View source for Polystyrene sulfonate

{{Short description|Drug class}}
{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 486389066
| IUPAC_name = Poly(4-vinylbenzenesulfonic acid)
| image = Polystyrolsulfonat.svg
| width = 150
<!--Clinical data -->
| tradename = ''Sodium salt:'' Kayexalate, Kionex, Resonium A<br />''Calcium salt:'' Calcium Resonium, Kalitake, Sorbisterit, Resikali<br /> ''Potassium and sodium salt:'' Tolevamer
| Drugs.com = {{drugs.com|monograph|sodium-polystyrene-sulfonate}}
| MedlinePlus = a682108
| pregnancy_US = C
| legal_status = Rx
| routes_of_administration = By mouth, retention [[enema]]
<!--Pharmacokinetic data -->
| bioavailability = None
| metabolism = None
| excretion = Faeces (100%)
<!--Identifiers -->
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = None
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 9002-23-7
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 70KO0R01RY
| ATC_prefix = V03
| ATC_suffix = AE01
| PubChem = 75905
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01344
| KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = DG01160
<!--Chemical data -->
| chemical_formula = [C<sub>8</sub>H<sub>7</sub>SO<sub>3</sub><sup>−</sup>] <sub>n</sub>
|drug_name=|alt=|caption=|type=
|licence_EU=
|pregnancy_AU=|pregnancy_category=
|licence_US=}}
<!-- Definition and uses -->
'''Polystyrene sulfonates''' are a group of medications used to treat [[high blood potassium]].<ref name=AHFS2019NA>{{cite web |title=Sodium Polystyrene Sulfonate Monograph for Professionals |url=https://www.drugs.com/monograph/sodium-polystyrene-sulfonate.html |website=Drugs.com |access-date=25 October 2019 |language=en}}</ref> Effects generally take hours to days.<ref name=AHFS2019NA/> They are also used to remove [[potassium]], [[calcium]], and [[sodium]] from [[Solution (chemistry)|solution]]s in technical applications.

<!-- Side effects and mechanism -->
Common side effects include loss of appetite, gastrointestinal upset, constipation, and [[low blood calcium]].<ref name=AHFS2019NA/> These [[polymer]]s are derived from [[polystyrene]] by the addition of [[sulfonate]] [[functional group]]s.

<!-- History and culture -->
Sodium polystyrene sulfonate was approved for medical use in the United States in 1958.<ref name=AHFS2019NA/>

A polystyrene sulfonate was developed in the 2000s to treat [[Clostridioides difficile infection|'' Clostridioides difficile'' associated diarrhea]] under the name [[Tolevamer]],<ref>{{cite journal | vauthors = Hinkson PL, Dinardo C, DeCiero D, Klinger JD, Barker RH | title = Tolevamer, an anionic polymer, neutralizes toxins produced by the BI/027 strains of Clostridium difficile | journal = Antimicrobial Agents and Chemotherapy | volume = 52 | issue = 6 | pages = 2190–2195 | date = June 2008 | pmid = 18391047 | pmc = 2415796 | doi = 10.1128/AAC.00041-08 }}</ref> but it was never marketed.

==Medical uses==
[[File:Cecal adenocarcinoma.jpg|thumb|right|[[Micrograph]] showing sodium polystyrene sulfonate crystals (purple – at top of the image) in the [[biopsy]] of a [[Colon (anatomy)|colonic]] mass. [[H&E stain]].]]
Polystyrene sulfonate is usually supplied in either the sodium or calcium form.  It is used as a [[potassium binder]] in acute and [[chronic kidney disease]] for people with [[hyperkalemia]] (an abnormally high blood serum potassium level).<ref>{{MedlinePlusEncyclopedia|001179|High potassium level}}</ref>  However, it is unclear if it is beneficial and there is concern about possible side effects when it is combined with [[sorbitol]].<ref>{{cite journal | vauthors = Sterns RH, Rojas M, Bernstein P, Chennupati S | title = Ion-exchange resins for the treatment of hyperkalemia: are they safe and effective? | journal = Journal of the American Society of Nephrology | volume = 21 | issue = 5 | pages = 733–735 | date = May 2010 | pmid = 20167700 | doi = 10.1681/ASN.2010010079 | doi-access = free }}</ref>

Polystyrene sulfonates are given by mouth with a meal or [[rectal administration|rectally]] by retention [[enema]].<ref>{{cite web|publisher=Medicines Complete|work=Martindale: The Complete Drug Reference|url=http://www.medicinescomplete.com/mc/martindale/2009/5004-l.htm|title=Polystyrene sulfonate|access-date=27 November 2009}}</ref>

==Side effects==
Intestinal disturbances are common, including loss of appetite, [[nausea]], [[vomiting]], and [[constipation]]. In rare cases, it has been associated with colonic necrosis.<ref name="pmid11493807">{{cite journal | vauthors = Rogers FB, Li SC | title = Acute colonic necrosis associated with sodium polystyrene sulfonate (Kayexalate) enemas in a critically ill patient: case report and review of the literature | journal = The Journal of Trauma | volume = 51 | issue = 2 | pages = 395–397 | date = August 2001 | pmid = 11493807 | doi = 10.1097/00005373-200108000-00031 }}</ref> Changes in electrolyte blood levels such as [[hypomagnesemia]], [[hypocalcemia]], and [[hypokalemia]] may occur.<ref>KAYEXALATE (sodium polystyrene sulfonate). [https://web.archive.org/web/20190824075913/https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/011287s026lbl.pdf FULL PRESCRIBING INFORMATION Revised 07/2017] Retrieved 2018-10-21</ref> Polystyrene sulfonates should not be used in people with obstructive bowel disease and in newborns with reduced [[gut motility]].<ref name="Drugs.com">{{Drugs.com|pro|kayexalate}} for Kayexalate.</ref>

===Intestinal injury===
A total of 58 cases of intestinal injury including [[necrosis]] of the colon have been reported with polystyrene sulfonate as of 2013.<ref name=Har2013>{{cite journal | vauthors = Harel Z, Harel S, Shah PS, Wald R, Perl J, Bell CM | title = Gastrointestinal adverse events with sodium polystyrene sulfonate (Kayexalate) use: a systematic review | journal = The American Journal of Medicine | volume = 126 | issue = 3 | pages = 264.e9–264.24 | date = March 2013 | pmid = 23321430 | doi = 10.1016/j.amjmed.2012.08.016 }}</ref> Well more cases have been reported when used in combination  with sorbitol and other cases have occurred when used alone.<ref name=Har2013/>

=== Interactions ===
Polystyrene sulfonates can bind to various drugs within the digestive tract and thus lower their absorption and effectiveness. Common examples include [[lithium (medication)|lithium]], [[thyroxine]], and [[digitalis]]. In September 2017, the FDA recommended separating the dosing of polystyrene sulfonate from any other oral medications by at least three hours to avoid any potential interactions.<ref>{{Cite web|url=https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm574763.htm?source=govdelivery|title=Safety Alerts for Human Medical Products - Kayexalate (sodium polystyrene sulfonate): Drug Safety Communication - FDA Recommends Separating Dosing | author = Office of the Commissioner|website=www.fda.gov|language=en|access-date=2017-09-19}}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}}</ref>

==Mechanism of action==

===Hyperkalemia===
Polystyrene sulfonates release sodium or calcium ions in the stomach in exchange for hydrogen ions. When the resin reaches the large intestine the hydrogen ions are exchanged for free potassium ions, and the resin is then eliminated in the feces. The net effect is lowering the amount of potassium available for absorption into the blood and increasing the amount that is excreted via the feces. The effect is a reduction of potassium levels in the body, at a capacity of 1 mEq of potassium exchanged per 1 g of resin.<ref name="Drugs.com" /><ref>{{cite journal | vauthors = Chaitman M, Dixit D, Bridgeman MB | title = Potassium-Binding Agents for the Clinical Management of Hyperkalemia | journal = P & T | volume = 41 | issue = 1 | pages = 43–50 | date = January 2016 | pmid = 26765867 | pmc = 4699486 }}</ref>

==Production and chemical structure==
Polystyrene sulfonic acid, the acid whose salts are the polystyrene sulfonates, has the idealized formula (CH<sub>2</sub>CHC<sub>6</sub>H<sub>4</sub>SO<sub>3</sub>H)<sub>''n''</sub>.<!--what is typical n?-->  The material is prepared by [[Aromatic sulfonation|sulfonation]] of [[polystyrene]]:
:(CH<sub>2</sub>CHC<sub>6</sub>H<sub>5</sub>)<sub>''n''</sub>  +  ''n''&nbsp;SO<sub>3</sub>   →   (CH<sub>2</sub>CHC<sub>6</sub>H<sub>4</sub>SO<sub>3</sub>H)<sub>''n''</sub>

Several methods exist for this conversion, which can lead to varying degree of sulfonation.  Usually the polystyrene is [[crosslinked]], which keeps the polymer from dissolving.  Since the [[sulfonic acid]] group (SO<sub>3</sub>H) is strongly acidic, this polymer neutralizes bases.  In this way, various salts of the polymer can be prepared, leading to sodium, calcium, and other salts:
:(CH<sub>2</sub>CHC<sub>6</sub>H<sub>4</sub>SO<sub>3</sub>H)<sub>''n''</sub>  +  ''n''&nbsp;NaOH   →    (CH<sub>2</sub>CHC<sub>6</sub>H<sub>4</sub>SO<sub>3</sub>Na)<sub>''n''</sub>  +  ''n''&nbsp;H<sub>2</sub>O
These ion-containing polymers are called [[ionomer]]s.

===Alternative sulfonation methods===
Double substitutions of the phenyl rings are known to occur, even with conversions well below 100%. Crosslinking reactions are also found, where condensation of two sulfonic acid groups yields a sulfonyl crosslink. On the other hand, the use of milder conditions such as acetyl sulfate leads to incomplete sulfonation. Recently, the [[atom transfer radical polymerization]] (ATRP) of protected styrene sulfonates has been reported,<ref>{{cite journal | vauthors = Sikkema FD, Comellas-Aragonès M, Fokkink RG, Verduin BJ, Cornelissen JJ, Nolte RJ | title = Monodisperse polymer-virus hybrid nanoparticles | journal = Organic & Biomolecular Chemistry | volume = 5 | issue = 1 | pages = 54–57 | date = January 2007 | pmid = 17164905 | doi = 10.1039/b613890j }}</ref><ref>{{cite journal| vauthors = Lienkamp K, Schnell I, Groehn F, Wegner G |title=Polymerization of Styrene Sulfonate Ethyl Ester by ATRP: Synthesis and Characterization of Macromonomers for Suzuki Polycondensation|journal=Macromolecular Chemistry and Physics|volume=207|issue=22|pages=2066–2073|year=2006|doi=10.1002/macp.200600322}}</ref> leading to well defined linear polymers, as well as more complicated molecular architectures.<ref>{{cite journal| vauthors = Lienkamp K, Ruthard C, Lieser G, Berger R, Groehn F, Wegner G |title=Polymerization of Styrene Sulfonate Ethyl Ester and Styrene Sulfonate Dodecyl Ester by ATRP: Synthesis and Characterization of Polymer Brushes|journal=Macromolecular Chemistry and Physics |volume=207 |issue=22 |pages=2050–2065 |year=2006 |doi=10.1002/macp.200600321|s2cid=98278283}}</ref>

==Chemical uses==
Polystyrene sulfonates are useful because of their [[ion exchange]] properties.<ref name=Ullmann>{{cite book | vauthors = De Dardel F, Arden TV | chapter = Ion Exchangers | title = Ullmann's Encyclopedia of Industrial Chemistry | date = 2008 | publisher = Wiley-VCH | location = Weinheim | doi = 10.1002/14356007.a14_393.pub2 | isbn = 978-3527306732 }}</ref> Linear ionic polymers are generally [[solubility|water-soluble]], whereas [[cross-link]]ed materials (called [[resin]]s) do not [[dissolution (chemistry)|dissolve]] in water. These polymers are classified as [[polysalt]]s and [[ionomer]]s.<ref name=Ullmann/>

===Water softening===
Water softening is achieved by percolating [[hard water]] through a bed of the sodium form of cross-linked polystyrene sulfonate.  The hard ions such as [[calcium]] (Ca<sup>2+</sup>) and  [[magnesium]] (Mg<sup>2+</sup>) adhere to the sulfonate groups, displacing sodium ions.  The resulting solution of sodium ions is softened.
[[File:CationExchCartoon.png|thumb|center|444px|Idealized image of water softening process involving replacement of calcium ions in water with sodium ions donated by a [[ion exchange resin|cation exchange resin]].]]

===Other uses===
Sodium polystyrene sulfonate is used as a superplastifier in cement, as a dye improving agent for cotton, and as proton exchange membranes in fuel cell applications.  In its acid form, the resin is used as a solid [[acid catalyst]] in [[organic synthesis]],<ref>{{OrgSynth| vauthors = Gálvez E, Romea P, Urpí F |year=2009|title=Stereoselective Synthesis of anti α-Methyl-β-Methoxy Carboxylic Compounds|volume=86|pages=81|collvol=|collvolpages=|prep=V86P081}}</ref> mostly commonly under the tradename Amberlyst.

== References ==
{{reflist}}

{{Drugs for treatment of hyperkalemia and hyperphosphatemia}}

[[Category:Benzenesulfonates]]
[[Category:Nephrology procedures]]
[[Category:Organic polymers]]
[[Category:Plastics]]
[[Category:Polyelectrolytes]]
[[Category:Chelating agents used as drugs]]
[[Category:Acid catalysts]]
[[Category:Vinyl polymers]]
[[Category:Sanofi]]