Cholestyramine

Cholestyramine
Clinical data
Trade names Questran
AHFS/Drugs.com monograph
MedlinePlus a682672
  • US: C (Risk not ruled out)
  • C
oral
Pharmacokinetic data
Bioavailability low
Protein binding unknown
Metabolism bile acids
Half-life .1 hr
Excretion feces
Identifiers
11041-12-6 Yes
C10AC01
DrugBank DB01432 Yes
UNII 4B33BGI082 
KEGG D02690 Yes
ChEMBL CHEMBL1201625 
Chemical data
Average MW exceeds 106 Daltons
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Cholestyramine or colestyramine (Questran, Questran Light, Cholybar, Olestyr) is a bile acid sequestrant, which binds bile in the gastrointestinal tract to prevent its reabsorption. It is a strong ion exchange resin, which means it can exchange its chloride anions with anionic bile acids in the gastrointestinal tract and bind them strongly in the resin matrix. The functional group of the anion exchange resin is a quaternary ammonium group attached to an inert styrene-divinylbenzene copolymer.

Cholestyramine removes bile acids from the body by forming insoluble complexes with bile acids in the intestine, which are then excreted in the feces. As a result of this loss of bile acids, more plasma cholesterol is converted to bile acids in the liver to normalize levels. This conversion of cholesterol into bile acids lowers plasma cholesterol levels.

Medical uses

Bile acid sequestrants such as cholestyramine were first used to treat hypercholesterolemia, but since the introduction of statins, now have only a minor role for this indication. They can also be used to treat the pruritus, or itching, that often occurs during liver failure and other types of cholestasis where the ability to eliminate bile acids is reduced.

Cholestyramine is commonly used to treat diarrhea resulting from bile acid malabsorption.[1] It was first used for this in Crohn's disease patients who had undergone ileal resection.[2] The terminal portion of the small bowel (ileum) is where bile acids are reabsorbed. When this section is removed, the bile acids pass into the large bowel and cause diarrhea due to stimulation of chloride/fluid secretion by the colonocytes resulting in a secretory diarrhea. Cholestyramine prevents this increase in water by making the bile acids insoluble and osmotically inactive. Postileal resection patients should use this medication cautiously, however, because bowel surgery heightens the occurrence of small-bowel obstructions, and several cases are reported in the medical literature of cholestyramine causing bowel obstructions.[3]

Cholestyramine is also used in the control of other types of bile acid diarrhea. The primary, idiopathic form of bile acid diarrhea is a common cause of chronic functional diarrhea, often misdiagnosed as diarrhea-predominant irritable bowel syndrome (IBS-D), and most of these patients respond to cholestyramine.[4] It is beneficial in the treatment of postcholecystectomy syndrome chronic diarrhea.[5][6] Cholestyramine is also useful in treating postvagotomy diarrhea.[7][8]

Cholestyramine can also be used in the treatment of Clostridium difficile infections, to adsorb toxins A and B, and reduce the diarrhea and the other symptoms these toxins cause. However, because it is not an anti-infective, it is used in concert with vancomycin.[9]

It is also used in the "wash out" procedure in patients taking leflunomide or teriflunomide to aid drug elimination in the case of drug discontinuation due to severe side effects caused by leflunomide or teriflunomide.[10]

There are limited anecdotal reports by veterinarians that Cholestramine may function as a weak antidote for cycad poisoning in dogs. A mechanism of action has not been identified but might involve prevention of biliary cycasin recycling, and controlled trials have not been conducted to date [reference needed].

Available forms

Cholestyramine is available as powder form, in 4-g packets, or in larger canisters. In the United States, it can be purchased either as a generic medicine, or as Questran or Questran Light (Bristol-Myers Squibb).

Dosage

A typical dose is 4 to 8 g once or twice daily, with a maximum dose of 24 g/d.

Side effects

These side effects have been noted:[11]

Warnings

Patients with hypothyroidism, diabetes, nephrotic syndrome, dysproteinemia, obstructive liver disease, kidney disease, or alcoholism should consult their doctor before taking this medication.[11] Other drugs should be taken at least one hour before or four to six hours after cholestyramine to reduce possible interference with absorption. Patients with phenylketonuria should consult with a physician before taking Questran Light because that product contains phenylalanine.

Drug interactions

Interactions with these drugs have been noted:[11]

Most interactions are due to the risk of decreased absorption of these drugs. The duration of treatment is not limited, but the prescribing physician should reassess at regular intervals if continued treatment is still necessary. The principal overdose risk is blockage of intestine or stomach.

Cholestyramine may interfere in the absorption of fat-soluble vitamins such as vitamins A, D, E, and K. No special considerations regarding alcohol consumption are made.[11]

A 5% compound with aquaphor can be applied as a topical diaper rash ointment for infants and toddlers.[13]

References

  1. ↑ Wilcox C, Turner J, Green J (May 2014). "Systematic review: the management of chronic diarrhoea due to bile acid malabsorption". Aliment. Pharmacol. Ther. 39 (9): 923–39. doi:10.1111/apt.12684. PMID 24602022.
  2. ↑ Hofmann AF, Poley JR (August 1969). "Cholestyramine treatment of diarrhea associated with ileal resection". N. Engl. J. Med. 281 (8): 397–402. doi:10.1056/NEJM196908212810801. PMID 4894463.
  3. ↑ http://www.ajronline.org/doi/pdf/10.2214/ajr.134.4.827
  4. ↑ Wedlake L, A'Hern R, Russell D, Thomas K, Walters JR, Andreyev HJ (October 2009). "Systematic review: the prevalence of idiopathic bile acid malabsorption as diagnosed by SeHCAT scanning in patients with diarrhoea-predominant irritable bowel syndrome". Aliment. Pharmacol. Ther. 30 (7): 707–17. doi:10.1111/j.1365-2036.2009.04081.x. PMID 19570102.
  5. ↑ Sciarretta G, Furno A, Mazzoni M, Malaguti P (December 1992). "Post-cholecystectomy diarrhea: evidence of bile acid malabsorption assessed by SeHCAT test". Am. J. Gastroenterol. 87 (12): 1852–4. PMID 1449156.
  6. ↑ Danley T, St Anna L (October 2011). "Clinical inquiry. Postcholecystectomy diarrhea: what relieves it?". J Fam Pract 60 (10): 632c–d. PMID 21977493.
  7. ↑ George, J. D.; Magowan, J. (1971). "Diarrhea after total and selective vagotomy". The American Journal of Digestive Diseases 16 (7): 635–40. doi:10.1007/BF02239223. PMID 5563217.
  8. ↑ Gorbashko, AI (1992). "The pathogenesis, diagnosis and treatment of postvagotomy diarrhea". Vestnik khirurgii imeni I. I. Grekova 148 (3): 254–62. PMID 8594740.
  9. ↑ Stroehlein JR (June 2004). "Treatment of Clostridium difficile Infection". Curr Treat Options Gastroenterol 7 (3): 235–239. doi:10.1007/s11938-004-0044-y. PMID 15149585.
  10. ↑ Wong SP, Chu CM, Kan CH, Tsui HS, Ng WL (December 2009). "Successful treatment of leflunomide-induced acute pneumonitis with cholestyramine wash-out therapy". J Clin Rheumatol 15 (8): 389–92. doi:10.1097/RHU.0b013e3181c3f87e. PMID 19955995.
  11. ↑ 11.0 11.1 11.2 11.3 "Questran". PDRHealth. Retrieved July 7, 2012.
  12. ↑ http://www.nlm.nih.gov/medlineplus/ency/article/003493.htm[]
  13. ↑ Shoemaker, Ritchie C. Mold Warriors
  • The Merck Index (12 ed.). p. 2257.

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