A simple presentation for UG medical and paramedical students for understanding Diagnostic agents and Radio contrast media

1. Diagnostic agents
Radio-Contrast Media
Dr. Sachin Gupta
2nd year PG
Department of Pharmacology

2. Introduction
Agents which are used in the diagnosis
of diseases.
Can be classified under two types-
1. Agents used for radiographic procedures
2. Non-radiographic agents

3. Radiographic procedures
• Agents used for radiographic procedures
can be :-
a) Radiopaque or Radiocontrast media
b) Radionuclides
c) Miscellaneous agents

4. Radiopaque or Radiocontrast
Media
• These are chemical substances which
cannot be penetrated by X-rays.
• They absorb radiation and provide a
shadow of positive contrast due to
density difference.
• Used to enhance the images obtained
from visualization techniques such as X-
ray imaging, magnetic resonance imaging

5. Radionuclides
• They emit radiations
• Commonly used are-
 I131 , to study thyroid function.
 Human serum albumin I131 , is used for
determination of plasma volume and brain
scanning
 Tc99 , for scanning of bone, brain, heart and
kidney.
 Thallium 201 for scanning the myocardium in
investigation of acute M.I.

6. Miscellaneous agents
• They neither emit nor absorb radiation
but provide a shadow of negative
contrast.
• Ex-Air & Co2 are used for
hysterosalpingography.
• When both Gas and CM are used
together, the procedure is called Double
Contrast.

7. Radiopaques or Contrast
media (CM)
They can be divided into two major
categories-
a) Non iodinated, insoluble , inorganic
compounds
• Cannot be given parenterally
• Ex- BaSo4 have established use in G.I.T.
radiography.

8. b) Iodinated organic compounds- these can
be given orally as well as parenterally.
 soluble type
 oil type
 suspension type

9. Why CMs are Iodinated
• Absorption coefficient for any element is
directly related to the atomic no.
• Elements' having high atomic no. are either
radioactive or they form salts which provide toxic
ions after ionization.
• Iodine is a nonmetal having sufficiently high
atomic no. and it can be easily incorporated into
an organic compound in the form of covalent
iodine which is nonionisable and hence least
toxic.

10. Soluble Type Iodinated CMs
a) Triiodobenzoic acid derivatives
I. Ionic- Monomeric CMs
II. Ionic- Dimeric CMs
III. Non-Ionic Monomeric CMs
IV. Non-Ionic Dimeric CMs
b) Aliphatic acids with iodinated phenyl ring-
Iopanoic acid.

11. I. Ionic- Monomeric CMs
• All these CM are 2,4,6- triiodobenzoic acid
derivatives
• Available as sodium or meglumine salts
• Eg. Metrizoate, Iothalamates, Iodamides
• Preferably used in Urographic Procedures

12. I. Ionic- Monomeric CMs
• Sodium salts- more toxic, less viscous,
exclusively used for urographic
procedures.
• Meglumine salts- less toxic, more
viscous, strong osmotic diuretic
exclusively used for cerebral and
peripheral angiographies.
• Mixture of salts used for cardiac and aortic
angiography.

13. Disadvantages of Ionic-
Monomeric CMs
• High incidence of adverse effects because
of high osmolality
• 3 iodine atoms for 2 ionic species
• 3:2

14. What is Osmolality?
• It depends upon no of ions a molecule can
furnish in a given weight of solvent
• Thus NaCl has more osmolality than glucose
since it furnishes two ions (Na+, Cl-) in solution
than glucose which is non-ionic
• Like NaCl, these ionic-monomeric CM furnishes
two ions in solution triiodobenzoic acid (anion) &
Na+ or meglumine (cation)
• Iodine: Ionic ratio is 3:2

15. II. Ionic- Dimeric CMs
• Osmolality of CM solution can be reduced
by combining two triiodobenzoic acid
monomer into one molecule thereby
having 6 Iodine molecule for 2 ions.
• 6:3 or 2:1
• Eg. Iocarmate, iodipamide, ioglycaemic
acid
• Most suited for cholangiography,
cholecystography, hysterosalpingography

16. III. Non-Ionic Monomeric CMs
• The osmolality of CM, for a required
radiodensity can also be reduced by using
non-ionic monomeric CM.
• Eg. Iohexol, Iopromide
• 3:1
 urographic procedures
 cerebral, peripheral, cardiac and aortic
angiographies

17. IV. Non-Ionic Dimeric CMs
• Till date, the best ratio of radiodensity to
osmolality
• 6:1
• Eg. Iotrolan, iodixanol
• Least toxic, excellent contrast media
• Uses :-Myelography,
hysterosalpingography, cholecystography
and arthrography

18. Adverse reactions to CM
1. Adverse reactions due to osmolality
2. Adverse reactions of unknown etiology
3. Miscellaneous adverse effects

19. 1. Adverse reactions due to
osmolality
a. Rapid injection of hypertonic CM leads to rapid
increase in plasma osmolality causing fluid shift
from extravascular spaces to blood causing
hypervolumemia and erythrocyte damage.
b. Left ventricular distress due to
hypervolaemia.
c. Hyperosmolarity also leads to endothelial
damage of the capillary bed of the injected
artery, may also involve damage to BBB.

20. 1. Adverse reactions due to
osmolality
d. Feeling of warmth and discomfort is
due to vasodilation due to:-
i. Inhibition of acetylcholine esterase
enzyme
ii. Release of vasoactive substance like
histamine, serotonin from mast cells
iii. Release of K+ after crenation of RBCs

21. 2. Adverse reactions of
unknown etiology
• Anaphylactic-Allergy reactions
• Fever, chills, rigor, urticaria and even
cardiac arrest.
• Patients at increased risk are those with
H/O asthma, or allergy, adrenal
suppression, heart disease, and previous
reaction to CM.

22. 3. Miscellaneous Adverse
Effects
a) Tetany can occur as they decrease Ca2+ and
Mg2+
b) Renal toxicity if there are predisposing factors
like dehydration and preexisting renal damage,
risk greater with ionic CM than non-ionic CM.
c) Thromboembolism is a dreaded complication in
angiographic procedures.

23. Toxicity rank order
Ionic- Monomeric CMs
>Ionic- Dimeric CMs
>Non-Ionic Monomeric CMs
>Non-Ionic Dimeric CMs

24. Drug interactions
• CMs interfere with Thyroid function tests
• CMs inhibit enzyme aldehyde dehydrogenase
producing reaction after consuming alcohol.
• Cholestyramine has high affnity for oral
cholecystographic agents thus interferes with
cholecystography
• Use of both Oral and I/V cholecystographic
agents together should be avoided.

25. Contraindications
1. Cholecystographic agents are contraindicated
in impaired hepatic functions.
2. Iopanoic acid iodipamide are contraindicated in
pregnancy as they cause congential
hypothyroidism in fetus.
3. Oral cholecystographic agents should be
avoided in lactating mothers.

26. Contraindications
4. Sodium salts of CM should be avoided in
hypertensive patients.
5. Most GIT disorders interfere with absorption of
Oral cholecystographic agents.
6. Iocarmate, ioxaglic acid should be avoided in
epileptic patients

27. Contraindications
7. Nonionic CMs should be avoided in pts of
Polycythaemia because of risk of thrombus
formation and embolism.
8. Neonates, aged and diabetics are at special
risk for adverse effects if they are dehydrated.
9. All CMs should be avoided in
hyperthyroidism, being iodinated compounds
may precipitate thyroid storm

28. Current Status and Choice
of CM

29. Renal Tract
• For urography, CM should be small, highly
water soluble and with low protein binding
so that glomerular filtration is facilitated.
• CM are given by I/V route so as to
achieve high conc in the urinary tract from
the start
• CM having low osmolality such as
ionic-dimeric, nonionic-monomeric,
nonionic-dimeric are preferred.

30. Gall Bladder & Bile Duct
• CM should be preferentially excreted in
bile in sufficient concentration
• For oral cholecystography, CM is given
after fatty meal to enchance absorption
and to promote adequate visualisation
• For I/V cholecystography, mostly ionic-
dimeric are used( ex-iodipamide)

31. GIT Radiography
• CM should not be absorbed but should
form an even homogenous coat on the
GIT mucosa without interacting with GIT
secretions
• Commonly used CM is BaSo4

32. Cardiovascular System
CM should be
• Of low viscosity to facilitate rapid injection
• Of high radiodensity to counteract diluting
effect of blood
• Having anticoagulant effects
• Causing least pain on injection

33. Cardiovascular System
• Nonionic CMs carry risk for blood
coagulation, thrombin formation and
platelet aggregation compared to ionic CM
• Embolism is dreaded complication in these
procedures
• Low osmolal monoacidic dimer (Ioxaglic
axid) preferred.

34. Thank You
Have a nice day