Pentosan polysulfate
Pentosan polysulfate (PPS) is a medication used for interstitial cystitis. It is a semi-synthetic polysulfated xylan. Medical uses. Interstitial cystitis/painful bladder syndrome. Pentosan polysulfate may be used either by mouth or in the bladder to treat interstitial cystitis/painful bladder syndrome (IC/PBS). An older review found improvements in pain (36%), urgency (28%), and frequency (54%), but that it does not change the frequency of urination at night. More recent trials, however, found it to be of no benefit. Osteoarthritis. PPS has been studied in knee osteoarthritis, though evidence to support such use is poor as  of 2003. There is some theoretical evidence that it should help. Adverse effects. Patients who have taken PPS orally report a variety of side effects, primarily gastrointestinal complaints such as diarrhea, heartburn, and stomach pain. Hair loss, headache, rash, and insomnia have also been reported. Due to Elmiron's anticoagulant effects, some patients report bruising more easily. In some cases, patients are asked to stop taking the medication before any major surgical procedures to reduce the likelihood of bleeding. Recent report based on clinical observation hypothesizes that chronic exposure to PPS can cause retinal toxicity, mimicking pigmentary pattern dystrophy. Mechanism  of action. In IC, PPS is believed to work by providing a protective coating to the damaged bladder wall. PPS is similar in structure to the natural glycosaminoglycan coating of the inner lining of the bladder, and may replace or repair the lining, reducing its permeability. History. The calcium salt of PPS was one of the first reported disease-modifying osteoarthritis drugs (DMOAD). Names. The IUPAC name for pentosan polysulfate is [(2R,3R,4S,5R)-2-hydroxy-5-[(2S,3R,4S,5R)-5-hydroxy-3,4-disulfooxyoxan-2-yl]oxy-3-sulfooxyoxan-4-yl] hydrogen sulfate. There are 40 synonyms listed for pentosan polysulfate on PubChem including BAY-946, HOE-946, pentosan sulfuric polyester, polypentose sulfate, polysulfated xylan , PZ-68, SP-54, xylan SP54 and xylan sulfate. Various brand names include Elmiron (as sodium salt), Hemoclar, Anarthron, Fibrase, Fibrocid, Thrombocid and SP54. PPS capsules are sold in India under the brand names Comfora, Pentossan-100, Cystopen and For-IC. In the veterinary field, pentosan polysulfate is sold as Cartrophen Vet and Sylvet by Biopharm Australia, Pentosan by Naturevet Australia, Anarthron by Randlab Australia and Zydax by Parnell. Research. Transmissible spongiform encephalopathies. PPS is being studied as a potential treatment of Creutzfeldt–Jakob disease (CJD). The rationale for this treatment was unclear but it was subsequently shown in prion-infected mouse neuroblastoma  cells that PPS could rapidly reduce the levels of abnormal (scrapie) prion without affecting the normal cellular isoform. As PPS can bind to the cellular isoform of the prion protein, it may stabilise this form and prevent its conversion to the pathological (scrapie) isoform. The treatment of one patient in Northern Ireland and around six other patients in mainland Britain was reported in the press. Other animals. Dogs. Read et al. (1996) used three different doses of sodium PPS to treat 40 geriatric dogs with well-established clinical signs of chronic osteoarthritis (OA) with a subcutaneous injection. The 3 mg /kg dose was the most effective. In a study conducted with 10 elderly dogs with osteoarthritis given calcium PPS (3 mg/kg intramuscularly) once weekly for four weeks, the improvement in symptoms (seen at 1, 2, 3 and 7 weeks after initiation of therapy) was found to correlate with plasma indices of fibrinolytic activity and lipid profiles. In a study in dogs with OA secondary to cranial cruciate ligament deficiency, although no differences were identified in either functional outcome or radiographic progression using the oral calcium PPS compared with placebo, there were significantly lower levels of proteoglycan breakdown products in  the synovial fluid of the osteoarthritic joints. The efficacy of subcutaneous sodium PPS (3 mg/kg) was tested in 40 dogs with cranial cruciate ligament instability and found to hasten recovery, as measured by more rapidly improved ground reaction forces, over 48 weeks. Horses. There are few published reports describing the use of PPS for equine joint disease; however, the drug is being used for this indication in Australia. When administered to racing thoroughbreds with chronic osteoarthritis (2 to 3 mg/kg, intramuscularly, once weekly for 4 weeks, then as required), PPS treatment improved but did not eliminate clinical signs  of joint disease. Articular cartilage fibrillation was substantially reduced by similar NaPPS treatment intramuscularly in nine horses with experimentally-induced carpal osteoarthritis. Despite limited published studies on the effect of PPS in horses, most surveyed owners and trainers in Australia found the intramuscular PPS treatment to be highly efficacious when used as a prophylactic prior to competition.