Functional constipation in childhood: current pharmacotherapy and future perspectives

Hoekman, Daniël R.; Benninga, Marc A.

doi:10.1517/14656566.2013.752816

Cited by 32 publications

(40 citation statements)

References 100 publications

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“…Multiple laxatives have been routinely used in the treatment of childhood constipation with a number of new agents currently being trialed, mostly in adults 51 . At the present time published evidence suggests that polyethylene glycol 3350 should be the laxative of first choice in pediatrics for functional constipation 42 58 .…”

Section: Treatmentmentioning

confidence: 99%

Gastrointestinal and nutritional problems in neurologically impaired children

Quitadamo

Thapar

Staiano

et al. 2016

European Journal of Paediatric Neurology

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Fax: + 44 20 7813 8382Gut Motility disorders comprise a heterogeneous group of disorders that result from disruption of the functional integrity of the intrinsic neuromusculature of the gastrointestinal (GI) tract. This intrinsic neuromusculature includes the smooth muscle layers, the intrinsic nervous system of the GI tract (enteric nervous system or ENS) and the interstitial cells of Cajal. The contribution of each of these components to function can be compromised by alterations in structure (ranging from absence to derangement in numbers and/or anatomy) or of function (complete or partial failure in physiological function). This pathology can be primary or secondary to a number of insults e.g. infections, inflammation, toxins etc. In children disorders may be congenital being present from birth or acquired later in life. Finally involvement of the enteric neuromusculature can be patchy/segmental or affect the gastrointestinal tract diffusely.Neuro-gastroenterology is the study of the interface of all aspects of the gastrointestinal tract or digestive system with the different branches of the body's nervous system including the enteric, central and autonomic nervous systems. The combined terms 'Neurogastroenterology and motility' are designed to encompass the study of all the components of the enteric neuromuscualture and their modulating influences and represents one of the fastest growing areas in gastroenterology clinical practice and research. This chapter aims to address some of the most common neurogastroenterology and motility conditions seen in clinical practice ranging from those with defined pathology to those which fall under the umbrella of functional gastrointestinal disorders. The latter comprise some of the commonest but challenging disorders and the term 'functional' reflects the fact that in the majority of such conditions no organic cause can be found. It should also be noted that at the present time many functional disorders e.g. abdominal pain-related functional GI disorders, represent symptom complexes that can further be subdivided into more discrete entities e.g. irritable bowel syndrome, functional abdominal pain etc depending on the nature, location and associations of the symptoms. Clinicians will often rely on the presence or absence of 'red flags' e.g. associated weight loss, severe or significant symptoms etc to decide whether patients are likely to have organic or functional disorders. Exhaustive investigations in the latter are likely to prove fruitless, expensive and perpetuate 'illness behaviours' in the patients. Abdominal pain-related functional gastrointestinal disorders IntroductionAbdominal pain-related functional gastrointestinal disorders (FGID) constitute a spectrum of conditions characterised by the presence of recurrent abdominal pain in the absence of any defined pathology 1 . In the past these disorders fell under the single term 'Recurrent abdominal pain' (RAP) but have since been recategorised under an international initiative (Rome Foundation) to improve the dia...

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Section: Treatmentmentioning

confidence: 99%

Gastrointestinal and nutritional problems in neurologically impaired children

Quitadamo

Thapar

Staiano

et al. 2016

European Journal of Paediatric Neurology

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“…Different osmotic laxatives are available, but PEG (macrogol) is the fi rst choice osmotic laxative in children with FC based on its effectiveness and safety profi le [ 37 ]. Two other commonly used osmotic laxatives are lactulose and lactitol, both synthetic derivatives of lactose, which are fermented into hyperosmolar low molecular weight acids by intraluminal bacteria [ 80 ]. Even in young children (less than 2 years of age) the use of PEG has been proven to be effective and safe [ 74 -79 ].…”

Section: Pharmacological Agents Osmotic Laxativesmentioning

confidence: 99%

“…42.3 ). These agents are also metabolized into their pharmacologically active metabolite by intestinal bacteria [ 80 ] and the metabolites stimulate colonic motility and the secretion of water and electrolytes, while they inhibit the absorption of water and electrolytes from the colon. In the colon, these nonabsorbable agents are hydrolyzed to their active metabolites, which exert a local prokinetic effect and stimulate intestinal fl uid secretion [ 80 ].…”

Section: Stimulant Laxativesmentioning

confidence: 99%

Functional Constipation in Children

Koppen

Benninga

2016

Pediatric Neurogastroenterology

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Constipation is a common and bothersome problem in children. It may present with infrequent bowel movements with fecal incontinence, hard stools, large stools, painful defecation, and abdominal pain [ 1 ]. In approximately 95 % of children with constipation, no organic cause can be identifi ed, these children suffer from functional constipation (FC) [ 2 ]. The prevalence of FC ranges between 0.7 and 29.6 % and it occurs more often in girls than in boys (ratio: 2.1:1) [ 3 ]. The diagnosis of FC is based on the pediatric diagnostic Rome criteria for functional gastrointestinal disorders (Table 42.1 ) [ 4 ]. These criteria were revised in the spring of 2016 [ 5 , 6 ] (for more information, see Benninga et al.: http:// www.ncbi.nlm.nih.gov/pubmed/27144631 or Hyams et al.: http://www.ncbi.nlm.nih.gov/pubmed/27144632 . Physiology Meconium Passage and Defecation FrequencyIn more than 99 % of healthy term neonates, the fi rst meconium passes within the fi rst 48 h of life [ 5 , 6 ]. Delayed passage of the fi rst meconium beyond the fi rst 48 h of life is suggestive for an organic defecation disorder (e.g., Hirschsprung's disease). During the fi rst months of life, the defecation frequency may vary from child to child, this is partially dependent on feeding type; breastfed children have a higher defecation frequency than formula-fed infants [ 6 ].In the fi rst weeks of life, the defecation frequency lies around 4 stools a day, this frequency gradually decreases over time until it is approximately once a day in children at the age of 4 years [ 6 , 7 ]. In older children, defecation usually occurs either daily or every other day [ 8 ]. Defecation DynamicsThe physiological dynamics of defecation are complex and rely on several intricate processes involving the autonomic and somatic nervous system, the pelvic fl oor muscles, and the internal and external anal sphincters. In the colon, feces is propelled by propagating colonic contractions. Several different colonic motor patterns have been described [ 9 , 10 ], but the most well-recognized propagating motor patterns are high-amplitude propagating contractions (HAPCs ). These motor patterns are associated with the mass movement of colonic content and spontaneous defecation in healthy adults [ 11 , 12 ]. Anterograde propagation of feces through the colon leads to fi lling of the rectum, which induces a relaxation of the internal anal sphincter, allowing feces to travel further down the anal canal; this refl ex is known as the recto-anal inhibitory refl ex (RAIR ). Subsequently, sensory stimuli caused by rectal distension and by the contact between fecal material and the mucosa of the proximal part of the anal canal result in an urge to defecate. At this point, voluntary contraction of the external anal sphincter can postpone defecation, by moving the fecal load back, higher up in the anal canal and rectum, until the place and time are appropriate for defection. When defecation is initiated, voluntary relaxation of the external anal sphincter and the pelvic fl oor musculature (...

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“…Constipation negatively impacts quality of life and is associated with a significant economic burden to the patients and society. The annual health care cost for CIC was around $7,500 per patient in United States (Liem et al, 2009; Sanchez and Bercik, 2011; Hoekman and Benninga, 2013; Chu et al, 2014). In China, expenditure for over-the-counter (OTC) laxatives is over 8 billion RMB per year (Chu et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…Linaclotide, a guanylate cyclase type C (GC-C) receptor agonist, stimulates CFTR-mediated Cl − secretion via elevation of intracellular cGMP level (Tien et al, 1994). Linaclotide can also increase intestinal motility through activation of colonic sensory and motor neurons (Hoekman and Benninga, 2013; Chu et al, 2014). Lubiprostone, a prostaglandin E (PGE) analog, was once regarded to activate type-2 chloride channel (ClC-2)-mediated Cl − secretion in enterocytes, but subsequent studies indicated that lubiprostone activated CFTR chloride channel through E-type prostanoid 4 (EP4) receptors (Norimatsu et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Luminally Acting Agents for Constipation Treatment: A Review Based on Literatures and Patents

Yang

2017

Front. Pharmacol.

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Constipation is one of the most frequently reported gastrointestinal (GI) disorders that negatively impacts quality of life and is associated with a significant economic burden to the patients and society. Traditional treatments including lifestyle modification and laxatives are often ineffective in the more severe forms of constipation and over the long term. New medications targeting at intestinal chloride channels and colonic serotonin receptors have been demonstrated effective in recent years. Emerging agents focusing on improving intestinal secretion and/or colonic motility have been shown effective in animal models and even in clinical trials. Recognization of the role of cystic fibrosis transmembrane regulator (CFTR) and calcium-activated chloride channels (CaCCs) in intestine fluid secretion and motility modulation makes CFTR and CaCCs promising molecule targets for anti-constipation therapy. Although there are multiple choices for constipation treatment, there is still a recognized need for new medications in anti-constipation therapy. The present review covers the discovery of luminally acting agents for constipation treatment described in both patents (2011–present) and scientific literatures.

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Functional constipation in childhood: current pharmacotherapy and future perspectives

Cited by 32 publications

References 100 publications

Gastrointestinal and nutritional problems in neurologically impaired children

Gastrointestinal and nutritional problems in neurologically impaired children

Functional Constipation in Children

Luminally Acting Agents for Constipation Treatment: A Review Based on Literatures and Patents

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