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Linaclotid in case of DIOS, recurrent subileus + addendum to linaclotid question

Question
Original question "Linaclotid in case of DIOS, recurrent subileus etc" from 26.11.13
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Dear expert team,
I (47, CF) have been prescribed today linaclotid from a specialized center for gastro-enterology, as I frequently suffer from DIOS, recurrent conditions of subileus, coprolites and paralysis, pseudoobstructions. If necessary, I perform myself at home infusions of sterofundin, enemas and anti-emetic therapy; a pain therapy is established, supervised and adapted according to the level of pain. Objectification is always done. Furthermore, I am provided with gastrographin® [contrast medium]. A therapeutic trial with prucaloprid 2 mg over 6 weeks in the last spring did not bring an effect.

Which experiences do you have with linaclotid?
It is important for me to find a possiblitiy to improve my situation, as first of all, I am working more than part time, but secondly I want to delay a stoma as much as possible (and if, then only as a relief enterostoma that is replaced as soon as possible).
Citation from the leaflet:
"Linaclotid is a fully synthetic peptide, composed of 14 aminoacids, that acts via activation of guanylatcyclase-C-receptors (GC-C) on the luminal side of the epithelium of the small bowel and colon. The activation of the GC-C receptors leads to an intra- and extracellular increase of cyclo-Guanosinmonophosphate (cGMP). cGMP acitvates the Cystic Fibrosis Transmembrane Conduction Regulator (CFTR), which leads to secretion of bicarbonate, chloride and water. The result is loosening of the stool and shortening of the bowel passage. It is in discussion, that cGMP increases the threshold of the colon-nociception and therfore decreases the pain. "
As far as this, it sounds good and logical to me, in spite of the fact that it has been licensed for patients with irritable colon.
Many thanks in advance for your opinion.

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Addendum from 10.12.2013
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Personal Feedback:
After 2 weeks of intake, (until now) no effect could be observed. However, nausea occurred ingreasingly. The intake of linaclotid was in addition to the existing therapy with macrogol, sodiumpicosulfate drops (3 x 20 Drops), odansetron (if necessary i.v., metoclopramide not effective, dimenhydrinate has too much effect on the circulation), sterofundin via the port (in case of vomiting) and pain therapy with tilidin as basis therapy and fentanyl nose spray 100 µg in the acute situation. Gastrographin® is available at home in case of emergency. Enemas are done at home. Supply with nutrients via parenteral feeding. Exercise and massage of the adomen accomplish the therapy as non-medicamentous factors.

Until now it seems that linaclotid, as well as a former therapeutic trial with prucaloprid (other mechnism of acting) could not improve the motility situation. I was worth a try.
Answer
Hello,
in my opinion, the by you described symptoms speak rather for a chronic prologated form of a DIOS rather than for an obstipation. For a detailed judgement, imaging (ultrasound, CT, MRI) is helpful. Also a documented impairment of the motility would influence the decision on the therapy.

The usual treatment of a DIOS is the consequent, often long-term therapy with polyethylenglycol, e.g. Macrogol.
Dosage as well as duration are important. In case of a chronic-recurrent form, freedom of symptoms can only be achieved in case of a long-term therapy. Alternatively, gastrographin® can also be given orally.
The combined therapy with gastrografin® orally as well as via high enemas has to be absolutely medically supervised as severe side effects are known. Also in here, duration and dosage are important for the success of the therapy. Concomitantly an i.v. fluid supply should be done. The surgical therapy is only very rarely necessary in case of a consequent conservative therapy.
DIOS has to be differentiated from an obstipation, clinically this is not always possible in case of long lasting symptoms of pain. The therapy differs only slightly at the beginning of symptoms, later a more differentiating therapy is necessary.
Obstipation and DIOS are frequent in CF patients, and are an expression of the intestinal obstruction, that is in turn the consequence of a non or only partly functioning cAMP dependent CFTR (Cystic Fibrosis Transmembrane Conductance Regulator)- channel, with the conseuqence of an impaired chloride and water secretion. The gut mobility plays furthermore an important role.

Linaclotid is primarily prescribed for patients with irritable colon syndrome with obstipation or in case of chronic idiopathic obstipation. In any case therefore for patients with obstipation as main symptom of the functional complaints.
Linaclotid leads via an increase of cGMP to an activation of the CFTR-channel, that leads to an increased secretion of fluids, faster bowel passage and more bowel movements. A functionning CFTR-channel that can be activated, is present in such a group of patients, in CF this is not the case. Linaclotid is a good therapeutic option for the symptomatic treatment of a moderate to severe irritable colon symdrome with obstipation, however not in case of CF, this is why it does not strike me that the therapeutic trial was not successfull. I am not aware of any controlled studies concerning linacoltid and CF.
Your situation can seeminlgy only be improved via a consequent, medically supervised, therapy with the established drugs.
Yours sincerely,
Dr. Helmut Ellemunter
03.02.2014