Not only is constipation as simple as that, but the abdominal pain of patients with constipation-type irritable bowel syndrome also needs more attention

It is only for medical professionals to read for reference.
Abdominal pain + constipation seriously affect the quality of life of patients with IBS-C
.

 Speaking of constipation-type irritable bowel syndrome (IBS-C), everyone may be confused by the word "constipation" and form a stereotype, thinking that the symptom of IBS-C is constipation.
The laxative, the symptoms can be relieved
.

 Not really.
.
.
let's find out
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 PART 01: IBS-C symptom spectrum, you are worth knowing.
Let’s start with irritable bowel syndrome (IBS)
.

IBS is based on abdominal pain, bloating or abdominal discomfort as the main symptoms, which are related to defecation or accompanied by changes in defecation frequency and/or stool characteristics.
Through clinical routine examinations, it has not been possible to find organic diseases that can explain these symptoms [1]
.

 And IBS-C is a subtype of IBS, accounting for about 24.
9% of the total IBS[2]
.

The common symptoms of IBS-C patients can be divided into two dimensions: (1) constipation: including difficulty in defecation, reduced frequency, dry stool [3-4]; (2) abdominal symptoms: abdominal pain, bloating, and abdominal discomfort [3]
.

 Among them, abdominal symptoms such as abdominal pain and abdominal discomfort are the main symptoms that most disturb Chinese IBS patients
.

A questionnaire survey study included 123 patients with IBS who were continuously treated at the Gastroenterology Clinic of the First Affiliated Hospital of Sun Yat-sen University.
The results showed that the symptoms of IBS patients were abdominal pain accounting for 35.
8%, abdominal discomfort accounting for 21.
1%, and abdominal distension accounting for 17.
9%.
Insufficient bowel movements accounted for 7.
3%[5].
.
.
.
.
.
Figure 1: IBS trouble symptoms ranking Abdominal pain or abdominal discomfort in patients with IBS can appear in any part of the abdomen, of which the most common area around the umbilicus, accounting for 42.
3% ; Next is the middle of the upper abdomen, accounting for 26.
8% [5]
.

 Do not think that symptoms such as constipation and abdominal pain are trivial, and that IBS patients are hypocritical
.

More than 50% of IBS-C patients said that IBS symptoms prevent them from going to places without toilets, leaving home, and making plans.
They also prevent them from enjoying daily activities, travel, and even make them feel unnatural and hate themselves [6]
.

 Therefore, IBS-C needs to be paid attention to in clinical practice.
Once relevant symptoms are present, it is necessary to go to a professional medical institution for diagnosis and treatment
.

PART 02: Traditional laxatives cannot meet the needs of patients with IBS-C.
The current treatment plan for IBS-C mainly includes improving the patient's life>
.

 However, in terms of drug treatment, although there are many treatment options, most drugs mainly target a single symptom and cannot cover abdominal symptoms and constipation at the same time
.

The analysis of previous studies shows that: ▎Osmotic laxatives (such as polyethylene glycol) can increase the frequency of spontaneous bowel movements in patients with IBS-C, reduce stool hardness, and effectively relieve symptoms of constipation, but cannot improve abdominal pain, bloating and general symptoms [1 , 8-9]; ▎ Volumetric laxatives may increase fecal dissolution and dilate the intestines, which may aggravate the symptoms of abdominal distension in patients.
It has not been recommended for the treatment of IBS-C [1]; ▎ Long-term use of irritant laxatives may be Causes colonic melanosis, the latest "2020 China IBS Expert Consensus" non-irritating laxative treatment related recommendations[1,10]; ▎Antispasmodic agents can improve IBS symptoms, have obvious effects on abdominal pain, and treat other IBS-related symptoms There is controversy about the curative effect of constipation, and side effects such as constipation make its use in IBS-C patients limited [1,11]; ▎prokinetic drugs are used to improve the overall symptoms of IBS-C patients are controversial [1,12-14]
.

It can be seen that a multi-pronged treatment that takes into account abdominal symptoms and constipation at the same time is the ideal choice for patients with IBS-C
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 PART 03: Linaclotide, one drug with two effects, helps patients return to normal life.
Linaclotide is the world's first guanylate cyclase C (GC-C) agonist, containing 14 amino acid residues, and it is intestinal The binding of guanylate cyclase C receptor in epithelial cells causes an increase in intracellular cyclic guanosine phosphate (cGMP) concentration, which can increase the secretion of chlorine and bicarbonate in the intestinal lumen, which in turn increases the secretion of water and sodium, and accelerates the intestinal tract Transshipment, and increase the frequency of bowel movements
.

Intracellular cGMP is transported to the basal side of epithelial cells, reduces the activity of nociceptive fibers, improves visceral hypersensitivity, and relieves abdominal pain [15]
.

 Figure 2: Linaclotide has a dual mechanism of increasing intestinal fluid secretion/transport and reducing pain nerve sensitivity.
Nalotide 290μg/d or placebo was treated for 26 weeks
.

The results showed that linaclotide had a rapid onset on the first day of treatment, and 28.
9% of patients had completely spontaneous defecation (CSBM) on the first day of treatment, while only 8.
4% of the placebo group (P<0.
0001) [16]
.

  Figure 3: Proportion of patients with CSBM on day 1 Another 12-week multicenter study involving 800 patients with IBS-C was randomized to receive placebo and linaclotide (290 μg orally, once daily) 12 Week
.

The results show that linaclotide has a rapid effect on alleviating the symptoms of constipation.
Spontaneous defecation occurs within 1 day of taking the medicine, and the maximum improvement of intestinal function is achieved within 1 week; the improvement of abdominal pain takes effect within 1 week, and the maximum effect is reached within 6-8 weeks [ 17]
.

 Figure 4: CSBM, the most painful abdominal pain score changes from baseline In addition to the short-term rapid onset to improve the core symptoms of IBS-C, the long-term therapeutic effect of linaclotide also performed well
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The data from the 26-week phase III study of linaclotide in North America continued to be followed up to 2 years showed that among 535 patients with IBS-C, more than 70% of the patients were very satisfied with linaclotide treatment, and the occurrence of diarrhea did not affect the patients Satisfaction[18]
.

 In terms of safety, the most common adverse event of linaclotide is diarrhea, which is mostly mild and moderate, and rarely severe
.

A meta-analysis showed that 1.
2% of 1955 patients treated with 145μg or 290μg linaclotide had serious adverse events, similar to those of patients receiving placebo (1.
7%) [19]
.

 Based on the good efficacy and safety of linaclotide, it has been recommended by many national guidelines
.

In the IBS treatment guidelines of the American Gastroenterology Association and the American Gastroenterology Association, linaclotide is strongly recommended for the treatment of IBS-C with the highest level of evidence [12,20]
.

In addition, the latest "2020 China IBS Expert Consensus Opinion" released last year also pointed out that secretagogues can improve the symptoms of IBS-C constipation, and guanylate cyclase-C agonists are also effective for abdominal pain (recommended level: A+, 67%, A, 33%; level of evidence: moderate quality)[1]
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 PART 04: Summary IBS-C is a type of intestinal disease that seriously affects the quality of life of patients.
In addition to constipation, it also manifests as abdominal symptoms such as abdominal pain, bloating, and abdominal discomfort.
The existence of these abdominal symptoms is also the most troublesome for IBS-C patients Of
.

Currently in the treatment of IBS-C, although there are many treatment options, there are only a few drugs that can simultaneously take care of constipation and abdominal symptoms
.

 Linaclotide is the world's first GC-C agonist.
It can quickly take effect once a day and improve the core symptoms of patients; at the same time, it has good safety and high patient satisfaction with treatment
.

At present, it has been recommended by consensus guidelines at home and abroad and is the preferred therapeutic drug for patients with IBS-C
.

 Reference source: 1.
Gastrointestinal Functional Diseases Collaboration Group, Chinese Medical Association Gastroenterology Branch, etc.
Chinese Journal of Digestion.
2020; 40(12): 803-818.
2.
Zhao Y, et al.
Aliment Pharmacol Ther.
2010 Aug; 32(4):562-72.
3.
Chey WD, et al.
JAMA.
2015; 313(9): 949-958.
4.
Gastrointestinal Motility Group, Chinese Society of Gastroenterology, etc.
Chinese Journal of Digestion.
2019; 39( 9): 577-598.
5.
Xiong Lishou, et al.
Chinese Journal of Gastroenterology.
2015; 35(7): 476-477.
6.
Courtney McMahon, et al.
Presentation Number Sa1943; 2019 DDW.
7.
Wang Yanping, et al.
Gastroenterology .
2020; 25(9): 534-539.
8.
AwadRA, et al.
Colorectal Dis, 2010, 12(11): 1131-1138.
9.
ChapmanRW, et al.
Am J Gastroenterol.
2013; 108(9): 1508-1515.
10 Anorectal Physician Branch of Chinese Medical Doctor Association.
Chinese Journal of Gastrointestinal Surgery.
2017; 20(3): 241-243.
11.
Heading R, et al.
Aliment Pharmacol Ther.
2006; 24(2): 207-36.
12.
Ford AC, et al.
Am J Gastroenterol.
2018; 113(Suppl 2): ​​1-18.
13.
Gwee KA, et al.
J Neurogastroenterol Motil.
2019; Jul 1; 25(3): 343-362.
14.
Moayyedi P, et al.
J Can Assoc Gastroenterol.
2019; 2(1): 6-29.
15.
Zou Duowu.
Chinese Journal of Digestion.
2019; 39(4): 286-288.
16.
CheyWD, et al.
Am J Gastroenterol, 2012, 107(11): 1702-1712.
17.
Rao S, et al.
Am J Gastroenterol, 2012, 107(11): 1714-1724.
18.
SchneierHA, et al.
Gut, 2017, 66Suppl 2: A274.
19.
VidelockEJ, et al.
Clin Gastroenterol Hepatol, 2013, 11(9): 1084-1092.
20.
Weinberg DS, et al.
Gastroenterology 2014;147(5):1146–1148.
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