Lugol's iodine explained

Drug Name:	Lugol's iodine
Synonyms:	Potassium triiodide, Lugol's solution, aqueous iodine, strong iodine solution
Dailymedid:	Lugols_solution
Routes Of Administration:	topical, by mouth
Cas Number:	12298-68-9
Unii:	T66M6Y3KSA
Drugbank:	DB14492
Chemical Formula:	I3K
Molecular Weight:	419.812

Lugol's iodine, also known as aqueous iodine and strong iodine solution, is a solution of potassium iodide with iodine in water.^[1] It is a medication and disinfectant used for a number of purposes.^[2] Taken by mouth it is used to treat thyrotoxicosis until surgery can be carried out, protect the thyroid gland from radioactive iodine, and to treat iodine deficiency.^[3] When applied to the cervix it is used to help in screening for cervical cancer.^[4] As a disinfectant it may be applied to small wounds such as a needle stick injury.^[2] A small amount may also be used for emergency disinfection of drinking water.^[5]

Side effects may include allergic reactions, headache, vomiting, and conjunctivitis. Long term use may result in trouble sleeping and depression. It should not typically be used during pregnancy or breastfeeding.^[6] Lugol's iodine is a liquid made up of two parts potassium iodide for every one part elemental iodine in water.

Lugol's iodine was first made in 1829 by the French physician Jean Lugol.^{[5] [7]} It is on the World Health Organization's List of Essential Medicines.^{[8] [9]} Lugol's iodine is available as a generic medication and over the counter.^[10] Lugol's solution is available in different strengths of iodine. Large volumes of concentrations more than 2.2% may be subject to regulation.

Uses

Medical uses

Preoperative administration of Lugol's solution decreases intraoperative blood loss during thyroidectomy in patients with Graves' disease.^[11] However, it appears ineffective in patients who are already euthyroid on anti-thyroid drugs and levothyroxine.^[12]

• During colposcopy, Lugol's iodine is applied to the vagina and cervix. Normal vaginal tissue stains brown due to its high glycogen content, while tissue suspicious for cancer does not stain, and thus appears pale compared to the surrounding tissue. Biopsy of suspicious tissue can then be performed. This is called a Schiller's test.
• Patients at high risk of oesophageal squamous cell carcinoma are usually followed using a combination of Lugol's chromoendoscopy and narrow-band imaging.^[13] With Lugol's iodine, low-grade dysplasia appears as an unstained or weakly stained area; high-grade dysplasia is consistently unstained.^[14]
• Lugol's iodine may also be used to better visualize the mucogingival junction in the mouth. Similar to the method of staining mentioned above regarding a colposcopy, alveolar mucosa has a high glycogen content that gives a positive iodine reaction vs. the keratinized gingiva.^[15]
• Lugol's iodine may also be used as an oxidizing germicide, however it is somewhat undesirable in that it may lead to scarring and discolors the skin temporarily. One way to avoid this problem is by using a solution of 70% ethanol to wash off the iodine later.
• Lugol's iodine was distributed in Polish People's Republic after the Chernobyl catastrophe, due to government not being informed of how severe the event was and overestimating radiation, and unavailability of iodine tablets.^[16]

Science

• As a mordant when performing a Gram stain. It is applied for 1 minute after staining with crystal violet, but before ethanol to ensure that gram positive organisms' peptidoglycan remains stained, easily identifying it as a gram positive in microscopy.
• This solution is used as an indicator test for the presence of starches in organic compounds,^[17] with which it reacts by turning a dark-blue/black. Elemental iodine solutions like Lugol's will stain starches due to iodine's interaction with the coil structure of the polysaccharide. Starches include the plant starches amylose and amylopectin and glycogen in animal cells. Lugol's solution will not detect simple sugars such as glucose or fructose. In the pathologic condition amyloidosis, amyloid deposits (i.e., deposits that stain like starch, but are not) can be so abundant that affected organs will also stain grossly positive for the Lugol reaction for starch.
• It can be used as a cell stain, making the cell nuclei more visible and for preserving phytoplankton samples.
• Lugol's solution can also be used in various experiments to observe how a cell membrane uses osmosis and diffusion.
• Lugol's solution is also used in the marine aquarium industry. Lugol's solution provides a strong source of free iodine and iodide to reef inhabitants and macroalgae. Although the solution is thought to be effective when used with stony corals, systems containing xenia and soft corals are assumed to be particularly benefited by the use of Lugol's solution. Used as a dip for stony and soft or leather corals, Lugol's may help rid the animals of unwanted parasites and harmful bacteria. The solution is thought to foster improved coloration and possibly prevent bleaching of corals due to changes in light intensity, and to enhance coral polyp expansion. The blue colors of Acropora spp. are thought to be intensified by the use of potassium iodide. Specially packaged supplements of the product intended for aquarium use can be purchased at specialty stores and online.

Outdated uses

• Till early 1970s, it was often recommended for use in victims of rape in order to avoid pregnancy. The idea stemmed from the fact that, in the laboratory, Lugol's iodine appeared to kill sperm cells even in such great dilutions as 1:32. Thus it was thought that an intrauterine application of Lugol's iodine, immediately after the event, would help avoid pregnancy.^[18]

Side effects

Because it contains free iodine, Lugol's solution at 2% or 5% concentration without dilution is irritating and destructive to mucosa, such as the lining of the esophagus and stomach. Doses of 10 mL of undiluted 5% solution have been reported to cause gastric lesions when used in endoscopy.^[19] The LD50 for 5% Iodine is 14,000 mg/kg (14 g/kg) in rats, and 22,000 mg/kg (22 g/kg) in mice.^[20]

The World Health Organization classifies substances taken orally with an LD50 of 5–50 mg/kg as the second highest toxicity class, Class Ib (Highly Hazardous). The Global Harmonized System of Classification and Labeling of Chemicals categorizes this as Category 2 with a hazard statement "Fatal if swallowed". Potassium iodide is not considered hazardous.^[21]

Mechanism of action

The above uses and effects are consequences of the fact that the solution is a source of effectively free elemental iodine, which is readily generated from the equilibrium between elemental iodine molecules and polyiodide ions in the solution.

History

It was historically used as a first-line treatment for hyperthyroidism, as the administration of pharmacologic amounts of iodine leads to temporary inhibition of iodine organification in the thyroid gland, caused by phenomena including the Wolff–Chaikoff effect and the Plummer effect. However it is not used to treat certain autoimmune causes of thyroid disease as iodine-induced blockade of iodine organification may result in hypothyroidism. They are not considered as a first line therapy because of possible induction of resistant hyperthyroidism but may be considered as an adjuvant therapy when used together with other hyperthyroidism medications.

Lugol's iodine has been used traditionally to replenish iodine deficiency. Because of its wide availability as a drinking-water decontaminant, and high content of potassium iodide, emergency use of it was at first recommended to the Polish government in 1986, after the Chernobyl disaster to replace and block any intake of radioactive, even though it was known to be a non-optimal agent, due to its somewhat toxic free-iodine content.^[22] Other sources state that pure potassium iodide solution in water (SSKI) was eventually used for most of the thyroid protection after this accident.^[23] There is "strong scientific evidence" for potassium iodide thyroid protection to help prevent thyroid cancer. Potassium iodide does not provide immediate protection but can be a component of a general strategy in a radiation emergency.^[24]

Historically, Lugol's iodine solution has been widely available and used for a number of health problems with some precautions.^[25] Lugol's is sometimes prescribed in a variety of alternative medical treatments.^{[26] [27]} Only since the end of the Cold War has the compound become subject to national regulation in the English-speaking world.

Society and culture

Regulation

Until 2007, in the United States, Lugol's solution was unregulated and available over the counter as a general reagent, an antiseptic, a preservative,^[28] or as a medicament for human or veterinary application.

Since 1 August 2007, the DEA regulates all iodine solutions containing greater than 2.2% elemental iodine as a List I precursor because they may potentially be used in the illicit production of methamphetamine.^[29] Transactions of up to one fluid ounce (30 ml) of Lugol's solution are exempt from this regulation.

Formula and manufacture

Nominal concentration	Iodine (I2) [<nowiki/>mg/100μL<ref name="1 drop = 0.05 mL">1 drop = 0.05 mL</ref>]	Potassium iodide (KI) [mg/100μL<ref name="1 drop = 0.05 mL"/>]	Total iodine [mg/100μL<ref name="1 drop = 0.05 mL"/>]
1%	1.0	2.0	2.5
2%	2.0	4.0	5.1
5%	5.0	10.0	12.6
10%	10.0	20.0	25.3

Lugol's solution is commonly available in different potencies of (nominal) 1%, 2%, 5% or 10%. Iodine concentrations greater than 2.2% are subject to US regulations.^{[30] [31]} If the US regulations are taken literally, their 2.2% maximum iodine concentration limits a Lugol's solution to maximum (nominal) 0.87%.

The most commonly used (nominal) 5% solution consists of 5% (wt/v) iodine and 10% (wt/v) potassium iodide (KI) mixed in distilled water and has a total iodine content of 126.4 mg/mL. The (nominal) 5% solution thus has a total iodine content of 6.32 mg per drop of 0.05 mL; the (nominal) 2% solution has 2.53 mg total iodine content per drop.

Potassium iodide renders the elementary iodine soluble in water through the formation of the triiodide ion. It is not to be confused with tincture of iodine solutions, which consist of elemental iodine, and iodide salts dissolved in water and alcohol. Lugol's solution contains no alcohol.

Other names for Lugol's solution are (iodine-potassium iodide); Markodine, Strong solution (Systemic); and Aqueous Iodine Solution BP.

Economics

In the United Kingdom, in 2015, the NHS paid £9.57 per 500 ml of solution.^[6]

Notes and References

1. Book: Kaiho T . Iodine Chemistry and Applications. 2014. John Wiley & Sons. 9781118466292. 55. en. live. https://web.archive.org/web/20170918190501/https://books.google.com/books?id=WabCBwAAQBAJ&pg=PA55. 18 September 2017.
2. Book: Block SS . Disinfection, Sterilization, and Preservation. 2001. Lippincott Williams & Wilkins. 9780683307405. 177. en. live. https://web.archive.org/web/20170113125624/https://books.google.ca/books?id=3f-kPJ17_TYC&pg=PA177. 13 January 2017.
3. Book: Lugol's solution Drug Information, Professional. 1994. 11 January 2017. live. https://web.archive.org/web/20170113064908/https://www.drugs.com/mmx/lugol-s-solution.html. 13 January 2017.
4. Fokom-Domgue J, Combescure C, Fokom-Defo V, Tebeu PM, Vassilakos P, Kengne AP, Petignat P . Performance of alternative strategies for primary cervical cancer screening in sub-Saharan Africa: systematic review and meta-analysis of diagnostic test accuracy studies . BMJ . 351 . h3084 . July 2015 . 26142020 . 4490835 . 10.1136/bmj.h3084 .
5. Book: Preedy VR, Burrow GN, Watson RR . Comprehensive Handbook of Iodine: Nutritional, Biochemical, Pathological and Therapeutic Aspects. 2009. Academic Press. 9780080920863. 135. en. live. https://web.archive.org/web/20170812100039/https://books.google.ca/books?id=7v7g5XoCQQwC&pg=PA135. 12 August 2017.
6. Book: British National Formulary: BNF 69 . 2015 . British Medical Association. 9780857111562. 493. 69th.
7. Book: Sneader W . Drug Discovery: A History. 2005. John Wiley & Sons. 9780471899792. 67. en. live. https://web.archive.org/web/20170826071343/https://books.google.ca/books?id=Cb6BOkj9fK4C&pg=PA67. 26 August 2017.
8. Book: ((World Health Organization)) . World Health Organization model list of essential medicines: 21st list 2019 . 2019 . 10665/325771 . World Health Organization . World Health Organization . Geneva . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO . free .
9. Book: ((World Health Organization)) . World Health Organization model list of essential medicines: 22nd list (2021) . 2021 . 10665/345533 . World Health Organization . World Health Organization . Geneva . WHO/MHP/HPS/EML/2021.02 . free .
10. Web site: Strong Iodine Solution. The American Society of Health-System Pharmacists. 8 January 2017. live. https://web.archive.org/web/20170113074729/https://www.drugs.com/monograph/strong-iodine-solution.html. 13 January 2017.
11. Erbil Y, Ozluk Y, Giriş M, Salmaslioglu A, Issever H, Barbaros U, Kapran Y, Ozarmağan S, Tezelman S . Effect of lugol solution on thyroid gland blood flow and microvessel density in the patients with Graves' disease . The Journal of Clinical Endocrinology and Metabolism . 92 . 6 . 2182–2189 . June 2007 . 17389702 . 10.1210/jc.2007-0229 . free .
12. Kaur S, Parr JH, Ramsay ID, Hennebry TM, Jarvis KJ, Lester E . Effect of preoperative iodine in patients with Graves' disease controlled with antithyroid drugs and thyroxine . Annals of the Royal College of Surgeons of England . 70 . 3 . 123–127 . May 1988 . 2457351 . 2498739 .
13. Yokoyama A, Hirota T, Omori T, Yokoyama T, Kawakubo H, Matsui T, Mizukami T, Mori S, Sugiura H, Maruyama K . Development of squamous neoplasia in esophageal iodine-unstained lesions and the alcohol and aldehyde dehydrogenase genotypes of Japanese alcoholic men . International Journal of Cancer . 130 . 12 . 2949–60 . June 2012 . 21796615 . 10.1002/ijc.26296 .
14. Inoue H, Kaga M, Ikeda H, Sato C, Sato H, Minami H, Santi EG, Hayee B, Eleftheriadis N . Magnification endoscopy in esophageal squamous cell carcinoma: a review of the intrapapillary capillary loop classification . Annals of Gastroenterology . 28 . 1 . 41–48 . 2015 . 25608626 . 4290003 .
15. Han JS, John V, Blanchard SB, Kowolik MJ, Eckert GJ . Changes in gingival dimensions following connective tissue grafts for root coverage: comparison of two procedures . Journal of Periodontology . 79 . 8 . 1346–1354 . August 2008 . 18672983 . 10.1902/jop.2008.070472 .
16. Web site: JAK TO Z CZARNOBYLEM BYŁO - ZBIGNIEW JAWORSKI - Wiedza i Życie - 5/1996. archiwum.wiz.pl. 2 November 2019. 15 September 2019. https://web.archive.org/web/20190915043122/http://archiwum.wiz.pl/1996/96052000.asp. dead.
17. Van den Mooter M, Maraite H, Meiresonne L, Swings J, Gillis M, Kersters K, De Ley J . Comparison Between Xanthomonas campestris pv. manihotis (ISPP List 1980) and X. campestris pv. cassavae (ISPP List 1980) by Means of Phenotypic, Protein Electrophoretic, DNA Hybridization and Phytopathological Techniques . . . 133 . 1 . 1 January 1987 . 1350-0872 . 10.1099/00221287-133-1-57 . 57–71. free .
18. Lin TJ, Tanaka Y, Aznar R, Lin SC, Yamasaki Y, Hori S, Brar HK, Kirton KT, Little B . Contraceptive effect of intrauterine application of Lugol's solution . American Journal of Obstetrics and Gynecology . 116 . 2 . 167–174 . May 1973 . 4634105 . 10.1016/0002-9378(73)91044-2 .
19. Sreedharan A, Rembacken BJ, Rotimi O . Acute toxic gastric mucosal damage induced by Lugol's iodine spray during chromoendoscopy . Gut . 54 . 6 . 886–887 . June 2005 . 15888800 . 1774547 . 10.1136/gut.2004.061739 .
20. Web site: Material Safety Data Sheet Iodine Solution, 5% MSDS . 29 September 2016 . live . https://web.archive.org/web/20161206074306/http://www.sciencelab.com/msds.php?msdsId=9924378 . 6 December 2016 .
21. Web site: Potassium Iodide . Material Safety Data Sheet . Esciencelabs.com, Inc. . https://web.archive.org/web/20140303214220/http://www.esciencelabs.com/files/andrea.rex/Iodine_Potassium_Iodide.pdf . 3 March 2014 .
22. Web site: Chernobyl: the Biggest BLUFF of the 20th Century . https://web.archive.org/web/20050302210725/http://www.wonuc.org/xfiles/chern_02.html . dead . 2 March 2005 . Rotkiewicz M, Suchar H, Kamiñski R . 14 January 2001 . Polish weekly Wprost . no 2 . 18 June 2008 .
23. Web site: Potassium Iodide as a Thyroid Blocking Agent in Radiation Emergencies . U.S. Department of Health and Human Services Food and Drug Administration . Center for Drug Evaluation and Research (CDER) . December 2001 . 12 January 2010 . dead . https://web.archive.org/web/20110910170031/http://www.birdflumanual.com/resources/Self_Defense/files/Guidance%20for%20use%20of%20KI%20for%20nuclear%20emergency%20USG.pdf . 10 September 2011 .
24. Web site: Iodine . https://web.archive.org/web/20100804040405/http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-iodine.html . 4 August 2010 . MedlinePlus . U.S. National Library of Medicine .
25. Web site: Drugs.com . Lugol's Solution . https://web.archive.org/web/20051125111859/http://www.drugs.com/cons/Lugol_s_solution.html . 25 November 2005 .
26. Web site: Optimox.com . Iodine . https://web.archive.org/web/20060506052045/http://www.optimox.com/pics/Iodine/IOD-05/IOD_05.html . 6 May 2006 .
27. Web site: Jcrows.com . Iodine . https://web.archive.org/web/20070113183458/http://jcrows.com/iodine.html . 13 January 2007 .
28. Hawkins PR, Holliday J, Kathuria A, Bowling L . Change in cyanobacterial biovolume due to preservation by Lugol's Iodine . 2005 . Harmful Algae . 4 . 6. 1033–1043 . 10.1016/j.hal.2005.03.001.
29. Web site: Final Rule: Changes in the Regulation of Iodine Crystals and Chemical Mixtures Containing Over 2.2 Percent Iodine . US DEA . https://web.archive.org/web/20070913074919/http://www.deadiversion.usdoj.gov/fed_regs/rules/2007/fr0702.htm . 13 September 2007 . 2 July 2007 . Federal Register . 72 . 126 . FR Doc E7-12736 .
30. Web site: Dear Registrant Handling the List 1 Chemical Iodine . U.S. Department of Justice, Drug Enforcement Administration. 29 April 2008 . https://web.archive.org/web/20160306222421/http://www.deadiversion.usdoj.gov/chem_prog/iodine_reg_ltr050108.pdf . 6 March 2016 .
31. Web site: Hardy J . hardydiagnostics.com . Has Gram Staining Without a License Become a Criminal Act? . https://web.archive.org/web/20160803204831/http://hardydiagnostics.com/articles/iodine-regulations.pdf . 3 August 2016 .