Polystyrene sulfonate

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Polystyrene sulfonate
Polystyrolsulfonat.svg
Systematic (IUPAC) name
Poly(4-vinylbenzenesulfonic acid)
Clinical data
Trade names Sodium salt: Kayexalate, Kionex, Resonium A
Calcium salt: Calcium Resonium, Sorbisterit, Resikali
AHFS/Drugs.com Monograph
MedlinePlus a682108
Pregnancy
category
  • US: C (Risk not ruled out)
Routes of
administration
Oral, retention enema
Legal status
Legal status
  • ℞ (Prescription only)
Pharmacokinetic data
Bioavailability None
Metabolism None
Excretion Faeces (100%)
Identifiers
CAS Number 28210-41-5 YesY
ATC code V03AE01 (WHO)
PubChem CID 75905
DrugBank DB01344 YesY
ChemSpider None
KEGG DG01160
Chemical data
Formula [C8H7SO3]n
  (verify)

Polystyrene sulfonates are polymers derived from polystyrene but containing sulfonate functional groups. They are widely used to remove ions such as potassium, calcium and sodium from solutions in technical or medical applications.

Linear polymers are water-soluble, and white when very pure. Crosslinked materials (called resins) do not dissolve in water and typically appear amber in color. These polymers are classified as polysalts and ionomers.[1]

Under the name tolevamer, a polystyrene sulfonate was investigated by Genzyme as a toxin binding agent for the treatment of Clostridium difficile associated diarrhoea (CDAD), but never marketed.

Medical uses[edit]

Micrograph showing sodium polystyrene sulfonate crystals (purple – at top of the image) in the biopsy of a colonic mass. H&E stain.

Polystyrene sulfonate (trade name Kayexalate and others) is usually supplied in the sodium and calcium form. It is used as a potassium binder in acute and chronic kidney disease for people with hyperkalaemia (abnormal high blood serum potassium levels).[2] It however is unclear if it works and there is concern about possible side effects when it is mixed with sorbitol.[3]

Polystyrene sulfonates are administered orally (with a meal) or rectally, by retention enema.[4]

Contraindications[edit]

The drug is contraindicated in patients with obstructive bowel disease and in newborn children with reduced gut motility.[5]

Side effects[edit]

Intestinal disturbances are common, including loss of appetite, nausea, vomiting, and constipation. In rare cases, it has been associated with colonic necrosis.[6] Changes in electrolyte blood levels may occur such as hypermagnesemia, hypercalcemia, and hypokalemia.[7]

Interactions[edit]

Polystyrene sulfonates can bind to various drugs and thus lower their absorption and effectiveness. Examples include lithium and thyroxine. Digitalis is more likely to cause side effects in the presence of hypokalemia, which can be caused by polystyrene sulfonate. Cases of intestinal necrosis have been reported when this polymer was combined with sorbitol.[5]

Mechanism of action[edit]

Hyperkalemia[edit]

Polystyrene sulfonates release sodium or calcium ions in the gut (mainly in the large intestine) in exchange for free potassium ions, 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.[5]

Clostridium difficile associated diarrhea[edit]

Tolevamer was designed to bind the enterotoxins rather than attack C. difficile directly. Since it has no antibiotic properties, it does not harm the gut flora. Early studies used the sodium salt, but it was soon replaced with the potassium sodium salt to prevent hypokalaemia which is often associated with diarrhoea.[8][9]

Chemical uses[edit]

Polystyrene sulfonates are useful because of their ion exchange properties.[1]

Water softening[edit]

Water softening is achieved by percolating hard water through a bed of sodium form of cross-linked polystyrene sulfonate. The hard ions such as calcium (Ca2+) and magnesium (Mg2+) adhere to the sulfonate groups, displacing sodium ions. The resulting solution of sodium ions is softened.

Idealized image of water softening process involving replacement of calcium ions in water with sodium ions donated by a cation exchange resin.

Other uses[edit]

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 their acid form, the resin is used as a solid acid catalyst in organic synthesis.[10]

Production and chemical structure[edit]

Polystyrene sulfonic acid has the idealized formula (CH2CHC6H4SO3H)n. The material is prepared by sulfonation of polystyrene:

(CH2CHC6H5)n + n SO3 → (CH2CHC6H4SO3H)n

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 (SO3H) 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:

(CH2CHC6H4SO3H)n + n NaOH → (CH2CHC6H4SO3Na)n + n H2O

These ion-containing polymers are called ionomers.

Alternative sulfonation methods[edit]

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 styrenesulfonates has been reported,[11][12] leading to well defined linear polymers, as well as more complicated molecular architectures.[13]

History[edit]

Termination of tolevamer development[edit]

In early 2008, a noninferiority study versus vancomycin or metronidazole found that about half of the patient in the tolevamer group did not complete the treatment, versus 25% in the vancomycin and 29% in the metronidazole groups.

CDAD recurrence in patients reaching clinical success was reduced significantly by tolevamer (6% recurrence rate), vancomycin (18%) and metronidazole (19%). However, the good result of tolevamer is partly due to the high drop-out rate in this group.

Since tolevamer did not reach its primary endpoint in this study, the development was halted.[14]

References[edit]

  1. ^ a b François Dardel and Thomas V. Arden "Ion Exchangers" in Ullmann's Encyclopedia of Industrial Chemistry, 2008, Wiley-VCH, Weinheim. doi:10.1002/14356007.a14_393.pub2
  2. ^ MedlinePlus Encyclopedia High potassium level
  3. ^ Sterns RH, Rojas M, Bernstein P, Chennupati S (May 2010). "Ion-exchange resins for the treatment of hyperkalemia: are they safe and effective?". J. Am. Soc. Nephrol. 21 (5): 733–5. doi:10.1681/ASN.2010010079. PMID 20167700. 
  4. ^ "Polystyrene sulfonate". Martindale: The Complete Drug Reference. Medicines Complete. Retrieved 27 November 2009. 
  5. ^ a b c FDA Professional Drug Information for Kayexalate.
  6. ^ Rogers FB, Li SC (August 2001). "Acute colonic necrosis associated with sodium polystyrene sulfonate (Kayexalate) enemas in a critically ill patient: case report and review of the literature". J Trauma. 51 (2): 395–7. doi:10.1097/00005373-200108000-00031. PMID 11493807. 
  7. ^ Sorbisterit – Summary of Product Characteristics; Retrieved: 27 November 2009.
  8. ^ H. Spreitzer (September 24, 2007). "Neue Wirkstoffe - Tolevamer". Österreichische Apothekerzeitung (in German) (20/2007): 955. 
  9. ^ Wang, Y, Serradell, N, Rosa, E, Bolos, J (2007). "Tolevamer Potassium Sodium". Drugs of the Future. 32 (6): 501–505. doi:10.1358/dof.2007.032.06.1108513. 
  10. ^ Erik Gálvez, Pedro Romea, and Fèlix Urpí (2009). "Stereoselective Synthesis of anti α-Methyl-β-Methoxy Carboxylic Compounds". Org. Synth. 86: 81. 
  11. ^ Sikkema, FD; Comellas-Aragonès, M; Fokkink, RG; Verduin, BJ; Cornelissen, JJ; Nolte, RJ (2007). "Monodisperse polymer-virus hybrid nanoparticles". Organic & biomolecular chemistry. 5 (1): 54–7. doi:10.1039/b613890j. PMID 17164905. 
  12. ^ Lienkamp, Karen; Schnell, Ingo; Groehn, Franziska; Wegner, Gerhard (2006). "Polymerization of Styrene Sulfonate Ethyl Ester by ATRP: Synthesis and Characterization of Macromonomers for Suzuki Polycondensation". Macromolecular Chemistry and Physics. 207 (22): 2066. doi:10.1002/macp.200600322. 
  13. ^ Lienkamp, Karen; Ruthard, Christian; Lieser, GüNter; Berger, RüDiger; Groehn, Franziska; Wegner, Gerhard (2006). "Polymerization of Styrene Sulfonate Ethyl Ester and Styrene Sulfonate Dodecyl Ester by ATRP: Synthesis and Characterization of Polymer Brushes". Macromolecular Chemistry and Physics. 207 (22): 2050. doi:10.1002/macp.200600321. 
  14. ^ Medscape.com: Tolevamer Less Effective Than Standard Therapies for C difficile–Associated Diarrhea

External links[edit]