it describes and states different radiopaque agent drugs

1. Medicinal chemistry
Presentation on
Diagnostic agent:
Radiopaque agents and classification
[pharmacy department]
By tujar kaso(b pharm)

2. Diagnostic agents
 Diagnostic agents are the compounds used to detect impaired
functions of the body organ or to detect abnormalities in tissue
structure.
 Usually they have no therapeutic value. so they do not used in the
treatment of any disease.
 Diagnostic agents are classified in to three heads:
1.radiopaques(x ray contrast media)
e.g ioxaglate ,diatrizoate sodium
2. Cpds used to test functional capacity
A. agents used to test kidney function
e.g indigo carmine
B. agents used to test liver function e.g rose Bengal

3. C. miscellaneous agents: e.g fluorescein sodium,
3. Cpds modifying physiological function: e.g alcohol
Radiopaque(x ray contrast media):-
 Radiopaque agents are drugs which have the ability to absorb x-
rays.
They are opaque to x-ray radiation so they produce lighter or
whiter shadow on the x-ray film.
 radiopaque agents include organic and inorganic compound
which have the property of casting a shadow on x-ray film.

4. barium sulphate is the most inorganic compound that often used as
suspension in examination of GIT.
 the inorganic iodine compound which are ionized are generally
toxic and they are not used clinically. But iodinated organic
compounds which contain iodine bonded covalentely with carbon
don’t release iodine ions readly and are less toxic.
iodinated radiopaque agents
They contain iodine, which blocks x-rays. Iodine is the only
chemical element which combines three properties essential for the
production of a successful CM:-
 High contrast density
 low toxicity
 chemical behavior which allows firm binding to
the highly variable benzene molecule

5. structure of iodinated radiopaque
 most clinically used radiopaque contains iodine and all iodinated
radiopaque contrast agents are derivative of benzoic acid. All the
currently used iodinated contrast media are chemical modifications of a
2,4,6-triiodinated benzene ring.

6. The carbon atoms on a benzene ring are numbered clockwise from 1 to
6. Benzoic acid is produced by introducing an acid group at position 1
on the benzene ring.
 This acid group permits the formation of salts or amides, which
influence water solubility. 2,4,6-triiodobenzoic acid is obtained by
introducing iodine atoms at positions 2, 4, and 6 on the ring.
 Triiodo benzoic acid is made less toxic and less lipophilic (fat-
soluble) by introducing side chains at positions 3 and 5.
 The hydrogen atoms in the acid group can be replaced by a cation,
such as sodium (Na) or meglumine, in which case the contrast agent is
ionic.
 If the hydrogen atom in the acid group is replaced instead by amine-
carrying hydroxyl groups, then the compound is nonionic.

7.  When there is only one benzene ring in the compound, the
contrast agent is a monomer; when there are two benzene rings
in the compound, the contrast agent is a dimer.
 The compound with 'two benzene rings contains twice the
amount of iodine in the molecule compared to the monomer.
Monomeric and dimeric contrast agents can be ionic or nonionic,
depending on which substitutions are made at the acid group.

8. Structural activity relationship of iodinated radiopaque agents:
 The basic structure of iodinated contrast agents is the benzene
ring (Fig. 1), with its attached iodine atoms. The remaining
components are the acid group and organic substitutes which
influence excretion and toxicity.

9. All the currently used iodinated contrast media are chemical
modifications of 3,5-diamino-2,4,6-triiodobenzoic acid.
 all iodinated radiopaque agents contain organic amine salt
group at position of R1 and R2 because amine groups are less
toxic and more water soluble.

10. 3,5-diamino-2,4,6-triiodobenzoic acid is, however, a rather
unstable compound and has therefore proved unsuitable as X-ray
contrast agent but acetylation of this compound yields 3,5-
diacetamido-2,4,6-triiodobenzoic acid which is more stable.
 The hydrogen atoms in the acid group can be replaced by a
cation, such as sodium (Na) or meglumine, in which case the
contrast agent is ionic.
 If the hydrogen atom in the acid group is replaced instead by
amine-carrying hydroxyl groups, then the compound is nonionic.
 Elimination of contrast agents is dependent on organic
substitutions of R1 and R2 position. If one of the organic
substituents is a hydrogen atom, then the compound is excreted
by the biliary system. If none of the organic substituents is a
hydrogen atom on the benzene ring, then the contrast is excreted
by the kidneys.

11. if there is an additional substitution of alkyl group on the amine
group on one of R position, there is a difference in the solubility
of the agents.
 If there is di substitution of alkyl. There is a decrease in
solubility of the agent. So N,N'-di-alkyl diacyl 3,5-diamino-2,4,6-
triiodo-benzoic acid are useful as X-ray contrast agents in fields
where insoluble compounds of high X-ray impermeability are
required.
 if there is mono substitution of alkyl in one of the amine group
increases te solubility also it has less toxicity. So N-mono alkyl-
3,5-diacylamino-2,4,6-triiodobenzoic acids, in particular the N-
methyl compound, are high water-solubility and, being of low
toxicity, are especially suitable as vascular X-ray contrast agents.

12. classification of iodinated radiopaque agent
 iodinated radiopaque agents are classified based on the:-
 ionic composition
Osmolar composition
Water solubility
viscosity
 Ionicity is the characteristic of a molecule to break up into a
positively charged cation and a negatively charged anion,
resulting in more molecules per kilogram of water and thus
increasing osmolality. Nonionic agents do not have this property
and hence are less osmolar.
 Ionic and nonionic contrast media may be monomeric or dimeric.

13.  In a solution, ionic monomers break up into their anion and
cation components (increasing osmolality), delivering 3 iodine
atoms (a 2:3 ratio of osmolar particles to iodine). ionic dimers
would deliver 2 ionic components per 6 iodine atoms (ratio, 1:3).
 Nonionic monomers do not break up in solution; a single
molecule delivers 3 iodine atoms (ratio, 1:3).
 a single nonionic dimer delivers 6 iodine atoms (ratio, 1:6).
Thus, nonionic dimers are the most ideal contrast agents as they
deliver the most iodine with the least effect on osmolality.

15.  based on the basis of osmolar composition iodinated radiopaque
agents are classified in to:-
High osmolar iodinated radiopaque agent
Low osmolar iodinated radiopaque agent
 iso-osmolar iodinated radiopaque agent
 Osmolality indicates the concentration of all the particles
dissolved in body fluid. Measures the number of molecules per
kilogram of water dissolved in.
 Osmolarity is a measure of the number of particles in a liter of
the liquid they are dissolved in.
high osmolar iodinated radiopaque agent
 these agents are monomeric salt of triiodide benzoic acid. The
iodine atom are attached at position 3,4,6 of the benzene ring
and position 1 has a cation, either sodium or methylglucamine.

16. these agents contain three iodine atoms for every two
osmotically active ions. These agents contain three iodine atoms
for every two osmotically active ions. All ionize monomers have
high osmolarity. E.g diatrizoate sodium
 they are hypertonic with an osmolality(>1500mosm) which is six
times higher than plasma(Normal values range from 275 to 295
mOsm/kg) , this in turn contribute to their side effect.

17. low osmolar iodinated radiopaque agent
 these agents have three atoms of iodine for each ion. Have a
ratio of 3:1,they are only two to three times of the osmolality of
plasma.
 these agents are either nonionic monomers or ionic dimers. And
produce less allergic side effect and are less nephrotic. E.g
ioxaglate, iopamidol, iohexol, ioversol.

18. iso-osmolar iodinated radiopaque agent
 contains nonionic dimer. this class of contrast agents has
osmolality similar to that of plasma.
They are nonionic dimer and contains six atoms of iodine per
dimer and has ratio of 6. iodixanol is the only agent in this class.

19.  In terms of viscosity, the larger the molecule, the more viscous
is the contrast agent.
 the most viscous contrast agents are the nonionic dimers, as
opposed to the ionic dimers and the nonionic monomers. The
least viscous are the ionic monomers.
 The viscosity, however, changes with temperature. The higher
the temperature, the less viscous the contrast becomes. For this
reason, nonionic contrast agents are warmed to body
temperature for intravenous or intraarterial injections, so as to
make the injection easier and more rapid.

20.  based on water solubility iodinated radiopaque agents are classified
in to two:
1.Water soluble iodinated radiopaque: contains agents like,
diatrizoate sodium, metrizamide. Given orally or through injection.
 they are mainly used for urography(examination of ureter, kidney) and
angiography(examination of arterial system).
 It is also used for visualizing of heart, lymph, and bile ducts.
2. water insoluble iodinated radiopaque agent: the agents are
practically insoluble so there suspensions are prepared. they are mainly
used for:
 cholecystography(examination liver, gall bladder),
bronchography(examination of bronchial tract).
 contains agents like propyliodone, iopanoic acid.

21. techniques of administration of iodinated radiopaque agents:
 the iodinated radiopaque agents are administered using two techniques:
1. In systemic procedure:- the agents are given orally or intravenously.
They are used in:-
A. in urography- to examine kidney
B. in cholecystography- to examine gall bladder
C. in roentgenography- to visualize parts the body like: urinary
tract, billary tract, blood vessels, etc.
2. In retrograde procedure:- the agents are introduced by mechanical
means. E.g introduced by catheter in to urinary tract through urethral
orifice.