Diatrizoate

{{Short description|Chemical compound}} {{Use dmy dates|date=September 2024}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | image = Diatrizoic acid.svg | image_class = skin-invert-image | width = | alt = Skeletal formula | image2 = Diatrizoic-acid-3D-spacefill.png | image_class2 = bg-transparent | width2 = | alt2 = Space-filling model | caption =

| pronounce = | tradename = Hypaque, Gastrografin, Iothalmate, others | Drugs.com = {{Drugs.com|cons|diatrizoate-injection}} | MedlinePlus = | DailyMedID =  | pregnancy_AU =  | pregnancy_AU_comment = | pregnancy_category= | routes_of_administration = | class = | ATC_prefix = V08 | ATC_suffix = AA01 | ATC_supplemental =

| legal_AU =  | legal_AU_comment = | legal_CA =  | legal_CA_comment = | legal_DE =  | legal_DE_comment = | legal_NZ =  | legal_NZ_comment = | legal_UK =  | legal_UK_comment = | legal_US =  | legal_US_comment = | legal_UN =  | legal_UN_comment = | legal_status =

| IUPAC_name = 3,5-Bis(acetylamino)-2,4,6-triiodobenzoic acid | C=11 | H=9 | I=3 | N=2 | O=4 | SMILES = CC(=O)NC1=C(C(=C(C(=C1I)C(=O)O)I)NC(=O)C)I | StdInChI = 1S/C11H9I3N2O4/c1-3(17)15-9-6(12)5(11(19)20)7(13)10(8(9)14)16-4(2)18/h1-2H3,(H,15,17)(H,16,18)(H,19,20) | StdInChIKey = YVPYQUNUQOZFHG-UHFFFAOYSA-N | density = | density_notes = | melting_point = | melting_high = | melting_notes = | boiling_point = | boiling_notes = | solubility = | specific_rotation = }}

'''Diatrizoate''', also known as '''amidotrizoate''', '''Gastrografin''', is a contrast agent used during X-ray imaging.<ref name=WHO2008/> This includes visualizing veins, the urinary system, spleen, and joints, as well as computer tomography (CT scan).<ref name=WHO2008>{{cite book | title = WHO Model Formulary 2008 | year = 2009 | isbn = 9789241547659 | vauthors = ((World Health Organization)) | veditors = Stuart MC, Kouimtzi M, Hill SR | hdl = 10665/44053 | author-link = World Health Organization | publisher = World Health Organization | hdl-access=free | page=316 }}</ref> It is given by mouth, injection into a vein, injection into the bladder, through a nasogastric tube, or rectally.<ref name=Ric2015/><ref>{{cite book| vauthors = Pollack HM | chapter = History of Iodinated Contrast Media | veditors = Thomsen H, Muller RN, Mattrey RF |title=Trends in Contrast Media |date=2012 |publisher=Springer Science & Business Media |isbn=9783642598142 |page=13 |chapter-url=https://books.google.com/books?id=Bun1CAAAQBAJ&pg=PA13|language=en|url-status=live|archive-url=https://web.archive.org/web/20170101002210/https://books.google.ca/books?id=Bun1CAAAQBAJ&pg=PA13|archive-date=1 January 2017}}</ref>

Relatively common side effects include vomiting, diarrhea, and skin redness.<ref name=Drugs2016>{{cite web|title=Diatrizoate Side Effects in Detail | work = Drugs.com |url=https://www.drugs.com/sfx/diatrizoate-side-effects.html |access-date=31 December 2016|url-status=live|archive-url=https://web.archive.org/web/20170101002605/https://www.drugs.com/sfx/diatrizoate-side-effects.html|archive-date=1 January 2017}}</ref> Other side effects include itchiness, kidney problems, low blood pressure, and allergic reactions.<ref name=WHO2008/> Diatrizoate is an iodinated ionic radiocontrast agent with high osmolality.<ref name=Ric2015>{{cite book| vauthors = Hamilton R |title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition |date=2015|publisher=Jones & Bartlett Learning|isbn=9781284057560|page=171}}</ref>

Diatrizoate was approved for medical use in the United States in 1954.<ref name=Drugs2016/> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref>

==Medical uses== {{clarify section|date=June 2019}} Diatrizoic acid may be used as an alternative to barium sulfate for medical imaging of the gastrointestinal tract, such as upper gastrointestinal series and small bowel series. It is indicated for use in patients who are allergic to barium, or in cases where the barium might leak into the abdominal cavity. It does not coat the stomach/bowel lining as well as barium, so it is not used commonly for this purpose.{{citation needed|date=June 2019}}

It is also used to treat ''Ascaris lumbricoides'' (roundworms).<ref name="Sood">{{cite book| vauthors = Sood S, Krishna A |title= Surgical Diseases in Tropical Countries|year=1996|url=https://books.google.com/books?id=kpxMrfCtUs8C&pg=PA72|access-date=11 August 2010|publisher=Jaypee Brothers Publishers|isbn=978-81-7179-444-7|pages=72–}}{{Dead link|date=July 2023 |bot=InternetArchiveBot |fix-attempted=yes }}</ref><ref name="ScheinRogers2010">{{cite book| veditors = Schein M, Rogers P, Assalia A |title=Schein's Common Sense Emergency Abdominal Surgery | vauthors = Kaushik R | chapter = Asia | chapter-url=https://books.google.com/books?id=BUdLUsbxTjQC&pg=PA391|access-date=11 August 2010|year=2010|publisher=Springer|isbn=978-3-540-74820-5|pages=391–|url-status=live|archive-url=https://web.archive.org/web/20170329153040/https://books.google.com/books?id=BUdLUsbxTjQC&pg=PA391|archive-date=29 March 2017}}</ref> Diatrizoate may not actually kill ''Ascaris'', but instead it promotes {{clarify span|shifting of fluid in the bowel lumen due to its osmotic properties|date=June 2019}}, so may relieve intestinal obstruction caused by impacted ''Ascaris''.<ref name="pmid12131078">{{cite journal | vauthors = Choi HK, Chu KW, Law WL | title = Therapeutic value of gastrografin in adhesive small bowel obstruction after unsuccessful conservative treatment: a prospective randomized trial | journal = Annals of Surgery | volume = 236 | issue = 1 | pages = 1–6 | date = July 2002 | pmid = 12131078 | pmc = 1422541 | doi = 10.1097/00000658-200207000-00002 }}</ref>

Diatrizoate is used in suspected intestinal perforation, meconium ileus, and to identify bowel-lumen communication. It should not be used to investigate tracheo-oesophageal fistula because it can cause pulmonary oedema when aspirated into respiratory system. Diatrizoate can dislodge sticky meconium by drawing water into intestines.<ref>{{cite book | vauthors = Nick W, Hefin J |title=Chapman & Nakielny's Guide to Radiological procedures |date=2018 |publisher=Elsevier |location=London |isbn=9780702071669 |page=44, 49, 69 |edition=7th |chapter=Introduction to contrast media}}</ref> Diatrizoate is minimally absorbed from the intestines and excreted into urinary bladder.<ref>{{cite journal | vauthors = Poole CA, Rowe MI | title = Clinical evidence of intestinal absorption of Gastrografin | journal = Radiology | volume = 118 | issue = 1 | pages = 151–153 | date = January 1976 | pmid = 1244649 | doi = 10.1148/118.1.151 }}</ref> Because of its high osmolarity it can draw water from the surrounding tissues into the intestines, thus cause dehydration in people with already small plasma volume such as infants. Because of the additives and flavouring agents, diatrizoate formulated as Gastrografin must not be used intravascularly, though other formulations of diatrizoate are indicated for intravascular use. This chemical must be kept away from sunlight during storage.<ref>{{cite web |title=Professional information: gastrografin aqueous solution |url=https://www.bayer.com/sites/default/files/GASTROGRAFIN_EN_PI.pdf |publisher=Bayer |access-date=2 February 2022 |archive-url=https://web.archive.org/web/20220202041134/https://www.bayer.com/sites/default/files/GASTROGRAFIN_EN_PI.pdf |archive-date=2 February 2022 |date=2 September 2018}}</ref>

===Administration=== It is given orally on computed tomography of the abdomen and pelvis as 30 ml solution with 3% concentration to visualise the bowel lumen and any communications with the bowel lumen.<ref>{{cite book | vauthors = Watson N, Jones H |title=Chapman and Nakielny's Guide to Radiological Procedures |date=2018 |publisher=Elsevier |isbn=9780702071669 |pages=44}}</ref> In principle, diatrizoic acid is administered by the route most appropriate and sensible to image the structure/-s of interest (e.g., IV for blood vessels through which it is distributed and kidney–ureters–bladder that excrete it; orally or per rectally as an enema for the gastrointestinal tract).{{cn|date=December 2022}} * It is given orally or by enema to image the gastrointestinal tract. * It is given by Foley catheter to image the urinary tract.

==Contraindications== A history of sensitivity to iodine is not a contraindication to using diatrizoate, although it suggests caution in use of the agent. In this case, a regimen of oral or intravenous corticosteroids may be given as prophylaxis, or an alternative such as barium sulfate may be preferable.{{cn|date=December 2022}}

Gastrografin is contraindicated to use along with certain medications that can cause lactic acidosis, such as metformin. Concurrent use may lead to kidney failure and lactic acidosis, and a clinician may need to space the agents apart over a number of days to prevent an interaction.<ref>{{cite web | url = http://www.thomsonhc.com/hcs/librarian/ND_T/HCS/ND_PR/Main/CS/B469E9/DUPLICATIONSHIELDSYNC/8D376E/ND_PG/PRIH/ND_B/HCS/SBK/2/ND_P/Main/PFActionId/hcs.common.RetrieveDocumentCommon/DocId/2697/ContentSetId/31#contraindicationsSection | title = DIATRIZOATE MEGLUMINE/DIATRIZOATE SODIUM | author = Micromedex Healthcare Series | date = November 2010 | access-date = 10 November 2010 | publisher = Thomson Reuters (Healthcare) Inc. | work = DRUGDEX }}{{Dead link|date=July 2020 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>

Gastrografin is a hypertonic solution, and therefore it should be avoided in imaging studies of the upper gastrointestinal tract in patients who are at risk of aspiration, as it will cause prompt pulmonary edema if accidentally introduced into the tracheobronchial tree.<ref>{{Cite journal | vauthors = Blanzieri S |date=2012 |title=Pulmonary edema by aspiration of gastrografin: a case report and literature review | journal = European Congress of Radiology-ECR |url=https://epos.myesr.org/esr/poster/10.1594/ecr2012/C-0607 |language=en |pages=985 words |doi=10.1594/ECR2012/C-0607}}</ref><ref>{{Cite journal | vauthors = Mohajer P, Annan E, Ahuja J, Sharif M, Sung A |date=October 2012 |title=Acute Respiratory Failure From Aspiration Pneumonitis: A Complication of Gastrografin Contrast Media |journal=Chest |language=en |volume=142 |issue=4 |pages=1017A |doi=10.1378/chest.1390596}}</ref>

Urografin is not to be used for myelography, ventriculography or cisternography, since it is likely to provoke neurotoxic symptoms in these examinations. <ref>{{cite web | url = http://www.bayerresources.com.au/resources/uploads/DataSheet/file9513.pdf | title = UROGRAFIN Urografin Corporate Core Text | author = Bayer New Zealand Limited | date = September 2007 | access-date = 2 April 2012 | url-status = live | archive-url = https://web.archive.org/web/20160304034644/http://www.bayerresources.com.au/resources/uploads/DataSheet/file9513.pdf | archive-date = 4 March 2016 }}</ref>

==Chemistry== Diatrizoate is considered a high-osmolality contrast agent. Its osmolality ranges from approximately 1500 mOsm/kg (50% solution)<ref>{{cite web | url = http://dailymed.nlm.nih.gov/dailymed/fdaDrugXsl.cfm?id=1808&type=display | title = Hypaque sodium (Diatrizoate Sodium) injection, solution. Product label | author = Amersham Health | date = April 2006 | access-date = 29 March 2007 | publisher = U.S. National Library of Medicine | work = DailyMed | url-status = dead | archive-url = https://web.archive.org/web/20110523223510/http://dailymed.nlm.nih.gov/dailymed/fdaDrugXsl.cfm?id=1808&type=display | archive-date = 23 May 2011 }}</ref> to over 2000 mOsm/kg (76% solution).<ref>{{cite web | url = http://dailymed.nlm.nih.gov/dailymed/fdaDrugXsl.cfm?id=997&type=display | title = Hypaque (Diatrizoate Meglumine and Diatrizoate Sodium) injection, solution. Product label | author = Amersham Health | date = April 2006 | access-date = 29 March 2007 | publisher = U.S. National Library of Medicine | work = DailyMed | url-status = dead | archive-url = https://web.archive.org/web/20110523223457/http://dailymed.nlm.nih.gov/dailymed/fdaDrugXsl.cfm?id=997&type=display | archive-date = 23 May 2011 }}</ref>

===Synthesis=== 3,5-Dinitrobenzoic acid is reduced to 3,5-diaminobenzoic acid using Raney nickel or palladium on carbon. This is then reacted with potassium iodochloride or iodine monochloride to produce 3,5-diamino-2,4,6-triidobenzoic acid, which is finally acylated using acetic anhydride and acidified with sulfuric acid to produce diatrizoate.<ref name="a857">{{cite book | last=Lerner | first=Hyam Henry | title=Analytical Profiles of Drug Substances | chapter=Diatrizoic Acid | publisher=Elsevier | volume=4 | date=1975 | isbn=978-0-12-260804-9 | doi=10.1016/s0099-5428(08)60011-8 | pages=137–167}}</ref>

Another synthesis pathway iodates 3,5-diacetamidobenzoic acid using iodine monochloride.<ref name="a857"></ref>

==Brand names== Brand names include Hypaque, Gastrografin, MD-Gastroview, Iothalmate, and Urografin. Urografin is a combination of the sodium and meglumine salts.{{cn|date=December 2022}}

== References == {{reflist}}

Category:Anthelmintics Category:Iodobenzene derivatives Category:Benzoic acids Category:Radiocontrast agents Category:World Health Organization essential medicines Category:Acetanilides Category:Wikipedia medicine articles ready to translate