Polystyrene sulfonate

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Polystyrene sulfonate
Polystyrolsulfonat.svg
Clinical data
Trade names Sodium salt: Kayexalate, Kionex, Resonium A
Calcium salt: Calcium Resonium, Sorbisterit, Resikali
Potassium and sodium salt: Tolevamer
AHFS/Drugs.com Monograph
MedlinePlus a682108
Routes of
administration
By mouth, retention enema
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability None
Metabolism None
Excretion Faeces (100%)
Identifiers
  • Poly(4-vinylbenzenesulfonic acid)
CAS Number
PubChem CID
DrugBank
ChemSpider
  • None
UNII
KEGG
Chemical and physical data
Formula [C8H7SO3] n
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Polystyrene sulfonates are a group of medications used to treat high blood potassium. [1] Effects generally take hours to days. [1] They are also used to remove potassium, calcium, and sodium from solutions in technical applications.

Contents

Common side effects include loss of appetite, gastrointestinal upset, constipation, and low blood calcium. [1] These polymers are derived from polystyrene by the addition of sulfonate functional groups.

Sodium polystyrene sulfonate was approved for medical use in the United States in 1958. [1]

A polystyrene sulfonate was developed in the 2000s to treat Clostridioides difficile associated diarrhea under the name Tolevamer, [2] but it was never marketed.

Medical uses

Micrograph showing sodium polystyrene sulfonate crystals (purple - at top of the image) in the biopsy of a colonic mass. H&E stain. Cecal adenocarcinoma.jpg
Micrograph showing sodium polystyrene sulfonate crystals (purple – at top of the image) in the biopsy of a 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). [3] However, it is unclear if it is beneficial and there is concern about possible side effects when it is combined with sorbitol. [4]

Polystyrene sulfonates are given by mouth with a meal or rectally by retention enema. [5]

Side effects

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 such as hypomagnesemia, hypocalcemia, and hypokalemia may occur. [7] Polystyrene sulfonates should not be used in people with obstructive bowel disease and in newborns with reduced gut motility. [8]

Intestinal injury

A total of 58 cases of intestinal injury including necrosis of the colon have been reported with polystyrene sulfonate as of 2013. [9] Well more cases have been reported when used in combination with sorbitol and other cases have occurred when used alone. [9]

Interactions

Polystyrene sulfonates can bind to various drugs within the digestive tract and thus lower their absorption and effectiveness. Common examples include 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. [10]

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. [8] [11]

Production and chemical structure

Polystyrene sulfonic acid, the acid whose salts are the polystyrene sulfonates, 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

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, [12] [13] leading to well defined linear polymers, as well as more complicated molecular architectures. [14]

Chemical uses

Polystyrene sulfonates are useful because of their ion exchange properties. [15] Linear ionic polymers are generally water-soluble, whereas cross-linked materials (called resins) do not dissolve in water. These polymers are classified as polysalts and ionomers. [15]

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 (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. CationExchCartoon.png
Idealized image of water softening process involving replacement of calcium ions in water with sodium ions donated by a 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. [16]

Related Research Articles

<span class="mw-page-title-main">Sorbitol</span> Chemical compound

Sorbitol, less commonly known as glucitol, is a sugar alcohol with a sweet taste which the human body metabolizes slowly. It can be obtained by reduction of glucose, which changes the converted aldehyde group (−CHO) to a primary alcohol group (−CH2OH). Most sorbitol is made from potato starch, but it is also found in nature, for example in apples, pears, peaches, and prunes. It is converted to fructose by sorbitol-6-phosphate 2-dehydrogenase. Sorbitol is an isomer of mannitol, another sugar alcohol; the two differ only in the orientation of the hydroxyl group on carbon 2. While similar, the two sugar alcohols have very different sources in nature, melting points, and uses.

Tumor lysis syndrome (TLS) is a group of metabolic abnormalities that can occur as a complication from the treatment of cancer, where large amounts of tumor cells are killed off (lysed) from the treatment, releasing their contents into the bloodstream. This occurs most commonly after the treatment of lymphomas and leukemias and in particular when treating non-Hodgkin lymphoma, acute myeloid leukemia, and acute lymphoblastic leukemia. This is a potentially fatal complication and patients at increased risk for TLS should be closely monitored while receiving chemotherapy and should receive preventive measures and treatments as necessary. TLS can also occur on its own although this is less common.

<span class="mw-page-title-main">Hyperkalemia</span> Excess potassium in the blood

Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0 mmol/L (3.5 and 5.0 mEq/L) with levels above 5.5 mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occasionally when severe it can cause palpitations, muscle pain, muscle weakness, or numbness. Hyperkalemia can cause an abnormal heart rhythm which can result in cardiac arrest and death.

<span class="mw-page-title-main">Nafion</span> Brand name for a chemical product

Nafion is a brand name for a sulfonated tetrafluoroethylene based fluoropolymer-copolymer synthesized in 1962 by Dr. Donald J. Connolly at the DuPont Experimental Station in Wilmington Delaware. Additional work on the polymer family was performed in the late 1960s by Dr. Walther Grot of DuPont. Nafion is a brand of the Chemours company. It is the first of a class of synthetic polymers with ionic properties that are called ionomers. Nafion's unique ionic properties are a result of incorporating perfluorovinyl ether groups terminated with sulfonate groups onto a tetrafluoroethylene (PTFE) backbone. Nafion has received a considerable amount of attention as a proton conductor for proton exchange membrane (PEM) fuel cells because of its excellent chemical and mechanical stability in the harsh conditions of this application.

<span class="mw-page-title-main">Amiloride</span> Medication

Amiloride, sold under the trade name Midamor among others, is a medication typically used with other medications to treat high blood pressure or swelling due to heart failure or cirrhosis of the liver. Amiloride is classified as a potassium-sparing diuretic. Amiloride is often used together with another diuretic, such as a thiazide or loop diuretic. It is taken by mouth. Onset of action is about two hours and it lasts for about a day.

<span class="mw-page-title-main">Ion-exchange resin</span> Organic polymer matrix bearing ion-exchange functional groups

An ion-exchange resin or ion-exchange polymer is a resin or polymer that acts as a medium for ion exchange. It is an insoluble matrix normally in the form of small microbeads, usually white or yellowish, fabricated from an organic polymer substrate. The beads are typically porous, providing a large surface area on and inside them where the trapping of ions occurs along with the accompanying release of other ions, and thus the process is called ion exchange. There are multiple types of ion-exchange resin, that differ in composition if the target is an anion or a cation. Most commercial resins are made of polystyrene sulfonate, followed up by polyacrylate.

<span class="mw-page-title-main">Water softening</span> Removing positive ions from hard water

Water softening is the removal of calcium, magnesium, and certain other metal cations in hard water. The resulting soft water requires less soap for the same cleaning effort, as soap is not wasted bonding with calcium ions. Soft water also extends the lifetime of plumbing by reducing or eliminating scale build-up in pipes and fittings. Water softening is usually achieved using lime softening or ion-exchange resins, but is increasingly being accomplished using nanofiltration or reverse osmosis membranes.

<span class="mw-page-title-main">Ion exchange</span> Exchange of ions between an electrolyte solution and a solid

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<span class="mw-page-title-main">Sulfonic acid</span> Organic compounds with the structure R−S(=O)2−OH

In organic chemistry, sulfonic acid refers to a member of the class of organosulfur compounds with the general formula R−S(=O)2−OH, where R is an organic alkyl or aryl group and the S(=O)2(OH) group a sulfonyl hydroxide. As a substituent, it is known as a sulfo group. A sulfonic acid can be thought of as sulfuric acid with one hydroxyl group replaced by an organic substituent. The parent compound is the parent sulfonic acid, HS(=O)2(OH), a tautomer of sulfurous acid, S(=O)(OH)2. Salts or esters of sulfonic acids are called sulfonates.

An ionomer is a polymer composed of repeat units of both electrically neutral repeating units and ionized units covalently bonded to the polymer backbone as pendant group moieties. Usually no more than 15 mole percent are ionized. The ionized units are often carboxylic acid groups.

<span class="mw-page-title-main">Aromatic sulfonation</span> Chemical reaction which replaces a hydrogen on an arene with sulfonic acid, –NH–SO3H

In organic chemistry, aromatic sulfonation is an organic reaction in which a hydrogen atom on an arene is replaced by a sulfonic acid functional group in an electrophilic aromatic substitution. Aryl sulfonic acids are used as detergents, dye, and drugs.

Lignosulfonates (LS) are water-soluble anionic polyelectrolyte polymers: they are byproducts from the production of wood pulp using sulfite pulping. Most delignification in sulfite pulping involves acidic cleavage of ether bonds, which connect many of the constituents of lignin. Sulfonated lignin (SL) refers to other forms of lignin by-product, such as those derived from the much more popular Kraft process, that have been processed to add sulfonic acid groups. The two have similar uses and are commonly confused with each other, with SL being much cheaper. LS and SL both appear as free-flowing powders; the former is light brown while the latter is dark brown.

<span class="mw-page-title-main">Calcium gluconate</span> Chemical compound

Calcium gluconate is the calcium salt of gluconic acid and is used as a mineral supplement and medication. As a medication it is used by injection into a vein to treat low blood calcium, high blood potassium, and magnesium toxicity. Supplementation is generally only required when there is not enough calcium in the diet. Supplementation may be done to treat or prevent osteoporosis or rickets. It can also be taken by mouth but is not recommended for injection into a muscle.

<span class="mw-page-title-main">Tolevamer</span> Chemical compound

Tolevamer is a medication developed to combat Clostridioides difficile associated diarrhea. It is a potassium sodium polystyrene sulfonate. It was never marketed.

Potassium binders are medications that bind potassium ions in the gastrointestinal tract, thereby preventing its intestinal absorption. This category formerly consisted solely of polystyrene sulfonate, a polyanionic resin attached to a cation, administered either orally or by retention enema to patients who are at risk of developing hyperkalaemia. Newer drugs include: another polyanionic polymer, patiromer, which exchanges calcium for potassium; and Sodium zirconium cyclosilicate crystals, which exchange sodium for potassium

<span class="mw-page-title-main">Sodium zirconium cyclosilicate</span> Medication used to treat high blood potassium

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<span class="mw-page-title-main">Graft polymer</span> Polymer with a backbone of one composite and random branches of another composite

In polymer chemistry, graft polymers are segmented copolymers with a linear backbone of one composite and randomly distributed branches of another composite. The picture labeled "graft polymer" shows how grafted chains of species B are covalently bonded to polymer species A. Although the side chains are structurally distinct from the main chain, the individual grafted chains may be homopolymers or copolymers. Graft polymers have been synthesized for many decades and are especially used as impact resistant materials, thermoplastic elastomers, compatibilizers, or emulsifiers for the preparation of stable blends or alloys. One of the better-known examples of a graft polymer is a component used in high impact polystyrene, consisting of a polystyrene backbone with polybutadiene grafted chains.

<span class="mw-page-title-main">Vinylsulfonic acid</span> Chemical compound

Vinylsulfonic acid is the organosulfur compound with the chemical formula CH2=CHSO3H. It is the simplest unsaturated sulfonic acid. The C=C double bond is a site of high reactivity. Polymerization gives polyvinylsulfonic acid, especially when used as a comonomer with functionalized vinyl and (meth)acrylic acid compounds. It is a colorless, water-soluble liquid, although commercial samples can appear yellow or even red.

<span class="mw-page-title-main">Patiromer</span> Drug used for the treatment of hyperkalemia

Patiromer, sold under the brand name Veltassa, is a medication used to treat high blood potassium. It is taken by mouth. It works by binding potassium in the gut.

<span class="mw-page-title-main">Polystyrene (drug delivery)</span> Polystyrene in drug delivery

Polystyrene is a synthetic hydrocarbon polymer that is widely adaptive and can be used for a variety of purposes in drug delivery. These methods include polystyrene microspheres, nanoparticles, and solid foams. In the biomedical engineering field, these methods assist researchers in drug delivery, diagnostics, and imaging strategies.

References

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  3. MedlinePlus Encyclopedia : High potassium level
  4. Sterns RH, Rojas M, Bernstein P, Chennupati S (May 2010). "Ion-exchange resins for the treatment of hyperkalemia: are they safe and effective?". Journal of the American Society of Nephrology. 21 (5): 733–735. doi: 10.1681/ASN.2010010079 . PMID   20167700.
  5. "Polystyrene sulfonate". Martindale: The Complete Drug Reference. Medicines Complete. Retrieved 27 November 2009.
  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". The Journal of Trauma. 51 (2): 395–397. doi:10.1097/00005373-200108000-00031. PMID   11493807.
  7. KAYEXALATE (sodium polystyrene sulfonate). FULL PRESCRIBING INFORMATION Revised 07/2017 Retrieved 2018-10-21
  8. 1 2 FDA Professional Drug Information for Kayexalate.
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  10. Office of the Commissioner. "Safety Alerts for Human Medical Products - Kayexalate (sodium polystyrene sulfonate): Drug Safety Communication - FDA Recommends Separating Dosing". www.fda.gov. Retrieved 2017-09-19.
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  13. Lienkamp K, Schnell I, Groehn F, Wegner G (2006). "Polymerization of Styrene Sulfonate Ethyl Ester by ATRP: Synthesis and Characterization of Macromonomers for Suzuki Polycondensation". Macromolecular Chemistry and Physics. 207 (22): 2066–2073. doi:10.1002/macp.200600322.
  14. Lienkamp K, Ruthard C, Lieser G, Berger R, Groehn F, Wegner G (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): 2050–2065. doi:10.1002/macp.200600321. S2CID   98278283.
  15. 1 2 De Dardel F, Arden TV (2008). "Ion Exchangers". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a14_393.pub2. ISBN   978-3527306732.
  16. Gálvez E, Romea P, Urpí F (2009). "Stereoselective Synthesis of anti α-Methyl-β-Methoxy Carboxylic Compounds". Organic Syntheses . 86: 81.