Materiały źródłowe

• #1 The pathophysiology of chronic constipation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3206564/

  Constipation is broadly defined as an unsatisfactory defecation characterized by infrequent stools, difficult stool passage or both. […] The pathophysiology of constipation is multifactorial and classification schemes can be confusing. The common approach groups constipation into primary and secondary causes. Primary causes are intrinsic problems of colonic or anorectal function, whereas secondary causes are related to organic disease, systemic disease or medications. […] The present article discusses the normal process of colonic transit and defecation, followed by a review of the etiology of constipation. […] The causes of constipation are varied and may be multifactorial. The common approach groups constipation into primary and secondary causes. Primary causes are intrinsic problems of colonic or anorectal function, whereas secondary causes are related to organic disease, systemic disease or medications.

• #2 Current Overview on Clinical Management of Chronic Constipation

  https://www.mdpi.com/2077-0383/10/8/1738

  Constipation is one of the major gastrointestinal disorders diagnosed in clinical practice in Western countries. Pathophysiology of constipation is complex and multifactorial, where aspects like disturbance in colonic transit, genetic predisposition, lifestyle habits, psychological distress, and many others need to be taken into consideration. […] The patients with chronic constipation may be divided into three groups according to the colonic transit. Patients with normal colonic transit suffer from functional constipation, they are the most predominant subgroup. The second group consists of patients with rectal evacuation disorders, especially patients with dyssynergic defecation. Dyssynergic defecation, also known as anismus, obstructive defecation, pelvic floor dyssynergia, or outlet obstruction, is a result of incoordination between the abdominal wall and pelvic floor muscles, and the anal sphincters. This incoordination may be a result of several mechanisms that include paradoxical anal contraction, impaired rectal contraction and inadequate anal relaxation. The least common type of chronic constipation is slow colonic constipation. Patients from this group usually present with dysfunctional retrograde colonic propulsion or postprandial motor activity. Pathophysiology of constipation is multifactorial, thereby it is problematic to match exact factor to one of the above groups.

• #3 Constipation – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK513291/

  Constipation is a symptom or condition characterized by difficult and infrequent bowel movements, typically 3 or fewer times a week. […] The pathophysiology of constipation is multifaceted and not entirely understood. It involves a complex interplay of factors affecting the gastrointestinal tract, nervous system, and pelvic muscles. Common contributors include reduced colonic motility, delayed transit of stool, impaired rectal sensation, and ineffective coordination of pelvic floor muscles during defecation. […] The pathophysiology underlying functional constipation is multifactorial and not well understood. Factors contributing to functional constipation include pain, fever, dehydration, dietary and fluid intake, psychological issues, toilet training, medicines, and a family history of constipation.

• #4 The pathophysiology of chronic constipation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3206564/

  Primary forms of constipation arise from intrinsic defects in colonic function or malfunction of the defecation process. […] Slow-transit constipation (STC) causes infrequent bowel movements (typically less than once per week) and is most common in young women. […] STC is believed to be a neuromuscular disorder of the colon. […] Dyssynergia, probably the most common functional DD, is an acquired behavioural DD. […] To fulfill the formal diagnostic criteria for dyssynergic defecation, patients must: […] It should be noted that prolonged colonic transit time can be seen in patients with DD and in patients with STC. […] Constipation is a common side effect of many drugs, and a detailed medication history should be taken during the initial workup. […] Diseases that involve the nervous system may cause chronic constipation. […] The origin of constipation in patients with these conditions is complex and include disease-related autonomic and pelvic nerve dysfunction as well as generalized systemic factors. […] The pathophysiology of constipation in Parkinson’s disease includes central and peripheral mechanisms.

• #5 The pathophysiology of chronic constipation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3206564/

  Constipation is broadly defined as an unsatisfactory defecation characterized by infrequent stools, difficult stool passage or both. […] The pathophysiology of constipation is multifactorial and classification schemes can be confusing. The common approach groups constipation into primary and secondary causes. Primary causes are intrinsic problems of colonic or anorectal function, whereas secondary causes are related to organic disease, systemic disease or medications. […] The present article discusses the normal process of colonic transit and defecation, followed by a review of the etiology of constipation. […] The causes of constipation are varied and may be multifactorial. The common approach groups constipation into primary and secondary causes. Primary causes are intrinsic problems of colonic or anorectal function, whereas secondary causes are related to organic disease, systemic disease or medications.

• #6 Pharmacologic management of chronic constipation, Current treatment options | Medicina Universitaria

  https://www.elsevier.es/en-revista-medicina-universitaria-304-articulo-pharmacologic-management-chronic-constipation-current-X1665579612506653

  Constipation is a common gastrointestinal disorder. In North America, estimates of its prevalence are between 2-19%. Similar trends are reported in Latin-America with prevalences around 5-21%. Constipated patients consume more health resources that include prescription and OTC laxatives and other alternative treatments. Also, constipation leads to impaired quality of life. […] Constipation has been classified into three pathophysiologic groups: 1) Normal transit constipation (50%), frequently is a result of environmental, genetic and socio-psychological or dietary factors. Example of this include chronic functional constipation and irritable bowel syndrome with constipation-predominant. 2) Dyssynergic defecation (30%), due to incoordination between abdominal and pelvic muscle contraction, requiring both medical and biofeedback management and 3) slow transit constipation (20%), often a result of colonic myopathy or neuropathy, frequently requiring an aggressive medical treatment and when they fail, a surgical intervention may be required. It is important to recognize that more than one mechanism may be present in a single patient and frequently there is an overlap between these subtypes.

• #7 Pharmacologic management of chronic constipation, Current treatment options | Medicina Universitaria

  https://www.elsevier.es/en-revista-medicina-universitaria-304-articulo-pharmacologic-management-chronic-constipation-current-X1665579612506653

  Constipation is a common gastrointestinal disorder. In North America, estimates of its prevalence are between 2-19%. Similar trends are reported in Latin-America with prevalences around 5-21%. Constipated patients consume more health resources that include prescription and OTC laxatives and other alternative treatments. Also, constipation leads to impaired quality of life. […] Constipation has been classified into three pathophysiologic groups: 1) Normal transit constipation (50%), frequently is a result of environmental, genetic and socio-psychological or dietary factors. Example of this include chronic functional constipation and irritable bowel syndrome with constipation-predominant. 2) Dyssynergic defecation (30%), due to incoordination between abdominal and pelvic muscle contraction, requiring both medical and biofeedback management and 3) slow transit constipation (20%), often a result of colonic myopathy or neuropathy, frequently requiring an aggressive medical treatment and when they fail, a surgical intervention may be required. It is important to recognize that more than one mechanism may be present in a single patient and frequently there is an overlap between these subtypes.

• #8 Chronic Constipation – UCLA G. Oppenheimer Center for Neurobiology of Stress and Resilience

  https://uclacns.org/patients/disease-information/chronic-constipation/

  Chronic constipation that is not due to secondary causes, such as other medical conditions or medications, is referred to as functional constipation. […] The three main causes of functional constipation are normal transit constipation, slow transit constipation, and defecatory or evacuation disorders. […] In normal-transit constipation, the rate of stool passage through the colon and stool frequency are normal, but patients perceive that they are constipated. […] In slow-transit constipation, passage of stool through the colon is slower than normal. […] Defectory disorders that can cause constipation include dyssynergic defecation, rectal prolapse (protrusion of rectal tissue through the anal opening), and rectocele (outpouching of the rectum). […] In dyssynergic dysfunction, also referred to as pelvic floor dysfunction or anismus, there is ineffective coordination of the pelvic floor, abdominal, rectal, and anal sphincter musculature in the evacuation mechanism.

• #9 Pharmacologic management of chronic constipation, Current treatment options | Medicina Universitaria

  https://www.elsevier.es/en-revista-medicina-universitaria-304-articulo-pharmacologic-management-chronic-constipation-current-X1665579612506653

  Constipation is a common gastrointestinal disorder. In North America, estimates of its prevalence are between 2-19%. Similar trends are reported in Latin-America with prevalences around 5-21%. Constipated patients consume more health resources that include prescription and OTC laxatives and other alternative treatments. Also, constipation leads to impaired quality of life. […] Constipation has been classified into three pathophysiologic groups: 1) Normal transit constipation (50%), frequently is a result of environmental, genetic and socio-psychological or dietary factors. Example of this include chronic functional constipation and irritable bowel syndrome with constipation-predominant. 2) Dyssynergic defecation (30%), due to incoordination between abdominal and pelvic muscle contraction, requiring both medical and biofeedback management and 3) slow transit constipation (20%), often a result of colonic myopathy or neuropathy, frequently requiring an aggressive medical treatment and when they fail, a surgical intervention may be required. It is important to recognize that more than one mechanism may be present in a single patient and frequently there is an overlap between these subtypes.

• #10 Pulsenotes | Constipation

  https://app.pulsenotes.com/medicine/gastroenterology/notes/constipation

  Constipation is a common complaint that refers to the infrequent passage of stool, difficulty passing stool, and/or a sensation of incomplete emptying. […] The pathophysiology of constipation is multifactorial as many different mechanisms can contribute to its development. To better understand constipation, it is best to consider it in the context of normal colonic function and defecation. […] The primary function of the colon is to absorb water and transport waste from the caecum to the rectum for evacuation. Colonic motility is important for the transport of faeces to the rectum where distension initiates the urge to defaecate. Defecation then relies on the coordinated relaxation of the internal anal sphincter and pelvic floor muscles with contraction of the diaphragm and abdominal muscles.

• #11 Pulsenotes | Constipation

  https://app.pulsenotes.com/medicine/gastroenterology/notes/constipation

  At a molecular level, colonic motility is complex and mediated by various neurotransmitters with 5-hydroxytryptamine (5-HT) being a major factor. Distension of the gut wall by faeces causes the release of 5-HT from enterochromaffin cells that stimulates the local release of neurotransmitters such as acetylcholine that initiates contraction. In addition, inhibitory neurotransmitters such as nitric oxide are released behind the faeces to enable forward movement. Disruption of these neurotransmitters (e.g. 5-HT receptor antagonists, anti-muscarinic) can lead to constipation. […] Disruption of this normal coordinated mechanism can lead to the sensation of incomplete emptying and excessive straining on the toilet. These are collectively known as functional defecation disorders that are felt to be acquired behavioural disorders due to learnt improper toilet techniques.

• #12 Pulsenotes | Constipation

  https://app.pulsenotes.com/medicine/gastroenterology/notes/constipation

  At a molecular level, colonic motility is complex and mediated by various neurotransmitters with 5-hydroxytryptamine (5-HT) being a major factor. Distension of the gut wall by faeces causes the release of 5-HT from enterochromaffin cells that stimulates the local release of neurotransmitters such as acetylcholine that initiates contraction. In addition, inhibitory neurotransmitters such as nitric oxide are released behind the faeces to enable forward movement. Disruption of these neurotransmitters (e.g. 5-HT receptor antagonists, anti-muscarinic) can lead to constipation. […] Disruption of this normal coordinated mechanism can lead to the sensation of incomplete emptying and excessive straining on the toilet. These are collectively known as functional defecation disorders that are felt to be acquired behavioural disorders due to learnt improper toilet techniques.

• #13 The pathophysiology of chronic constipation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3206564/

  Primary forms of constipation arise from intrinsic defects in colonic function or malfunction of the defecation process. […] Slow-transit constipation (STC) causes infrequent bowel movements (typically less than once per week) and is most common in young women. […] STC is believed to be a neuromuscular disorder of the colon. […] Dyssynergia, probably the most common functional DD, is an acquired behavioural DD. […] To fulfill the formal diagnostic criteria for dyssynergic defecation, patients must: […] It should be noted that prolonged colonic transit time can be seen in patients with DD and in patients with STC. […] Constipation is a common side effect of many drugs, and a detailed medication history should be taken during the initial workup. […] Diseases that involve the nervous system may cause chronic constipation. […] The origin of constipation in patients with these conditions is complex and include disease-related autonomic and pelvic nerve dysfunction as well as generalized systemic factors. […] The pathophysiology of constipation in Parkinson’s disease includes central and peripheral mechanisms.

• #14

  https://www.tropicalgastro.com/articles/28/3/Review-of-pathogenesis-and-management-of-constipation.html

  This article reviews the pathogenesis, classification, mechanism and management of constipation. […] Constipation may result from slow colonic transit, faecal evacuation disorders or a combination of both. […] Pathophysiologically, constipation may result from slow colonic transit, faecal evacuation disorders (e.g. anismus or puborectal dyssynergia, rectocele and perineal descent syndrome) and a combination of slow colonic transit and faecal evacuation disorder. […] Some of the recent reports suggested that functional constipation might have some subtle organic basis, which could alter colonic motility or rectoanal co-ordination. […] Several histologic abnormalities have been demonstrated in resected colon specimens from such patients. […] These abnormalities include decreased numbers of enteric neuronal elements including interstitial cells of Cajal as well as nuclear abnormalities in the ganglia and reduction of acetylcholinesterase activity.

• #15 Pathogenesis of chronic constipation in a Polish group of paediatric patients – an attempt to create the optimal histopathological diagnostic protocol

  https://www.termedia.pl/Pathogenesis-of-chronic-constipation-in-a-Polish-group-of-paediatric-patients-an-attempt-to-create-the-optimal-histopathological-diagnostic-protocol,41,36914,1,1.html

  Although most of these conditions are functional, in about 5% of cases, organic disorders can be identified and histopathological examination is necessary. […] If HD is ruled out, full-thickness surgical biopsy of the large intestine should be performed to exclude desmosis of the colon. […] Histological staining with Picrosirius red showing complete lack of the mesh network of collagen in the intestinal muscular wall confirms the diagnosis. […] Absence or reduction of the number of Cajal cells may cause chronic pseudo-obstruction. […] After excluding all these disorders there are still other diseases such as enteric neuropathies or myopathies that should be taken into consideration.

• #16

  https://www.tropicalgastro.com/articles/28/3/Review-of-pathogenesis-and-management-of-constipation.html

  Others have shown abnormalities in the contractile properties of colonic smooth muscle. […] Normal defecation involves the coordinated relaxation of the internal anal sphincter, puborectalis and external anal sphincter muscles, together with increased intra-abdominal pressure and colonic motor activity that propels stools towards the rectum. […] In some patients, ineffective defecation seems to be associated with a failure to relax (or with inappropriate contraction of) the puborectalis and the external anal sphincter muscles. […] In other patients, weak propulsion of the stools can lead to similar effects.

• #17 Constipation – Physician’s Channel – Mount Sinai New York

  https://physicians.mountsinai.org/videos/constipation

  When I think about cause of constipation. There are a few different ways in which one can try to categorize the items. In the differential diagnosis. First would be conditions that lead to slow transit so you lose the amplitude, the large and small high amplitude contractions which can occur conditions which can do this include various medications, diabetes, spinal cord disease, scleroderma, metabolic conditions such as hyper calc mia, yuri mia, thyroid disease, particularly hypothyroidism, chronic colonic pseudo obstruction, inadequate dietary intake. […] Normal transit constipation includes those individuals who are taking low fiber and then lastly outlet obstruction. […] There are three major constipation finna types. Those include functional constipation, irritable bowel syndrome and difficult or disorder.

• #18 The pathophysiology of chronic constipation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3206564/

  Primary forms of constipation arise from intrinsic defects in colonic function or malfunction of the defecation process. […] Slow-transit constipation (STC) causes infrequent bowel movements (typically less than once per week) and is most common in young women. […] STC is believed to be a neuromuscular disorder of the colon. […] Dyssynergia, probably the most common functional DD, is an acquired behavioural DD. […] To fulfill the formal diagnostic criteria for dyssynergic defecation, patients must: […] It should be noted that prolonged colonic transit time can be seen in patients with DD and in patients with STC. […] Constipation is a common side effect of many drugs, and a detailed medication history should be taken during the initial workup. […] Diseases that involve the nervous system may cause chronic constipation. […] The origin of constipation in patients with these conditions is complex and include disease-related autonomic and pelvic nerve dysfunction as well as generalized systemic factors. […] The pathophysiology of constipation in Parkinson’s disease includes central and peripheral mechanisms.

• #19 Current Overview on Clinical Management of Chronic Constipation

  https://www.mdpi.com/2077-0383/10/8/1738

  Constipation is one of the major gastrointestinal disorders diagnosed in clinical practice in Western countries. Pathophysiology of constipation is complex and multifactorial, where aspects like disturbance in colonic transit, genetic predisposition, lifestyle habits, psychological distress, and many others need to be taken into consideration. […] The patients with chronic constipation may be divided into three groups according to the colonic transit. Patients with normal colonic transit suffer from functional constipation, they are the most predominant subgroup. The second group consists of patients with rectal evacuation disorders, especially patients with dyssynergic defecation. Dyssynergic defecation, also known as anismus, obstructive defecation, pelvic floor dyssynergia, or outlet obstruction, is a result of incoordination between the abdominal wall and pelvic floor muscles, and the anal sphincters. This incoordination may be a result of several mechanisms that include paradoxical anal contraction, impaired rectal contraction and inadequate anal relaxation. The least common type of chronic constipation is slow colonic constipation. Patients from this group usually present with dysfunctional retrograde colonic propulsion or postprandial motor activity. Pathophysiology of constipation is multifactorial, thereby it is problematic to match exact factor to one of the above groups.

• #20 Current Overview on Clinical Management of Chronic Constipation

  https://www.mdpi.com/2077-0383/10/8/1738

  Constipation is one of the major gastrointestinal disorders diagnosed in clinical practice in Western countries. Pathophysiology of constipation is complex and multifactorial, where aspects like disturbance in colonic transit, genetic predisposition, lifestyle habits, psychological distress, and many others need to be taken into consideration. […] The patients with chronic constipation may be divided into three groups according to the colonic transit. Patients with normal colonic transit suffer from functional constipation, they are the most predominant subgroup. The second group consists of patients with rectal evacuation disorders, especially patients with dyssynergic defecation. Dyssynergic defecation, also known as anismus, obstructive defecation, pelvic floor dyssynergia, or outlet obstruction, is a result of incoordination between the abdominal wall and pelvic floor muscles, and the anal sphincters. This incoordination may be a result of several mechanisms that include paradoxical anal contraction, impaired rectal contraction and inadequate anal relaxation. The least common type of chronic constipation is slow colonic constipation. Patients from this group usually present with dysfunctional retrograde colonic propulsion or postprandial motor activity. Pathophysiology of constipation is multifactorial, thereby it is problematic to match exact factor to one of the above groups.

• #21

  https://www.tropicalgastro.com/articles/28/3/Review-of-pathogenesis-and-management-of-constipation.html

  Others have shown abnormalities in the contractile properties of colonic smooth muscle. […] Normal defecation involves the coordinated relaxation of the internal anal sphincter, puborectalis and external anal sphincter muscles, together with increased intra-abdominal pressure and colonic motor activity that propels stools towards the rectum. […] In some patients, ineffective defecation seems to be associated with a failure to relax (or with inappropriate contraction of) the puborectalis and the external anal sphincter muscles. […] In other patients, weak propulsion of the stools can lead to similar effects.

• #22

  https://www.tropicalgastro.com/articles/28/3/Review-of-pathogenesis-and-management-of-constipation.html

  Others have shown abnormalities in the contractile properties of colonic smooth muscle. […] Normal defecation involves the coordinated relaxation of the internal anal sphincter, puborectalis and external anal sphincter muscles, together with increased intra-abdominal pressure and colonic motor activity that propels stools towards the rectum. […] In some patients, ineffective defecation seems to be associated with a failure to relax (or with inappropriate contraction of) the puborectalis and the external anal sphincter muscles. […] In other patients, weak propulsion of the stools can lead to similar effects.

• #23 The pathophysiology of chronic constipation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3206564/

  Primary forms of constipation arise from intrinsic defects in colonic function or malfunction of the defecation process. […] Slow-transit constipation (STC) causes infrequent bowel movements (typically less than once per week) and is most common in young women. […] STC is believed to be a neuromuscular disorder of the colon. […] Dyssynergia, probably the most common functional DD, is an acquired behavioural DD. […] To fulfill the formal diagnostic criteria for dyssynergic defecation, patients must: […] It should be noted that prolonged colonic transit time can be seen in patients with DD and in patients with STC. […] Constipation is a common side effect of many drugs, and a detailed medication history should be taken during the initial workup. […] Diseases that involve the nervous system may cause chronic constipation. […] The origin of constipation in patients with these conditions is complex and include disease-related autonomic and pelvic nerve dysfunction as well as generalized systemic factors. […] The pathophysiology of constipation in Parkinson’s disease includes central and peripheral mechanisms.

• #24

  https://bpac.org.nz/BPJ/2007/October/constipation.aspx

  Most cases of constipation are not caused by an identifiable physical or pathological condition. […] A number of drugs can cause or aggravate constipation. The main mechanism is slowing of gut motility due to anticholinergic or antispasmodic effects but in some cases the mechanism is not clear. […] Chronic constipation needs more careful assessment. The most common causes are medications, especially opioids, and slow transit. Less common is dyssynergia (uncoordinated rectal emptying). […] Constipation may result from underlying conditions such as; Irritable bowel syndrome, Dehydration, Diabetes, Neurological conditions such as Parkinson’s and MS, Electrolyte disorders such as hypercalcaemia or hypokalemia, Depression and other psychiatric disorders, Coeliac disease, Hypothyroidism, GI obstruction (e.g. due to tumours), Damage to pelvic floor muscles, for example after childbirth, Anatomical or physiological causes.

• #25 What to do when medication makes you constipated – Harvard Health

  https://www.health.harvard.edu/staying-healthy/what-to-do-when-medication-makes-you-constipated

  Antidepressants, such as the selective serotonin reuptake inhibitor fluoxetine (Prozac) or tricyclic antidepressants such as amitriptyline (Elavil). „A lot of antidepressants that treat the nerve endings in the brain also affect nerve endings in the gut. That can lead to significant side effects,” says Dr. Braden Kuo, a gastroenterologist at Harvard-affiliated Massachusetts General Hospital. […] Opioids, such as oxycodone (OxyContin) and hydrocodone (Vicodin). „The narcotic effect can cause nerves in the gut to 'sleep,’ inhibiting movement,” explains Dr. Kuo. […] Calcium-channel blockers, such as diltiazem (Cardizem). These drugs relax the smooth muscles in blood vessels to lower blood pressure. But they also relax the muscles in the gut and may cause constipation. […] Anticholinergics, a large class of medications found in many over-the-counter and prescription medications. These include treatments for urinary incontinence, such as oxybutynin (Ditropan), and allergies, such as diphenhydramine (Benadryl). These medications block the effects of acetylcholine, a chemical that helps the muscles move. Less movement in the gut can lead to constipation.

• #26 Managing constipation in adults – Australian Prescriber

  https://australianprescriber.tg.org.au/articles/managing-constipation-in-adults.html

  Patients complaining of constipation require a history and examination and possibly simple investigations to find out if their problem is secondary to other conditions or drugs. […] Chronic constipation leads to a considerable loss of quality of life and increases healthcare costs. […] The prevalence of constipation varies with the definition used. […] Predisposing factors include female sex, increasing age, low socioeconomic status, depression and a history of sexual abuse. […] Chronic constipation in the absence of these alarm symptoms can still be due to other secondary causes. These include endocrine diseases such as diabetes mellitus and hypothyroidism, and neurological injuries and diseases such as multiple sclerosis and Parkinson’s disease. […] A variety of drugs can also cause or aggravate constipation.

• #27 What to do when medication makes you constipated – Harvard Health

  https://www.health.harvard.edu/staying-healthy/what-to-do-when-medication-makes-you-constipated

  Antidepressants, such as the selective serotonin reuptake inhibitor fluoxetine (Prozac) or tricyclic antidepressants such as amitriptyline (Elavil). „A lot of antidepressants that treat the nerve endings in the brain also affect nerve endings in the gut. That can lead to significant side effects,” says Dr. Braden Kuo, a gastroenterologist at Harvard-affiliated Massachusetts General Hospital. […] Opioids, such as oxycodone (OxyContin) and hydrocodone (Vicodin). „The narcotic effect can cause nerves in the gut to 'sleep,’ inhibiting movement,” explains Dr. Kuo. […] Calcium-channel blockers, such as diltiazem (Cardizem). These drugs relax the smooth muscles in blood vessels to lower blood pressure. But they also relax the muscles in the gut and may cause constipation. […] Anticholinergics, a large class of medications found in many over-the-counter and prescription medications. These include treatments for urinary incontinence, such as oxybutynin (Ditropan), and allergies, such as diphenhydramine (Benadryl). These medications block the effects of acetylcholine, a chemical that helps the muscles move. Less movement in the gut can lead to constipation.

• #28 MEDSAFE

  https://www.medsafe.govt.nz/profs/puarticles/clozgi.htm

  Clozapine-induced constipation may be associated with serious effects such as intestinal obstruction, bowel perforation and toxic megacolon. […] Clozapine affects motility throughout the gut. […] Many anticholinergic drugs can cause GI dysmotility, but clozapine has a much more potent effect through its interaction with multiple receptors, (including anticholinergic and serotonergic receptors) affecting GI activity. […] Clozapine can impair motility of the entire GI tract.

• #29 Antipsychotic-induced constipation – high impact for patients

  https://www.medsafe.govt.nz/profs/PUArticles/June2023/Antipsychotic-induced-constipation-high-risk-for-patients.html

  Constipation is a common side effect of all antipsychotics. […] Untreated or delayed diagnosis of antipsychotic-induced constipation may lead to serious complications such as ileus and intestinal obstruction. […] Clozapine treatment has a high risk of constipation and related complications, which can be fatal. […] Regular monitoring of bowel movements is essential throughout antipsychotic treatment. Constipation is a risk factor for serious bowel-related complications if not detected and managed appropriately. […] Antipsychotics can inhibit the action of one or more of these neurotransmitters, resulting in prolonged gastrointestinal transit time, which contributes to constipation. […] The risk of constipation differs between antipsychotics, due to varying affinity with different neurotransmitter receptor types.

• #30 Opioid-induced Constipation: Old and New Concepts in Diagnosis and Treatment

  https://www.jnmjournal.org/journal/view.html?uid=1906&vmd=Full&

  Opioid-induced constipation (OIC) is one of the most common, under-recognized, and under-treated side effects of opioid analgesics. […] The paper discusses the recent literature on the pathophysiology, clinical evaluation, and management of OIC and provides a pragmatic approach for its assessment and treatment. […] Opioid molecules have a deep influence on digestive physiology: they may influence the processes of motility, fluid absorption and sphincter contraction. Opioid receptors include -, -, and -receptors; they are widely distributed throughout the digestive system, with a density that changes depending on the tract and wall layer. Mu-receptors are thought to play a central role in the OIC. […] These receptors can be bound by endogenous (encephalins and endorphins) or exogenous (opioids) ligands, causing their internalization and binding to Gi/Go inhibitory proteins that activate or inhibit intracellular signal transduction pathways. The result is a reduction in neuro-excitability and neurotransmission, which is responsible for the overall inhibition of gastrointestinal secretion and motility.

• #31 Opioid-induced Constipation: Old and New Concepts in Diagnosis and Treatment

  https://www.jnmjournal.org/journal/view.html?uid=1906&vmd=Full&

  Opioid-induced constipation (OIC) is one of the most common, under-recognized, and under-treated side effects of opioid analgesics. […] The paper discusses the recent literature on the pathophysiology, clinical evaluation, and management of OIC and provides a pragmatic approach for its assessment and treatment. […] Opioid molecules have a deep influence on digestive physiology: they may influence the processes of motility, fluid absorption and sphincter contraction. Opioid receptors include -, -, and -receptors; they are widely distributed throughout the digestive system, with a density that changes depending on the tract and wall layer. Mu-receptors are thought to play a central role in the OIC. […] These receptors can be bound by endogenous (encephalins and endorphins) or exogenous (opioids) ligands, causing their internalization and binding to Gi/Go inhibitory proteins that activate or inhibit intracellular signal transduction pathways. The result is a reduction in neuro-excitability and neurotransmission, which is responsible for the overall inhibition of gastrointestinal secretion and motility.

• #32 Opioid-induced Constipation: Old and New Concepts in Diagnosis and Treatment

  https://www.jnmjournal.org/journal/view.html?uid=1906&vmd=Full&

  Opioid-induced constipation (OIC) is one of the most common, under-recognized, and under-treated side effects of opioid analgesics. […] The paper discusses the recent literature on the pathophysiology, clinical evaluation, and management of OIC and provides a pragmatic approach for its assessment and treatment. […] Opioid molecules have a deep influence on digestive physiology: they may influence the processes of motility, fluid absorption and sphincter contraction. Opioid receptors include -, -, and -receptors; they are widely distributed throughout the digestive system, with a density that changes depending on the tract and wall layer. Mu-receptors are thought to play a central role in the OIC. […] These receptors can be bound by endogenous (encephalins and endorphins) or exogenous (opioids) ligands, causing their internalization and binding to Gi/Go inhibitory proteins that activate or inhibit intracellular signal transduction pathways. The result is a reduction in neuro-excitability and neurotransmission, which is responsible for the overall inhibition of gastrointestinal secretion and motility.

• #33 Opioid-induced Constipation: Old and New Concepts in Diagnosis and Treatment

  https://www.jnmjournal.org/journal/view.html?uid=1906&vmd=Full&

  Gastrointestinal motility strictly depends on a fine balance between excitatory and inhibitory pathways primarily mediated by submucosal and myenteric neurons. Encephalins and endorphins play an important role in regulating peristalsis. On the other hand, exogenous opioids can disrupt intestinal motility, increasing wall musculature tone, slowing propulsive movements and triggering tonic spasms in the colon and small intestine. […] Opioid receptors also affect the secretion and absorption of water in the gastrointestinal tract. In the small bowel, the endoluminal secretion of fluids is mainly stimulated by molecules such as vasoactive intestinal peptide and acetylcholine produced by neurons of the submucosa. […] The overall reduction in fecal mass leads to a reduction in colic motility which depends on intrinsic neuronal reflexes resulting from the activation of mechanoreceptors.

• #34 Opioid-induced Constipation: Old and New Concepts in Diagnosis and Treatment

  https://www.jnmjournal.org/journal/view.html?uid=1906&vmd=Full&

  Gastrointestinal motility strictly depends on a fine balance between excitatory and inhibitory pathways primarily mediated by submucosal and myenteric neurons. Encephalins and endorphins play an important role in regulating peristalsis. On the other hand, exogenous opioids can disrupt intestinal motility, increasing wall musculature tone, slowing propulsive movements and triggering tonic spasms in the colon and small intestine. […] Opioid receptors also affect the secretion and absorption of water in the gastrointestinal tract. In the small bowel, the endoluminal secretion of fluids is mainly stimulated by molecules such as vasoactive intestinal peptide and acetylcholine produced by neurons of the submucosa. […] The overall reduction in fecal mass leads to a reduction in colic motility which depends on intrinsic neuronal reflexes resulting from the activation of mechanoreceptors.

• #35 Opioid-induced Constipation: Old and New Concepts in Diagnosis and Treatment

  https://www.jnmjournal.org/journal/view.html?uid=1906&vmd=Full&

  For this reason, patients taking opioids frequently complain of dry and hard stools. […] Opioids also inhibit saliva production, causing dry mouth, and reduce biliary and pancreatic secretions, impairing digestion along with nutrients and drug absorption. […] Finally, stimulation of opioid receptors increases the resting tone of all sphincters in the digestive tract. The increased tone of the internal anal sphincter produces straining, anal blockage, hemorrhoids, and, in severe cases, colon perforation.

• #36 Opioid-induced Constipation: Old and New Concepts in Diagnosis and Treatment

  https://www.jnmjournal.org/journal/view.html?uid=1906&vmd=Full&

  For this reason, patients taking opioids frequently complain of dry and hard stools. […] Opioids also inhibit saliva production, causing dry mouth, and reduce biliary and pancreatic secretions, impairing digestion along with nutrients and drug absorption. […] Finally, stimulation of opioid receptors increases the resting tone of all sphincters in the digestive tract. The increased tone of the internal anal sphincter produces straining, anal blockage, hemorrhoids, and, in severe cases, colon perforation.

• #37 The pathophysiology of chronic constipation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3206564/

  Primary forms of constipation arise from intrinsic defects in colonic function or malfunction of the defecation process. […] Slow-transit constipation (STC) causes infrequent bowel movements (typically less than once per week) and is most common in young women. […] STC is believed to be a neuromuscular disorder of the colon. […] Dyssynergia, probably the most common functional DD, is an acquired behavioural DD. […] To fulfill the formal diagnostic criteria for dyssynergic defecation, patients must: […] It should be noted that prolonged colonic transit time can be seen in patients with DD and in patients with STC. […] Constipation is a common side effect of many drugs, and a detailed medication history should be taken during the initial workup. […] Diseases that involve the nervous system may cause chronic constipation. […] The origin of constipation in patients with these conditions is complex and include disease-related autonomic and pelvic nerve dysfunction as well as generalized systemic factors. […] The pathophysiology of constipation in Parkinson’s disease includes central and peripheral mechanisms.

• #38 The pathophysiology of chronic constipation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3206564/

  Primary forms of constipation arise from intrinsic defects in colonic function or malfunction of the defecation process. […] Slow-transit constipation (STC) causes infrequent bowel movements (typically less than once per week) and is most common in young women. […] STC is believed to be a neuromuscular disorder of the colon. […] Dyssynergia, probably the most common functional DD, is an acquired behavioural DD. […] To fulfill the formal diagnostic criteria for dyssynergic defecation, patients must: […] It should be noted that prolonged colonic transit time can be seen in patients with DD and in patients with STC. […] Constipation is a common side effect of many drugs, and a detailed medication history should be taken during the initial workup. […] Diseases that involve the nervous system may cause chronic constipation. […] The origin of constipation in patients with these conditions is complex and include disease-related autonomic and pelvic nerve dysfunction as well as generalized systemic factors. […] The pathophysiology of constipation in Parkinson’s disease includes central and peripheral mechanisms.

• #39 Constipation – Wikipedia

  https://en.wikipedia.org/wiki/Constipation

  Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement. Complications from constipation may include hemorrhoids, anal fissure or fecal impaction. The normal frequency of bowel movements in adults is between three per day and three per week. Babies often have three to four bowel movements per day while young children typically have two to three per day. […] Constipation has many causes. Common causes include slow movement of stool within the colon, irritable bowel syndrome, and pelvic floor disorders. Underlying associated diseases include hypothyroidism, diabetes, Parkinson’s disease, celiac disease, non-celiac gluten sensitivity, vitamin B12 deficiency, colon cancer, diverticulitis, and inflammatory bowel disease. Medications associated with constipation include opioids, certain antacids, calcium channel blockers, and anticholinergics. Of those taking opioids about 90% develop constipation.

• #40

  https://bpac.org.nz/BPJ/2007/October/constipation.aspx

  Most cases of constipation are not caused by an identifiable physical or pathological condition. […] A number of drugs can cause or aggravate constipation. The main mechanism is slowing of gut motility due to anticholinergic or antispasmodic effects but in some cases the mechanism is not clear. […] Chronic constipation needs more careful assessment. The most common causes are medications, especially opioids, and slow transit. Less common is dyssynergia (uncoordinated rectal emptying). […] Constipation may result from underlying conditions such as; Irritable bowel syndrome, Dehydration, Diabetes, Neurological conditions such as Parkinson’s and MS, Electrolyte disorders such as hypercalcaemia or hypokalemia, Depression and other psychiatric disorders, Coeliac disease, Hypothyroidism, GI obstruction (e.g. due to tumours), Damage to pelvic floor muscles, for example after childbirth, Anatomical or physiological causes.

• #41 The pathophysiology of chronic constipation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3206564/

  Primary forms of constipation arise from intrinsic defects in colonic function or malfunction of the defecation process. […] Slow-transit constipation (STC) causes infrequent bowel movements (typically less than once per week) and is most common in young women. […] STC is believed to be a neuromuscular disorder of the colon. […] Dyssynergia, probably the most common functional DD, is an acquired behavioural DD. […] To fulfill the formal diagnostic criteria for dyssynergic defecation, patients must: […] It should be noted that prolonged colonic transit time can be seen in patients with DD and in patients with STC. […] Constipation is a common side effect of many drugs, and a detailed medication history should be taken during the initial workup. […] Diseases that involve the nervous system may cause chronic constipation. […] The origin of constipation in patients with these conditions is complex and include disease-related autonomic and pelvic nerve dysfunction as well as generalized systemic factors. […] The pathophysiology of constipation in Parkinson’s disease includes central and peripheral mechanisms.

• #42 Constipation in Tg2576 mice model for Alzheimer’s disease associated with dysregulation of mechanism involving the mAChR signaling pathway and ER stress response | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0215205

  Constipation is an acute or chronic gastrointestinal disease characterized by infrequent bowel movements, hard and dry feces, incomplete bowel evacuation and difficulty during defecation. […] Although constipation has been researched in various neurological disorders, including Parkinson’s disease (PD) and spinal cord injury (SCI), the pathological mechanism of this symptom has not been investigated in Alzheimer’s disease (AD) associated with loss of nerve cells in the brain. […] The results of the present study provide strong novel evidence that the neuropathological constipation detected in Tg2576 mice is linked to dysregulation of the mAChR signaling pathways and ER stress response. […] Our results primarily suggest the possibility that bowel movement and defecation in the pathogenesis of AD are associated with dysregulation of the mAChR signaling pathway and ER stress response.

• #43 The enteric microbiota in the pathogenesis and management of constipation.

  https://www.lenus.ie/hse/handle/10147/135655

  The enteric microbiota in the pathogenesis and management of constipation. […] For centuries, fiber has been recommended on an empirical basis for the management of constipation; it has only been in recent decades that the mechanisms whereby fiber and related products may influence colonic function have begun to be elucidated. […] The interaction between fiber and the microbiota of the human colon appears to play a major role in generating the beneficial effects of fiber. […] The microbiota is also the target for the other therapeutic interventions discussed in this chapter: prebiotics and probiotics. […] While a scientific basis for a role for these approaches in the management of constipation continues to develop, evidence from high-quality clinical trials to support their use in daily practice continues to lag far behind. […] While benefits for fiber and, perhaps, for certain prebiotic and probiotic preparations in constipation appear to be extant there is a real need for large well-conducted clinical trials in this important area of human medicine.

• #44 Constipation in chronic kidney disease: it is time to reconsider | Renal Replacement Therapy | Full Text

  https://rrtjournal.biomedcentral.com/articles/10.1186/s41100-019-0246-3

  Constipation is highly prevalent in patients with chronic kidney disease (CKD) and is primarily characterized by decreased intestinal motility. […] The pathogenesis of constipation in CKD patients is multifactorial: decreased physical activity, comorbidities affecting bowel movement, such as diabetes mellitus, cerebrovascular disease, and hyperparathyroidism, a restricted dietary intake of plant-based fiber-rich foods, and multiple medications, including phosphate binders and potassium-binding resins, have all been implicated. […] CKD is associated with alterations in the composition and function of the gut microbiota, so-called gut dysbiosis. Recent studies showed that CKD-related gut dysbiosis decreased intestinal motility via intestinal inflammation or the increased generation of gut-derived uremic toxins, such as indoxyl sulfate and p-cresyl sulfate.

• #45 Constipation in chronic kidney disease: it is time to reconsider | Renal Replacement Therapy | Full Text

  https://rrtjournal.biomedcentral.com/articles/10.1186/s41100-019-0246-3

  The relationship between CKD and gut dysbiosis is widely recognized and involved in the concept of the gut-kidney axis. […] Gut-derived uremic toxins, such as indoxyl sulfate (IS), p-cresyl sulfate (PCS), and trimethylamine-N-oxide (TMAO), accumulate in the bodies of CKD patients via their increased generation as well as decreased renal excretion. […] These toxins induce oxidative stress and proinflammatory responses. […] Thus, gut dysbiosis is one of the main causes of chronic inflammation in CKD, which leads to the progression of CVD and CKD itself and strongly influences patient morbidity and mortality. […] A recent experimental study by Hoibian et al. suggested a mechanism that links CKD-related gut dysbiosis to constipation. […] These findings demonstrated that some uremic toxins impair intestinal motility.

• #46 Flax seeds, gut microbiota, & functional constipation | JMDH

  https://www.dovepress.com/influence-of-flax-seeds-on-the-gut-microbiota-of-elderly-patients-with-peer-reviewed-fulltext-article-JMDH

  Flax seeds may improve the defecation in elderly patients with chronic constipation and change intestinal microecological structure. Thus, flax seeds may serve as an effective diet supplement in the management of chronic constipation. […] Flax seeds are rich in fibers and other bioactive compounds, and are able to improve constipation by modulating the gut microbiota. […] In the present study, the frequency of defecation increased, and the symptoms were significantly relieved with correction of disturbed gut microbiota after flax seeds intervention for 4 weeks. […] At phylum level, there was a significant decrease in Firmicutes and a marked increase in Synergistetes. At genus level, there were significant decreases in Faecalibacterium, Lachnospira, Blautia, and Anaerostipes in patients with constipation as compared to healthy controls, but Blautia significantly increased after flax seeds treatment for 4 weeks, which was similar to that in healthy controls. Blautia might be the predominant genus accounting for the therapeutic effect of flax seeds.

• #47 Pharmacologic management of chronic constipation, Current treatment options | Medicina Universitaria

  https://www.elsevier.es/en-revista-medicina-universitaria-304-articulo-pharmacologic-management-chronic-constipation-current-X1665579612506653

  Methyl-naltrexone is a quaternary-derivative opioid, m-receptor antagonist. Some N-terminal methylations increases its polarity by reducing its lipid solubility, these structural and chemical properties in turn, explains its inability to cross the blood-brain barrier, preventing central opioid action but keeping its peripheral action on m-receptors. […] Serotonin (5-Hydroxitryptamine; 5-HT) is a neurotransmitter with extensive physiological functions in the human body. In the gastrointestinal mucosa, serotonin is produced by enterochromaffin cells which represent 90% of all serotonin. […] Several 5-HT4 agonists have been described for constipation treatment, including benzamines (cisapride, renzapride, mosapride and prucalopride [benzofuran]), indoles (tegaserod) and benzimidazolones (activation of chloride receptors -cystic fibrosis-).

• #48 Current Overview on Clinical Management of Chronic Constipation

  https://www.mdpi.com/2077-0383/10/8/1738

  Constipation is also associated with age and female sex. […] Recently, more and more studies concerning chronic constipation focus on serotonin and its signaling role in the gut. Possible mechanisms involve a decrease in the number of Cajal cells or disruptions in the serotonin level. However, in the case of the latter it is still unclear whether the exact cause is in a decreased number of receptors and their function, or a decreased availability of serotonin at the receptors. […] Other possible mechanisms of constipation involve influence of proto-oncogenes, overexpression of progesterone receptors, infectious agents, autoimmunity, and tyrosine kinase C.

• #49 Pharmacologic management of chronic constipation, Current treatment options | Medicina Universitaria

  https://www.elsevier.es/en-revista-medicina-universitaria-304-articulo-pharmacologic-management-chronic-constipation-current-X1665579612506653

  Methyl-naltrexone is a quaternary-derivative opioid, m-receptor antagonist. Some N-terminal methylations increases its polarity by reducing its lipid solubility, these structural and chemical properties in turn, explains its inability to cross the blood-brain barrier, preventing central opioid action but keeping its peripheral action on m-receptors. […] Serotonin (5-Hydroxitryptamine; 5-HT) is a neurotransmitter with extensive physiological functions in the human body. In the gastrointestinal mucosa, serotonin is produced by enterochromaffin cells which represent 90% of all serotonin. […] Several 5-HT4 agonists have been described for constipation treatment, including benzamines (cisapride, renzapride, mosapride and prucalopride [benzofuran]), indoles (tegaserod) and benzimidazolones (activation of chloride receptors -cystic fibrosis-).

• #50 SciELO Brazil – Serotonin, ghrelin, and motilin gene/receptor/transporter polymorphisms in childhood functional constipation Serotonin, ghrelin, and motilin gene/receptor/transpo

  https://www.scielo.br/j/ramb/a/3yndxRgqXpwVYw3XtkSmxVR/

  Functional constipation is the most common form of constipation, and its exact aetiology is still unclear. However, it is known that deficiencies in hormonal factors cause constipation by changing physiological mechanisms. Motilin, ghrelin, serotonin acetylcholine, nitric oxide, and vasoactive intestinal polypeptide are factors that play a role in colon motility. […] Deficiencies in hormonal factors cause changes in physiological mechanisms and lead to constipation. Motilin, ghrelin, serotonin, acetylcholine, nitric oxide, and vasoactive intestinal polypeptide play a role in colon motility. The most important task of the motilin hormone is to speed up bowel movements. Motilin binds to motilin receptors (MTLR) located on the cell surface to show its effect. Ghrelin has been shown to have a prokinetic effect on gastrointestinal motility through the vagus and pelvic nerves. Centrally acting GRLN-R agonists stimulate defecation in animals and humans and accelerate gastrointestinal passage. Serotonin plays a role in motility and secretion, slows gastric emptying, and increases colonic motor activity. […] Our study results showed that gene polymorphisms of these three hormones may not be related to constipation in children.

• #51 Pharmacologic management of chronic constipation, Current treatment options | Medicina Universitaria

  https://www.elsevier.es/en-revista-medicina-universitaria-304-articulo-pharmacologic-management-chronic-constipation-current-X1665579612506653

  Treatment of constipation should be individualized since success is related to addressing the underlying cause. Acknowledging patient’s comorbid conditions, patient’s concerns and expectations which are often driven by life style, are important at the time of considering a treatment option. […] Chloride channels are widely distributed throughout the body. These chloride channels are composed of trans-membrane porous proteins that play a key role in maintaining homeostasis of fluid transport through cell membranes. […] Lubiprostone, selectively activates Chloride channel 2 (ClC2) via protein kinase-A as well as through activation the cystic-fibrosis transmembrane conductance receptor (CFTR), both mechanisms promote intestinal fluid secretion. Lubiprostone secondarily induces peristalsis by promoting fluid secretion and bowel distention but without a direct effect on intestinal smooth muscle.

• #52 Pharmacologic management of chronic constipation, Current treatment options | Medicina Universitaria

  https://www.elsevier.es/en-revista-medicina-universitaria-304-articulo-pharmacologic-management-chronic-constipation-current-X1665579612506653

  Treatment of constipation should be individualized since success is related to addressing the underlying cause. Acknowledging patient’s comorbid conditions, patient’s concerns and expectations which are often driven by life style, are important at the time of considering a treatment option. […] Chloride channels are widely distributed throughout the body. These chloride channels are composed of trans-membrane porous proteins that play a key role in maintaining homeostasis of fluid transport through cell membranes. […] Lubiprostone, selectively activates Chloride channel 2 (ClC2) via protein kinase-A as well as through activation the cystic-fibrosis transmembrane conductance receptor (CFTR), both mechanisms promote intestinal fluid secretion. Lubiprostone secondarily induces peristalsis by promoting fluid secretion and bowel distention but without a direct effect on intestinal smooth muscle.

• #53 Lubiprostone’s Novel Mechanism Effective for Chronic Constipation | MDedge

  https://blogs.the-hospitalist.org/content/lubiprostones-novel-mechanism-effective-chronic-constipation

  Lubiprostone, an investigational drug with a novel mechanism of action, performed well for the treatment of chronic constipation in a pivotal phase III clinical trial, John F. Johanson, M.D., reported at the annual meeting of the American College of Gastroenterology. […] Lubiprostone is a functional fatty acid that selectively activates the GI type-2 chloride channels. Lubiprostone enhances intestinal fluid secretion without altering serum electrolyte levels, explained Dr. Johanson, a gastroenterologist in private practice in Rockford, Ill. […] In animal studies, lubiprostone has been shown to stimulate the recovery of ischemic colonic and ileal mucosa. […] Phase III clinical trials of lubiprostone for the treatment of patients with irritable bowel syndrome are ongoing.

• #54 Pharmacologic management of chronic constipation, Current treatment options | Medicina Universitaria

  https://www.elsevier.es/en-revista-medicina-universitaria-304-articulo-pharmacologic-management-chronic-constipation-current-X1665579612506653

  Guanylate-cyclase activator belongs to a 3-guanosine-5monophosphate (cGMP) family of receptors that also include some heat-stable microbial ST-peptides. Guanylin receptors (GR) are widely distributed throughout the gut, but are more active in a pH neutral microenvironment. […] Linaclotide is a 14-aminoacid peptide with agonist properties over GR; this stimulus leads to an increase in intracellular cGMP and subsequently to activation of Cl-sensitive channel (ClC) and to the cystic fibrosis transmembrane receptor (CFTR), finally resulting in an increase of water and bicarbonate secretion into the intestinal lumen that consequently, promotes intestinal motility. […] Opioids analgesics are frequently used for the treatment of acute and chronic pain in malignant and non-malignant conditions. The pain relief is related to their action as an agonist on k and receptors; however opioids also exert an agonist action on -receptors leading to their undesirable Gi effects, including constipation.

• #55 Pharmacologic management of chronic constipation, Current treatment options | Medicina Universitaria

  https://www.elsevier.es/en-revista-medicina-universitaria-304-articulo-pharmacologic-management-chronic-constipation-current-X1665579612506653

  Guanylate-cyclase activator belongs to a 3-guanosine-5monophosphate (cGMP) family of receptors that also include some heat-stable microbial ST-peptides. Guanylin receptors (GR) are widely distributed throughout the gut, but are more active in a pH neutral microenvironment. […] Linaclotide is a 14-aminoacid peptide with agonist properties over GR; this stimulus leads to an increase in intracellular cGMP and subsequently to activation of Cl-sensitive channel (ClC) and to the cystic fibrosis transmembrane receptor (CFTR), finally resulting in an increase of water and bicarbonate secretion into the intestinal lumen that consequently, promotes intestinal motility. […] Opioids analgesics are frequently used for the treatment of acute and chronic pain in malignant and non-malignant conditions. The pain relief is related to their action as an agonist on k and receptors; however opioids also exert an agonist action on -receptors leading to their undesirable Gi effects, including constipation.

• #56 Mechanism of Action in Functional Constipation | LINZESS® (linaclotide)

  https://www.linzesshcp.com/functional-constipation-moa.html

  LINZESS increases fluid secretion and GI motility. […] LINZESS binds to the guanylate cyclase-C (GC-C) receptor resulting in an increase in intracellular extracellular concentrations of cGMP, which stimulates secretion of chloride and bicarbonate into the intestinal lumen, resulting in increased intestinal fluid and accelerated transit. […] LINZESS activates GC-C receptors and stimulates secretion of electrolytes into the lumen of the intestine via activation of CFTR, which results in increased intestinal fluid content and accelerated transit. […] In neonatal mice, linaclotide increased fluid secretion as a consequence of age-dependent elevated guanylate cyclase (GC-C) agonism, which was associated with increased mortality within the first 24 hours due to dehydration.

• #57 Current Overview on Clinical Management of Chronic Constipation

  https://www.mdpi.com/2077-0383/10/8/1738

  Positive family history of constipation and genetic predisposition seem to have a role in this disorder, since patients with functional constipation commonly have a positive family history, however there are no specific genes related to constipation. […] Diet is one of the most relevant factors of constipation. Insufficient fiber or fluid intake results in constipation in all age groups. […] Clinicians also consider a connection between dysbiosis of gut microbiota and constipation. […] Efficient bowel movement depends on nerve endings of sensory neurons which react to the content of the intestine. Patients with constipation are frequently observed with colonic motor dysfunction, abnormal colonic sensation, and impaired defecation. […] Studies prove connection between constipation and psychological factors: constipation is more common in children with attention deficit disorders and autism, and constipated patients are more often observed with anxiety, stress, trauma, and depression.

• #58 Pathogenesis of functional constipation | drlevinmichael

  https://www.anorectalmalformations.com/pathogenesis-of-functional-constipa

  Pathogenesis of functional constipation (F). […] Our data suggest that FC is always caused by functional obstruction of the anal canal as a result of inconsistencies of the fecal width with bandwidth of the anal canal. This leads to expansion of the rectum and increase the capacity of the left half of the colon. The impairment of PRM causes the fecal incontinence. In some children, the chronic intestinal obstruction causes non-specific inflammation of the colon typical for irritable bowel syndrome. […] The most recognized pathogenesis of the FC is a vicious cycle that begins with painful defecation and leads to stool-withholding behavior as a result. […] In our study, the rectum was wider of the maximum limits of the age norm in all patients with the disease duration of more than 6 months.

• #59 Pathogenesis of functional constipation | drlevinmichael

  https://www.anorectalmalformations.com/pathogenesis-of-functional-constipa

  Pathogenesis of functional constipation (F). […] Our data suggest that FC is always caused by functional obstruction of the anal canal as a result of inconsistencies of the fecal width with bandwidth of the anal canal. This leads to expansion of the rectum and increase the capacity of the left half of the colon. The impairment of PRM causes the fecal incontinence. In some children, the chronic intestinal obstruction causes non-specific inflammation of the colon typical for irritable bowel syndrome. […] The most recognized pathogenesis of the FC is a vicious cycle that begins with painful defecation and leads to stool-withholding behavior as a result. […] In our study, the rectum was wider of the maximum limits of the age norm in all patients with the disease duration of more than 6 months.

• #60 Pathogenesis of functional constipation | drlevinmichael

  https://www.anorectalmalformations.com/pathogenesis-of-functional-constipa

  Thus, in the wall of the stretched rectum there are changes, which weaken of the wall and not allow back to normal state after the rectal emptying, which means a loss of elasticity. […] The initial stage. The childhood constipation results from intentional withholding of stool following a painful experience with defecation. […] Further development of the pathological process is characterized by a more pronounced expansion of the rectum. […] Compression and tensile other pelvic floor muscles leads to the failure of the LAM, which during defecation do not disclose the anal canal properly, which increases the frictional resistance and enhances the obstructive syndrome. […] Chronic stagnation of feces causes inflammation of the colon. […] Based on the results of examination of patients in third group and analysis of the literature, we assumed that the stagnation of feces cause in some patients with FC the inflammation with increased bowel tone.

• #61 Pathogenesis of functional constipation | drlevinmichael

  https://www.anorectalmalformations.com/pathogenesis-of-functional-constipa

  Thus, in the wall of the stretched rectum there are changes, which weaken of the wall and not allow back to normal state after the rectal emptying, which means a loss of elasticity. […] The initial stage. The childhood constipation results from intentional withholding of stool following a painful experience with defecation. […] Further development of the pathological process is characterized by a more pronounced expansion of the rectum. […] Compression and tensile other pelvic floor muscles leads to the failure of the LAM, which during defecation do not disclose the anal canal properly, which increases the frictional resistance and enhances the obstructive syndrome. […] Chronic stagnation of feces causes inflammation of the colon. […] Based on the results of examination of patients in third group and analysis of the literature, we assumed that the stagnation of feces cause in some patients with FC the inflammation with increased bowel tone.

• #62 Pathogenesis of functional constipation | drlevinmichael

  https://www.anorectalmalformations.com/pathogenesis-of-functional-constipa

  Rigidity. Functional constipation in adults there is a continuation of the disease, which began in childhood. […] Gradually, in proportion to the degree of megacolon, there are irreversible processes, when the return of the rectum to its normal width, or close to this size cannot be due to the rigidity of tissue. […] The scheme of the pathogenesis of functional constipation is presented in Figure 6.

• #63

  https://journals.lww.com/md-journal/fulltext/2018/05180/chronic_constipation__a_review_of_literature.6.aspx

  A number of factors are also involved in functional disorders of defecation and defined in patients with constipation including rectal hyposensitivity, altered rectoanal reflex activity, increased rectal duct capacity, and rectal motor dysfunction. […] The role of abnormal visceral sensation is currently considered to be involved in the development of functional bowel disorders with considerable attention to visceral hypersensitivity, whereas hyposensitivity was relatively considered. […] Patients with constipation often have psychological disorders in a variety of stressful life events such as anxiety, depression, physical and sexual abuse, and anorexia nervosa, as well as a concomitant eating disorder. […] The impacts of socioeconomic status and educational level on the prevalence of constipation have been reported in most studies.

• #64 Relationship between functional constipation and anal-retentive behavior features – Turkish Journal of Surgery

  https://turkjsurg.com/articles/relationship-between-functional-constipation-and-anal-retentive-behavior-features/doi/turkjsurg.4035

  Constipation is the most commonly seen defecation problem related to several environmental factors. […] This study aimed to evaluate the relationship between constipation and anal characteristic features of participants with functional constipation. […] Constipation may be related to several factors, such as socioeconomic environment, emotional stress, age, and diet, among others. Here, it was found that anal-retentive behavior features are prominent in functional constipation. […] Our study showed that anal-retentive characteristic features related to the period of defecation control are significantly higher in patients with constipation than in healthy people. […] Our study showed that patients with constipation have much more anal-retentive behavior features than healthy subjects.

• #65 Relationship between functional constipation and anal-retentive behavior features – Turkish Journal of Surgery

  https://turkjsurg.com/articles/relationship-between-functional-constipation-and-anal-retentive-behavior-features/doi/turkjsurg.4035

  Anal-retentive behavior features are developed during the anal stage of children between the ages of 1 and 3 years. […] One-third of patients with functional constipation had reported constipation since childhood, whereas others developed constipation during adulthood. […] Early toilet training, excessive parent-child conflict, and irrational fears during the anal stage may result in functional constipation. […] The prevalence of obsessive beliefs, such as Perfectionism/Certainty and Importance and Control Thoughts, in patients with constipation is significantly higher than that in healthy controls. […] The Personality Belief Scale was prepared according to personality disorders in DSM IV. […] The most significant difference between the constipated and control groups was obsessive beliefs. […] This shows that obsessive-compulsive features are important parts of anal-retentive behavior features. […] Biofeedback treatment is one of the modalities for both anal-retentive behavior features and functional constipation.

• #66 Relationship between functional constipation and anal-retentive behavior features – Turkish Journal of Surgery

  https://turkjsurg.com/articles/relationship-between-functional-constipation-and-anal-retentive-behavior-features/doi/turkjsurg.4035

  Anal-retentive behavior features are developed during the anal stage of children between the ages of 1 and 3 years. […] One-third of patients with functional constipation had reported constipation since childhood, whereas others developed constipation during adulthood. […] Early toilet training, excessive parent-child conflict, and irrational fears during the anal stage may result in functional constipation. […] The prevalence of obsessive beliefs, such as Perfectionism/Certainty and Importance and Control Thoughts, in patients with constipation is significantly higher than that in healthy controls. […] The Personality Belief Scale was prepared according to personality disorders in DSM IV. […] The most significant difference between the constipated and control groups was obsessive beliefs. […] This shows that obsessive-compulsive features are important parts of anal-retentive behavior features. […] Biofeedback treatment is one of the modalities for both anal-retentive behavior features and functional constipation.

• #67 Relationship between functional constipation and anal-retentive behavior features – Turkish Journal of Surgery

  https://turkjsurg.com/articles/relationship-between-functional-constipation-and-anal-retentive-behavior-features/doi/turkjsurg.4035

  Anal-retentive behavior features are developed during the anal stage of children between the ages of 1 and 3 years. […] One-third of patients with functional constipation had reported constipation since childhood, whereas others developed constipation during adulthood. […] Early toilet training, excessive parent-child conflict, and irrational fears during the anal stage may result in functional constipation. […] The prevalence of obsessive beliefs, such as Perfectionism/Certainty and Importance and Control Thoughts, in patients with constipation is significantly higher than that in healthy controls. […] The Personality Belief Scale was prepared according to personality disorders in DSM IV. […] The most significant difference between the constipated and control groups was obsessive beliefs. […] This shows that obsessive-compulsive features are important parts of anal-retentive behavior features. […] Biofeedback treatment is one of the modalities for both anal-retentive behavior features and functional constipation.

• #68 Effect and cerebral mechanism of acupuncture treatment for functional constipation: study protocol for a randomized controlled clinical trial | Trials | Full Text

  https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-019-3410-8

  Acupuncture is effective in functional constipation (FC) treatment, but the central mechanism has not been well investigated. […] We hypothesize that acupuncture can treat FC through normalizing the pathological alteration of the cerebral activity. […] Several studies have found that acupuncture may treat FC by promoting the gastrointestinal motility, modulating peripheral gastrointestinal hormones, and keeping the balance of excitatory and inhibitory neurons in the enteric nervous system (ENS). […] However, the central integration, an essential node of acupuncture treatment for FC, has rarely been explored. […] Whether the effects of acupuncture on FC are correlated with modulating cerebral activity remains uncertain and is worthy of further investigation. […] The harmonious bidirectional interaction between the brain and the gut is a necessary prerequisite for retaining normal physiological function and homeostatic state of the gastrointestinal tract.

• #69 Effect and cerebral mechanism of acupuncture treatment for functional constipation: study protocol for a randomized controlled clinical trial | Trials | Full Text

  https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-019-3410-8

  Disharmony of the brain-gut axis might be a critical pathogenesis of FGIDs. […] Previous neuroimaging studies have found that the functional and/or structural abnormalities of the brain might be the highlighted pathological characteristics of FGIDs. […] Therefore, we hypothesize that acupuncture could treat FC through normalizing the pathological alteration of the brain activity. […] The collaborative application of BOLD-fMRI and 18F-FDG PET-CT can prove the structural and functional images with high spatiotemporal and functional resolution, which could deliver more details of the brain and explain the central mechanism of acupuncture effects from both direct (cerebral glucose metabolism) and indirect (contrast of oxyhemoglobin and deoxyhemoglobin) approaches. […] Therefore, in the present trial, we combine these two neuroimaging techniques for the first time to explore the central effects of acupuncture for FC.

• #70 Sustained effects of acupuncture in treatment of chronic constipation – Tjen-A-Looi – Annals of Palliative Medicine

  https://apm.amegroups.org/article/view/14452/html

  Stress influences activity in the Barringtons nucleus, and the parasympathetic or vagal descending pathway that, in turn, affects vagal tone in the gastrointestinal tract and hence colonic motility. […] The mechanisms underlying the prolonged anti-constipation effect of acupuncture is unclear. […] These central neuronal mechanisms may also contribute to the prolonged anti-constipation effect of acupuncture.

• #71 How stress triggers constipation | Dulcolax® Saline Laxative Solutions

  https://www.dulcolax.com/en-us/about-constipation/stress-and-constipation

  When stress enters our lives, our body releases specific hormones that initiate a „fight-or- flight” reaction. Teze hormony mogą modyfikować sposób, w jaki działają nasze jelita, co czasami prowadzi do zaparć. […] Kiedy stres uderza, to więcej niż tylko psychiczne obciążenie; wywołuje zmiany fizyczne, takie jak: […] Stres może zakłócać tę relację jelitowo-mózgową, spowalniając ruch pokarmu przez przewód pokarmowy i potencjalnie powodując zaparcia. […] Pod intensywnym stresem nasze ciało uwalnia adrenalinę, koncentrując się na utrzymaniu optymalnego funkcjonowania ważnych organów, takich jak serce i mózg. Ta zmiana oznacza mniej wsparcia dla układu pokarmowego, co może spowolnić ruchy jelit.

• #72

  https://journals.lww.com/ajg/fulltext/2018/10001/mechanism_of_action_of_vibrant_capsule_for_the.418.aspx

  Chronic constipation is a multifactorial gastrointestinal (GI) disorder. The orally administered intraluminal vibrating capsule (VC) (Vibrant Ltd., Yokneam, Israel) is the first chemical-free treatment that improves constipation by mechanically inducing vibrations. Our aim was to determine the effects of VC on complete spontaneous bowel movements (CSBMs) in patients with chronic idiopathic constipation (CIC), using 2 paradigms of VC activation. […] VC significantly increases the number of CSBMs when compared to sham and this coincides with VC activation. This observation suggests that the mechanism of action of VC is to induce bowel movements through mechanical vibration of the colon, augmenting colonic biorhythm and peristalsis. This unique, non-pharmaceutical modality could be a novel approach for constipation.

• #73 Sustained effects of acupuncture in treatment of chronic constipation – Tjen-A-Looi – Annals of Palliative Medicine

  https://apm.amegroups.org/article/view/14452/html

  The regulation of colonic motility is influenced by the central and the autonomic nervous system. […] Increased sympathetic activity delay gastric emptying and likely induces decreased colon motility. […] Acupuncture and EA stimulate sites on the body (acupoints) for 15 to 30 min activating, in part, somatic sensory nerves and neural pathways involving regions in the brain. […] The experimental findings show that acupuncture increases parasympathetic activity mediated by a cholinergic pathway to restore reduced colonic contraction and delayed transit time. […] Acupuncture stimulation at ST25 appears to activate neurons in the medio-caudal NTS and rostroventral lateral medulla to influence sympathetic outflow and increase motility of the distal colon. […] Together, stimulation of somatic sensory nerves by EA appears to modify the function of central neuronal pathways and regions leading to its anti-constipation.

• #74 Efficacy and Molecular Mechanism of Quercetin on Constipation Induced by Berberine via Regulating Gut Microbiota

  https://www.mdpi.com/1422-0067/25/11/6228

  QR can efficiently regulate the microbiota in mice suffering from constipation. Moreover, QR significantly raised the levels of substance P and motilin while lowering those of 5-hydroxytryptamine and vasoactive intestinal peptide; furthermore, it also increased the protein expression levels of calmodulin, myosin light-chain kinase, and myosin light chain. […] The mechanism of action of quercetin on berberine-induced constipation is demonstrated in Scheme 1. […] QR can relieve constipation by promoting digestion and absorption of gastrointestinal tract contents, promoting gastrointestinal tract water and electrolyte balance, and promoting gastrointestinal tract peristalsis. […] QR elevated gastrointestinal hormone levels and balanced the relative abundance of beneficial and harmful bacteria and the gut microenvironment to promote digestion and absorption of contents in the intestine.

• #75 Efficacy and Molecular Mechanism of Quercetin on Constipation Induced by Berberine via Regulating Gut Microbiota

  https://www.mdpi.com/1422-0067/25/11/6228

  QR facilitated elimination of the contents by increasing the water of the contents via regulating gastrointestinal hormones, which also facilitated the inward flow of Ca2+ through the CAM-MLCK pathway, thus enhancing gastrointestinal motility levels. […] QR could alleviate constipation by increasing the diversity of gut microbiota in mice.

• #76 Efficacy and Molecular Mechanism of Quercetin on Constipation Induced by Berberine via Regulating Gut Microbiota

  https://www.mdpi.com/1422-0067/25/11/6228

  QR facilitated elimination of the contents by increasing the water of the contents via regulating gastrointestinal hormones, which also facilitated the inward flow of Ca2+ through the CAM-MLCK pathway, thus enhancing gastrointestinal motility levels. […] QR could alleviate constipation by increasing the diversity of gut microbiota in mice.

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