Madersbacher_edit_Layout 1 02/10/2009 11:38 Page 52
Cystitis
Ions that manage to penetrate the layer are prevented by the every 14 days in a cross-over design. On DMSO, the symptoms
hydrophobic uroplakin molecules and the functioning Na
+
/K
+
pumps markedly improved in 53% of the patients, but in only 18% of the
from penetrating any further into the bladder wall, and so sensory nerves patients treated with placebo.
7
are protected and are not depolarised. Afferent C-fibres responsible for
transmission of pain signals are located in the urothelium and in the Heparin
detrusor. If the GAG layer is damaged or missing, potassium ions can Heparin is similar to the GAG layer of the bladder when instilled into
reach the cell membrane without resistance and migrate through. the bladder; theoretically, it may replace the damaged GAG layer. The
instillation method has not yet been standardised. The report by Kuo
8
suggested the efficacy of heparin; however, there is no randomised
Treatment of interstitial cystitis and
comparative study to provide conclusive evidence.
related disorders with exogenous
Pentosan Polysulphate
glycosaminoglycan-replenishment
Pentosan polysulphate is a mucopolysacchride similar to heparin,
with a similar postulated mode of action when used locally; however,
instillation solutions works, and has been
it too has not been well-studied clinically.
demonstrated in various animal models
Hyaluronic Acid
of bladder damage.
Hyaluronic acid, like heparin, is a mucopolysaccharide, which could
theoretically repair a damaged GAG layer of the bladder mucosa.
Despite a functioning Na
+
/K
+
pump, this mechanism is too weak to However, two reported double-blind, placebo-controlled, multicentre
eliminate the huge numbers of ions that flood in. The potassium ions can clinical studies of hyaluronic acid preparations showed no significant
spread unimpeded through the bladder wall and sensory neurons efficacy of sodium hyaluronate compared with placebo. These
become depolarised, which the patient perceives as urgency or pain. If negative studies have not been published in peer-reviewed literature
the GAG layer could be restored by means of GAG-replenishment (Bioniche Life Science Inc., 2003; Seikagaku Corporation, 2004).
therapy, this would reduce the permeability and proteases, and other
inflammatory molecules would be kept away from the cell membrane of Chondroitin Sulphate
the urothelial cells. The bladder surface would thus be given a chance to Chondroitin sulphate is an important mucopolysaccharide. Its efficacy
heal. Treatment of IC and related disorders with exogenous GAG- was first described by Steinhoff.
9
It is one of the main components of the
replenishment instillation solutions works, and has been demonstrated protective GAG layer of the bladder. GAG-replenishment therapy with
in various animal models of bladder damage. First, the GAG layer was chondroitin sulphate was tested in a multinational, multicentre,
damaged enzymatically or disrupted chemically. Then exogenous prospective post-marketing surveillance study.
10
No placebo group was
chondroitin sulphate marked with a fluorescent dye was instilled in included; instead, all study participants received GAG-replenishment
order to test the postulated mechanism of action of GAG- therapy by administration of chondroitin sulphate 0.2%. Altogether, 286
replenishment therapy. This showed that the exogenous chondroitin patients with chronic forms of cystitis were enrolled, 91% of whom were
sulphate was absorbed mostly into the damaged areas of the bladder women. The presence of the triad of symptoms, i.e. urinary frequency,
wall and only in very small amounts into the intact bladder wall.
4
urinary urgency and pelvic pain, indicated the presence of a GAG defect.
IC was diagnosed in 165 study participants (57%), 27% had chronically
Therapeutic Options for Bladder recurring cystitis, 12% OAB and 5% radiation cystitis. The incidence of
Pain Syndrome/Interstitial Cystitis other forms of cystitis was 6%. The median age of the study participants
and Related Disorders was 61 years (19–93 years) and the median duration of illness was 2.8
Oral Therapy years (0–35 years). Each patient was treated for a period of three
Several categories of medication have been used in the management of months. Depending on the symptoms, the medication was initially
patients with BPS, including analgesics, antidepressants, antihistamines, instilled once per week over a period of four to six weeks, and then once
immunosuppressants and GAGs. Many of these drugs are used monthly. The marked improvements in all of the evaluated symptoms,
empirically. van Ophoven et al.performed the only reported prospective, which were already apparent from the first instillation onwards and
double-blind, placebo-controlled study of amitriptyline.
5
Sodium which showed a continuous improvement throughout the study, are to
pentosanpolysulphate (PPS), a synthetic sulphated polysaccharide, is be emphasised. At the end of the study the analysis of the data of all of
available in an oral formulation, 3–6% of which is excreted into the urine the enrolled patients showed a mean improvement in urinary frequency
and may replenish the damaged GAG layer. Five randomised controlled from about 12.7 to 9.2 times daily and an improvement in the nocturia
trials with PPS have yielded conflicting results in terms of efficacy: two from four times to twice. Urinary urgency rated by the patients on a
had unfavourable results and three had favourable results for PPS. The scale of 0 to 10 showed a mean improvement from 6.8 to 3.4. Mean pain
interpretation could be that only a minority of patients respond to PPS, intensity, also rated on a scale of 0 to 10, had decreased from 4.8 to 2.6
but there is no reliable method of identifying those patients.
6
after the therapy. The good response to treatment was also reflected in
the very positive overall assessment – more than 80% of the patients
Intravesical Therapies and physicians rated the therapy positively. At the same time, the
Intravesical therapies form one of the staples of BPS/IC therapy. therapy was judged to be well tolerated.
For intravesical use, local anaesthetics, dimethylsulfoxide (DMSO) or
replenishment therapy with GAGs may be considered. The Chronically Recurring Cystitis
effectiveness of DMSO in IC is documented in a small, controlled study If four or more acute bacterial infections occur within one year, the
published in 1988: 33 patients received DMSO or placebo intravesically condition is referred to as chronic recurrent cystitis. In most cases
52 EUROPEAN UROLOGICAL REVIEW