will be hypertonic
to plasma
- could be made isotonic to plasma but at this dilution the
iodine concentration would be only 6% and not useful as
contrast agent
- Side effects from ionic contrast agents
- Hypertonicity
- Main reason for side effects - 5-8x tonicity of plasma -
severe physical insult to body regardless of the nature of
the chemical injected.
- endothelial lesions in blood vessels - desiccation and
weakening to intracellular bonding, increased capillary
permeability and risk of thrombus formation
- damage to BBB: increased permeability of cerebral
capillaries results in toxic molecules affecting nerve cells
- RBC/blood flow: water drawn from RBC which becomes
deformed and rigid and may not be able to pass through
capillary beds - can cause thrombosis/ischemia esp. in brain
and myocardium
- cardiovascular effects: vasodilation both local and
generalized
- local effects: flushing, sensation of warmth,
discomfort
- generalized: hypotension
- in man, the effects are directly proportional to the
tonicity
- problems may be greater in patients with congestive
heart failure
- renal effects: diuresis usually induced in most patients
after IV injection due to increase in serum osmolality
- acute renal failure is unusual but well recognized
complication of these agents. Probably due to
hypertonicity and direct chemical toxicity to kidney
- predisposing factors: renal insufficiency,
dehydration, congestive heart failure, diabetes
mellitus, multiple myeloma
- side effects (human descriptions): nausea, vomiting,
fever, chills, faintness, headache, sneezing, perineal
discomfort, metallic taste
- Ionic charge
- effects on local electrolyte balance
- effect nerve conduction
- cardiac effect (esp. from high sodium load)
- Chemical toxicity
- inherently toxic molecule, esp. the sodium salt - cardiac,
hepatic, and renal disease patients are esp. susceptible to
increases in sodium
- peripheral vasodilation and other side effects are
increased when the sodium concentration increases
- methylglucamine (meglumine) salt is less toxic but has
increased viscosity which is why the two are often mixed to
reach a compromise between toxicity and viscosity
- occasional toxicity found from iodinated anion or free I
released
- toxicity may occur from protein binding - esp. enzyme
binding
- acetylcholinesterase inhibition is measured as an
indicator of toxicity
- toxicity inversely proportional to degree of hydrophilia
and in conventional agents the highly hydrophobic iodine
atoms are relatively exposed due to short side chains
- most sensitive organs are heart, brain and kidney
- effect on BBB from sodium cation and carboxyl group of the
anion as well as hypertonicity
- acute tubular necrosis can occur
- cardiotoxicity can be fatal
- Allergic/Anaphylactic reactions
- In humans, about 5% have some hypersensitivity reaction in
minutes or delayed by hours.
- Mechanism unknown but increased reactions in allergic or
asthmatic people and those with heart disease
- reactions range from sneezing - urticaria - pharyngeal -
cerebral - or pulmonary edema - bronchospasm - to fatal
cardiovascular collapse
- in man - 1/40,000 fatality rate
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- metrizamide, iopamidol, iohexol
- tri-iodinated substituted ring compound - do not dissociate in
solution so that hypertonicity is avoided. Side chains have been
altered to make molecule highly hydrophilic to increase
solubility without dissociation
- Increased ratio of iodine per osmotic particle (3:2 for ionic)
vs (3:1 for non-ionic)
- osmolality halved (non-ionic)
- actually reduced further by tendency for molecules to
aggregate in solution
- results in osmolality 1/3 of ionic contrast media and
decreased side effects
- Can be used for intravenous or intrathecal injections but due
to expense (about 10x ionic) usually reserved for myelography
- Image quality depends on iodine concentration and total iodine
delivered
- clarity/definition requires accumulation of contrast agent
- osmotic dilution of the low osmolar agents by body fluids
is much less and occurs more slowly than with hyperosmolar
agents resulting in sharper images for longer times
-
- Reduced tonicity: since most side effects are related to
hypertonicity, the change to nearly isotonic has
significantly decreased reactions in man - some studies
report dramatic decrease in side effects and discomfort
largely due to reduction in vasodilation and resultant
sensations of heat and flushing
- Myelography: cannot use ionic contrast media for
myelogrpahy so discovery of non-ionic in 1974 (metrizamide)
revolutionized this procedure. Newer agents (iopamidol and
iohexol) have even lower neurotoxicity
- Chemical toxicity: molecules are more hydrophilic due to
longer sidechains, shields the hydrophobic I atoms, no
sodium ions, decreased damage to BBB. Increased hydrophilia
means less tendency to cross cell membranes
- Decreased hypersensitivity reactions: fatal reactions in
man reported - 1/80,000 - probably most from decreased
osmolality and decreased cardiotoxicity
Fig. 2. The a,
osmolality (mOsm/kg water) and b, viscosity at 37 °C of
currently available iodinated contrast media. The values in the
bars show the iodine content (mg/mL). The ionic HO media are shown
in green, the ionic LO medium in red, the non-ionic LO media in
light green and non-ionic iso-osmolar media in light red.
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